A combination of finerenone and an SGLT2 inhibitor for the treatment and / or prevention of cardiovascular and / or renal disease.

Abstract

An object of the present invention is to improve the treatment and / or prevention of cardiovascular and renal diseases compared to already known monotherapies. A further object of the present invention is to provide a combination of pharmaceutical active ingredients for treating cardiovascular diseases, particularly cardiac and renal failure, characterized by chronic sodium retention, which reduces patient mortality and / or morbidity. Another object of the present invention is to improve the treatment and / or prevention of cardiovascular and renal diseases by administering a combination comprising finerenone and an SGLT2 inhibitor. [Solution] The present invention relates to pharmaceutical compositions and combinations comprising finerenone or its hydrate, solvate, or pharmaceutically acceptable salt or polymorph thereof, and an SGLT2 inhibitor or its hydrate, solvate, or pharmaceutically acceptable salt or polymorph thereof. The combinations can be used for the treatment and / or prevention of cardiovascular and / or renal diseases in humans and other mammals.

Description

Technical Field

[0001] The present invention relates to finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph, and an SGLT2 inhibitor, its hydrate, solvate, pharmaceutically acceptable salt, or polymorph, in combination for treating and / or preventing cardiovascular disease and / or kidney disease. In particular, these diseases may be characterized by chronic sodium retention.

Background Art

[0002] The body's fluid content is subject to various physiological control mechanisms, the purpose of which is to keep it constant (volume homeostasis). In this process, both the volume filling of the vascular system and the volume osmolality of the plasma are continuously recorded by appropriate sensors (baroreceptors and osmoreceptors). The information supplied by these sensors to the relevant centers in the brain regulates drinking behavior and controls fluid excretion via the kidneys by means of fluid and neural signals.

[0003] The steroid hormone aldosterone promotes sodium retention and potassium secretion in the epithelium of the distal nephron, thus contributing to maintaining fluid and electrolyte homeostasis by keeping the extracellular volume constant and thus regulating blood pressure. In addition to this, aldosterone shows a direct effect on the structure and function of the heart and vascular system, but the underlying mechanism has not yet been fully explained (R.E. Booth, J.P. Johnson, J.D. Stockand, Adv. Physiol. Educ. 26(1), 8 - 20(2002)).

[0004] (S)-4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide, finerenone, a compound of formula (I)

Chemical Formula

[0005] Sodium-glucose cotransporter-2 (SGLT2) is expressed in the proximal tubules and reabsorbs approximately 97% of filtered glucose. SGLT2 inhibitors block the reabsorption of both glucose and sodium, thus acting on glucosuria and natriuresis, resulting in antihyperglycemia, diuretic effects, blood pressure reduction, weight loss, and increased insulin sensitivity. This is an outcome benefit among diabetic patients with chronic heart failure (CHF) and chronic kidney disease (CKD). Interestingly, SGLT2 inhibition has recently been demonstrated to exert cardiovascular and renal benefits not mediated through changes in blood glucose, namely, reduced morbidity and mortality in both diabetic and non-diabetic patients. Although the precise and beneficial mechanisms of action of SGLT2 inhibition, particularly in non-diabetic CHF and / or CKD, are not fully understood, one key component of these benefits is natriuretic activity, as pathological hyperreabsorption of sodium in the early proximal tubules is primarily mediated by increased SGLT2 activity in diabetic kidneys [Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu Rev Med. 2015;66:255-70]. This increased reabsorption reduces sodium delivery to the macula densa, which, via tubuloglomerular feedback, leads to afferent arteriole dilation and glomerular hyperfiltration. Attenuation of this proximal tubular hyperreabsorption of sodium by SGLT2 causes afferent vasoconstriction, thereby reducing glomerular hyperfiltration and renal damage, and improving renal function in the long term. However, the natriuretic effect of SGLT2 inhibitors has been reported to be transient; for example, natriuresis was dose-dependently induced by dapagliflozin during the first 24 hours in healthy individuals, but returned to baseline after 13 days of intervention. Another previous study showed that urinary Na+ excretion tended to increase on day 1 after canagliflozin administration, but returned to baseline between days 2 and 5.

[0006] Therefore, while SGLT2 inhibitors can potently induce diabetes and thus osmotic diuresis, their natriuretic efficacy appears to be limited.

[0007] Known SGLT2 inhibitors include canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0008] (2S,3R,4R,5S,6R)-2-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)-6-(hydroxymethyl)oxan-3,4,5-triol (CAS number: 842133-18-0), canagliflozin represented by the following formula (II) or (IIa) (hemihydrate). [ka] Canagliflozin, also known as Invokana® (for example, the marketed product by Janssen Pharmaceuticals contains canagliflozin hydrate), is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in conjunction with lifestyle modifications, including diet and exercise, to manage type 2 diabetes. It is described in U.S. Patent Nos. 7,943,582, 7,943,788, 8,222,219, and 8,513,202. It was first approved by the FDA in 2013 for the management of diabetes and in 2018 for a second indication: to reduce the risk of cardiovascular events in patients diagnosed with type 2 diabetes. Canagliflozin was the first oral antidiabetic drug approved for the prevention of cardiovascular events in patients with type 2 diabetes. Cardiovascular disease is the most common cause of death in these patients.

[0009] (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol, which is dapagliflozin as shown in formula (III) below. [ka] In particular, it is a medication marketed under the trade name Farxiga® and used to treat type 2 diabetes and, with certain limitations, type 1 diabetes. It belongs to the gliflozin class. It was developed by Bristol-Myers Squibb in collaboration with AstraZeneca. Dapagliflozin is described in U.S. Patent Nos. 6414126, 6515117, 6936590, 7456254, 7851502, 7919598, 8221786, 8329648, 8361972, 8431685, 8461105, 8501698, 8685934, 8716251, 8721615, 8906851, 9198925, and 9238076.

[0010] (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxan-3,4,5-triol, which is empagliflozin represented by the following formula (IV). [ka] In particular, it is a medicine marketed under the trade name Jardiance and used in conjunction with diet and exercise to treat type 2 diabetes. It is described in U.S. Patent Nos. 7,579,449, 7,713,938, 8,551,957, 9,949,997, 9,949,998 and 1,025,8637.

[0011] (1S,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol, which is erzggliflozin represented by the following formula (V). [ka] It is marketed under the trade name Steglatro® and is a drug used to treat type 2 diabetes. It is described in U.S. Patent No. 8080580. In the United States, it has been approved by the Food and Drug Administration for use as monotherapy and in fixed-dose combination with either sitagliptin or metformin.

[0012] Ipragliflozin shown in the following formula (VI) [ka] Ipragliflozin is a drug used to treat type 2 diabetes. Developed jointly by Astellas Pharma and Kotobuki Pharmaceutical, ipragliflozin was approved in Japan on January 17, 2014, and in Russia on May 22, 2019. Its trade name is Suglat®. The compound and its synthesis method are described in International Publication Nos. 2004 / 080990, International Publication Nos. 2005 / 012326, and International Publication Nos. 2007 / 114475.

[0013] Lemogliflozin represented by the following formula (VII) and ethanolate remogliflozin represented by the following formula (VIIa) [ka] Lemogliflozin is a gliflozin-class drug used to treat non-alcoholic steatohepatitis ("NASH") and type 2 diabetes. Discovered by the Japanese company Kissei Pharmaceutical, it is currently under development by BHV Pharma. It is used as remogliflozin ethavone (ethyl[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[5-methyl-1-propan-2-yl-4-[(4-propan-2-yloxyphenyl)methyl]pyrazole-3-yl]oxyoxan-2-yl]methyl carbonate; CAS 442201-24-3; remogliflozin ethavone). "Ethavone" refers to the ethyl carbonate group. The remaining structure, which is the active substance, is called remogliflozin.

[0014] Cergliflozin, represented by formula (VIII) and (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[2-[(4-methoxyphenyl)methyl]phenoxy]oxan-3,4,5-triol, and cergliflozin ethanolate, represented by formula (VIIIa) below and ethyl[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[2-[(4-methoxyphenyl)methyl]phenoxy]oxan-2-yl]methyl carbonate. [ka] It is an investigational antidiabetic drug under development by GlaxoSmithKline in the form of cergliflozin ethavone. "Ethavone" refers to the ethyl carbonate group. The remaining structure, which is the active substance, is called cergliflozin.

[0015] (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol, sotagliflozin represented by the following formula (IX) [Chemical formula] is a drug approved in the EU for certain patients with type I diabetes. It is marketed under the trade name Zynquista® and was developed by Sanofi. International Publication No. WO 2017 / 202351 describes the crystalline forms of sotagliflozin, methods for its preparation and its use.

[0016] Tofogliflozin represented by the following formula (X) [Chemical formula] is a drug for treating diabetes and is under development by Chugai Pharma jointly with Kowa and Sanofi. It is an inhibitor of SGLT2. The name tofogliflozin adopted in the United States applies to the monohydrate, which is the form used as a drug. The international non-proprietary name tofogliflozin applies to the anhydrous compound, and the drug form is called tofogliflozin hydrate.

[0017] In summary, sodium excretion via urine ("natriuresis") is a specific therapeutic target for cardiovascular diseases. For example, neurohumoral stimulation by the renin-angiotensin-aldosterone system (RAAS) or increased SGLT2 expression in the proximal renal tubules contribute to persistent sodium retention and related extracellular volume overload in the development of chronic heart failure and renal insufficiency. In particular, when there is often renal dysfunction associated with heart failure, the body can no longer perform effective natriuresis. Therefore, maintaining effective natriuresis would be useful for the treatment and / or prevention of cardiovascular diseases and / or renal diseases. [Prior art documents]5] [Patent documents]

[0018] [Patent Document 1] International Publication No. 2008 / 104306 Pamphlet [Patent Document 2] International Publication No. 2016 / 016287 Brochure [Patent Document 3] U.S. Patent No. 7943582 [Patent Document 4] U.S. Patent No. 7943788 [Patent Document 5] U.S. Patent No. 8222219 [Patent Document 6] U.S. Patent No. 8513202 [Patent Document 7] U.S. Patent No. 6414126 [Patent Document 8] U.S. Patent No. 6515117 [Patent Document 9] U.S. Patent No. 6936590 [Patent Document 10] U.S. Patent No. 7456254 [Patent Document 11] U.S. Patent No. 7851502 [Patent Document 12] U.S. Patent No. 7919598 [Patent Document 13] U.S. Patent No. 8221786 [Patent Document 14] U.S. Patent No. 8329648 [Patent Document 15] U.S. Patent No. 8361972 [Patent Document 16] U.S. Patent No. 8431685 [Patent Document 17] U.S. Patent No. 8461105 [Patent Document 18] U.S. Patent No. 8501698 [Patent Document 19] U.S. Patent No. 8685934 [Patent Document 20] U.S. Patent No. 8716251 [Patent Document 21] U.S. Patent No. 8721615 [Patent Document 22] U.S. Patent No. 8906851 [Patent Document 23] U.S. Patent No. 9198925 [Patent Document 24] U.S. Patent No. 9238076 [Patent Document 25] U.S. Patent No. 7579449 [Patent Document 26] U.S. Patent No. 7713938 [Patent Document 27] U.S. Patent No. 8551957 [Patent Document 28] U.S. Patent No. 9949997 [Patent Document 29] U.S. Patent No. 9949998 [Patent Document 30] U.S. Patent No. 10258637 [Patent Document 31] U.S. Patent No. 8080580 [Patent Document 32] International Publication No. 2004 / 080990 Pamphlet [Patent Document 33] International Publication No. 2005 / 012326 Pamphlet [Patent Document 34] International Publication No. 2007 / 114475 Pamphlet [Patent Document 35] International Publication No. 2017202351 brochure [Non-patent literature]

[0019] [Non-Patent Document 1] REBooth, JP Johnson, JDStockand, Adv.Physiol.Educ.26(1), 8~20(2002) [Non-Patent Document 2] Vallon V.The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus.Annu Rev Med.2015;66:255-70 [Overview of the project] [Problems that the invention aims to solve]

[0020] The objective of the present invention is to improve the treatment and / or prevention of cardiovascular and renal diseases compared to already known monotherapies.

[0021] A further object of the present invention is to provide a combination of pharmaceutical active ingredients for treating cardiovascular diseases characterized by chronic sodium retention, particularly cardiac and renal failure, which reduces patient mortality and / or morbidity.

[0022] Another objective of the present invention is to improve the treatment and / or prevention of cardiovascular and renal diseases by administering a combination of finerenone and an SGLT2 inhibitor. [Means for solving the problem]

[0023] This invention relates to a combination comprising finerenone and an SGLT2 inhibitor.

[0024] The present invention provides a combination of pharmaceutical active ingredients, namely finerenone and an SGLT2 inhibitor, for treating cardiovascular or renal diseases characterized by chronic sodium retention. Cardiovascular diseases include, for example, congestive heart failure independent of ejection fraction (i.e., heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF)). Renal diseases include, for example, chronic kidney disease (CKD) and diabetic nephropathy, as well as other syndromes, such as cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, or end-organ injury affecting the heart and kidneys, which contribute to increased mortality and / or morbidity in patients.

[0025] Surprisingly, the combination of finerenone and an SGLT2 inhibitor shows a significant improvement in efficacy compared to the combined efficacy of each monotherapy: The combination of finerenone and an SGLT2 inhibitor results in over-additive sodium excretion compared to the monotherapy of finerenone or the SGLT2 inhibitor alone. This over-additive effect was unpredictable and exceeds the pure additive effect of the monotherapy of finerenone and the SGLT2 inhibitor. Since finerenone and the SGLT2 inhibitor target different receptors and / or homeostatic points, the over-additive effect achieved by the combination according to this invention was also unpredictable.

[0026] Since sodium is the most important ion in maintaining bodily volume homeostasis, the additive sodium excretion resulting from the combination according to the present invention leads to a reduction in subsequent congestion. Sodium excretion leads to further water excretion. Water excretion removes undesirable water retention in body tissues. In particular, there is a reduction in cardiac preload. The cardiovascular system is relieved. Thus, therapeutic improvement is achieved by the combination according to the present invention. The combination therapy according to the present invention can provide permanent relief to the entire circulation. This improved natriuretic efficacy is a major clinical goal in the treatment of cardiovascular and renal diseases.

[0027] The combination according to the present invention may provide a lower dose of the therapeutic agent being administered. The combination according to the present invention may provide a longer survival time for treated patients compared to standard treatment.

[0028] Finally, some preliminary data strongly suggest that both finerenone and SGLT2 inhibitors provide renal protection in preclinical non-diabetic hypertensive nephropathy. The combination of these two modes of action at low doses revealed a significant reduction in proteinuria and mortality, demonstrating strong potential for concomitant clinical use in their respective cardiorenal patient populations.

[0029] The present invention relates to a combination comprising a compound of formula (I), finerenone, or its hydrate, solvate, or pharmaceutically acceptable salt, or a polymorph thereof, and an SGLT2 inhibitor, or its hydrate, solvate, or pharmaceutically acceptable salt, or a polymorph thereof, which is a compound of formula (II).

[0030] The "active ingredients" used in the combination according to the present invention are finerenone and an SGLT2 inhibitor. The terms “compound of formula (I)” or “finerenone” refer to ((S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide or ent-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (International Publication No. 2008 / 104306, Example 5, (-) enantiomer) or its hydrate, solvate, pharmaceutically acceptable salt or polymorph thereof. ((S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide and ent -4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide is a synonym. Hereafter, when "finerenone" is referred to herein, it also means its hydrate, solvate, pharmaceutically acceptable salt, or polymorph. Thus, "finerenone" is sometimes used as a synonym for "finerenone, or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph." According to the present invention, finerenone can be used in combination in the form of its hydrate, solvate, pharmaceutically acceptable salt, or polymorph. The polymorphs of finerenone are described in International Publication No. 201616287. The term "finerenone" also includes its anhydrous form.

