Treatment methods using vadadustat

Abstract

The present invention provides methods for the treatment of anemia in patients with chronic kidney disease (CKD) using vadadustat (Compound 1), including methods suitable for patient conversion, correction, and maintenance therapy. For example, the methods described herein are durable, with efficacy observed for 24 to 52 weeks. The methods described herein may be particularly beneficial for patients converting from previous anemia treatments involving administration of erythropoietin-stimulating agents (ESAs) such as darbepoetin alfa (DA), CKD patients on dialysis (e.g., peritoneal dialysis or hemodialysis), or CKD patients with certain hemoglobin (Hb) levels.

Description

Technical field

[0001] Cross-reference to related applications This application is based on U.S. Provisional Application No. 62 / 928,994, filed October 31, 2019, U.S. Provisional Application No. 62 / 931,458, filed November 6, 2019, dated November 8, 2019. No. 62 / 933,077, filed on September 2, 2020, and U.S. Provisional Patent Application No. 63 / 073,612, filed September 2, 2020, the contents of which are each incorporated by reference. is incorporated herein in its entirety. [Background technology]

[0002] Treatment of anemia associated with chronic kidney disease (CKD) using erythropoiesis-stimulating agents (ESAs) such as epoetin alfa, epoetin beta, darbepoetin, or peginesatide is often undesirable, including hypertension and thromboembolic events. Produces long-term physiological erythropoietin (EPO) levels that are associated with increased cardiovascular side effects. Therefore, there is a need for treatment of anemia associated with chronic kidney disease (CKD) without long-term physiological erythropoietin (EPO) levels. [Outline of the Invention]

[0003] The present invention provides effective methods for the treatment of patients with anemia associated with chronic kidney disease (CKD), including methods suitable for patient conversion, correction, and maintenance therapy. For example, the methods described herein were durable and efficacy was observed for at least about 24-52 weeks or at least about 260 weeks. Although the methods described herein may be useful in general, patients converting from prior anemia therapy that includes administration of an erythropoietin stimulating agent (ESA) (e.g., darbepoetin alfa (DA), epoetin alfa, or epoetin) beta), patients with little or no previous ESA exposure, dialysis-dependent CKD patients (DD-CKD patients), non-dialysis-dependent CKD patients (NDD-CKD patients), or certain hemoglobin (Hb) levels may be particularly beneficial for CKD patients with

[0004] Methods of the invention include methods of treating anemia.

[0005] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0006] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0007] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0008] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0009] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0010] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0011] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0012] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 10 U / kg to about 500 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 10 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 100 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0013] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0014] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0015] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg to about 1.20 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg to about 1.20 mcg / kg once a month.

[0016] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0017] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0018] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0019] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0020] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0021] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0022] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0023] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0024] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0025] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0026] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0027] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0028] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks.

[0029] In another aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3 -chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 52 weeks, Doses contain about 150-600 mg of Compound 1 and are administered once daily.

[0030] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 52 weeks, A dose contains about 150-600 mg of Compound 1 and is administered once a week.

[0031] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 52 weeks, Doses contain approximately 150-600 mg of Compound 1, and doses are administered three times weekly.

[0032] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of Compound 1. Including, the dose is administered once daily.

[0033] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of Compound 1. Including, the dose is administered once a week.

[0034] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of Compound 1. Including, doses are administered three times a week.

[0035] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks.

[0036] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0037] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0038] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0039] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0040] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0041] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0042] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0043] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0044] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0045] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0046] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0047] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0048] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0049] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0050] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0051] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0052] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0053] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0054] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0055] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0056] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0057] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0058] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks, Doses contain about 150-600 mg of Compound 1 and are administered once daily.

[0059] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks, A dose contains about 150-600 mg of Compound 1 and is administered once a week.

[0060] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks, Doses contain approximately 150-600 mg of Compound 1, and doses are administered three times weekly.

[0061] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL.

[0062] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0063] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0064] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0065] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0066] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0067] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0068] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0069] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0070] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0071] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0072] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0073] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0074] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0075] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0076] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0077] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0078] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0079] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0080] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0081] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0082] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0083] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0084] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0085] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, and the dose comprises about 150-600 mg of Compound 1, and the dose is administered once daily.

[0086] In another aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3 -chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a pharmaceutically acceptable salt thereof orally for at least about 52 weeks, wherein the patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, and the dose is about 150 g / dL to about 13.0 g / dL; Doses containing ~600 mg Compound 1 are administered once daily.

[0087] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, and the dose comprises about 150-600 mg of Compound 1, and the dose is administered once weekly.

[0088] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, and the dose comprises about 150-600 mg of Compound 1, and the dose is administered three times weekly.

[0089] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, and the patient has a serum ferritin level of about ≧100 ng / mL and / or a transferrin saturation (TSAT) of ≧20%.

[0090] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or a transferrin saturation (TSAT) of ≧20%, and the dose contains approximately 150-600 mg of Compound 1, and the dose is administered once daily.

[0091] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or a transferrin saturation (TSAT) of ≧20%, and the dose contains approximately 150-600 mg of Compound 1, and doses are administered once weekly.

[0092] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or a transferrin saturation (TSAT) of ≧20%, and the dose contains approximately 150-600 mg of Compound 1, and doses are administered three times weekly.

[0093] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of a pharmaceutically acceptable salt thereof, obtaining the patient's hemoglobin (Hb) level, and the patient's hemoglobin (Hb) level <11.0 g / dL or >11.5 g / dL and then adjusting the dose by about 150 mg Compound 1 only.

[0094] In embodiments, the patient has a hemoglobin level of about <11.0 g / dL. In embodiments, the patient has a hemoglobin level of about >11.5 g / dL. In embodiments, the patient has a hemoglobin level from about ≧9.5 g / dL to about <11.0 g / dL. In embodiments, the patient has a hemoglobin level from about ≧8.0 g / dL to about <11.0 g / dL. In embodiments, the patient has a hemoglobin level of about ≧12.0 g / dL. In embodiments, the patient has a hemoglobin level of about ≧13.0 g / dL.

[0095] In embodiments, the method comprises titrating only about 150 mg of Compound 1 if the patient's hemoglobin (Hb) level is <10.0 g / dL or >11.5 g / dL. In embodiments, the method comprises titrating only about 150 mg of Compound 1 if the patient's hemoglobin (Hb) level is <10.0 g / dL or >12.5 g / dL. In embodiments, the method comprises titrating only about 150 mg of Compound 1 if the patient's hemoglobin (Hb) level is <10.0 g / dL. In embodiments, the method comprises titrating only about 150 mg of Compound 1 if the patient's hemoglobin (Hb) level is >11.5 g / dL.

[0096] In embodiments, adjusting the dose occurs no more than once every two weeks at least. In embodiments, adjusting the dose occurs no more than once every four weeks at least. In embodiments, adjusting the dose occurs no more than once every six weeks at least.

[0097] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0098] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0099] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0100] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0101] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0102] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0103] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0104] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0105] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0106] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0107] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0108] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0109] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0110] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0111] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0112] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0113] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0114] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0115] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0116] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0117] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of a pharmaceutically acceptable salt thereof, obtaining a hemoglobin (Hb) level in the patient, and the hemoglobin (Hb) level in the patient is <10.0 g / dL or >11.5 g / dL and then adjusting the dose by about 150 mg Compound 1 only.

[0118] In embodiments, the patient has a hemoglobin level of about <10.0 g / dL. In embodiments, the patient has a hemoglobin level of about >11.5 g / dL. In embodiments, the patient has a hemoglobin level from about 9.5 g / dL to about <10.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about <10.0 g / dL. In embodiments, the patient has a hemoglobin level of about >12.0 g / dL. In embodiments, the patient has a hemoglobin level of about >13.0 g / dL.