[0031] The term "SGLT2 inhibitor" is well known in the art. SGLT2 inhibitors, or gliflozin, act by inhibiting sodium-glucose transport protein 2 (SGLT2), thereby inhibiting glucose reabsorption in the kidneys and thus lowering blood glucose levels. Therefore, SGLT2 inhibitors are used to treat type 2 diabetes mellitus (T2DM).

[0032] Examples of SGLT2 inhibitors include canagliflozin, dapagliflozin, empagliflozin, erzgliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin. This list is not exhaustive. The term SGLT2 inhibitor includes its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. Hereafter, when “SGLT2 inhibitor” is referred to herein, it also means its hydrate, solvate, pharmaceutically acceptable salt, prodrug, or its polymorph.

[0033] In one embodiment, the combination according to the present invention includes two or more SGLT2 inhibitors.

[0034] In one embodiment, the SGLT2 inhibitor used in the combination according to the present invention is selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0035] In one embodiment, the SGLT2 inhibitor used in the combination according to the present invention is selected from the group consisting of canagliflozin, dapagliflozin, and empagliflozin.

[0036] In one embodiment, the SGLT2 inhibitor is canagliflozin. The terms “compound according to formula (II)” or “compound according to formula (IIa)” or “canagliflozin” refer to (2S,3R,4R,5S,6R)-2-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)-6-(hydroxymethyl)oxan-3,4,5-triol (CAS number: 842133-18-0), or its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph; or (1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]-methyl]-4-methylphenyl]-D-glucitol, or its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. "Canagliflozin" is also known by the following terms: (1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]-methyl]-4-methylphenyl]-D-glucitol hemihydrate or the commercial product Invokana® (including canagliflozin hydrate, CAS: 928672-86-0), TA 7284, cagliflozin; canagliflozin, JNJ 28431754, canagliflozin, JNJ 24831754ZAE, JNJ 28431754AAA. This list is not exhaustive, as several commercial products containing canagliflozin or further synonyms are available on the market. Hereafter, when "canagliflozin" is referred to herein, it also means the above synonyms / terms.

[0037] In one embodiment, the SGLT2 inhibitor is dapagliflozin. The terms “compound according to formula (III)” or “dapagliflozin” refer to (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol (CAS number: 461432-26-8), or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph. "Dapagliflozin" is also known by the following terms: BMS-512148, Forxiga®, Farxiga®, BMS 512148, UNII-1ULL0QJ8UC, 1ULL0QJ8UC, and (1S)-1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol. This list is not exhaustive, as several commercial products containing dapagliflozin or further synonyms are available on the market. Hereafter, when "dapagliflozin" is referred to herein, it means all of the above synonyms / terms.

[0038] In one embodiment, the SGLT2 inhibitor is empagliflozin. The terms “compound according to formula (IV)” or “empagliflozin” refer to (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxan-3,4,5-triol (CAS number: 864070-44-0), its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. “Empagliflozin” is also known by the following terms: 1-chloro-4-(glucopyranose-1-yl)-2-(4-(tetrahydrofuran-3-yloxy)benzyl)benzene, Jardiance®, BI 10773, BI-10773 and BI10773. This list is not exhaustive, as several commercial products containing empagliflozin or further synonyms are available on the market. Hereafter, when "empagliflozin" is referred to herein, it means all of the above synonyms / terms.

[0039] In one embodiment, the SGLT2 inhibitor is ertugliflozin. The terms “compound according to formula (V)” or “ertugliflozin” refer to (1S,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol (CAS number: 1210344-57-2), its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. "Ertugliflozin" is also known by the following terms: 5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-hydroxymethyl-6,8-dioxabicyclo(3.2.1)octane-2,3,4-triol, PF 04971729, PF-04971729, PF04971729 and 1,6-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-5-C-(hydroxymethyl)-β-L-idopyranose. This list is not exhaustive, as several commercial products containing ertugliflozin or further synonyms are available on the market. Hereafter, when "ertugliflozin" is referred to herein, it means all of the above synonyms / terms.

[0040] In one embodiment, the SGLT2 inhibitor is ipragliflozin. The terms “compound according to formula (VII)” or “ipragliflozin” refer to (2S,3R,4R,5S,6R)-2-[3-(1-benzothiophen-2-ylmethyl)-4-fluorophenyl]-6-(hydroxymethyl)oxane-3,4,5-triol (CAS number: 761423-87-4), its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. "Ipragliflozin" is also known by the following terms: Ipragliflozin L-proline ((2S,3R,4R,5S,6R)-2-[3-(1-benzothiophen-2-ylmethyl)-4-fluorophenyl]-6-(hydroxymethyl)oxane-3,4,5-triol; (2S)-pyrrolidine-2-carboxylic acid; CAS number: 951382-34-6), (1S)-1,5-anhydro-1-(3-(1-benzothiophen-2-ylmethyl)-4-fluorophenyl)-D-glucitol, ASP-1941, ASP1941 and Suglat® (trademark). This list is not exhaustive, as several commercial products containing "ipragliflozin" or further synonyms are available on the market. Hereafter, when "ipragliflozin" is referred to herein, it means all of the above synonyms / terms.

[0041] In one embodiment, the SGLT2 inhibitor is remogliflozin. The terms “compound according to formula (VII)” or “compound according to formula (VIIa)” or “lemogliflozin” refer to remogliflozin, or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph. “Lemogliflozin” is also known by the following terms: remogliflozin etavonate, UNII-TR0QT6QSUL, GSK-189075, TR0QT6QSUL, 442201-24-3, GSK 189075, KGT-1681, GSK-189075A, or SCHEMBL721678. This list is not exhaustive, as several commercial products containing “lemogliflozin” or further synonyms are available on the market. Hereafter, when “lemogliflozin” is referred to herein, it means all of the above synonyms / terms, including “lemogliflozin ethavone” or any anhydrous, hydrate, solvate, or pharmaceutically acceptable salt thereof.

[0042] In one embodiment, the SGLT2 inhibitor is cergliflozin. The terms “compound according to formula (VIII)” or “cergliflozin” refer to its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. The prodrug is, for example, cergliflozin ethavone (CAS: 408504-26-7; ethyl[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[2-[(4-methoxyphenyl)methyl]phenoxy]oxan-2-yl]methyl carbonate). "Sergliflozin" or "Sergliflozin etavonate" are the following terms: (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[2-[(4-methoxyphenyl)methyl]phenoxy]oxane-3,4,5-triol, 2-[(4-methoxyphenyl)methylphenyl 6-O-(ethoxycarbonyl)-β-D-glucopyranoside, Sergliflozin etavonate, SERGLIFLOZIN A, UNII-AR34521QFL, AR34521QFL, CHEMBL270766, O-glucoside, 4a, SCHEMBL2574820, BDBM20878, β-D-glucopyranoside, 2-((4-methoxyphenyl)methyl)phenyl, HFLCZNNDZKKXCS-OUUBHVDSSA-N, J3.551.075C, ethyl[(2R,3S,4S,5R ,6S)-3,4,5-trihydroxy-6-[2-[(4-methoxyphenyl)methyl]phenoxy]oxan-2-yl]methyl carbonate, UNII-4HY3523466, GW869682X, 4HY3523466, also known as 2-(4-methoxybenzyl)phenyl 6-O-(ethoxycarbonyl)-β-D-glucopyranoside, CHEMBL450044. This list is not exhaustive, as several commercial products containing “cergliflozin” or further synonyms are available on the market. Hereafter, when “cergliflozin” is referred to herein, it means all of the above synonyms / terms.

[0043] In one embodiment, the SGLT2 inhibitor is sotagliflozin. The terms “compound according to formula (IX)” or “sotagliflozin” or “(2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol” (CAS number: 1018899-04-1) refer to its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. “Sotagliflozin” is also known by the following terms: (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol, Zynquista® (trademark), LX-4211, and LX4211. This list is not exhaustive, as several commercial products containing "sotagliflozin" or further synonyms exist on the market. Hereafter, when "sotagliflozin" is referred to herein, it means all of the above synonyms / terms.

[0044] In one embodiment, the SGLT2 inhibitor is tofogliflozin. The terms “compound according to formula (X)” or “tofogliflozin” or “(3S,3'R,4'S,5'S,6'R)-5-[(4-ethylphenyl)methyl]-6'-(hydroxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-3',4',5'-triol” refer to its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph. The CAS number for the hydrate is 1201913-82-7, and the CAS number for the anhydrous is 903565-83-3. The name adopted in the United States, tofogliflozin, applies to the monohydrate, which is the form used as a drug. The international generic name tofogliflozin applies to the anhydrous compound, and the drug form is called tofogliflozin hydrate. "Tofogliflozin" is also known by the following terms: 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol, (3S,3'R,4'S,5'S,6'R)-5-[(4-ethylphenyl)methyl]-6'-(hydroxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-3',4',5'-triol, Apleway, CSG452, Deberza, tofogliflozin anhydrous, or tofogliflozin hydrate. This list is not exhaustive, as several commercial products containing "tofogliflozin" or further synonyms are available on the market. Hereafter, when "tofogliflozin" is referred to herein, it means all of the above synonyms / terms.

[0045] For the purposes of this invention, a "solvate" is a compound or a salt thereof containing, but not limited to, water, ethanol, and methanol, in which solvent molecules form a stoichiometric complex in the solid state.

[0046] A "hydrate" is a specific form of a solvate in which the solvent molecule is water. The hydrates of the compounds or salts of the present invention are, for example, monohydrates, dihydrates, trihydrates, hemihydrates, sesquihydrates, and other stoichiometric compositions of the compounds or salts with water.

[0047] For the purposes of the present invention, the “salt” is preferably a “pharmaceutically acceptable salt” of finerenone and / or an SGLT2 inhibitor. Suitable pharmaceutically acceptable salts that can be used in combinations according to the present invention are well known to those skilled in the art and include salts of inorganic acids, organic acids, inorganic bases, alkaline cations, alkaline earth cations and organic bases. In one embodiment, the pharmaceutically acceptable salt is hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 1-naphthalenesulfonic acid, 2-naphthalenesulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid and mandelic acid, acetate, benzoic acid, besilate, bromide, cansylate, carbonate, citrate, edisylate, estrate, fumarate, gluceptate The following may be selected: luconate, glucuronate, hippurate, iodide, isethionate, lactate, lactobionate, malate, maleate, mesylate, methylsulfate, napsylate, nitrate, oxalate, pamoate, phosphate, stearate, succinate, sulfate, tartrate, bisartrate, tosylate, calcium, diolamine, lithium, lysine, magnesium, meglumine, N-methylglucamine, olamine, potassium, tromethamine, tris(hydroxymethyl)aminomethane, benzenesulfonate, ethanesulfonate, and zinc.

[0048] In one embodiment, the pharmaceutically acceptable salt may be selected from hydrochloride, sulfate, mesylate, tosylate, tartrate, citrate, benzenesulfonate, ethanesulfonate, maleate, and phosphate.

[0049] The term “combination” in this invention is used as is known to those skilled in the art. A combination comprises or consists of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof and an SGLT2 inhibitor, its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof. For the purposes of this invention, “combinations” include fixed combinations, combination packs, parts kits, unfixed combinations and / or components (finerenone, SGLT2 inhibitor) administered simultaneously or sequentially. The term “component” refers to finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and an SGLT2 inhibitor, its hydrate, solvate, or pharmaceutically acceptable salt, i.e., one component of a combination according to this invention is finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and the other component is an SGLT2 inhibitor, its hydrate, solvate, or pharmaceutically acceptable salt. Combinations according to this invention may also contain further components.

[0050] In one embodiment of the present invention, the combination is a fixed combination. The term “fixed combination” in the present invention is used as is known to those skilled in the art. It is defined as a combination that contains or includes finerenone and an SGLT2 inhibitor in one pharmaceutical dosage form or one single entity. An example of a “fixed combination” is a pharmaceutical composition in which finerenone and an SGLT2 inhibitor are present in a mixed state. Another example of a “fixed combination” is a pharmaceutical combination in which finerenone and an SGLT2 inhibitor are present in one dosage form without being mixed. Another example of a “fixed combination” is a pharmaceutical combination in which finerenone and an SGLT2 inhibitor are present in which they are present in at least a partial mixed state.

[0051] "Medical dosage form" and "dosage form" are synonymous. A "medicinal dosage form" or "dosage form" is the physical manifestation of a product containing or including active and / or inactive components (e.g., carriers, excipients) intended to be delivered to a patient. "Dosage form" is a term used in the European Pharmacopoeia. While "dosage form" was previously used in standard terminology, the term "medicinal dosage form" is now used to harmonize with the vocabulary used for drug identification (see https: / / www.edqm.eu / sites / default / files / standard_terms_introduction_and_guidance_for_use.pdf). Common dosage forms include pills, tablets, capsules, syrups, aerosols, injections, powders, or solid crystals. Further pharmaceutical formulations or dosage forms are disclosed below. The route of administration for drug delivery depends on the dosage form of the active ingredient.

[0052] In one embodiment of the present invention, the combination is a combination pharmaceutical dosage form. The term “combination pharmaceutical dosage form” is used to describe a pharmaceutical consisting of two or more manufactured products that are intended to be combined to produce a single pharmaceutical product for administration to a patient, by combining two or more pharmaceutical dosage forms into a single term. A combination pharmaceutical dosage form is not used to combine pharmaceutical dosage forms that are packaged together but administered separately, rather than being combined to produce a single pharmaceutical product (see combination pack instead). In one embodiment, the combination pharmaceutical dosage form comprises a soluble powder, tablet or granule containing finerenone and / or an SGLT2 inhibitor, as well as a solvent for dissolving or dispersing the powder, tablet or granule. The combination pharmaceutical dosage form is not limited to this exemplary embodiment. Various combinations of dosage forms disclosed herein are suitable for combinations according to the present invention.

[0053] In one embodiment of the present invention, the combination is an unfixed combination or parts kit. In the present invention, an “unfixed combination” or “parts kit” is defined as a combination in which finerenone and an SGLT2 inhibitor are present in two or more units or dosage forms, as used as known to those skilled in the art. The components of an unfixed combination or parts kit can be administered separately, sequentially, simultaneously, concurrently, or chronologically staggered. In one embodiment of an unfixed combination or parts kit, finerenone and the SGLT2 inhibitor are present separately. In one embodiment, the unfixed combination or parts kit comprises a pharmaceutical composition containing finerenone and a pharmaceutical composition containing an SGLT2 inhibitor. In one embodiment, the unfixed combination or parts kit comprises a dosage form containing finerenone and a dosage form containing an SGLT2 inhibitor. An unfixed combination or parts kit is not limited to one or more of these exemplary embodiments. Various combinations of dosage forms disclosed herein are suitable for combinations according to the present invention.

[0054] Non-fixed combinations or parts kits are particularly advantageous when separate components must be administered in different dosage forms or at different dosing intervals.

[0055] In one embodiment, the combination according to the present invention is a combination pack.

[0056] In a "combination pack," the active substance is contained in separate dosage forms that are marketed in the same package. Combination packs are used to combine two or more dosages to describe products that are packaged together but administered separately as independent pharmaceutical products, sequentially, simultaneously, concurrently, or alternately. A combination is different from a combination pharmaceutical dosage form. In one embodiment, a combination pack contains a first dosage form containing finerenone and a second dosage form containing an SGLT2 inhibitor. In one embodiment, a combination pack contains a first oral dosage form containing finerenone and a second oral dosage form containing an SGLT2 inhibitor. The oral dosage forms can be selected from the oral dosage forms described herein and in any combination. In one embodiment, a combination pack contains a tablet containing finerenone and granules for oral solution containing an SGLT2 inhibitor, and vice versa. In this embodiment, the combination contains a tablet as an administerable dosage form and an oral solution as an administerable dosage form.