[0119] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of a pharmaceutically acceptable salt thereof, obtaining the patient's hemoglobin (Hb) level, and the patient's hemoglobin (Hb) level <10.0 g / dL or >12.5 g / dL and then adjusting the dose by about 150 mg Compound 1 only.

[0120] In embodiments, the patient has a hemoglobin level of about <10.0 g / dL. In embodiments, the patient has a hemoglobin level of about >12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.5 g / dL to about <10.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about <10.0 g / dL. In embodiments, the patient has a hemoglobin level of about >12.5 g / dL. In embodiments, the patient has a hemoglobin level of about >13.0 g / dL.

[0121] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof; obtaining a hemoglobin (Hb) level in the patient; and reducing the dose by about 150 mg Compound 1 if the increase >2.0 g / dL over the 4-week period.

[0122] In embodiments, the dose reduction occurs no more than once every two weeks at least.

[0123] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0124] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0125] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0126] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0127] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0128] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0129] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0130] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0131] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0132] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0133] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0134] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0135] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0136] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0137] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0138] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0139] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0140] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0141] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0142] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0143] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0144] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the hemoglobin level is less than or equal to baseline hemoglobin in the patient Levels are increased to about 10.0-13.0 g / dL.

[0145] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0146] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0147] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0148] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0149] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0150] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0151] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0152] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0153] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0154] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0155] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0156] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0157] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0158] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0159] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0160] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0161] In embodiments, the baseline hemoglobin level in the patient is about <10 g / dL. In embodiments, the baseline hemoglobin level in the patient is about ≦9 g / dL. Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, wherein the hemoglobin level is increased from the baseline hemoglobin level in the patient to about 10.0-13.0 g / dL.

[0162] In embodiments, the hemoglobin level is increased to about 10.0-12.0 g / dL. In embodiments, the hemoglobin level is increased to about 10.0-11.0 g / dL. In embodiments, the hemoglobin level is increased to about 11.0-13.0 g / dL.

[0163] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0164] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0165] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0166] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0167] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0168] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, wherein the hemoglobin level is increased from the baseline hemoglobin level in the patient to about 10.0-13.0 g / dL.

[0169] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, the dose comprising about 150-600 mg of Compound 1, the dose administered once daily, hemoglobin Levels are increased from baseline hemoglobin levels in the patient to approximately 10.0-13.0 g / dL.

[0170] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, wherein the dose comprises about 150-600 mg of Compound 1, the dose is administered once weekly, and the hemoglobin level is increased from baseline hemoglobin levels in patients to approximately 10.0-13.0 g / dL.

[0171] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, the dose comprising about 150-600 mg of Compound 1, the dose being administered three times a week, and the hemoglobin level is increased from baseline hemoglobin levels in patients to approximately 10.0-13.0 g / dL.

[0172] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of the compound 1, the dose is administered once daily and the hemoglobin level is increased from baseline hemoglobin levels in the patient to about 10.0-13.0 g / dL.

[0173] In one aspect, the invention provides a method of increasing levels in a patient with anemia associated with or secondary to chronic kidney disease, the method comprising the structure of Compound 1 {[5-(3-chlorophenyl )-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of the compound 1, the dose is administered once weekly, and the hemoglobin level is increased from baseline hemoglobin levels in the patient to about 10.0-13.0 g / dL.

[0174] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of the compound 1, doses are administered three times weekly, and hemoglobin levels are increased from baseline hemoglobin levels in the patient to about 10.0-13.0 g / dL.

[0175] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 53-260 weeks, wherein the hemoglobin level is increased from the baseline hemoglobin level in the patient to about 10.0-13.0 g / dL .

[0176] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0177] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0178] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0179] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0180] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0181] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0182] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0183] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0184] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0185] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0186] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0187] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0188] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0189] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0190] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0191] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0192] In embodiments, the baseline hemoglobin level in the patient is about <10 g / dL. In embodiments, the baseline hemoglobin level in the patient is about ≦9 g / dL. In embodiments, the baseline hemoglobin level in the patient is about ≦8 g / dL.

[0193] In embodiments, the hemoglobin level is increased to about 10.0-12.0 g / dL. In embodiments, the hemoglobin level is increased to about 10.0-11.0 g / dL. In embodiments, the hemoglobin level is increased to about 11.0-13.0 g / dL.

[0194] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0195] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0196] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0197] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0198] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0199] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally administered to the patient for at least about 53-250 weeks, the dose comprising about 150-600 mg of Compound 1, the dose being administered once daily. , the hemoglobin level is increased from the baseline hemoglobin level in the patient to approximately 10.0-13.0 g / dL.

[0200] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally administered to the patient for at least about 53-260 weeks, the dose comprising about 150-600 mg of Compound 1, the dose administered once weekly; Hemoglobin levels are increased from baseline hemoglobin levels in the patient to about 10.0-13.0 g / dL.

[0201] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally administered to the patient for at least about 53-260 weeks, the dose comprising about 150-600 mg of Compound 1, the dose administered three times a week; Hemoglobin levels are increased from baseline hemoglobin levels in the patient to about 10.0-13.0 g / dL.

[0202] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, and the hemoglobin level is increased from the baseline hemoglobin level in the patient to about 10.0-13.0 g / dL. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0203] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0204] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0205] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0206] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0207] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0208] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0209] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0210] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0211] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0212] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0213] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0214] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0215] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0216] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0217] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0218] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0219] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0220] In embodiments, the patient has a baseline hemoglobin level of about ≧8.0 to about <10.0 g / dL prior to administration of the Compound 1 dose. In embodiments, the patient has a baseline hemoglobin level of about ≧8.0 g / dL. In embodiments, the patient has a baseline hemoglobin level of about <10.0 g / dL. In embodiments, the patient has a baseline hemoglobin level of about ≧8.0-9.5 g / dL. In embodiments, the patient has a baseline hemoglobin level of about ≧9.0 g / dL. In embodiments, the patient has a baseline hemoglobin level of about ≧9.0 to about <10.0 g / dL.

[0221] In embodiments, the hemoglobin level is increased to about 10.0-12.0 g / dL. In embodiments, the hemoglobin level is increased to about 10.0-11.0 g / dL. In embodiments, the hemoglobin level is increased to about 11.0-13.0 g / dL.

[0222] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0223] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0224] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0225] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0226] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0227] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the dose comprises about 150-600 mg of Compound 1, and the dose is about 150-600 mg Compound 1 per day. Administered once. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0228] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the dose comprises about 150-600 mg Compound 1, the dose is once weekly. administered once. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0229] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the dose comprises about 150-600 mg Compound 1, and the dose is 3 times weekly. administered once. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0230] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a basal hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the patient has a serum ferritin level of about >100 ng / mL and / or a serum ferritin level of >20%. Has transferrin saturation (TSAT). Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0231] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or ≧20% with a transferrin saturation (TSAT) of about 150-600 mg of Compound 1, administered once daily. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0232] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or ≧20% with a transferrin saturation (TSAT) of about 150-600 mg of Compound 1, and doses are administered once weekly. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0233] In one aspect, the invention provides a method of increasing hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is increased to about 10.0-13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or ≧20% with a transferrin saturation (TSAT) of about 150-600 mg of Compound 1, and doses are administered three times weekly. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0234] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, the patient receiving an erythropoiesis stimulating agent (ESA) have been previously treated with

[0235] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0236] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0237] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0238] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0239] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0240] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0241] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0242] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0243] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0244] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0245] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0246] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0247] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0248] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly. In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0249] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0250] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0251] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0252] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0253] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0254] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0255] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0256] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 52 weeks, The patient has been previously treated with an erythropoiesis-stimulating agent (ESA).

[0257] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof for at least about 52 weeks, The patient has been previously treated with an erythropoiesis-stimulating agent (ESA), with a dose comprising about 150-600 mg, administered once daily.

[0258] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and A dose contains about 150-600 mg of Compound 1 and is administered once a week.

[0259] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and Doses contain approximately 150-600 mg of Compound 1, and doses are administered three times weekly.

[0260] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, the patient receiving an erythropoiesis stimulating agent (ESA) and the dose comprises about 150-600 mg of Compound 1, administered once daily.

[0261] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, the patient receiving an erythropoiesis stimulating agent (ESA) and the dose comprises about 150-600 mg of Compound 1, and the dose is administered once weekly.

[0262] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, the patient receiving an erythropoiesis stimulating agent (ESA) and the dose comprises approximately 150-600 mg of Compound 1, and the dose is administered three times weekly.

[0263] In one aspect, the invention provides a method of treating anemia, wherein the method comprises treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA).

[0264] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0265] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0266] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0267] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0268] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0269] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0270] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0271] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0272] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0273] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0274] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0275] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0276] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0277] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0278] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0279] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0280] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0281] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0282] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0283] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0284] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0285] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0286] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally for at least about 53 to 260 weeks, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and Doses contain about 150-600 mg of Compound 1 and are administered once daily.

[0287] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and A dose contains about 150-600 mg of Compound 1 and is administered once a week.

[0288] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] orally administering a dose of or a pharmaceutically acceptable salt thereof for at least about 53 to 260 weeks, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and Doses contain approximately 150-600 mg of Compound 1, and doses are administered three times weekly.

[0289] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, wherein the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL.

[0290] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0291] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53-260 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0292] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0293] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0294] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0295] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0296] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0297] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0298] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0299] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0300] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0301] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0302] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0303] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0304] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0305] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0306] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0307] In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 13.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level from about 8.0 g / dL to about 11.0 g / dL. In embodiments, the patient has a hemoglobin level from about 9.0 g / dL to about 12.0 g / dL. In embodiments, the patient has a hemoglobin level of about 9.5 g / dL to about 12.0 g / dL, and the patient has a hemoglobin level of about 9.0 g / dL to about 12.5 g / dL.

[0308] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0309] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0310] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0311] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0312] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0313] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the dose is about 150-600 mg Compound 1. and the dose is administered once daily.

[0314] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the dose is about 150-600 mg Compound 1. and doses are administered once weekly.

[0315] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the dose is about 150-600 mg Compound 1. and doses are administered three times a week.

[0316] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the patient has a serum level of about ≧100 ng / mL Have ferritin levels and / or transferrin saturation (TSAT) > 20%.

[0317] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the patient has a serum level of about ≧100 ng / mL With ferritin levels and / or transferrin saturation (TSAT) > 20%, doses comprise approximately 150-600 mg of Compound 1, doses administered once daily.

[0318] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, the patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the patient has a hemoglobin level of about ≧100 ng / dL; The method wherein the serum ferritin level is in mL and / or the transferrin saturation (TSAT) is ≧20%, the dose comprises about 150-600 mg of Compound 1, and the dose is administered once weekly.

[0319] In one aspect, the invention provides a method of treating anemia, the method comprising treating a patient with anemia associated with or secondary to chronic kidney disease having the structure of Compound 1 {[5-(3- a compound that is chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a dose of a pharmaceutically acceptable salt thereof, The patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the patient has a serum level of about ≧100 ng / mL With ferritin levels and / or transferrin saturation (TSAT) > 20%, doses contain about 150-600 mg of Compound 1, doses are administered three times weekly.

[0320] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a pharmaceutically acceptable salt dose thereof for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks to the patient, wherein the hemoglobin level is about 10.0-13.0 g maintained or controlled at / dL.

[0321] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0322] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0323] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0324] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0325] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0326] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0327] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0328] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0329] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0330] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0331] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0332] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0333] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0334] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0335] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0336] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0337] In embodiments, hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 10.0-12.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 11.0-13.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 10.0-11.0 g / dL.

[0338] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0339] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0340] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0341] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0342] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0343] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, wherein the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL.

[0344] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, the dose comprising about 150-600 mg of Compound 1, the dose being administered once daily, hemoglobin Levels are maintained or controlled at approximately 10.0-13.0 g / dL.

[0345] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, the dose comprising about 150-600 mg of Compound 1, the dose being administered once weekly, and the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL.

[0346] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 52 weeks, the dose comprising about 150-600 mg of Compound 1, the dose being administered three times a week, and the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL.

[0347] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of the compound 1, the dose is administered once daily and the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL.

[0348] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of the compound 1, doses are administered weekly and hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL.

[0349] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the dose is about 150-600 mg of the compound 1, doses are administered three times weekly, and hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL.

[0350] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] Orally administering to the patient a dose of or a pharmaceutically acceptable salt thereof for at least about 53-260 weeks, wherein the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL.

[0351] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0352] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0353] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0354] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0355] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0356] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0357] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0358] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0359] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0360] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0361] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0362] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0363] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0364] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0365] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0366] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0367] In embodiments, hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 10.0-12.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 11.0-13.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 10.0-11.0 g / dL.

[0368] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0369] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0370] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0371] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0372] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0373] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally administered to the patient for at least about 53-260 weeks, the dose comprising about 150-600 mg of Compound 1, the dose being administered once daily. , the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL.

[0374] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally administered to the patient for at least about 53-260 weeks, the dose comprising about 150-600 mg of Compound 1, the dose administered once weekly; Hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL.

[0375] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or a dose of a pharmaceutically acceptable salt thereof orally administered to the patient for at least about 53-260 weeks, the dose comprising about 150-600 mg of Compound 1, the dose administered three times a week; Hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL.

[0376] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, and the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0377] In embodiments, the dose of Compound 1 is administered to the patient for at least about 24 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 28 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 32 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 36 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 40 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 44 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 48 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 52 weeks.

[0378] In embodiments, the dose of Compound 1 is administered to the patient for at least about 53 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 64 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 76 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 88 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 104 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 116 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 128 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 140 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 156 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 168 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 180 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 192 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 208 weeks. In embodiments, the dose of Compound 1 is administered to the patient for at least about 260 weeks.

[0379] In embodiments, the patient has nondialysis-dependent chronic kidney disease (NDD-CKD). In embodiments, the patient has dialysis-dependent chronic kidney disease (DD-CKD).

[0380] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA). In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 8 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the patient has been previously treated with an erythropoiesis stimulating agent (ESA) within about 6 weeks prior to or during the screening period prior to administering a dose of Compound 1. In embodiments, the screening period is up to about 8 weeks. In embodiments, the screening period is up to about 6 weeks. In embodiments, the screening period is up to about 4 weeks.

[0381] In embodiments, the erythropoiesis stimulating agent is epoetin, darbepoetin alfa, methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), or a combination thereof. In embodiments, the erythropoiesis stimulating agent preparation is epoetin. In embodiments, the erythropoiesis stimulating agent preparation is darbepoetin alfa. In embodiments, the erythropoiesis stimulating agent preparation is methoxypolyethylene glycol-epoetin beta (epoetin beta pegol).

[0382] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0383] In embodiments, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA) at any of the ESA dosages described herein.

[0384] In embodiments, the patient has been previously treated with epoetin alfa in an amount of about 50 U / kg to about 300 U / kg three times per week. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta at a dose of about 1.2 mcg / kg once every two weeks.

[0385] In embodiments, the patient has been previously treated with epoetin at a dose of about ≧4500 IU weekly. In embodiments, the patient has been previously treated with epoetin at a dose of about <4500 IU.