[0057] In one embodiment, the combination according to the present invention, finerenone and an SGLT2 inhibitor, are administered sequentially or separately. In the combination according to the present invention, the compounds are administered in at least two distinct dosage forms.

[0058] In one embodiment, the distinct dosage forms are identical. In one example of this embodiment, the combination includes a first tablet containing finerenone and a second tablet containing an SGLT2 inhibitor (in this specification, since both dosage forms are tablets, the distinct dosage forms are identical). This embodiment is not limited to a combination of two tablets. Further dosage forms that can be used in this embodiment are disclosed below. This embodiment in which the distinct dosage forms are identical can be used, for example, in combination drug administration forms, unfixed combinations, parts kits and / or combination packs.

[0059] In one embodiment, different dosage forms are used. In one example of this embodiment, the combination includes a tablet containing finerenone and a capsule containing an SGLT2 inhibitor (in this specification, different dosage forms are used because the dosage forms are different from each other). This embodiment is not limited to a combination of tablets and capsules. Further dosage forms that can be used in this embodiment are disclosed below. This embodiment with different dosage forms can be used, for example, in combination drug administration forms, unfixed combinations, parts kits and / or combination packs.

[0060] The release of one or more drugs in a combination can also be controlled, as needed, to provide the desired therapeutic activity, whether they are in single dosage forms, combination packs, parts kits, or separate, independent dosage forms.

[0061] In one embodiment, the combination according to the present invention is administered once or multiple times daily. The combination according to the present invention can be administered once daily (once-daily administration). In one embodiment, administration is carried out once or multiple times daily via the oral route. The combination according to the present invention may also include two distinct dosage forms, each of which is given at a different time.

[0062] The present invention includes pharmaceutical compositions or dosage forms comprising a pharmaceutically effective amount of an SGLT2 inhibitor and finerenone, and a pharmaceutically acceptable carrier and / or excipient. The “pharmaceutically effective amount” of finerenone or the SGLT2 inhibitor (active ingredient) is the amount that produces a result or effect on the particular condition being treated. A “pharmaceutically acceptable carrier” is any carrier that is relatively non-toxic and harmless to the patient, at a concentration that is in harmony with the effective activity of the active ingredient, so that any side effects caused by the carrier do not negate the beneficial effects of the active ingredient. “Excipients” are used as is known in the art. These are substances formulated together with the active ingredient of a pharmaceutical, for example, for the purpose of long-term stabilization, bulking up a solid formulation containing a small amount of potent active ingredient (hence often called a “bulker,” “filler,” or “diluent”), or to impart therapeutic enhancement to the active ingredient in the final dosage form, such as promoting drug absorption, reducing viscosity, or increasing solubility. Excipients can also be useful in the manufacturing process to alleviate concerns regarding the handling of active materials, such as by promoting powder flowability or non-stick properties, in addition to aiding in vitro stability, including preventing denaturation or aggregation over the expected shelf life. The selection of an appropriate excipient also depends on the route of administration and dosage form, as well as the active ingredient and other factors. Some excipients are listed below.

[0063] Commonly used pharmaceutical ingredients that can be appropriately used to formulate compositions for the intended route of administration include the following: • Acidifying agents (examples include, but are not limited to, acetic acid, citric acid, fumaric acid, hydrochloric acid, and nitric acid); • Alkalinizing agents (examples include, but are not limited to, ammonia solution, ammonium carbonate, diethanolamine, monoethanolamine, potassium hydroxide, sodium borate, sodium carbonate, sodium hydroxide, triethanolamine, and trolamine); • Adsorbents (examples include, but are not limited to, powdered cellulose and activated carbon); • Aerosol sprays (examples include, but are not limited to, carbon dioxide, CCl2F2, F2ClC-CClF2, and CClF3); • Air replacement agents (examples include, but are not limited to, nitrogen and argon); • Antifungal preservatives (examples include, but are not limited to, benzoic acid, butylparaben, ethylparaben, methylparaben, propylparaben, and sodium benzoate); • Antimicrobial preservatives (examples include, but are not limited to, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, phenylmercury nitrate, and thimerosal); • Antioxidants (examples include, but are not limited to, ascorbic acid, ascorbyl palmitate, butylhydroxyanisole, butylhydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde sulfoxylate, and sodium pyrosulfite); • Binding materials (examples include, but are not limited to, block polymers, natural and synthetic rubbers, polyacrylates, polyurethanes, silicones, polysiloxanes, and styrene-butadiene copolymers); • Buffering agents (examples include, but are not limited to, potassium metaphosphate, dipotassium phosphate, sodium acetate, anhydrous sodium citrate, and sodium citrate dihydrate); • Carriers (examples include, but are not limited to, acacia syrup, aromatic syrup, aromatic elixir, cherry syrup, cocoa syrup, orange syrup, syrup, corn oil, mineral oil, peanut oil, sesame oil, bacteriostatic saline injection, and bacteriostatic water for injection); • Chelating agents (examples include, but are not limited to, disodium edetate and edetate); • Colorants (examples include, but are not limited to, FD&C Red No. 3, FD&C Red No. 20, FD&C Yellow No. 6, FD&C Blue No. 2, D&C Green No. 5, D&C Orange No. 5, D&C Red No. 8, caramel, and iron oxide red); • Clarifying agents (for example, but not limited to these, bentonite is one example); • Emulsifiers (examples include, but are not limited to, acacia, cetomacrogol, cetyl alcohol, glyceryl monostearate, lecithin, sorbitan monooleate, and polyoxyethylene 50 monostearate); • Encapsulating agents (examples include, but are not limited to, gelatin and cellulose phthalate acetate); • Flavoring agents (examples include, but are not limited to, anise oil, cinnamon oil, cocoa, menthol, orange oil, peppermint oil, and vanillin); • Moisturizers (examples include, but are not limited to, glycerol, propylene glycol, and sorbitol); • Polishing agents (examples include, but are not limited to, mineral oil and glycerin); • Oils (examples include, but are not limited to, peanut oil, mineral oil, olive oil, sesame oil, and vegetable oil); • Ointment bases (examples include, but are not limited to, lanolin, hydrophilic ointments, polyethylene glycol ointments, petrolatum, hydrophilic petrolatum, white ointments, yellow ointments, and rose water ointments); • Penetration enhancers (transdermal delivery) (Examples include, but are not limited to, monohydroxy or polyhydroxy alcohols, monohydric or polyhydric alcohols, saturated or unsaturated fatty alcohols, saturated or unsaturated fatty acid esters, saturated or unsaturated dicarboxylic acids, essential oils, phosphatidyl derivatives, cephalins, terpenes, amides, ethers, ketones, and ureas); • Plasticizers (examples include, but are not limited to, diethyl phthalate and glycerol); • Solvents (examples include, but are not limited to, ethanol, corn oil, cottonseed oil, glycerol, isopropanol, mineral oil, oleic acid, peanut oil, purified water, water for injection, sterile water for injection, and sterile water for washing); • Hardening agents (examples include, but are not limited to, cetyl alcohol, cetyl ester wax, microcrystalline wax, paraffin, stearyl alcohol, white wax, and yellow wax); • Suppository base (examples include, but are not limited to, cocoa butter and polyethylene glycol (a mixture)); • Surfactants (examples include, but are not limited to, benzalkonium chloride, nonoxynol 10, octoxynol 9, polysorbate 80, sodium lauryl sulfate, and sorbitan monopalmitate); • Suspensioning agents (examples include, but are not limited to, agar, bentonite, carbomer, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, kaolin, methylcellulose, tragacanth, and veegum); • Sweeteners (examples include, but are not limited to, aspartame, glucose, glycerol, mannitol, propylene glycol, sodium saccharin, sorbitol, and sucrose); • Tablet anti-adhesion agents (examples include, but are not limited to, magnesium stearate and talc); • Tablet binders (examples include, but are not limited to, acacia, alginic acid, sodium carboxymethylcellulose, compressed sugar, ethylcellulose, gelatin, glucose solution, methylcellulose, non-crosslinked polyvinylpyrrolidone, and pregelatinized starch); • Diluents for tablets and capsules (examples include, but are not limited to, calcium hydrogen phosphate, kaolin, lactose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sodium carbonate, sodium phosphate, sorbitol, and starch); • Tablet coating agents (examples include, but are not limited to, glucose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, cellulose phthalate acetate, and shellac); • Tablet direct compression excipients (examples include, but are not limited to, calcium hydrogen phosphate); • Tablet disintegrants (examples include, but are not limited to, alginic acid, carboxymethylcellulose calcium, microcrystalline cellulose, polariphosphate potassium, cross-linked polyvinylpyrrolidone, sodium alginate, sodium starch glycolate, and starch); • Tablet lubricants (examples include, but are not limited to, colloidal silica, corn starch, and talc); • Tablet lubricants (examples include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, and zinc stearate); • Tablet / capsule opacifying agents (examples include, but are not limited to, titanium dioxide); • Tablet polishing agents (examples include, but are not limited to, carnauba wax and white wax); • Thickening agents (examples include, but are not limited to, beeswax, cetyl alcohol, and paraffin); • Isotonic agents (examples include, but are not limited to, glucose and sodium chloride); • Thickening agents (examples include, but are not limited to, alginic acid, bentonite, carbomer, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, sodium alginate, and tragacanth); and • Humectants (examples include, but are not limited to, heptadecaethyleneoxycetanol, lecithin, sorbitol monooleate, polyoxyethylene sorbitol monooleate, and polyoxyethylene stearate).

[0064] Those skilled in the art can utilize the existing information to make the most of the present invention.

[0065] The combinations of the present invention can be administered in any form by any effective route, including, for example, oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), ocular, nasal, topical, parenteral, e.g., aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, rectal, vaginal, intra-arterial, and intrathecal. These can be administered alone or in combination with one or more of any components (active or inactive).

[0066] The combinations of the present invention can be converted in known ways into conventional dosage forms, pharmaceutical administration forms, or pharmaceutical formulations, which may be liquid or solid formulations, such as, but not limited to, tablets, coated tablets, capsules, pills, powders, granules, elixirs, tinctures, liquids, suspensions, syrups, solid and liquid aerosols, and emulsions.

[0067] In one embodiment, the combination according to the present invention is administered via oral administration. In one embodiment, the combination according to the present invention is contained in a dosage form for oral administration. For oral administration, the compounds can be formulated into solids or liquids and prepared according to methods known in the art for producing pharmaceutical compositions. Examples of dosage forms for oral administration of finerenone or SGLT2 inhibitors are described in International Publication No. 2008 / 104306 (see Section C of International Publication No. 2008 / 104306) and International Publication No. 2016 / 071212 (see Section C of International Publication No. 2016 / 071212) and in the examples of this application in Section A.1 “Tablets Containing Finerenone” below.

[0068] In one embodiment, the combination according to the present invention is contained in one dosage form. In one embodiment, the combination according to the present invention consists of two separate dosage forms. In one embodiment, the combination according to the present invention consists of two separate dosage forms for oral administration.

[0069] In one embodiment, the combination according to the present invention is a capsule. In one embodiment, the combination according to the present invention is a tablet. In one embodiment, the combination according to the present invention consists of a single tablet containing finerenone and an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises at least two tablets, one of which contains finerenone and the other contains an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises at least two tablets, one of which contains finerenone but not an SGLT2 inhibitor, and the other containing an SGLT2 inhibitor but not finerenone.

[0070] In another embodiment, the finerenone and / or SGLT2 inhibitors according to the present invention may be tableted using a conventional tablet base (such as lactose, sucrose, and corn starch) combined with a binder (such as acacia, corn starch, or gelatin), a disintegrant (such as potato starch, alginic acid, corn starch, and guar gum, tragacanth gum, or acacia) intended to aid in the disintegration and dissolution of the tablet after administration, a lubricant (e.g., talc, stearic acid, or magnesium stearate, calcium, or zinc) intended to improve the flow of the tablet granules and prevent the tablet material from adhering to the surface of the tablet mold and perforator, and dyes, colorants, and flavorings (such as peppermint, wintergreen oil, or saxifrage flavor) intended to improve the aesthetic quality of the tablet and make the tablet more acceptable to the patient. Suitable excipients for use in oral liquid dosage forms include dicalcium phosphate and diluents (water and alcohol, e.g., ethanol, benzyl alcohol, and polyethylene alcohol) with or without pharmaceutically acceptable surfactants, suspending agents, or emulsifiers. Various other materials may be present as coatings or to modify the physical form of the dosage form. For example, tablets, pills, or capsules may be coated with shellac, sugar, or both.

[0071] Dispersible powders and granules are suitable for preparing aqueous suspensions. These provide active ingredients mixed with dispersing or wetting agents, suspending agents, and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are indicated by those already mentioned above. Additional excipients, such as the sweeteners, flavoring agents, and coloring agents mentioned above, may be present.

[0072] The pharmaceutical composition of the present invention may also be in the form of an oil-in-water emulsion. The oil phase may be a vegetable oil, for example, liquid paraffin or a mixture of vegetable oils. Suitable emulsifiers may be (1) natural gums, for example, gum arabic and tragacanth gum; (2) natural phosphatides, for example, soy and lecithin; (3) esters or partial esters obtained from fatty acids and hexitol anhydrides, for example, sorbitan monooleate; or (4) condensates of the partial ester and ethylene oxide, for example, polyoxyethylene sorbitan monooleate. The emulsion may also contain sweeteners and flavorings.

[0073] Oily suspensions can be formulated by suspending the active ingredient in a vegetable oil, such as peanut oil, olive oil, sesame oil, or coconut oil, or in a mineral oil, such as liquid paraffin. Oily suspensions may also contain thickeners, such as beeswax, solid paraffin, or cetyl alcohol. The suspension may also contain one or more preservatives, such as ethyl p-hydroxybenzoate or n-propyl; one or more colorants; one or more flavoring agents; and one or more sweeteners, such as sucrose or saccharin.

[0074] Syrups and elixirs can be formulated using sweeteners, such as glycerol, propylene glycol, sorbitol, or sucrose. Such formulations may also contain lubricants, preservatives, such as methyl and propylparaben, as well as flavorings and colorings.

[0075] The pharmaceutical compositions of the present invention may also be in the form of dispersions. A "dispersion" is a system in which dispersed particles of one material are dispersed in a continuous phase (sometimes called a matrix) of another material. The two phases may be in the same or different states of matter. Dispersions are classified in several different ways, including how large the particles are relative to the particles of the continuous phase, whether or not precipitation occurs, and the presence or absence of Brownian motion. Generally, dispersions of particles large enough to settle are called suspensions, while dispersions of smaller particles are called colloids and solutions.

[0076] The pharmaceutical composition of the present invention may also be in the form of a solid dispersion. The solid dispersion may be a solid solution, a glass solution, a glass suspension, an amorphous precipitate in a crystalline carrier, a eutectic or penic crystal, a compound or complex formation, or a combination thereof.

[0077] A particularly interesting aspect of the present invention is a pharmaceutical composition comprising a solid dispersion containing a pharmaceutically acceptable carrier, the matrix of which is a polymer such as polyvinylpyrrolidone, vinylpyrrolidone / vinyl acetate copolymer, polyalkylene glycol (i.e., polyethylene glycol), hydroxyalkylcellulose (i.e., hydroxypropylcellulose), hydroxyalkylmethylcellulose (i.e., hydroxypropylmethylcellulose), carboxymethylcellulose, sodium carboxymethylcellulose, ethylcellulose, polymethacrylate, polyvinyl alcohol, polyvinyl acetate, vinyl alcohol / vinyl acetate copolymer, polyglycolized glycerides, xanthan gum, carrageenan, chitosan, chitin, polydextrin, dextrin, starch, and protein.

[0078] Another aspect of the present invention is a pharmaceutical composition comprising a solid dispersion in which the matrix comprises sugars and / or sugar alcohols and / or cyclodextrins, such as sucrose, lactose, fructose, maltose, raffinose, sorbitol, lactitol, mannitol, maltitol, erythritol, inositol, trehalose, isomalt, inulin, maltodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or sulfobutyl ether cyclodextrin.