[0386] In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once a week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week. In embodiments, the patient has been previously treated with darbepoetin alfa at a dose of about <15 μg per week.

[0387] In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 0.6 mcg / kg once every two weeks. In embodiments, the patient has been previously treated with epoetin beta pegol at a dose of about 1.20 mcg / kg once a month.

[0388] In embodiments, the patient has not been previously treated with an erythropoiesis-stimulating agent (ESA).

[0389] In embodiments, the dose comprises about 150-600 mg of Compound 1.

[0390] In embodiments, the dose comprises about 150 mg of Compound 1. In embodiments, the dose comprises about 300 mg of Compound 1. In embodiments, the dose comprises about 450 mg of Compound 1. In embodiments, the dose comprises about 600 mg of Compound 1.

[0391] In embodiments, the dose of Compound 1 is administered once daily. In embodiments, doses of Compound 1 are administered once weekly. In embodiments, doses of Compound 1 are administered three times weekly.

[0392] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered once daily. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered once daily.

[0393] In embodiments, the dose comprises about 150 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 300 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 450 mg of Compound 1 and the dose is administered three times weekly. In embodiments, the dose comprises about 600 mg of Compound 1 and the dose is administered three times weekly.

[0394] In embodiments, the patient has a baseline hemoglobin level of about ≧8 to about <10.0 g / dL prior to administration of the Compound 1 dose. In embodiments, the patient has a baseline hemoglobin level of about ≧8.0 g / dL. In embodiments, the patient has a baseline hemoglobin level of about <10.0 g / dL. In embodiments, the patient has a baseline hemoglobin level of about ≧8.0-9.5 g / dL. In embodiments, the patient has a baseline hemoglobin level of about ≧9.0 g / dL. In embodiments, the patient has a baseline hemoglobin level of about ≧9.0 to about <10.0 g / dL.

[0395] In embodiments, hemoglobin levels are maintained or controlled at about 10.0-13.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 10.0-12.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 11.0-13.0 g / dL. In embodiments, hemoglobin levels are maintained or controlled at about 10.0-11.0 g / dL.

[0396] In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL. In embodiments, the patient has a transferrin saturation (TSAT) of about ≧20%. In embodiments, the patient has a serum ferritin level of about ≧100 ng / mL and a transferrin saturation (TSAT) of about ≧20%.

[0397] In embodiments, the patient has an increase in total iron-binding capacity (TIBC) over baseline levels. The baseline level is the patient's TIBC level prior to Compound 1 administration.

[0398] In embodiments, the patient has decreased hepcidin levels relative to baseline levels. The baseline level is the patient's hepcidin level prior to administration of Compound 1.

[0399] In embodiments, the patient has decreased serum ferritin levels relative to baseline levels. The baseline level is the patient's serum ferritin level prior to administration of Compound 1.

[0400] In embodiments, the patient is an adult. In embodiments, the patient is ≧18 years old. In embodiments, the patient is ≧20 years old.

[0401] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, the dose comprises about 150-600 mg of Compound 1, the dose is It is administered once daily. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0402] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, the dose comprises about 150-600 mg of Compound 1, the dose is Administered once weekly. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0403] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, the dose comprises about 150-600 mg of Compound 1, the dose is It is administered 3 times a week. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0404] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a basal hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, and the patient has a serum ferritin level of about >100 ng / mL and / or >20 g / dL. % transferrin saturation (TSAT). Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0405] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or ≧ With a transferrin saturation (TSAT) of 20%, doses contain approximately 150-600 mg of Compound 1, and doses are administered once daily. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0406] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or ≧ With a transferrin saturation (TSAT) of 20%, doses contain approximately 150-600 mg of Compound 1 and are administered once weekly. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0407] In one aspect, the invention provides a method of maintaining or controlling hemoglobin levels in a patient with anemia associated with or secondary to chronic kidney disease, the method having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering to the patient a dose of a pharmaceutically acceptable salt thereof; The patient has a baseline hemoglobin level of about <10 g / dL, the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or ≧ With a transferrin saturation (TSAT) of 20%, doses contain approximately 150-600 mg of Compound 1, and doses are administered three times weekly. Baseline hemoglobin level is the patient's hemoglobin level prior to administration of Compound 1.

[0408] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0409] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0410] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received a daily dose of compound 1 of approximately 150-600 mg, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0411] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received a daily dose of compound 1 of approximately 150-600 mg, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was treated with an erythropoiesis-stimulating agent (ESA), Patients receive Compound 1 for at least about 52 weeks.

[0412] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0413] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0414] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0415] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0416] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0417] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0418] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received a daily dose of compound 1 of approximately 150-600 mg, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0419] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received a daily dose of compound 1 of approximately 150-600 mg, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0420] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received a daily dose of compound 1 of approximately 150-600 mg, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0421] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0422] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0423] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0424] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0425] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0426] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0427] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every 4 weeks.

[0428] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks.

[0429] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly.

[0430] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about ≧15 μg weekly.

[0431] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about <15 μg weekly.

[0432] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0433] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0434] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0435] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0436] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0437] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0438] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0439] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0440] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0441] In embodiments, the patient has been previously treated with epoetin, which was epoetin alpha, at a dose of about 50 U / kg to about 300 U / kg three times per week.

[0442] In embodiments, the patient was previously treated with epoetin, which was epoetin beta, at a dose of about 0.6 mcg / kg once every two weeks.

[0443] In embodiments, the patient has been previously treated with epoetin, which was epoetin beta, at a dose of about 1.2 mcg / kg once every two weeks.

[0444] In embodiments, the patient has been previously treated with epoetin at a dose > about 4500 IU weekly.

[0445] In embodiments, the patient has been previously treated with epoetin at a dose of < about 4500 IU weekly.

[0446] In embodiments, the patient receives a dose of Compound 1 that is about 150 mg.

[0447] In embodiments, the patient receives a dose of Compound 1 that is about 300 mg.

[0448] In embodiments, the patient receives a dose of Compound 1 that is about 450 mg.

[0449] In embodiments, the patient receives a dose of Compound 1 that is about 600 mg.

[0450] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0451] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0452] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0453] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0454] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0455] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0456] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0457] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0458] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0459] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0460] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0461] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0462] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0463] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0464] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0465] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0466] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0467] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0468] In embodiments, the dose of Compound 1 is about 150 mg.

[0469] In embodiments, the dose of Compound 1 is about 300 mg.

[0470] In embodiments, the dose of Compound 1 is about 450 mg.

[0471] In embodiments, the dose of Compound 1 is about 600 mg.

[0472] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dosage of the patient's previous ESA, the patient's hemoglobin (Hb) level, and / or the patient's dialysis status.

[0473] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA and / or the patient's previous dose of ESA.

[0474] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's hemoglobin (Hb) level.

[0475] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's hemoglobin (Hb) level of <about 11 g / dL.

[0476] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's dialysis status.

[0477] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on patients with non-dialysis dependent chronic kidney disease (NDD-CKD).

[0478] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on patients with dialysis-dependent chronic kidney disease (DD-CKD).

[0479] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dose of the patient's previous ESA, and the patient's hemoglobin (Hb) level.

[0480] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and

[0481] The initial dose of Compound 1 is selected based on the patient's previous ESA, the dose of the patient's previous ESA, and the patient's hemoglobin (Hb) level of <about 11 g / dL. In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the patient's previous dose of ESA, and the patient's dialysis status.

[0482] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the patient's previous dose of ESA, and the patient with non-dialysis-dependent chronic kidney disease (NDD-CKD).

[0483] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the patient's previous dose of ESA, and the patient with dialysis-dependent chronic kidney disease (DD-CKD).