[0079] Further suitable supports useful for forming a matrix of solid dispersions include, but are not limited to, alcohols, organic acids, organic bases, amino acids, phospholipids, waxes, salts, fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and urea.

[0080] The solid dispersion of finerenone in the matrix may contain certain additional pharmaceutically acceptable components.

[0081] The solid dispersions of the present invention are prepared according to methods known in the art for producing solid dispersions, such as fusion / melting techniques, hot melt extrusion, solvent evaporation (i.e., freeze-drying, spray-drying or lamination of granular powders), coprecipitation, supercritical fluid techniques, and electrospinning methods.

[0082] The compositions of the present invention may also contain other conventional pharmaceutically acceptable formulations, commonly referred to as carriers or diluents, as needed or desired. Conventional procedures can be utilized to prepare such compositions in appropriate dosage forms.

[0083] The amount of active ingredient administered can vary widely depending on factors such as the specific compound and dosage form used, the mode and timing of administration, the duration of treatment, the age, sex and general condition of the patient being treated, the nature and severity of the condition being treated, the rate of drug metabolism and excretion, and potential drug combinations and drug-drug interactions.

[0084] One embodiment of the present invention refers to a combination containing finerenone in an amount of 0.25 mg to 80 mg. One embodiment of the present invention refers to a combination containing finerenone in an amount of 0.25 mg to 40 mg. One embodiment of the present invention refers to a combination containing finerenone in an amount of 0.25 mg to 20 mg. One embodiment of the present invention refers to a combination containing finerenone in an amount of 0.25 mg to 10 mg. One embodiment of the present invention refers to a combination containing finerenone in an amount of 0.25 mg to 5 mg.

[0085] One embodiment of the present invention refers to a combination containing 5 to 80 mg of finerenone. In one embodiment, the combination according to the present invention contains 5 to 80 mg, 5 to 70 mg, 5 to 60 mg, 5 to 50 mg, 5 to 40 mg, 10 to 80 mg, 10 to 70 mg, 10 to 60 mg, 10 to 50 mg, or 10 to 40 mg of finerenone. In one embodiment, the combination according to the present invention contains 10 to 40 mg of finerenone. In one embodiment, the combination according to the present invention contains 20 to 40 mg of finerenone. In one embodiment, the combination according to the present invention contains finerenone in amounts of 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg. In one embodiment, the combination according to the present invention contains finerenone in amounts of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg. In one embodiment, the combination according to the present invention contains finerenone in amounts of 5 mg. In one embodiment, the combination according to the present invention contains finerenone in amounts of 10 mg. In one embodiment, the combination according to the present invention contains 15 mg of finerenone. In one embodiment, the combination according to the present invention contains 20 mg of finerenone. In one embodiment, the combination according to the present invention contains 25 mg of finerenone. In one embodiment, the combination according to the present invention contains 30 mg of finerenone. In one embodiment, the combination according to the present invention contains 35 mg of finerenone. In one embodiment, the combination according to the present invention contains 40 mg of finerenone. In one embodiment, the combination according to the present invention contains 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, or 40 mg of finerenone. In one embodiment, the combination according to the present invention contains 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone.

[0086] One embodiment of the present invention refers to a combination comprising an SGLT2 inhibitor in an amount of 0.5 to 400 mg. In one embodiment, the combination according to the present invention comprises an SGLT2 inhibitor in an amount of 0.5 to 300 mg, 1 to 300 mg, 2 to 200 mg, 3 to 100 mg, 5 to 100 mg, 5 to 90 mg, 5 to 80 mg, 5 to 70 mg, 5 to 60 mg, 5 to 50 mg, 5 to 40 mg, 5 to 30 mg, 10 to 90 mg, 10 to 80 mg, 10 to 70 mg, 10 to 60 mg, 10 to 50 mg or 10 to 40 mg, 10 to 30 mg, 15 to 90 mg, 15 to 80 mg, 15 to 70 mg, 15 to 60 mg, 15 to 50 mg, 15 to 40 mg or 15 to 30 mg.

[0087] In one embodiment, the combination according to the present invention contains an amount of 1 to 20 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains an amount of 3 to 15 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains an amount of 5 to 10 mg of an SGLT2 inhibitor.

[0088] In one embodiment, the combination according to the present invention comprises an amount of 1, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 mg of an SGLT2 inhibitor.

[0089] In one embodiment, the combination according to the present invention contains 3 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 5 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 10 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 15 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 20 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 25 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 30 mg of the SGLT2 inhibitor. The combination according to the present invention may include 35 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 40 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 50 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 60 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 65 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 70 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 80 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 90 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 95 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 100 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 125 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 150 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 175 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 200 mg of the SGLT2 inhibitor. In one embodiment, the combination according to the present invention contains 300 mg of the SGLT2 inhibitor.

[0090] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 300 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 300 mg of an SGLT2 inhibitor.

[0091] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 300 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 300 mg of an SGLT2 inhibitor.

[0092] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 200 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 200 mg of an SGLT2 inhibitor.

[0093] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 150 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 150 mg of an SGLT2 inhibitor.

[0094] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 100 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 100 mg of an SGLT2 inhibitor.

[0095] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 to 100 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 to 100 mg of an SGLT2 inhibitor.

[0096] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 10 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 25 mg of an SGLT2 inhibitor.

[0097] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 10 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 15 mg of an SGLT2 inhibitor.

[0098] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 3 to 10 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 3 to 10 mg of an SGLT2 inhibitor.

[0099] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 to 10 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 to 10 mg of an SGLT2 inhibitor.

[0100] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 100 mg of an SGLT2 inhibitor. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 100 mg of an SGLT2 inhibitor.

[0101] In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 3 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 5 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 10 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 100 mg of an SGLT2 inhibitor.

[0102] In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 3 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 5 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 10 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 100 mg of an SGLT2 inhibitor.

[0103] In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 3 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 5 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 10 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 100 mg of an SGLT2 inhibitor.

[0104] In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 3 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 5 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 10 mg of an SGLT2 inhibitor. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 100 mg of an SGLT2 inhibitor.

[0105] In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 5 to 400 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 5 to 300 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 5 to 150 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 50 to 150 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 90 to 110 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 100 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 150 mg. In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in an amount of 300 mg.

[0106] In one embodiment, the combination according to the present invention comprises finerenone and canagliflozin in amounts of 5, 10, 20, 30, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 mg.

[0107] In one embodiment, the combination according to the present invention comprises 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg of finerenone and canagliflozin.

[0108] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 to 150 mg of canagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 to 150 mg of canagliflozin.

[0109] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 100 mg of canagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 100 mg of canagliflozin.

[0110] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 100 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 100 mg of canagliflozin.

[0111] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 200 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 200 mg of canagliflozin.

[0112] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 300 mg of canagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 300 mg of canagliflozin.

[0113] In one embodiment, the combination according to the present invention comprises finerenone and 0.5 to 20 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 3 to 15 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 5 to 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 10 mg of dapagliflozin.

[0114] In one embodiment, the combination according to the present invention comprises finerenone and dapagliflozin in amounts of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg.

[0115] In one embodiment, the combination according to the present invention comprises 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg of finerenone and dapagliflozin.

[0116] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 20 mg of dapagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 20 mg of dapagliflozin.

[0117] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 mg of dapagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 mg of dapagliflozin.

[0118] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 5 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 5 mg of dapagliflozin.

[0119] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 20 mg of dapagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 20 mg of dapagliflozin.

[0120] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 10 mg of dapagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 10 mg of dapagliflozin.

[0121] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 10 mg of dapagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 10 mg of dapagliflozin.

[0122] In one embodiment, the combination according to the present invention comprises finerenone and 0.5 to 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 3 to 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 5 to 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises finerenone and 30 mg of empagliflozin.

[0123] In one embodiment, the combination according to the present invention comprises finerenone and empagliflozin in an amount of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30 mg.

[0124] In one embodiment, the combination according to the present invention comprises finerenone and empagliflozin in amounts of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg.

[0125] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 30 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 30 mg of empagliflozin.

[0126] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 mg of empagliflozin.

[0127] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 10 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 10 mg of empagliflozin.

[0128] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 15 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 15 mg of empagliflozin.

[0129] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 20 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 20 mg of empagliflozin.

[0130] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 25 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 25 mg of empagliflozin.

[0131] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 30 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 30 mg of empagliflozin.

[0132] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 5 mg of empagliflozin.

[0133] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 10 mg of empagliflozin.

[0134] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 15 mg of empagliflozin.

[0135] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 20 mg of empagliflozin.

[0136] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 25 mg of empagliflozin.

[0137] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 30 mg of empagliflozin.

[0138] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 30 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 30 mg of empagliflozin.

[0139] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 mg of empagliflozin.

[0140] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 10 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 10 mg of empagliflozin.

[0141] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 15 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 15 mg of empagliflozin.

[0142] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 20 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 20 mg of empagliflozin.

[0143] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 25 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 25 mg of empagliflozin.

[0144] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 30 mg of empagliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 30 mg of empagliflozin.

[0145] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 5 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 5 mg of empagliflozin.

[0146] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 10 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 10 mg of empagliflozin.

[0147] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 15 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 15 mg of empagliflozin.

[0148] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 20 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 20 mg of empagliflozin.

[0149] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 25 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 25 mg of empagliflozin.

[0150] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 30 mg of empagliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 30 mg of empagliflozin.

[0151] In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 0.5 to 20 mg. In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 3 to 15 mg. In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 5 to 15 mg. In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 5 mg. In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 10 mg. In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 15 mg. In one embodiment, the combination according to the present invention comprises finerenone and ertugliflozin in an amount of 20 mg.

[0152] In one embodiment, the combination according to the present invention comprises finerenone and erzgliflozin in an amount of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mg.

[0153] In one embodiment, the combination according to the present invention comprises 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg of finerenone and erzgliflozin.

[0154] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 20 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 20 mg of ertugliflozin.

[0155] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 mg of ertugliflozin.

[0156] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 10 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 10 mg of ertugliflozin.

[0157] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 15 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 15 mg of ertugliflozin.

[0158] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 20 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 20 mg of ertugliflozin.

[0159] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 5 mg of erzgliflozin.

[0160] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 10 mg of erzgliflozin.

[0161] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 15 mg of erzgliflozin.

[0162] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 20 mg of erzgliflozin.

[0163] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 0.5 to 20 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 0.5 to 20 mg of ertugliflozin.

[0164] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 5 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 5 mg of ertugliflozin.

[0165] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 10 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 10 mg of ertugliflozin.

[0166] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 15 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 15 mg of ertugliflozin.

[0167] In one embodiment, the combination according to the present invention comprises 5 to 80 mg of finerenone and 20 mg of ertugliflozin. In another embodiment, the combination according to the present invention comprises 10 to 40 mg of finerenone and 20 mg of ertugliflozin.

[0168] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 5 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 5 mg of erzgliflozin.

[0169] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 10 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 10 mg of erzgliflozin.

[0170] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 15 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 15 mg of erzgliflozin.

[0171] In one embodiment, the combination according to the present invention comprises 5 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 10 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 20 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 30 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 40 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 50 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 60 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 70 mg of finerenone and 20 mg of ertugliflozin. In one embodiment, the combination according to the present invention comprises 80 mg of finerenone and 20 mg of erzgliflozin.

[0172] Nevertheless, in some cases, it may be advantageous to deviate from the specified amount, depending on body weight, individual behavior to the active ingredient, formulation type, and the time or interval over which the administration is affected. For example, in some cases, less than the minimum amount may be sufficient, while in others, the specified upper limit must be exceeded.

[0173] When administering relatively large doses, it may be prudent to divide them into several individual doses per day.

[0174] The relative ratio of each compound in a combination can also be selected based on their respective mechanisms of action and disease biology. The relative ratio of each compound can vary considerably.

[0175] The present invention also relates to methods for using combinations and compositions thereof to treat cardiovascular disorders and / or renal and cardiorenal disorders.

[0176] These diseases may be characterized by chronic sodium retention, such as chronic heart failure and renal failure. This method includes the step of administering a combination of effective amounts to a mammal in need, including humans, to treat the disorder.

[0177] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of heart failure and / or chronic kidney disease.

[0178] The combination according to the present invention is suitable for the prevention and / or treatment of various disorders and disease-related conditions, particularly for the treatment and / or prevention of the following: • Cardiovascular disorders such as congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF); • Chronic kidney disease (CKD), diabetic and hypertensive nephropathy, cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, renal hypoperfusion, hypotension during dialysis, obstructive urinary tract disease, glomerulopathy, IgA nephropathy, glomerulonephritis, glomerulosclerosis, tubulointerstitial damage, nephropathy, e.g., primary and congenital kidney disease, nephritis, Alport syndrome, renal inflammation, immunological kidney disease, kidney transplant rejection, immune complex-induced kidney disease, toxic substance-induced nephropathy, contrast-induced nephropathy; minimal change glomerulonephritis (lipoid), focal segmental glomerulosclerosis (FSGS), amyloidosis, renal cysts, hyper Hypertensive nephrosclerosis and nephrotic syndrome (which may be diagnostically characterized by, for example, abnormally decreased creatinine and / or water excretion, abnormally elevated blood concentrations of urea, nitrogen, and creatinine, altered urine osmolality or urine volume, increased microalbuminuria, macroalbuminuria, glomerular and arteriole lesions, tubular dilation, hyperphosphatemia, and / or the need for dialysis), uremia, anemia, electrolyte abnormalities, abnormalities in bone and carbohydrate metabolism, and renal and cardiorenal disorders such as polycystic kidney disease (PCKD) and syndrome of inappropriate ADH secretion (SIADH); Edema, pulmonary edema, cerebral edema, renal edema, and heart failure-related edema; • Cirrhosis of the liver; • NASH (Non-Alcoholic Steatohepatitis); • Arterial hypertension, resistant hypertension, pulmonary hypertension; • Cardiovascular disorders such as hypertension, left ventricular dysfunction, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular arrhythmias, ventricular arrhythmias, atrial fibrillation, and atrial flutter. Cardiovascular disorders such as stable angina, unstable angina, myocardial infarction and its complications, aneurysms, harmful vascular remodeling, atherosclerosis, atrial fibrillation, and stroke; Shocks such as cardiogenic shock, septic shock, and anaphylactic shock; • Hypertensive nephropathy, peripheral artery disease (PAD) including claudication and severe limb ischemia, coronary microcirculatory disorders (CMD) including CMD types 1-4, primary and secondary Raynaud's phenomenon, microcirculatory disorders, peripheral and autonomic neuropathy, diabetic microangiopathy, diabetic retinopathy, diabetic limb ulcers, gangrene, CREST syndrome, erythematous disorders, rheumatic diseases, inflammatory diseases, asthmatic diseases, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), acute lung injury (ALI), α1-antitrypsin deficiency (AATD), pulmonary fibrosis, emphysema (e.g., smoking-induced emphysema), and cystic fibrosis (CF); • Pulmonary hypertension and other lung disorders, cardiopulmonary disorders, and central nervous system disorders; • Fibrosis and other disease symptoms (e.g., end-organ injuries affecting the brain, kidneys, or heart); Multiple injuries, including ischemia-reperfusion injury, contrast agent administration, cardiopulmonary bypass surgery, shock, and sepsis.

[0179] The combination according to the present invention is also suitable for the prevention and / or treatment of various disorders and disease-related conditions, particularly for the treatment and / or prevention of the following: • Cardiovascular disorders such as congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF); Chronic kidney disease (CKD), non-diabetic chronic kidney disease (ndCKD), diabetic nephropathy, hypertensive nephropathy, cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, renal hypoperfusion, hypotension during dialysis, obstructive urinary tract disease, glomerulopathy, IgA nephropathy, glomerulonephritis, glomerulosclerosis, tubulointerstitial damage, nephropathy, e.g., primary and congenital kidney disease, nephritis, Alport syndrome, renal inflammation, immunological nephropathy, kidney transplant rejection, immune complex-induced nephropathy, toxic substance-induced nephropathy, contrast-induced nephropathy; minimal change glomerulonephritis (lipoid), focal segmental glomerulosclerosis (FSGS), amyloidosis, renal cysts, hypertensive nephrosclerosis and nephrotic syndrome (which may be diagnostically characterized by, for example, abnormally decreased creatinine and / or water excretion, abnormally elevated blood concentrations of urea, nitrogen, potassium and / or creatinine, altered urine osmolality or urine volume, increased microalbuminuria, macroalbuminuria, lesions of the glomeruli and arterioles, tubular dilation, hyperphosphatemia and / or the need for dialysis), uremia, anemia, electrolyte abnormalities (for example, hyperkalemia, hyponatremia), abnormalities in bone and carbohydrate metabolism, and renal and cardiorenal disorders such as polycystic kidney disease (PCKD) and syndrome of inappropriate ADH secretion (SIADH); Edema, pulmonary edema, cerebral edema, renal edema, and heart failure-related edema; ·cirrhosis; • NASH (Non-Alcoholic Steatohepatitis); • Arterial hypertension, resistant hypertension, pulmonary hypertension, essential hypertension; • Cardiovascular disorders such as hypertension, left ventricular dysfunction, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular arrhythmias, ventricular arrhythmias, atrial fibrillation, and atrial flutter. Cardiovascular disorders such as stable angina, unstable angina, myocardial infarction and its complications, aneurysms, harmful vascular remodeling, atherosclerosis, atrial fibrillation, and stroke; Shocks such as cardiogenic shock, septic shock, and anaphylactic shock; • Hypertensive nephropathy, peripheral artery disease (PAD) including claudication and severe limb ischemia, coronary microcirculatory disorders (CMD) including CMD types 1-4, primary and secondary Raynaud's phenomenon, microcirculatory disorders, peripheral and autonomic neuropathy, diabetic microangiopathy, diabetic retinopathy, diabetic limb ulcers, gangrene, CREST syndrome, erythematous disorders, rheumatic diseases, inflammatory diseases, asthmatic diseases, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), acute lung injury (ALI), α1-antitrypsin deficiency (AATD), pulmonary fibrosis, emphysema (e.g., smoking-induced emphysema), and cystic fibrosis (CF); • Pulmonary hypertension and other lung disorders, cardiopulmonary disorders, and central nervous system disorders; • Fibrosis and other disease symptoms (e.g., end-organ injuries affecting the brain, kidneys, or heart); ·Sleep apnea; ·obesity; Coronary artery disease (CAD), • Acute kidney injury (AKI) • Chronic kidney disease following acute kidney injury (AKIM) after major surgery Multiple injuries, including ischemia-reperfusion injury, contrast agent administration, cardiopulmonary bypass surgery, shock, and sepsis.

[0180] In one embodiment, the combination according to the present invention is used to treat and / or prevent diseases characterized by sodium retention. These diseases include, for example: • Cardiovascular disorders such as congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF); • Renal and cardiorenal disorders such as chronic kidney disease (CKD), diabetic and hypertensive nephropathy, cardiorenal syndrome, and nephrotic syndrome; Edema, pulmonary edema, cerebral edema, renal edema, and heart failure-related edema; • Hardening; and / or • Arterial hypertension, resistant hypertension, pulmonary hypertension.

[0181] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of chronic kidney disease (CKD). The term chronic kidney disease includes the terms diabetic nephropathy (DKD) or non-diabetic chronic kidney disease (ndCKD), which includes CKD in diabetes (type 2 diabetes (T2D), type 1 diabetes (T1D)) and hypertensive CKD. In one example of chronic kidney disease, this may be chronic kidney disease in a patient with type 1 diabetes. In another example of chronic kidney disease, this may be chronic kidney disease in a patient with type 2 diabetes. In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of chronic kidney disease selected from chronic kidney disease in patients with type 1 diabetes and chronic kidney disease in patients with type 2 diabetes. In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of diabetic nephropathy (DKD). In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of non-diabetic chronic kidney disease (ndCKD).

[0182] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of diabetic retinopathy. In one example of diabetic retinopathy, this may be diabetic retinopathy in a patient with type 1 diabetes. In another example of diabetic retinopathy, this may be diabetic retinopathy in a patient with type 2 diabetes. In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of a disease selected from diabetic retinopathy in a patient with type 1 diabetes and diabetic retinopathy in a patient with type 2 diabetes.

[0183] In one embodiment, the combination according to the present invention is used to treat and / or prevent a disease selected from congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, chronic kidney disease in patients with type 2 diabetes, diabetic retinopathy in patients with type 1 diabetes; diabetic retinopathy in patients with type 2 diabetes.

[0184] In one embodiment, the combination according to the present invention is used to treat and / or prevent a disease selected from worsening chronic heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, chronic kidney disease in patients with type 2 diabetes, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0185] In one embodiment, the combination according to the present invention is used to treat and / or prevent a disease selected from worsening chronic heart failure (WCHF), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF). In one embodiment, the combination according to the present invention may be used to treat and / or prevent any of the diseases or disorders listed above, and the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0186] In one embodiment, the combination according to the present invention is used to treat and / or prevent heart failure (congestive, acute, worsening, and chronic, independent of ejection fraction), cardiorenal syndrome, CKD, diabetic and hypertensive nephropathy, nephrotic syndrome, hepatorenal syndrome, edema, cirrhosis, NASH (non-alcoholic steatohepatitis), and / or fibrotic disorders. In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0187] In one embodiment, the combination according to the present invention may be used for the prevention and / or treatment of heart failure (unrelated to ejection fraction) and / or chronic kidney disease. In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0188] In one embodiment, the combination according to the present invention is used to treat and / or prevent cardiovascular disorders such as congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF). In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0189] In one embodiment, the combination according to the present invention is used to treat chronic kidney disease (CKD), diabetic and hypertensive nephropathy, cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, renal hypoperfusion, hypotension during dialysis, obstructive urinary tract disease, glomerulopathy, IgA nephropathy, glomerulonephritis, glomerulosclerosis, tubulointerstitial damage, nephropathy, such as primary and congenital kidney disease, nephritis, Alport syndrome, renal inflammation, immunological kidney disease, kidney transplant rejection, immune complex-induced kidney disease, toxic substance-induced nephropathy, contrast-induced nephropathy; minimal change glomerulonephritis (lipoid), focal segmental glomerulosclerosis (FSGS), amyloidosis, renal cysts, hypertensive nephrosclerosis, and nephrotic syndrome. The group (which may be diagnostically characterized by, for example, abnormally decreased creatinine and / or water excretion, abnormally elevated blood concentrations of urea, nitrogen, potassium and / or creatinine, altered urine osmolality or urine volume, increased microalbuminuria, macroalbuminuria, glomerular and arteriole lesions, tubular dilation, hyperphosphatemia and / or the need for dialysis), uremia, anemia, electrolyte abnormalities (e.g., hyperkalemia, hyponatremia), abnormalities in bone and carbohydrate metabolism, polycystic kidney disease (PCKD) and / or syndrome of inappropriate ADH secretion (SIADH) is used for the treatment and / or prevention of renal and cardiorenal disorders. In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin and tofogliflozin.

[0190] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of edema, pulmonary edema, cerebral edema, renal edema and / or heart failure-related edema. In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin and tofogliflozin.

[0191] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of cirrhosis and / or NASH (non-alcoholic steatohepatitis). In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0192] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of essential hypertension, arterial hypertension, resistant hypertension and / or pulmonary hypertension. In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin and tofogliflozin.

[0193] In one embodiment, the combination according to the present invention is used for the treatment and / or prevention of arterial hypertension, resistant hypertension and / or pulmonary hypertension. In this embodiment, the SGLT2 inhibitor may be selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin and tofogliflozin.

[0194] In one embodiment, the combination comprises finerenone and canagliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0195] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 mg or 300 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0196] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0197] In one embodiment, the combination comprises 5 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0198] In one embodiment, the combination comprises 10 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0199] In one embodiment, the combination comprises 20 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0200] In one embodiment, the combination comprises 30 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0201] In one embodiment, the combination comprises 40 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0202] In one embodiment, the combination comprises 5 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0203] In one embodiment, the combination comprises 10 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0204] In one embodiment, the combination comprises 20 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0205] In one embodiment, the combination comprises 30 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0206] In one embodiment, the combination comprises 40 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0207] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 or 300 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0208] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0209] In one embodiment, the combination comprises 5 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0210] In one embodiment, the combination comprises 10 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0211] In one embodiment, the combination comprises 20 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0212] In one embodiment, the combination comprises 30 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0213] In one embodiment, the combination comprises 40 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0214] In one embodiment, the combination comprises 5 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0215] In one embodiment, the combination comprises 10 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0216] In one embodiment, the combination comprises 20 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0217] In one embodiment, the combination comprises 30 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0218] In one embodiment, the combination comprises 40 mg of finerenone and 300 mg of canagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0219] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetes patients and diabetic retinopathy in type 2 diabetes patients.

[0220] In one embodiment, the combination comprises 5 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetes patients, and diabetic retinopathy in type 2 diabetes patients.

[0221] In one embodiment, the combination comprises 10 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetes patients and diabetic retinopathy in type 2 diabetes patients.

[0222] In one embodiment, the combination comprises 20 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0223] In one embodiment, the combination comprises 30 mg of finerenone and 100 mg of canagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0224] In one embodiment, the combination comprises finerenone in an amount of 40 mg and canagliflozin in an amount of 100 mg, and the combination is used for the treatment of a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetic patients, and diabetic retinopathy in type 2 diabetic patients.

[0225] In one embodiment, the combination comprises finerenone in an amount of 5 mg and canagliflozin in an amount of 300 mg, and the combination is used for the treatment of a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetic patients, and diabetic retinopathy in type 2 diabetic patients.

[0226] In one embodiment, the combination comprises finerenone in an amount of 10 mg and canagliflozin in an amount of 300 mg, and the combination is used for the treatment of a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetic patients, and diabetic retinopathy in type 2 diabetic patients.

[0227] In one embodiment, the combination comprises finerenone in an amount of 20 mg and canagliflozin in an amount of 300 mg, and the combination is used for the treatment of a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetic patients, and diabetic retinopathy in type 2 diabetic patients.

[0228] In one embodiment, the combination comprises finerenone in an amount of 30 mg and canagliflozin in an amount of 300 mg, and the combination is used for the treatment of a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetic patients, and diabetic retinopathy in type 2 diabetic patients.

[0229] In one embodiment, the combination comprises finerenone in an amount of 40 mg and canagliflozin in an amount of 300 mg, and the combination is used for the treatment of a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetic patients, and diabetic retinopathy in type 2 diabetic patients. In one embodiment, the combination comprises finerenone and dapagliflozin. In one embodiment, this combination can be used for the treatment of hypertensive kidney disease, diabetic kidney disease (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF). In another embodiment, this combination can be used for the treatment of hypertensive kidney disease and / or diabetic kidney disease (DKD). In a further embodiment, this combination can be used for the treatment of heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF). In yet another embodiment, this combination can be used for the treatment of a disease characterized by sodium retention as defined above.

[0230] In one embodiment, the combination comprises finerenone in an amount of 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg and dapagliflozin in an amount of 5 mg or 10 mg, and the combination is used for the treatment of a disease selected from chronic kidney disease (CKD), hypertensive kidney disease, diabetic kidney disease (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in type 1 diabetic patients, and chronic kidney disease in type 2 diabetic patients.

[0231] In one embodiment, the combination comprises finerenone in an amount of 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg and dapagliflozin in an amount of 5 mg, and the combination is used for the treatment of a disease selected from chronic kidney disease (CKD), hypertensive kidney disease, diabetic kidney disease (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in type 1 diabetic patients, and chronic kidney disease in type 2 diabetic patients.

[0232] In one embodiment, the combination comprises 5 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0233] In one embodiment, the combination comprises 10 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0234] In one embodiment, the combination comprises 20 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0235] In one embodiment, the combination comprises 30 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0236] In one embodiment, the combination comprises 40 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0237] In one embodiment, the combination comprises 5 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0238] In one embodiment, the combination comprises 10 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0239] In one embodiment, the combination comprises 20 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0240] In one embodiment, the combination comprises 30 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0241] In one embodiment, the combination comprises 40 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0242] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 mg of dapagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0243] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0244] In one embodiment, the combination comprises 5 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0245] In one embodiment, the combination comprises 10 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0246] In one embodiment, the combination comprises 20 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0247] In one embodiment, the combination comprises finerenone in an amount of 30 mg and dapagliflozin in an amount of 5 mg, and the combination is used for the treatment of a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).

[0248] In one embodiment, the combination comprises finerenone in an amount of 40 mg and dapagliflozin in an amount of 5 mg, and the combination is used for the treatment of a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).

[0249] In one embodiment, the combination comprises finerenone in an amount of 5 mg and dapagliflozin in an amount of 10 mg, and the combination is used for the treatment of a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).

[0250] In one embodiment, the combination comprises finerenone in an amount of 10 mg and dapagliflozin in an amount of 10 mg, and the combination is used for the treatment of a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).

[0251] In one embodiment, the combination comprises finerenone in an amount of 20 mg and dapagliflozin in an amount of 10 mg, and the combination is used for the treatment of a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).

[0252] In one embodiment, the combination comprises finerenone in an amount of 30 mg and dapagliflozin in an amount of 10 mg, and the combination is used for the treatment of a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with reduced ejection fraction (HFrEF).

[0253] In one embodiment, the combination comprises 40 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0254] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0255] In one embodiment, the combination comprises 5 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0256] In one embodiment, the combination comprises 10 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0257] In one embodiment, the combination comprises 20 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0258] In one embodiment, the combination comprises 30 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0259] In one embodiment, the combination comprises 40 mg of finerenone and 5 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0260] In one embodiment, the combination comprises 5 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0261] In one embodiment, the combination comprises 10 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0262] In one embodiment, the combination comprises 20 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0263] In one embodiment, the combination comprises 30 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0264] In one embodiment, the combination comprises 40 mg of finerenone and 10 mg of dapagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0265] In one embodiment, the combination comprises finerenone and empagliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0266] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 10 mg or 25 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0267] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0268] In one embodiment, the combination comprises 5 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0269] In one embodiment, the combination comprises 10 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0270] In one embodiment, the combination comprises 20 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0271] In one embodiment, the combination comprises 30 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0272] In one embodiment, the combination comprises 40 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0273] In one embodiment, the combination comprises 5 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0274] In one embodiment, the combination comprises 10 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0275] In one embodiment, the combination comprises 20 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0276] In one embodiment, the combination comprises 30 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0277] In one embodiment, the combination comprises 40 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0278] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 or 25 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0279] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0280] In one embodiment, the combination comprises 5 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0281] In one embodiment, the combination comprises 10 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0282] In one embodiment, the combination comprises 20 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0283] In one embodiment, the combination comprises 30 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0284] In one embodiment, the combination comprises 40 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0285] In one embodiment, the combination comprises 5 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0286] In one embodiment, the combination comprises 10 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0287] In one embodiment, the combination comprises 20 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0288] In one embodiment, the combination comprises 30 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0289] In one embodiment, the combination comprises 40 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0290] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0291] In one embodiment, the combination comprises 5 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0292] In one embodiment, the combination comprises 10 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0293] In one embodiment, the combination comprises 20 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0294] In one embodiment, the combination comprises 30 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0295] In one embodiment, the combination comprises 40 mg of finerenone and 10 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0296] In one embodiment, the combination comprises 5 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0297] In one embodiment, the combination comprises 10 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0298] In one embodiment, the combination comprises 20 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0299] In one embodiment, the combination comprises 30 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0300] In one embodiment, the combination comprises 40 mg of finerenone and 25 mg of empagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0301] In one embodiment, the combination comprises finerenone and ertugliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0302] In one embodiment, the combination comprises finerenone and ipragliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0303] In one embodiment, the combination comprises finerenone and remogliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0304] In one embodiment, the combination comprises finerenone and cergliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0305] In one embodiment, the combination comprises finerenone and sotagliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0306] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 200 mg or 400 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0307] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0308] In one embodiment, the combination comprises 5 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0309] In one embodiment, the combination comprises 10 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0310] In one embodiment, the combination comprises 20 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0311] In one embodiment, the combination comprises 30 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0312] In one embodiment, the combination comprises 40 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0313] In one embodiment, the combination comprises 5 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0314] In one embodiment, the combination comprises 10 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0315] In one embodiment, the combination comprises 20 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0316] In one embodiment, the combination comprises 30 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0317] In one embodiment, the combination comprises 40 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from chronic kidney disease (CKD), hypertensive nephropathy, diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0318] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 100 or 400 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0319] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0320] In one embodiment, the combination comprises 5 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0321] In one embodiment, the combination comprises 10 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0322] In one embodiment, the combination comprises 20 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0323] In one embodiment, the combination comprises 30 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0324] In one embodiment, the combination comprises 40 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0325] In one embodiment, the combination comprises 5 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0326] In one embodiment, the combination comprises 10 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0327] In one embodiment, the combination comprises 20 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0328] In one embodiment, the combination comprises 30 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0329] In one embodiment, the combination comprises 40 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0330] In one embodiment, the combination comprises 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0331] In one embodiment, the combination comprises 5 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0332] In one embodiment, the combination comprises 10 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0333] In one embodiment, the combination comprises 20 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0334] In one embodiment, the combination comprises 30 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetes patients and diabetic retinopathy in type 2 diabetes patients.