[0484] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level, and the patient's dialysis status.

[0485] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was selected based on the patient's previous ESA, the patient's previous ESA dosage, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and the patient's dialysis status. be.

[0486] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was based on the patient's previous ESA, the patient's previous ESA dose, the patient's hemoglobin (Hb) level, and patients with nondialysis-dependent chronic kidney disease (NDD-CKD). selected based on

[0487] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was determined according to the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level, and patients with dialysis-dependent chronic kidney disease (DD-CKD). selected based on

[0488] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was adjusted to the patient's previous ESA, the patient's previous ESA dose, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and nondialysis-dependent chronic kidney disease (NDD). -CKD).

[0489] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was based on the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and dialysis-dependent chronic kidney disease (DD- selected based on patients with CKD).

[0490] In embodiments, the erythropoiesis stimulating agent (ESA) is darbepoetin alfa.

[0491] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every 4 weeks.

[0492] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks.

[0493] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly.

[0494] In embodiments, the patient has been previously treated with a weekly dose of darbepoetin alfa of ≧about 15 μg.

[0495] In embodiments, the patient has been previously treated with a weekly dose of <about 15 μg of darbepoetin alfa.

[0496] In embodiments, the erythropoiesis stimulating agent (ESA) is epoetin.

[0497] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0498] In embodiments, the patient has been previously treated with epoetin, which was epoetin alpha, at a dose of about 50 U / kg to about 300 U / kg three times per week.

[0499] In embodiments, the patient was previously treated with epoetin, which was epoetin beta, at a dose of about 0.6 mcg / kg once every two weeks.

[0500] In embodiments, the patient has been previously treated with epoetin, which was epoetin beta, at a dose of about 1.2 mcg / kg once every two weeks.

[0501] In embodiments, the weekly dose of epoetin is ≧about 4500 IU.

[0502] In embodiments, the weekly dose of epoetin is <about 4500 IU.

[0503] In embodiments, the initial dose is about 150-600 mg Compound 1.

[0504] In embodiments, the initial dose is about 150 mg Compound 1.

[0505] In embodiments, the initial dose is about 300 mg Compound 1.

[0506] In embodiments, the initial dose is about 450 mg Compound 1.

[0507] In embodiments, the initial dose is about 600 mg Compound 1.

[0508] In embodiments, the method comprises administering a dose of Compound 1 daily.

[0509] In embodiments, the method comprises administering a dose of Compound 1 about once a week.

[0510] In embodiments, the method comprises administering doses of Compound 1 about three times a week.

[0511] In embodiments, the dose of Compound 1 is about 150 mg.

[0512] In embodiments, the dose of Compound 1 is about 300 mg.

[0513] In embodiments, the dose of Compound 1 is about 450 mg.

[0514] In embodiments, the dose of Compound 1 is about 600 mg.

[0515] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients will be assessed approximately 6 weeks after initiation of treatment with Compound 1 based on the ESA previously received by the patient, the dose of ESA previously received by the patient, the hemoglobin (Hb) level of the patient, and / or the dialysis status of the patient. The dose of Compound 1 will be increased within 24 hours.

[0516] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The patient receives a dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the ESA the patient previously received and / or the dose of ESA previously received by the patient.

[0517] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the patient's hemoglobin (Hb) level.

[0518] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive a dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the patient's hemoglobin (Hb) level of <about 11 g / dL.

[0519] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive dose escalation of Compound 1 within about 6 weeks after initiation of Compound 1 treatment based on the patient's dialysis status.

[0520] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 dose escalation within about 6 weeks after initiation of Compound 1 treatment based on patients with nondialysis-dependent chronic kidney disease (NDD-CKD).

[0521] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on patients with dialysis-dependent chronic kidney disease (DD-CKD).

[0522] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients are expected to complete a dose of Compound 1 within approximately 6 weeks of starting treatment with Compound 1 based on the patient's previous ESA, the dose of previous ESA the patient received, and the patient's hemoglobin (Hb) level. receive an increase.

[0523] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients will receive within about 6 weeks of starting treatment with Compound 1 based on the patient's previous ESA, the dose of the patient's previous ESA, and the patient's hemoglobin (Hb) level of < about 11 g / dL Receive dose escalation of Compound 1.

[0524] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive a dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the patient's previous ESA, the dose of previous ESA the patient received, and the patient's dialysis status. .

[0525] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were expected to recover approximately 6 months after starting treatment with Compound 1 based on the ESA they had previously received, the dose of ESA they had previously received, and patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Receive dose escalation of Compound 1 within a week.

[0526] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were assessed approximately 6 weeks after initiation of treatment with Compound 1 based on the patient's previous ESA, the dose of ESA the patient had previously received, and patients with dialysis-dependent chronic kidney disease (DD-CKD). The dose of Compound 1 will be increased within 24 hours.

[0527] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Within approximately 6 weeks after initiation of treatment with Compound 1, the patient will receive Receive dose escalation of Compound 1.

[0528] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were selected to initiate treatment with Compound 1 based on the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and the patient's dialysis status. Receive a dose escalation of Compound 1 within about 6 weeks thereafter.

[0529] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were assessed for their previous ESA, the dose of their previous ESA, their hemoglobin (Hb) level <approximately 11 g / dL, and nondialysis-dependent chronic kidney disease (NDD-CKD). Patients with Compound 1 receive dose escalation within about 6 weeks after initiation of Compound 1 treatment.

[0530] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patient has previous ESA, patient's previous dose of ESA, patient's hemoglobin (Hb) level <approximately 11 g / dL, and dialysis-dependent chronic kidney disease (DD-CKD) On a patient basis, dose escalation of Compound 1 is received within about 6 weeks after initiation of Compound 1 treatment.

[0531] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were assessed for their previous ESA, the dose of their previous ESA, their hemoglobin (Hb) level <approximately 11 g / dL, and nondialysis-dependent chronic kidney disease (NDD-CKD). Patients with Compound 1 receive dose escalation within about 6 weeks after initiation of Compound 1 treatment.

[0532] In one aspect, the invention features a method of treating anemia, comprising treating a patient with anemia associated with or secondary to chronic kidney disease with the structure {[5-(3-chlorophenyl)- a compound that is 3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were screened based on the patient's previous ESA, the dose of ESA the patient had previously received, the patient's hemoglobin (Hb) level, and patients with dialysis-dependent chronic kidney disease (DD-CKD). Receive dose escalation of Compound 1 within about 6 weeks after initiation of treatment with 1.

[0533] In embodiments, the erythropoiesis stimulating agent (ESA) is darbepoetin alfa.

[0534] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every 4 weeks.

[0535] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks.

[0536] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly.

[0537] In embodiments, the patient has been previously treated with a weekly dose of darbepoetin alfa of ≧about 15 μg.

[0538] In embodiments, the patient has been previously treated with a weekly dose of <about 15 μg of darbepoetin alfa.

[0539] In embodiments, the erythropoiesis stimulating agent (ESA) is epoetin.

[0540] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0541] In embodiments, the patient has been previously treated with epoetin, which was epoetin alpha, at a dose of about 50 U / kg to about 300 U / kg three times per week.

[0542] In embodiments, the patient was previously treated with epoetin, which was epoetin beta, at a dose of about 0.6 mcg / kg once every two weeks.

[0543] In embodiments, the patient has been previously treated with epoetin, which was epoetin beta, at a dose of about 1.2 mcg / kg once every two weeks.

[0544] In embodiments, the patient has been previously treated with a weekly dose of epoetin of ≧about 4500 IU.

[0545] In embodiments, the patient has been previously treated with a weekly dose of <about 4500 IU of epoetin.