[0335] In one embodiment, the combination comprises 40 mg of finerenone and 200 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0336] In one embodiment, the combination comprises 5 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0337] In one embodiment, the combination comprises 10 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0338] In one embodiment, the combination comprises 20 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0339] In one embodiment, the combination comprises 30 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0340] In one embodiment, the combination comprises 40 mg of finerenone and 400 mg of sotagliflozin, and the combination is used to treat a disease selected from diabetic retinopathy, diabetic retinopathy in type 1 diabetes patients and diabetic retinopathy in type 2 diabetes patients.

[0341] In one embodiment, the combination comprises finerenone and tofogliflozin. In one embodiment, this combination may be used to treat hypertensive nephropathy, diabetic nephropathy (DKD), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In another embodiment, this combination may be used to treat hypertensive nephropathy and / or diabetic nephropathy (DKD). In a further embodiment, this combination may be used to treat heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), or heart failure with impaired ejection fraction (HFrEF). In just another embodiment, this combination may be used to treat diseases characterized by sodium retention as defined above.

[0342] The present invention further provides the use of combinations of the present invention for preparing pharmaceutical compositions for treating the above-mentioned diseases. In this specification, the terms “disorder” and “disease” may be used synonymously.

[0343] The present invention further provides the use of a combination of the present invention for manufacturing a medicament for treating and / or preventing the above-mentioned diseases.

[0344] In one embodiment, the combination according to the present invention for manufacturing pharmaceuticals may be used to treat the above-mentioned disease.

[0345] Based on standard laboratory techniques known to evaluate compounds useful for the treatment of cardiovascular and / or renal and / or cardiorenal diseases, including standard tests and standard pharmacological assays for determining the treatment of the conditions identified above in mammals, and by comparing these results with the results of known drugs used to treat these conditions, the effective dose of finerenone and / or SGLT2 inhibitors for treating each desired indication can be readily determined. The amount of active ingredient to be administered for the treatment of any of these conditions can vary widely depending on considerations such as the specific compound and dosage form used, mode of administration, duration of treatment, age and sex of the patient being treated, and the nature and severity of the condition being treated.

[0346] Clause The following clauses form part of this disclosure and describe further embodiments of the present invention:

[0347] 1. A combination comprising finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and an SGLT2 inhibitor or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0348] 2. Fixed combinations, as described in Clause 1.

[0349] 3. A combination of the above, consisting of a single dosage form.

[0350] 4. A combination of two distinct dosage forms as described in any one of paragraphs 1 to 3.

[0351] 5. Ingredients: a. A dosage form comprising finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, b. One dosage form comprising an SGLT2 inhibitor, its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof. Any combination of the items in Clause 1 or 4, including the combinations described in Clause 1 or 4.

[0352] 6. The combination described in Clause 5, wherein components a. and b. are administered separately, sequentially, simultaneously, concurrently, or alternately with a time delay.

[0353] 7. A combination pack, a combination pack, a parts kit, or part of an unfixed combination, as described in any one of Clauses 1 through 6.

[0354] 8. A combination of any one of clauses 1 to 7, wherein the SGLT2 inhibitor is selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

[0355] 9. A combination of any one of the provisions 1 to 8, which is an oral dosage form.

[0356] 10. Any combination described in any one of the clauses 1 to 9, wherein the dosage form, or one or both of the dosage forms, is a tablet.

[0357] 11. Any combination described in any one of paragraphs 1 to 9, wherein the dosage form, or one or both of the dosage forms, is a capsule.

[0358] 12. Any combination described in any one of the clauses 1 to 10, wherein the dosage form, or one or both of the dosage forms, is a granular preparation.

[0359] 13. Combinations described in any one of clauses 1 to 12, comprising the following amounts of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof: -5~80mg; or -0.25mg to 80mg; or -0.25mg to 40mg; or -0.25mg to 20mg; or -0.25mg to 10mg; or -0.25mg to 5mg.

[0360] Combinations of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof in amounts of 14.5 to 80 mg, particularly 5 to 70 mg, 5 to 60 mg, 5 to 50 mg, 5 to 40 mg, 10 to 80 mg, 10 to 70 mg, 10 to 60 mg, 10 to 50 mg, or 10 to 40 mg, as described in any one of clauses 1 to 13.

[0361] A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof in amounts of 15.5-70 mg, 5-60 mg, 5-50 mg, 5-40 mg, 10-80 mg, 10-70 mg, 10-60 mg, 10-50 mg, or 10-40 mg, as described in any one of clauses 1 to 14.

[0362] A combination of any one of clauses 1 to 15, comprising 16.20 to 40 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0363] A combination of any one of clauses 1 to 16, comprising 17.40 mg, 30 mg, 20 mg, or 10 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0364] A combination of any one of clauses 1 to 17, comprising 18.40 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0365] A combination of any one of clauses 1 to 18, comprising 19.30 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0366] A combination of any one of clauses 1 to 20, comprising 20.20 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0367] A combination of any one of clauses 1 to 20, comprising 21.15 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0368] A combination of any one of clauses 1 to 21, comprising 22.10 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0369] 23.0.5 to 400 mg of an SGLT2 inhibitor, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph, as described in any one of the clauses 1 to 22.

[0370] 24.0.A combination of SGLT2 inhibitors in amounts of 5-300 mg, 1-300 mg, 2-200 mg, 3-100 mg, 5-100 mg, 5-90 mg, 5-80 mg, 5-70 mg, 5-60 mg, 5-50 mg, 5-40 mg, 5-30 mg, 10-90 mg, 10-80 mg, 10-70 mg, 10-60 mg, 10-50 mg or 10-40 mg, 10-30 mg, 15-90 mg, 15-80 mg, 15-70 mg, 15-60 mg, 15-50 mg, 15-40 mg or 15-30 mg, the hydrate thereof, the solvate thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, or a polymorph thereof, as described in any one of clauses 1 to 23.

[0371] 25.1, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 290, or 300 mg of an SGLT2 inhibitor, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph, as described in any one of the clauses 1 to 24.

[0372] 26.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and combinations of canagliflozin or its anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or polymorph thereof, as described in any one of clauses 1 to 25.

[0373] A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof in amounts of 27.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg, and dapagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof, as described in any one of Clauses 1 to 26.

[0374] A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof in amounts of 28.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg, and empagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof, as described in any one of Clauses 1 to 27.

[0375] A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof in amounts of 29.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80 mg, and erzgliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof, as described in any one of clauses 1 to 28.

[0376] 30. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, comprising 5, 10, 20, 30, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 mg of canagliflozin or anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or polymorph thereof, as described in any one of clauses 1 to 29.

[0377] 31. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, comprising 50, 100, 150, 200, 250, or 300 mg of canagliflozin or anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or polymorph thereof, as described in any one of clauses 1 to 30.

[0378] 32. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and any one of the combinations described in any one of the clauses 1 to 31, comprising 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg of dapagliflozin or anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph thereof.

[0379] 33. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and 5 or 10 mg of dapagliflozin or anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph thereof, as described in any one of clauses 1 to 32.

[0380] 34. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and any one of the combinations described in any one of the clauses 1 to 33, comprising 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30 mg of empagliflozin or anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph thereof.

[0381] 35. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and any one of the combinations described in any one of Clauses 1 to 34, comprising 5, 10, 15, 20, or 25 mg of empagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof.

[0382] 36. A combination of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mg of erzgliflozin or anhydrous, its hydrate, its solvate, its pharmaceutically acceptable salt, its prodrug, or its polymorph thereof, as described in any one of clauses 1 to 35.

[0383] 37.1 A combination of any one of the items in clauses 1 to 36 for once-daily administration.

[0384] 38. A pharmaceutical product containing any combination described in any one of the paragraphs 1 through 37.

[0385] 39.1 A pharmacopoeia according to Clause 28, comprising one or more inert, non-toxic, pharmaceutically appropriate excipients.

[0386] 40. A combination of any one of clauses 1 through 37 or any one of clauses 38 or 39, for use as a pharmaceutical product.

[0387] 41. The combinations described in Clause 40 for use as medicines for the treatment and / or prevention of disease.

[0388] 42. A combination of any one of Clauses 1 to 37 or any one of Clauses 38 or 39, for use as a medicine to treat and / or prevent a disease selected from the following: • Cardiovascular disorders such as congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF); Chronic kidney disease (CKD), diabetic and hypertensive nephropathy, cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, renal hypoperfusion, hypotension during dialysis, obstructive urinary tract disease, glomerulopathy, IgA nephropathy, glomerulonephritis, glomerulosclerosis, tubulointerstitial damage, nephropathy, e.g., primary and congenital kidney disease, nephritis, Alport syndrome, renal inflammation, immunological kidney disease, kidney transplant rejection, immune complex-induced kidney disease, toxic substance-induced nephropathy, contrast-induced nephropathy; minimal change glomerulonephritis (lipoid), focal segmental glomerulosclerosis (FSGS), amyloidosis, renal cysts, hypertensive nephrosclerosis and nephrotic syndrome Symptoms (which may be diagnostically characterized by, for example, abnormally decreased creatinine and / or water excretion, abnormally elevated blood concentrations of urea, nitrogen, potassium, and / or creatinine, altered urine osmolality or urine volume, increased microalbuminuria, macroalbuminuria, glomerular and arteriole lesions, tubular dilation, hyperphosphatemia, and / or the need for dialysis), uremia, anemia, electrolyte abnormalities (e.g., hyperkalemia, hyponatremia), abnormalities in bone and carbohydrate metabolism, and renal and cardiorenal disorders such as polycystic kidney disease (PCKD) and syndrome of inappropriate ADH secretion (SIADH); Edema, pulmonary edema, cerebral edema, renal edema, and heart failure-related edema; ·cirrhosis; • NASH (Non-Alcoholic Steatohepatitis); • Arterial hypertension, resistant hypertension, pulmonary hypertension; • Cardiovascular disorders such as hypertension, left ventricular dysfunction, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular arrhythmias, ventricular arrhythmias, atrial fibrillation, and atrial flutter. Cardiovascular disorders such as stable angina, unstable angina, myocardial infarction and its complications, aneurysms, harmful vascular remodeling, atherosclerosis, atrial fibrillation, and stroke; Shocks such as cardiogenic shock, septic shock, and anaphylactic shock; • Hypertensive nephropathy, peripheral artery disease (PAD) including claudication and severe limb ischemia, coronary microcirculatory disorders (CMD) including CMD types 1-4, primary and secondary Raynaud's phenomenon, microcirculatory disorders, peripheral and autonomic neuropathy, diabetic microangiopathy, diabetic retinopathy, diabetic limb ulcers, gangrene, CREST syndrome, erythematous disorders, rheumatic diseases, inflammatory diseases, asthmatic diseases, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), acute lung injury (ALI), α1-antitrypsin deficiency (AATD), pulmonary fibrosis, emphysema (e.g., smoking-induced emphysema), and cystic fibrosis (CF); • Pulmonary hypertension and other lung disorders, cardiopulmonary disorders, and central nervous system disorders; • Fibrosis and other disease symptoms (e.g., end-organ injuries affecting the brain, kidneys, or heart); Multiple injuries, including ischemia-reperfusion injury, contrast agent administration, cardiopulmonary bypass surgery, shock, and sepsis.

[0389] 43. A combination of the following conditions for use as described in either Clause 41 or 42, selected from heart failure (congestive, acute, exacerbating, and chronic, unrelated to ejection fraction), cardiorenal syndrome, CKD, diabetic and hypertensive nephropathy, nephrotic syndrome, hepatorenal syndrome, edema, cirrhosis, NASH (non-alcoholic steatohepatitis), and / or fibrotic disorders.

[0390] 44. A combination for use as described in either clause 41 or 42, wherein the disease is selected from heart failure (unrelated to ejection fraction) and / or chronic kidney disease.

[0391] 45. A combination of use as described in either Clause 41 or 42, wherein the disease is selected from cardiovascular disorders such as congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0392] 46. ​​Diseases including chronic kidney disease (CKD), diabetic and hypertensive nephropathy, cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, renal hypoperfusion, dialysis-induced hypotension, obstructive urinary tract disease, glomerulopathy, IgA nephropathy, glomerulonephritis, glomerulosclerosis, tubulointerstitial damage, nephropathy, e.g., primary and congenital kidney disease, nephritis, Alport syndrome, nephritis, immunological kidney disease, kidney transplant rejection, immune complex-induced kidney disease, toxic substance-induced nephropathy, contrast-induced nephropathy; minimal change glomerulonephritis (lipoid), focal segmental glomerulosclerosis (FSGS), amyloidosis, renal cysts, hypertensive nephrosclerosis and nephrotic syndrome (e.g., abnormally low creatinine levels). A combination for use as described in either Clause 41 or 42, selected from renal and cardiorenal disorders such as and / or polycystic kidney disease (PCKD) and / or syndrome of inappropriate ADH secretion (SIADH).

[0393] 47. A combination of the diseases selected from edema, pulmonary edema, cerebral edema, renal edema and / or heart failure-related edema, as described in either Clause 41 or 42.

[0394] 48. A combination for use as described in either clause 41 or 42, wherein the disease is selected from cirrhosis and / or NASH (non-alcoholic steatohepatitis).

[0395] 49. A combination for use as described in either clause 41 or 42, wherein the disease is selected from arterial hypertension, resistant hypertension, and / or pulmonary hypertension.

[0396] 50. A combination for use as described in either Clause 41 or 42, selected from chronic heart failure with worsening disease (WCHF), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD), non-diabetic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, chronic kidney disease in patients with type 2 diabetes, diabetic retinopathy in patients with type 1 diabetes, or diabetic retinopathy in patients with type 2 diabetes.

[0397] 51. A combination for use as described in any one of clauses 41, 42, or 50, selected from chronic heart failure with worsening disease (WCHF), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF).

[0398] 52. A combination of the diseases selected from chronic kidney disease (CKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes, for use as described in any one of clauses 41, 42, or 50.

[0399] 53. A combination for use as described in any one of Clauses 41, 42, or 50, wherein the disease is selected from diabetic retinopathy in patients with type 1 diabetes and diabetic retinopathy in patients with type 2 diabetes.

[0400] 54. A method of treatment for preventing and / or treating a target disease requiring the use of any combination of the medicinal products described in any one of paragraphs 1 to 37 or any one of paragraphs 38 or 39.

[0401] 55. The treatment method described in Clause 54, wherein the disease is selected from any of the diseases listed in Clauses 42 to 49 or Clauses 50 to 53.

[0402] 56. A method for treating and / or preventing a target disease requiring it, comprising the step of administering an effective dose of a mineralocorticoid receptor blocker and an SGLT2 inhibitor.

[0403] 57. A method for treating and / or preventing a disease of interest as described in Clause 56, comprising the step of administering an effective amount of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof and an SGLT2 inhibitor or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof.

[0404] 58. Use of any combination of the medicinal products described in any one of Clauses 1 to 37 or any one of Clauses 38 or 39 for the manufacture of medicinal products for the treatment and / or prevention of disease.

[0405] 59. Use as described in Clause 58, wherein the disease is selected from the diseases listed in any one of Clauses 42 to 49.

[0406] The combination, method, or use described in any one of Clauses 1 to 59, comprising 60.5 mg, 10 mg, 20 mg, or 40 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and 10 mg or 25 mg of empagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof.

[0407] The combination, method, or use described in any one of Clauses 1 to 59, comprising 61.5 mg, 10 mg, 20 mg, or 40 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and 5 mg or 10 mg of dapagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof.

[0408] The combination, method, or use described in any one of Clauses 1 to 59, comprising 62.5 mg, 10 mg, 20 mg, or 40 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and 100 mg or 300 mg of canagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof.

[0409] The combination, method, or use described in any one of Clauses 1 to 59, comprising 63.5 mg, 10 mg, 20 mg, or 40 mg of finerenone or its hydrate, solvate, pharmaceutically acceptable salt, or polymorph thereof, and 200 mg or 400 mg of sotagliflozin or its anhydrous, hydrate, solvate, pharmaceutically acceptable salt, prodrug, or polymorph thereof.

[0410] 64. Any combination, method, or use described in any one of Clauses 1 to 63, wherein the disease is selected from chronic kidney disease (CKD), diabetic nephropathy (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in patients with type 1 diabetes, and chronic kidney disease in patients with type 2 diabetes.

[0411] 65. A combination, method, or use described in any one of Clauses 1 to 63, wherein the disease is selected from diabetic retinopathy, diabetic retinopathy in patients with type 1 diabetes, and diabetic retinopathy in patients with type 2 diabetes.

[0412] 66. A combination, method, or use described in any one of clauses 1 to 63, selected from chronic heart failure with worsening disease (WCHF), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), or heart failure with reduced ejection fraction (HFrEF).

[0413] 67. A combination of the SGLT2 inhibitors selected from dapagliflozin, empagliflozin, and canagliflozin, as described in any one of clauses 1 to 66.

[0414] 68. A method for treating and / or preventing a disease or using any combination of the SGLT2 inhibitors described in any one of the clauses 1 to 66, wherein the SGLT2 inhibitor is selected from dapagliflozin, empagliflozin, and canagliflozin. [Brief explanation of the drawing]

[0415] [Figure 1a] This figure shows the effects of the SGLT2 inhibitor empagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on urine output in awakened Wistar rats with an activated renin-angiotensin-aldosterone system, tested 24 hours after oral administration of the substance in a metabolic cage, according to Section B, "Evaluation of Physiological Efficacy." n=6-8 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S represents the solvent (group A). 1 mg / kg empagliflozin (Group B), 3 mg / kg empagliflozin (Group C), 10 mg / kg empagliflozin (Group D), 1 mg / kg finerenone (Group E), 1 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group F), 3 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group G), 10 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group H). [Figure 1b]This figure shows the effects of the SGLT2 inhibitor empagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on urinary glucose concentration in awakened Wistar rats with an activated renin-angiotensin-aldosterone system, tested 24 hours after oral administration of the substance in a metabolic cage, according to Section B, "Evaluation of Physiological Efficacy." n=6-8 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not significant compared to the combination group. S means solvent (group A). 1 mg / kg empagliflozin (Group B), 3 mg / kg empagliflozin (Group C), 10 mg / kg empagliflozin (Group D), 1 mg / kg finerenone (Group E), 1 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group F), 3 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group G), 10 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group H). [Figure 1c] This figure shows the effects of the SGLT2 inhibitor empagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on urinary potassium concentration in awakened Wistar rats with an activated renin-angiotensin-aldosterone system, tested 24 hours after oral administration of the substance in a metabolic cage, according to Section B, "Evaluation of Physiological Efficacy." n=6-8 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S represents the solvent (group A). 1 mg / kg empagliflozin (Group B), 3 mg / kg empagliflozin (Group C), 10 mg / kg empagliflozin (Group D), 1 mg / kg finerenone (Group E), 1 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group F), 3 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group G), 10 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group H). [Figure 1d]This figure shows the effects of the SGLT2 inhibitor empagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on urinary sodium concentration in awakened Wistar rats with an activated renin-angiotensin-aldosterone system, tested 24 hours after oral administration of the substance in a metabolic cage, according to Section B, "Evaluation of Physiological Efficacy." n=6-8 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not significant compared to the combination group. S means solvent (group A). 1 mg / kg empagliflozin (Group B), 3 mg / kg empagliflozin (Group C), 10 mg / kg empagliflozin (Group D), 1 mg / kg finerenone (Group E), 1 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group F), 3 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group G), 10 mg / kg empagliflozin + 1 mg / kg finerenone combination (Group H). [Figure 2a] This figure shows the effects of two doses of the SGLT2 inhibitor empagliflozin (Groups B and C), two doses of the MR antagonist finerenone (Groups D and E), and a combination of low doses of empagliflozin (SGLT2 inhibitor) and finerenone (Group F) on the urine output of chronically treated awakened ZDF rats in groups A to F, tested for 24 hours in metabolic cages according to Section B, "Evaluation of Physiological Efficacy." n=14-16 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (Group A). 3 mg / kg empagliflozin (Group B), 10 mg / kg empagliflozin (Group C), 3 mg / kg finerenone (Group D), 10 mg / kg finerenone (Group E), and a combination of 3 mg / kg empagliflozin and 3 mg / kg finerenone (Group F). [Figure 2b]This figure shows the effects of two doses of the SGLT2 inhibitor empagliflozin (groups B and C), two doses of the MR antagonist finerenone (groups D and E), and a combination of low doses of empagliflozin (SGLT2 inhibitor) and finerenone (group F) on urinary glucose concentration in awake ZDF rats chronically treated in metabolic cages for 24 hours according to Section B, "Evaluation of Physiological Efficacy," below. n=14-16 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not significant compared to the combination group. S means solvent (group A). 3 mg / kg empagliflozin (Group B), 10 mg / kg empagliflozin (Group C), 3 mg / kg finerenone (Group D), 10 mg / kg finerenone (Group E), and a combination of 3 mg / kg empagliflozin and 3 mg / kg finerenone (Group F). [Figure 2c] This figure shows the effects of two doses of the SGLT2 inhibitor empagliflozin (Groups B and C), two doses of the MR antagonist finerenone (Groups D and E), and a combination of low doses of empagliflozin (SGLT2 inhibitor) and finerenone (Group F) on urinary potassium concentration in awake ZDF rats chronically treated in metabolic cages for 24 hours according to Section B, "Evaluation of Physiological Efficacy," below. n=14-16 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (Group A). 3 mg / kg empagliflozin (Group B), 10 mg / kg empagliflozin (Group C), 3 mg / kg finerenone (Group D), 10 mg / kg finerenone (Group E), and a combination of 3 mg / kg empagliflozin and 3 mg / kg finerenone (Group F). [Figure 2d]Figure 2d shows the effects of two doses of the SGLT2 inhibitor empagliflozin (groups B and C), two doses of the MR antagonist finerenone (groups D and E), and a combination of low doses of empagliflozin (SGLT2 inhibitor) and finerenone (group F) on urinary sodium concentration (Figure 2d) in awake ZDF rats chronically treated in groups A to F, tested for 24 hours in metabolic cages according to Section B, "Evaluation of Physiological Efficacy" below. n=14-16 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not significant compared to the combination group. S means solvent (group A). 3 mg / kg empagliflozin (Group B), 10 mg / kg empagliflozin (Group C), 3 mg / kg finerenone (Group D), 10 mg / kg finerenone (Group E), and a combination of 3 mg / kg empagliflozin and 3 mg / kg finerenone (Group F). [Figure 3a] This figure shows the results of testing mortality in 27 renin transgenic (mRen2) rats treated with hypertension and proteinuria L-NAME (20 mg / L). [Figure 3b] This figure shows the results of testing for proteinuria in 27 renin transgenic (mRen2) rats treated with L-NAME (20 mg / L) for hypertension and proteinuria. [Figure 4]This figure shows the effects of the SGLT2 inhibitor canagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on (a) urine volume (Figure 4a), (b) urinary glucose concentration (Figure 4b), (c) urinary potassium concentration (Figure 4c), and (d) urinary sodium concentration (Figure 4d) in awakened Wistar rats with an activated renin-angiotensin-aldosterone system, tested 24 hours after oral administration of the substance in a metabolic cage, according to Section B, "Evaluation of Physiological Efficacy" below. n=9-10 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (group A). 1 mg / kg canagliflozin (Group B), 3 mg / kg canagliflozin (Group C), 10 mg / kg canagliflozin (Group D), 1 mg / kg finerenone (Group E), combination of 1 mg / kg canagliflozin and 1 mg / kg finerenone (Group F), combination of 3 mg / kg canagliflozin and 1 mg / kg finerenone (Group G), combination of 10 mg / kg canagliflozin and 1 mg / kg finerenone (Group H). [Figure 5]This figure shows the effects of the SGLT2 inhibitor dapagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on (a) urine volume (Figure 5a), (b) urinary glucose concentration (Figure 5b), (c) urinary potassium concentration (Figure 5c), and (d) urinary sodium concentration (Figure 5d) in awakened Wistar rats with an activated renin-angiotensin-aldosterone system, tested 24 hours after oral administration of the substance in a metabolic cage, according to Section B, "Evaluation of Physiological Efficacy" below. n=10 rats / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (group A). 0.03 mg / kg dapagliflozin (Group B), 0.3 mg / kg dapagliflozin (Group C), 3 mg / kg dapagliflozin (Group D), 1 mg / kg finerenone (Group E), 0.03 mg / kg dapagliflozin + 1 mg / kg finerenone combination (Group F), 0.3 mg / kg dapagliflozin + 1 mg / kg finerenone combination (Group G), 3 mg / kg dapagliflozin + 1 mg / kg finerenone combination (Group H). [Modes for carrying out the invention]

[0416] Examples A - Pharmaceutical preparations / dosage forms A-1-1: Tablets containing finerenone (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of formula (I) A granular solution in purified water containing the crystalline compound of formula (I) in a micronized form, hypromellose 5cP, and sodium lauryl sulfate was prepared. Microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium were mixed in a container or fluidized bed granulator (premix). The premix and granular solution were granulated in a fluidized bed granulator. The granules were dried and sieved, and then magnesium stearate was added as a lubricant. A press mixture was thus prepared. The press mixture was pressed into tablets using a rotary tablet press.

[0417] A homogeneous coating suspension was prepared from hypromellose, talc, titanium dioxide, yellow iron oxide, red iron oxide, and purified water. The coating suspension was sprayed onto tablets in a suitable coating apparatus.

[0418] [Table 1]

[0419] A-1-2: Tablets containing finerenone (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of formula (I) A granular suspension in purified water of the crystalline compound of formula (I) in a micronized form, hypromellose, and sodium lauryl sulfate was prepared. Microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium were mixed in a container or fluidized bed granulator (premix). The premix and granular solution were granulated in a fluidized bed granulator. The granules were dried and sieved, and then magnesium stearate was added as a lubricant. A pressing mixture was thus prepared. Tablets were obtained by compressing the pressing mixture using a rotary tablet press. A homogeneous coating suspension was prepared from hypromellose, talc, titanium dioxide, yellow iron oxide, red iron oxide, and / or black iron oxide, as well as purified water. The coating suspension was sprayed onto tablets in a suitable coating apparatus. The compositions of tablets obtained by the described method are listed in Table 1-2.

[0420] [Table 2]

[0421] As a film coating, commercially available film coatings can be used on the tablets disclosed in Tables 1-1 and 1-2 above. Examples include Opadry® film coatings such as Opadry® 02A275000 Light Gray, Opadry® 02A240005 Light Pink, or Opadry® 02A220009 Light Yellow.

[0422] B - Evaluation of physiological efficacy In vivo assay for detecting natriuretic activity in awakened rats with B-1 activated RAAS Wistar rats (weighing approximately 250-500g) were raised with free access to feed (Altromin) and drinking water. Approximately 72 hours prior to the start of the experiment, the animals consumed a specially low-sodium diet containing 0.02% sodium chloride instead of their normal feed (ssniff R / MH, 10mm with 0.02% Na, S0602-E081, ssniff Spezialdiaten GmbH, D-59494 Soest). This low-sodium diet induced RAAS activation in the animals during a 3-day induction period, thus mimicking the neuroendocrine activation characteristic of cardiorenal disease. During the experiment, the animals were housed individually in metabolic cages suitable for rats of this weight class (Tecniplast Deutschland GmbH, D-82383 Hohenpeissenberg) and had free access to the low-sodium diet and drinking water for up to 24 hours. At the start of the study, the substance to be tested was administered by force-feeding with a suitable solvent (PEG400) at a volume of 2-3 ml per kg of body weight. Control animals received only the solvent ("S", i.e., the solvents in Table 2 below). The control and substance studies were conducted in parallel on the same day. Each control and substance administration group consisted of 6-10 animals. During the study, urine excreted by the animals was continuously collected in a receptacle at the bottom of the cage. The urine volume per collection time was determined separately for each animal, and the concentrations of glucose, sodium, and potassium excreted in the urine were measured by standard methods using a clinical chemistry analyzer system (ADVIA 2400, Siemens). Urine was typically collected in a metabolic cage for 24 hours.

[0423] B-2 In vivo assay for detecting natriuretic activity in chronically treated Zucker diabetic obese rats Zucker diabetic obese (ZDF) rats have a missense mutation (fa / fa) in the gene encoding the leptin receptor and spontaneously develop insulin resistance, type 2 diabetes (T2DM), hyperlipidemia, moderate hypertension and obesity, and progressive renal impairment. Homozygous males develop diabetes between weeks 7 and 19, which is reflected in marked hyperglycemia. In addition to diabetic cardiac lesions (e.g., hypertrophy), renal pathology develops with proteinuria, mesangial dilation, macrophage infiltration, and interstitial fibrosis. Heterozygous animals do not develop obesity or insulin resistance and are therefore useful non-diabetic control animals.

[0424] Obese (fa / fa) male Zuker rats (Charles River), 6-7 weeks old, were fed a high-energy diet (Purina Rodent LabDiet 5008, PMI Nutrition.Richmond.IN). When animals developed hyperglycemia, they were randomized to either a treatment group or a solvent group. Rats (n=14-16 / group) received either a solvent [ethanol / Solutol / H2O (10 / 40 / 50)] or a test compound in a solvent once daily (fa / fa) for 4-12 weeks.

[0425] During the experiment, systolic blood pressure (determined by the tail cuff), urinary parameters (e.g., protein, glucose, electrolytes, creatinine, urea, and uric acid), and plasma parameters (e.g., electrolytes, glucose, creatinine, urea, and uric acid) were determined at regular intervals.