[0546] In embodiments, the initial dose is about 150 mg Compound 1.

[0547] In embodiments, the initial dose is about 300 mg Compound 1.

[0548] In embodiments, the dose escalation results in a dose of compound 1 of about 450 mg.

[0549] In embodiments, the dose escalation results in a dose of compound 1 of about 600 mg.

[0550] In embodiments, the method further comprises administering a dose of Compound 1 daily.

[0551] In embodiments, the method further comprises administering a dose of Compound 1 about once a week.

[0552] In embodiments, the method further comprises administering doses of Compound 1 about three times a week.

[0553] In embodiments, the patient receives Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0554] In embodiments, the patient receives Compound 1 for at least about 44, 48, or 52 weeks.

[0555] In embodiments, the patient has been previously treated with ESA therapy within about 8 weeks of initiation of treatment with Compound 1 or initiation of an initial screening period prior to initiation of treatment with Compound 1.

[0556] In embodiments, the initial screening period is about 4 weeks or less.

[0557] In embodiments, the patient is an adult.

[0558] In embodiments, the method further comprises testing the patient's hemoglobin level weekly.

[0559] In embodiments, the method further comprises testing the patient's hemoglobin level once every two weeks.

[0560] In embodiments, the method further comprises testing the patient's hemoglobin level monthly.

[0561] In embodiments, the patient's hemoglobin level is maintained in the range of about 10.0 g / dL to about 13.0 g / dL.

[0562] In embodiments, the patient's hemoglobin level is maintained in the range of about 10.0 g / dL to about 12.0 g / dL, and the patient has anemia associated with or secondary to dialysis-dependent chronic kidney disease.

[0563] In embodiments, the patient's hemoglobin level is maintained in the range of about 11.0 g / dL to about 13.0 g / dL, and the patient has anemia associated with or secondary to non-dialysis-dependent chronic kidney disease.

[0564] In embodiments, the method further comprises adjusting the dose of the compound if the patient's hemoglobin level is less than 10.0 g / dL or greater than 13.0 g / dL.

[0565] In embodiments, adjusting the dose of the compound is reducing the dose by about 150 mg if the patient's hemoglobin level is greater than 13.0 g / dL or the patient's hemoglobin level is less than 11.0 g / dL In some cases, the patient has anemia associated with or secondary to nondialysis-dependent chronic kidney disease, including increasing the dose by about 150 mg.

[0566] In embodiments, adjusting the dose of the compound is reducing the dose by about 150 mg if the patient's hemoglobin level is greater than 12.0 g / dL or the patient's hemoglobin level is less than 10.0 g / dL In some cases, the patient has anemia associated with or secondary to dialysis-dependent chronic kidney disease, including increasing the dose by about 150 mg.

[0567] The invention also features a method of maintaining or controlling hemoglobin levels in a patient.

[0568] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0569] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0570] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0571] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0572] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0573] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0574] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0575] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0576] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0577] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 52 weeks.

[0578] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0579] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0580] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0581] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0582] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0583] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0584] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0585] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0586] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 52 weeks.

[0587] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every 4 weeks.

[0588] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks.

[0589] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly.

[0590] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about ≧15 μg weekly.

[0591] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about <15 μg weekly.

[0592] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0593] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0594] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received daily doses of approximately 150-600 mg of Compound 1, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0595] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0596] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0597] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0598] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0599] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0600] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 52 weeks.

[0601] In embodiments, the patient has been previously treated with epoetin, which was epoetin alpha, at a dose of about 50 U / kg to about 300 U / kg three times per week.

[0602] In embodiments, the patient was previously treated with epoetin, which was epoetin beta, at a dose of about 0.6 mcg / kg once every two weeks.

[0603] In embodiments, the patient has been previously treated with epoetin, which was epoetin beta, at a dose of about 1.2 mcg / kg once every two weeks.

[0604] In embodiments, the patient has been previously treated with epoetin at a dose > about 4500 IU weekly.

[0605] In embodiments, the patient has been previously treated with epoetin at a dose of < about 4500 IU weekly.

[0606] In embodiments, the patient receives a dose of Compound 1 that is about 150 mg.

[0607] In embodiments, the patient receives a dose of Compound 1 that is about 300 mg.

[0608] In embodiments, the patient receives a dose of Compound 1 that is about 450 mg.

[0609] In embodiments, the patient receives a dose of Compound 1 that is about 600 mg.

[0610] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0611] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0612] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0613] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0614] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0615] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0616] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0617] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0618] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has dialysis-dependent chronic kidney disease (DD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0619] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0620] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0621] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0622] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0623] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received daily doses of approximately 150-600 mg of Compound 1, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0624] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0625] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg once weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0626] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), darbepoetin alfa (DA), Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0627] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient has nondialysis-dependent chronic kidney disease (NDD-CKD), Patients received doses of Compound 1 that were approximately 150-600 mg three times weekly, The patient had previously been treated with an erythropoiesis-stimulating agent (ESA), epoetin, and Patients receive Compound 1 for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

[0628] In embodiments, the dose of Compound 1 is about 150 mg.

[0629] In embodiments, the dose of Compound 1 is about 300 mg.

[0630] In embodiments, the dose of Compound 1 is about 450 mg.

[0631] In embodiments, the dose of Compound 1 is about 600 mg.

[0632] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dosage of the patient's previous ESA, the patient's hemoglobin (Hb) level, and / or the patient's dialysis status.

[0633] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA and / or the patient's previous dose of ESA.

[0634] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's hemoglobin (Hb) level.

[0635] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's hemoglobin (Hb) level of <about 11 g / dL.

[0636] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's dialysis status.

[0637] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on patients with non-dialysis dependent chronic kidney disease (NDD-CKD).

[0638] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on patients with dialysis-dependent chronic kidney disease (DD-CKD).

[0639] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dose of the patient's previous ESA, and the patient's hemoglobin (Hb) level.

[0640] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dose of the patient's previous ESA, and the patient's hemoglobin (Hb) level of <about 11 g / dL.

[0641] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the patient's previous dose of ESA, and the patient's dialysis status.

[0642] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the patient's previous dose of ESA, and the patient with non-dialysis-dependent chronic kidney disease (NDD-CKD).

[0643] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the patient's previous dose of ESA, and the patient with dialysis-dependent chronic kidney disease (DD-CKD).

[0644] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 is selected based on the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level, and the patient's dialysis status.

[0645] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was selected based on the patient's previous ESA, the patient's previous ESA dosage, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and the patient's dialysis status. be.

[0646] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was based on the patient's previous ESA, the patient's previous ESA dose, the patient's hemoglobin (Hb) level, and patients with nondialysis-dependent chronic kidney disease (NDD-CKD). selected based on

[0647] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was determined according to the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level, and patients with dialysis-dependent chronic kidney disease (DD-CKD). selected based on

[0648] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was adjusted to the patient's previous ESA, the patient's previous ESA dose, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and nondialysis-dependent chronic kidney disease (NDD). -CKD).

[0649] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering an initial dose of a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The initial dose of Compound 1 was based on the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and dialysis-dependent chronic kidney disease (DD- selected based on patients with CKD).

[0650] In embodiments, the erythropoiesis stimulating agent (ESA) is darbepoetin alfa.

[0651] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every 4 weeks.

[0652] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks.

[0653] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly.

[0654] In embodiments, the patient has been previously treated with a weekly dose of darbepoetin alfa of ≧about 15 μg.

[0655] In embodiments, the patient has been previously treated with a weekly dose of <about 15 μg of darbepoetin alfa.

[0656] In embodiments, the erythropoiesis stimulating agent (ESA) is epoetin.

[0657] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0658] In embodiments, the patient has been previously treated with epoetin, which was epoetin alpha, at a dose of about 50 U / kg to about 300 U / kg three times per week.

[0659] In embodiments, the patient was previously treated with epoetin, which was epoetin beta, at a dose of about 0.6 mcg / kg once every two weeks.

[0660] In embodiments, the patient has been previously treated with epoetin, which was epoetin beta, at a dose of about 1.2 mcg / kg once every two weeks.

[0661] In embodiments, the patient has been previously treated with a weekly dose of epoetin of ≧about 4500 IU.

[0662] In embodiments, the patient has been previously treated with a weekly dose of <about 4500 IU of epoetin.

[0663] In embodiments, the initial dose is about 150-600 mg Compound 1.

[0664] In embodiments, the initial dose is about 150 mg Compound 1.

[0665] In embodiments, the initial dose is about 300 mg Compound 1.

[0666] In embodiments, the initial dose is about 450 mg Compound 1.

[0667] In embodiments, the initial dose is about 600 mg Compound 1.

[0668] In embodiments, the method comprises administering a dose of Compound 1 daily.

[0669] In embodiments, the method comprises administering a dose of Compound 1 about once a week.

[0670] In embodiments, the method comprises administering doses of Compound 1 about three times a week.

[0671] In embodiments, the dose of Compound 1 is about 150 mg.

[0672] In embodiments, the dose of Compound 1 is about 300 mg.

[0673] In embodiments, the dose of Compound 1 is about 450 mg.

[0674] In embodiments, the dose of Compound 1 is about 600 mg.

[0675] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients will be assessed approximately 6 weeks after initiation of treatment with Compound 1 based on the ESA previously received by the patient, the dose of ESA previously received by the patient, the hemoglobin (Hb) level of the patient, and / or the dialysis status of the patient. The dose of Compound 1 will be increased within 24 hours.

[0676] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and The patient receives a dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the ESA the patient previously received and / or the dose of ESA previously received by the patient.

[0677] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the patient's hemoglobin (Hb) level.

[0678] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive a dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the patient's hemoglobin (Hb) level of <about 11 g / dL.

[0679] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive dose escalation of Compound 1 within about 6 weeks after initiation of Compound 1 treatment based on the patient's dialysis status.

[0680] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive Compound 1 dose escalation within about 6 weeks after initiation of Compound 1 treatment based on patients with nondialysis-dependent chronic kidney disease (NDD-CKD).

[0681] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on patients with dialysis-dependent chronic kidney disease (DD-CKD).

[0682] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients are expected to complete a dose of Compound 1 within approximately 6 weeks of starting treatment with Compound 1 based on the patient's previous ESA, the dose of previous ESA the patient received, and the patient's hemoglobin (Hb) level. receive an increase.

[0683] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients will receive within about 6 weeks of starting treatment with Compound 1 based on the patient's previous ESA, the dose of the patient's previous ESA, and the patient's hemoglobin (Hb) level of < about 11 g / dL Receive an increased dose of Compound 1.

[0684] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients receive a dose escalation of Compound 1 within about 6 weeks after initiation of treatment with Compound 1 based on the patient's previous ESA, the dose of previous ESA the patient received, and the patient's dialysis status. .

[0685] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were expected to recover approximately 6 months after starting treatment with Compound 1 based on the ESA they had previously received, the dose of ESA they had previously received, and patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Receive dose escalation of Compound 1 within a week.

[0686] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were assessed approximately 6 weeks after initiation of treatment with Compound 1 based on the patient's previous ESA, the dose of ESA the patient had previously received, and patients with dialysis-dependent chronic kidney disease (DD-CKD). The dose of Compound 1 will be increased within 24 hours.

[0687] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Within approximately 6 weeks after initiation of treatment with Compound 1, the patient will receive Receive an increased dose of Compound 1.

[0688] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were selected to initiate treatment with Compound 1 based on the patient's previous ESA, the dose of the patient's previous ESA, the patient's hemoglobin (Hb) level of <approximately 11 g / dL, and the patient's dialysis status. Receive a dose escalation of Compound 1 within about 6 weeks thereafter.

[0689] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were assessed for their previous ESA, the dose of their previous ESA, their hemoglobin (Hb) level <approximately 11 g / dL, and nondialysis-dependent chronic kidney disease (NDD-CKD). Patients with Compound 1 receive dose escalation within about 6 weeks after initiation of Compound 1 treatment.

[0690] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patient has previous ESA, patient's previous dose of ESA, patient's hemoglobin (Hb) level <approximately 11 g / dL, and dialysis-dependent chronic kidney disease (DD-CKD) On a patient basis, dose escalation of Compound 1 is received within about 6 weeks after initiation of Compound 1 treatment.

[0691] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were assessed for their previous ESA, the dose of their previous ESA, their hemoglobin (Hb) level <approximately 11 g / dL, and nondialysis-dependent chronic kidney disease (NDD-CKD). Patients with Compound 1 receive dose escalation within about 6 weeks after initiation of Compound 1 treatment.

[0692] In one aspect, the invention features a method of maintaining or controlling hemoglobin levels in a patient, wherein the patient has anemia associated with or secondary to chronic kidney disease, having the structure of Compound 1 {[5-( 3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, [formation] or orally administering a pharmaceutically acceptable salt thereof, The patient was previously treated with an erythropoiesis-stimulating agent (ESA) and Patients were screened based on the patient's previous ESA, the dose of ESA the patient had previously received, the patient's hemoglobin (Hb) level, and patients with dialysis-dependent chronic kidney disease (DD-CKD). Receive dose escalation of Compound 1 within about 6 weeks after initiation of treatment with 1.

[0693] In embodiments, the erythropoiesis stimulating agent (ESA) is darbepoetin alfa.

[0694] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every 4 weeks.

[0695] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once every two weeks.

[0696] In embodiments, the patient has been previously treated with darbepoetin alfa (DA) at a dose of about 0.45 mcg / kg to about 0.75 mcg / kg once weekly.

[0697] In embodiments, the patient has been previously treated with a weekly dose of darbepoetin alfa of ≧about 15 μg.

[0698] In embodiments, the patient has been previously treated with a weekly dose of <about 15 μg of darbepoetin alfa.

[0699] In embodiments, the erythropoiesis stimulating agent (ESA) is epoetin.

[0700] In embodiments, the epoetin is epoetin alpha, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

[0701] In embodiments, the patient has been previously treated with epoetin, which was epoetin alpha, at a dose of about 50 U / kg to about 300 U / kg three times per week.

[0702] In embodiments, the patient was previously treated with epoetin, which was epoetin beta, at a dose of about 0.6 mcg / kg once every two weeks.

[0703] In embodiments, the patient has been previously treated with epoetin, which was epoetin beta, at a dose of about 1.2 mcg / kg once every two weeks.

[0704] In embodiments, the patient has been previously treated with a weekly dose of epoetin of ≧about 4500 IU.

[0705] In embodiments, the patient has been previously treated with a weekly dose of <about 4500 IU of epoetin.

[0706] In embodiments, the initial dose is about 150 mg Compound 1.

[0707] In embodiments, the initial dose is about 300 mg Compound 1.

[0708] In embodiments, the dose escalation results in a dose of compound 1 of about 450 mg.

[0709] In embodiments, the dose escalation results in a dose of compound 1 of about 600 mg.

[0710] In embodiments, the method further comprises administering a dose of Compound 1 daily.

[0711] In embodiments, the method further comprises administering a dose of Compound 1 about once a week.

[0712] In embodiments, the method further comprises administering doses of Compound 1 about three times a week.

[0713] In embo...

Claims

1. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Chemistry 1】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for treating anemia in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering the pharmaceutical composition to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks.

2. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Chemistry 2】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for increasing hemoglobin levels in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering the pharmaceutical composition to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the hemoglobin level is increased to about 10.0 to 13.0 g / dL from a baseline hemoglobin level in the patient.

3. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Transformation 3】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for maintaining or controlling hemoglobin levels in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering the pharmaceutical composition to the patient for at least about 24, 28, 32, 36, 40, 44, 48, or 52 weeks, wherein the hemoglobin level is maintained or controlled at about 10.0 to 13.0 g / dL.

4. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Chemistry 4】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for treating anemia in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering the pharmaceutical composition to the patient for at least about 53 to 260 weeks.

5. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Transformation 5】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for increasing hemoglobin levels in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering the pharmaceutical composition to the patient for at least about 53 to 260 weeks, wherein the hemoglobin level is increased to about 10.0 to 13.0 g / dL from a baseline hemoglobin level in the patient.

6. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Transformation 6】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for maintaining or controlling hemoglobin levels in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering the pharmaceutical composition to the patient for at least about 53 to 260 weeks, wherein the hemoglobin level is maintained or controlled at about 10.0 to 13.0 g / dL.

7. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Transformation 7】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for treating anemia in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering to the patient a dose of Compound 1 or a pharmaceutically acceptable salt thereof, and adjusting the dose of Compound 1 or a pharmaceutically acceptable salt thereof by about 150 mg increments if the patient's hemoglobin (Hb) level is <11.0 g / dL or >11.5 g / dL.

8. Compound 1, which is {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid having the following structure: 【Transformation 8】 or a pharmaceutically acceptable salt thereof, The pharmaceutical composition is used in a method for treating anemia in a patient having anemia associated with or secondary to chronic kidney disease, and The method comprises orally administering to the patient a dose of Compound 1 or a pharmaceutically acceptable salt thereof, wherein the dose of Compound 1 or a pharmaceutically acceptable salt thereof is decreased by about 150 mg increments if the patient's hemoglobin (Hb) level increases by >1.0 g / dL over a two-week period or >2.0 g / dL over a four-week period.

9. 4. The pharmaceutical composition of any one of claims 1 to 3, wherein the method comprises orally administering the pharmaceutical composition to the patient for at least about 40, 44, 48, or 52 weeks.

10. 7. The pharmaceutical composition of any one of claims 4 to 6, wherein the method comprises orally administering the pharmaceutical composition to the patient for at least about 53, 64, 76, 88, 104, 116, 128, 140, 156, 168, 180, 192, 208, or 260 weeks.

11. The pharmaceutical composition according to any one of claims 1 to 8, wherein the patient has non-dialysis-dependent chronic kidney disease (NDD-CKD) or dialysis-dependent chronic kidney disease (DD-CKD).

12. 9. The pharmaceutical composition of any one of claims 1 to 8, wherein the patient has been previously treated with an erythropoiesis stimulating agent (ESA), optionally within about 6 weeks or about 8 weeks before or during a screening period prior to administering a dose of Compound 1 or a pharmaceutically acceptable salt thereof.

13. 13. The pharmaceutical composition of claim 12, wherein the erythropoiesis-stimulating agent is epoetin, darbepoetin alfa (DA), or methoxypolyethylene glycol-epoetin beta (epoetin beta pegol), and optionally the epoetin is epoetin alfa, epoetin beta, epoetin gamma, epoetin kappa, or a combination thereof.

14. 14. The pharmaceutical composition of claim 13, wherein the patient has been previously treated with epoetin alfa in an amount of about 10 U / kg to about 500 U / kg, about 10 U / kg to about 300 U / kg, about 50 U / kg to about 300 U / kg, or about 50 U / kg to about 100 U / kg three times per week.

15. 14. The pharmaceutical composition of claim 13, wherein the patient has previously been treated with epoetin beta pegol at a dosage of about 0.6mcg / kg to about 1.20mcg / kg once every two weeks, about 0.6mcg / kg to about 1.20mcg / kg once a month, about 0.6mcg / kg once every two weeks, or about 1.2mcg / kg once every two weeks.

16. 14. The pharmaceutical composition of claim 13, wherein the patient has previously been treated with epoetin at a dose of about ≧4500 IU or about <4500 IU weekly.

17. 14. The pharmaceutical composition of claim 13, wherein the patient has previously been treated with darbepoetin alfa (DA) at a dosage of about 0.45 mcg / kg to about 0.75 mcg / kg once every four weeks, once every two weeks, or once every week.

18. 14. The pharmaceutical composition of claim 13, wherein the patient has been previously treated with darbepoetin alfa at a dose of about ≧15 μg per week or about <15 μg per week.

19. The pharmaceutical composition of any one of claims 1 to 8, wherein the patient has not been previously treated with an erythropoiesis stimulating agent (ESA).

20. 19. The pharmaceutical composition of any one of claims 1-8 and 13-18, wherein the patient is orally administered a dose comprising about 150-600 mg of Compound 1 or a pharmaceutically acceptable salt thereof, optionally about 150, 300, 450, or 600 mg of Compound 1 or a pharmaceutically acceptable salt thereof.

21. 21. The pharmaceutical composition of claim 20, wherein the dose of Compound 1 or a pharmaceutically acceptable salt thereof is administered once daily, once weekly, or three times weekly.

22. 3. The pharmaceutical composition of claim 2, wherein the hemoglobin level is increased to about 10.0-11.0, 10.0-12.0, or 11.0-13.0 g / dL.

23. 4. The pharmaceutical composition of claim 3, wherein the hemoglobin level is maintained or controlled at about 10.0-13.0 g / dL, optionally 10.0-11.0, 10.0-12.0, or 11.0-13.0 g / dL.

24. 10. The pharmaceutical composition of claim 1, wherein: (a) the method comprises orally administering to the patient, for at least about 52 weeks, Compound 1 or a pharmaceutically acceptable salt thereof, wherein the patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the dose of Compound 1 or a pharmaceutically acceptable salt thereof comprising about 150 to 600 mg of Compound 1 or a pharmaceutically acceptable salt thereof, and wherein the dose is administered once daily; (b) the patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has a serum ferritin level of about ≧100 ng / mL and / or a transferrin saturation (TSAT) of about ≧20%, the dose comprising about 150-600 mg of Compound 1 or a pharmaceutically acceptable salt thereof, and the dose is administered once daily; (c) obtaining a hemoglobin (Hb) level of the patient and adjusting the dose of Compound 1 or a pharmaceutically acceptable salt thereof by about 150 mg if the patient's hemoglobin (Hb) level is <10.0 g / dL or >11.5 g / dL; (d) the patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis stimulating agent (ESA), the dose comprising about 150 to 600 mg of Compound 1 or a pharmaceutically acceptable salt thereof, and the dose is administered once daily; (e) the patient has a hemoglobin level of about 8.0 g / dL to about 13.0 g / dL, the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the patient has a serum ferritin level of about ≧100 ng / mL and / or a transferrin saturation (TSAT) of about ≧20%, the dose comprises about 150 to 600 mg of Compound 1 or a pharmaceutically acceptable salt thereof, and the dose is administered once daily; or (f) the patient has been previously treated with an erythropoiesis-stimulating agent (ESA), and the patient receives an increase in the dose of Compound 1 or a pharmaceutically acceptable salt thereof within about 6 weeks of initiating treatment with Compound 1 or a pharmaceutically acceptable salt thereof based on the ESA the patient previously received, the dose of the ESA the patient previously received, the patient's hemoglobin (Hgb) level, and / or the patient's dialysis status. The pharmaceutical composition.

Images