[0426] To determine urinary parameters, animals were housed individually in metabolic cages suitable for rats of this weight class (Tecniplast Deutschland GmbH, D-82383 Hohenpeissenberg) and given free access to drinking water for up to 24 hours. Urine volume per collection time was determined separately for each animal, and the concentrations of urinary glucose and electrolyte ions excreted in the urine were measured by standard methods using a clinical chemistry analyzer system (ADVIA 2400, Siemens). Urine was typically collected in the metabolic cage for 24 hours. At the end of the chronic experiment, hemodynamic parameters (e.g., blood pressure, heart rate, maximal and minimum inotropy [dp / dt], relaxation time [τ], left ventricular pressure, left ventricular end-diastolic pressure [LVEDP]) were measured, the weights of the heart, kidneys, and lungs were determined, and plasma and urinary biomarkers (e.g., NT-proBNP) and gene expression of biomarkers were determined by RT / TaqMan PCR after RNA isolation from cardiac and renal tissues. Histopathological examinations will be performed using heart and kidney tissue derived from animals in both the treatment and placebo groups.

[0427] B-3 Comparison of monotherapy (finerenone or empagliflozin (SGLT2 inhibitor)) and combination therapy (finerenone and empagliflozin (SGLT2 inhibitor) combination) in awakened rats with activated RAAS In this comparison, eight different doses were administered (see groups A-H): Group A received only the solvent (PEG400). This group serves as a control group. Groups B, C, and D received only three escalating doses of empagliflozin (an SGLT2 inhibitor). This helps to detect the effect of SGLT2 inhibitor monotherapy. Group E received finerenone only. This helps to detect the effect of finerenone monotherapy. Groups F, G, and H received a combination of finerenone and three different doses of SGLT2 inhibitors, respectively. This helps to detect the effects of the combination therapy of finerenone and empagliflozin (an SGLT2 inhibitor) (the combination according to the present invention).

[0428] After the procedure, urine volume, urinary glucose, urinary sodium, and potassium concentrations were measured. The results are summarized in Table 2.

[0429] [Table 3]

[0430] The results are also shown in Figure 1. Figure 1: Awakened Wistar rats with an activated renin-angiotensin-aldosterone system were tested in a metabolic cage for 24 hours after oral administration of the substance, according to Section B, "Evaluation of Physiological Efficacy," above. (a) Urine volume (Figure 1a), (b) Urinary glucose concentration (Figure 1b) (c) Urinary potassium concentration (Figure 1c) (d) Urinary sodium concentration (Figure 1d) Effects of the SGLT2 inhibitor empagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on [specific organisms]. n=6-8 animals / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (group A). ​​1 mg / kg empagliflozin (group B), 3 mg / kg empagliflozin (group C), 10 mg / kg empagliflozin (group D), 1 mg / kg finerenone (group E), 1 mg / kg empagliflozin + 1 mg / kg finerenone combination (group F), 3 mg / kg empagliflozin + 1 mg / kg finerenone combination (group G), 10 mg / kg empagliflozin + 1 mg / kg finerenone combination (group H).

[0431] From Table 2 and Figures 1a-1d, we can conclude the following: Group A (solvent only), administered with the solvent (PEG400), shows physiological urine volume, potassium, and sodium excretion in awake rats over 24 hours under RAAS activation. Groups B, C, and D (empagliflozin (SGLT2 inhibitor) monotherapy) showed that administration of empagliflozin at indicated doses did not affect urine volume, urinary potassium, or urinary sodium, but resulted in a dose-dependent and potent increase in urinary glucose. Group E (finerenone monotherapy) showed that administration of 1 mg / kg of finerenone did not affect urine volume, urinary glucose, or urinary potassium, but caused an increase in urinary sodium. Groups F, G, and H (combinations of finerenone and empagliflozin (SGLT2 inhibitor)) showed that administration of a combination of 1 mg / kg finerenone and 1–10 mg / kg empagliflozin (SGLT2 inhibitor) did not increase urinary glucose and urinary potassium compared to administration of finerenone and empagliflozin (SGLT2 inhibitor) individually, but increased urine volume at higher combined doses and dose-dependently and potently induced sodium excretion in all combination groups compared to finerenone and empagliflozin (SGLT2 inhibitor) individually.

[0432] A comparison of Group A (solvent) with Groups F, G, and H (combinations of finerenone and empagliflozin (SGLT2 inhibitor)) shows that administration of the finerenone and empagliflozin (SGLT2 inhibitor) combination, i.e., chronic administration of the finerenone and SGLT2 inhibitor combination, increases urinary sodium excretion from 1.16±0.06 mmol (Group A) to 0.71±0.07 mmol (Group F, combination), 0.96±0.09 mmol (Group G, combination), and 0.89±0.09 mmol (Group H, combination). The comparison between groups B, C, D, and E (monotherapy with empagliflozin or finerenone) and groups F, G, and H (combination of finerenone and empagliflozin (SGLT2 inhibitor)) showed that administration of the combination of finerenone and empagliflozin (SGLT2 inhibitor), i.e., chronic administration of the combination of finerenone and an SGLT2 inhibitor, increased urinary sodium excretion from 0.15±0.05 mmol (group B, monotherapy with empagliflozin), 0.13±0.02 mmol (group C, monotherapy with empagliflozin), 0.17±0.03 mmol (group D, monotherapy with empagliflozin), 0.43±0.03 mmol (group E, monotherapy with empagliflozin) to 0.71±0.07 mmol (group F, combination), 0.96±0.09 mmol (group G, combination), and 0.89±0.09 mmol. This indicates an increase to mmol (H group, combination). This is surprising, as the combination of finerenone and empagliflozin (an SGLT2 inhibitor) shows an effect that outweighs the additive one.

[0433] It should be noted that urinary sodium concentrations are statistically significantly higher. Urinary sodium excretion from combination therapy is greater than the pure sum of each monotherapy. This results in an effect that exceeds the additive effect compared to each monotherapy. Therefore, the combination of finerenone and empagliflozin (SGLT2 inhibitor) under typical conditions of activated RAAS results in a significant improvement in natriuretic efficacy compared to the sum of the monotherapies. This improvement in natriuretic efficacy is a major clinical goal in the treatment of cardiovascular diseases and / or cardiorenal diseases such as heart failure and CKD.

[0434] B-4 Comparison of monotherapy (finerenone or SGLT2 inhibitor) and combination therapy (finerenone and SGLT2 inhibitor) in chronically treated Zucker diabetic obese rats In this comparison, six different doses were administered: Group A received only the solvent [ethanol / Solutol / H2O (10 / 40 / 50)]. This group serves as a control group. Groups B and C received only two escalating doses of empagliflozin (an SGLT2 inhibitor). This helps to detect the effect of empagliflozin monotherapy. Groups D and E received finerenone only at gradually increasing doses. This helps to detect the effect of finerenone monotherapy. Group F each received a low dose of empagliflozin (an SGLT2 inhibitor) and finerenone. This helps to detect the effect of the combination therapy of finerenone and empagliflozin (an SGLT2 inhibitor) (the combination according to the present invention).

[0435] After the procedure, urine volume, urinary glucose, urinary sodium, and potassium concentrations were measured. The results are summarized in Table 3.

[0436] [Table 4]

[0437] The results are also shown in Figure 2. Figure 2: Awakened ZDF rats, group A to F, were tested in a metabolic cage for 24 hours according to Section B, "Evaluation of Physiological Efficacy," above. (a) Urine volume (Figure 2a); (b) Urinary glucose concentration (Figure 2b) (c) Urinary potassium concentration (Figure 2c) (d) Urinary sodium concentration (Figure 2d) The effects of two doses of the SGLT2 inhibitor empagliflozin (Groups B and C), two doses of the MR antagonist finerenone (Groups D and E), and a combination of low doses of empagliflozin (SGLT2 inhibitor) and finerenone (Group F) on the target population. n=14-16 animals / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (Group A). ​​3 mg / kg empagliflozin (Group B), 10 mg / kg empagliflozin (Group C), 3 mg / kg finerenone (Group D), 10 mg / kg finerenone (Group E), and a combination of 3 mg / kg empagliflozin + 3 mg / kg finerenone (Group F).

[0438] From Table 3 and Figures 2(a) to 2(d), we can conclude the following: Group A (solvent), administered with the solvent ([ethanol / Solutol / H2O(10 / 40 / 50)]), shows urine volume, glucose, potassium, and sodium excretion in awake Zucker diabetic obese rats over 24 hours after a 9-week treatment period.

[0439] A comparison of Group A (solvent) with Groups B and C (empagliflozin (SGLT2 inhibitor) monotherapy) shows that chronic administration of SGLT2 inhibitors increases urine volume, urinary glucose, urinary potassium, and urinary sodium. Compared to empagliflozin (SGLT2 inhibitor) monotherapy, solvent group A showed 27.2% higher urinary sodium excretion compared to solvent control group A.

[0440] A comparison of Group A (solvent) with Groups D and E (finerenone monotherapy) shows that chronic administration of finerenone at the indicated doses of 3 and 10 mg / kg / day does not affect urine volume, urinary glucose, urinary potassium, and urinary sodium. Compared to finerenone monotherapy, solvent group A showed 20.1% higher urinary sodium excretion compared to solvent control group A.

[0441] A comparison of low-dose groups B (3 mg / kg empagliflozin (SGLT2 inhibitor), monotherapy) and D (3 mg / kg finerenone, monotherapy) with group F (combination of finerenone and empagliflozin (SGLT2 inhibitor)) shows that the combination of finerenone and empagliflozin (SGLT2 inhibitor) did not increase urine volume, urinary glucose, or urinary potassium compared to individual administrations of finerenone and SGLT2 inhibitors, but resulted in a statistically significant increase in urinary sodium excretion, approximately 41-58% higher than each monotherapy. This is surprising, as the combination of finerenone and empagliflozin (SGLT2 inhibitor) shows a greater-than-additive effect.

[0442] In summary, urinary sodium excretion was 27.2% and 20.1% higher, respectively, with 3 mg / kg empagliflozin (SGLT2 inhibitor) and 3 mg / kg finerenone compared to the solvent control (Group A). ​​However, combined urinary sodium excretion with the finerenone and empagliflozin combination was 78.25% higher compared to solvent control Group A, and therefore higher than the combined total of each monotherapy. Thus, the combined sodium excretion was approximately 41-58% higher compared to each monotherapy.

[0443] Therefore, the combination of finerenone and empagliflozin (an SGLT2 inhibitor) results in a significant improvement in natriuretic efficacy compared to the combined effects of monotherapy in typical chronic conditions including insulin resistance, type 2 diabetes, hyperlipidemia, hypertension and obesity, as well as progressive renal impairment. This improvement in natriuretic efficacy is a major clinical goal in the treatment of cardiovascular and / or cardiorenal diseases such as heart failure and CKD.

[0444] B-5 Efficacy of combination therapy with the nonsteroidal MR antagonist finerenone and the SGLT2 inhibitor empagliflozin in a non-diabetic cardiorenal rat model method: Cardiorenal morbidity and mortality were examined in 27 renin transgenic (mRen2) rats treated with hypertension and proteinuria using L-NAME (20 mg / L). Rats (10–11 week-old females, n=13–17 / group) were orally treated once daily for up to 7 weeks with placebo, finerenone (1 and 3 mg / kg), empagliflozin (3 and 10 mg / kg), or a combination of these at lower doses. Key outcome parameters included mortality, blood pressure, proteinuria, nephrology, and gene expression.

[0445] L-NAME treated transgenic renin rat (TGR(mRen2)27): The transgenic renin rat "TGR(mRen2)27" is a hypertensive rat strain developed by Mullins and Ganten that overexpresses the mouse Ren-2 gene. Further administration of the nitric oxide synthase inhibitor L-NAME induces endothelial dysfunction, which increases morbidity and mortality in this model. Unless lifelong antihypertensive therapy is administered, homozygous animals die from secondary complications such as heart failure and renal failure or stroke.

[0446] Female TGR(mRen2)27 renin rats aged 10–20 weeks were randomized to either a pharmacological treatment group or a placebo group. Additionally, the nitric oxide synthase inhibitor L-NAME was administered via drinking water at concentrations of 20–100 mg / l. Throughout the experiment, animals were allowed free access to drinking water and feed. The substance was administered daily for 4–10 weeks, either via feed or by forced feeding. Animals treated similarly except for receiving only the solvent or feed without the test substance were designated as the placebo group. During the experiment, systolic blood pressure was determined at regular intervals using a tail cuff, proteinuria (expressed as the ratio of urinary protein concentration to urinary creatinine concentration) and urinary electrolyte composition were determined by collecting urine in a metabolic cage, and mortality was recorded daily. At the end of the experiment, hemodynamic parameters (blood pressure, heart rate, inotropy [dp / dt], relaxation time [τ], maximum left ventricular pressure, left ventricular end-diastolic pressure [LVEDP]) are measured, the weights of the heart, kidneys, and lungs are determined, protein removal and biomarkers (e.g., ANP, RIA kit RK 005-24, Phoenix Pharmaceuticals, Inc., USA, cGMP; RIA kit RE29075, IBL International GmbH, Hamburg, Germany; renin, angiotensin I, RIA kit CA-1533, DiaSorin SpA, Italy; and aldosterone, P2714, DiaSorin SpA, Italy) are performed, renal and cardiac histopathology is performed, and the gene expression of biomarkers is determined by RT / TaqMan PCR after RNA isolation from cardiac and renal tissues.

[0447] To determine urinary parameters, animals were housed individually in metabolic cages suitable for rats of this weight class (Tecniplast Deutschland GmbH, D-82383 Hohenpeissenberg) and given free access to drinking water for up to 24 hours. Urine volume per collection time was determined separately for each animal, and the concentrations of urinary glucose and electrolyte ions excreted in the urine were measured using a standard method with a clinical chemistry analyzer system (ADVIA 2400, Siemens). Urine was typically collected in the metabolic cage for 24 hours.

[0448] result: Placebo-treated rats demonstrated a 50% mortality rate over a 7-week period (Figure 3a). Drug treatments yielded varying degrees of survival benefits, most significantly and statistically most pronounced in the low-dose combination group (Figure 3a). The low-dose combination demonstrated early, sustained, and effective reduction in proteinuria (-86%, p<0.05; Figure 3b) and was highly efficient against renal histological parameters. Monotherapy with finerenone (-27% at 1 mg / kg, p=ns; -87% at 3 mg / kg, p<0.05; Figure 3b) and empagliflozin (-38% at 3 mg / kg, p=ns; -64% at 10 mg / kg, p=ns; Figure 3b) dose-dependently reduced proteinuria, with higher doses providing comparable protection from renal lesions. Finerenone and combination therapy significantly reduced systolic blood pressure, while empagliflozin, both alone and in combination, had a potent glucosoric effect.

[0449] Conclusion: Both finerenone-based MRA and empagliflozin-based SGLT2 inhibitors provide renal protection in preclinical non-diabetic hypertensive nephropathy. The combination of these two modes of action at low doses demonstrated a significant reduction in proteinuria (see Figure 3b) and mortality, indicating strong potential for combined clinical use in their respective cardiorenal patient populations.

[0450] B-6 Comparison of monotherapy (finerenone or canagliflozin (SGLT2 inhibitor)) and combination therapy (finerenone and canagliflozin (SGLT2 inhibitor)) in awakened rats with activated RAAS In this comparison, eight different doses were administered (see groups A-H): Group A received only the solvent (PEG400). This group serves as a control group. Groups B, C, and D received only three progressively increasing doses of canagliflozin (an SGLT2 inhibitor). This helps to detect the effect of SGLT2 inhibitor monotherapy. Group E received finerenone only. This helps to detect the effect of finerenone monotherapy. Groups F, G, and H received a combination of finerenone and three different doses of SGLT2 inhibitors, respectively. This helps to detect the effects of the combination therapy of finerenone and canagliflozin (an SGLT2 inhibitor) (the combination according to the present invention).

[0451] The method described in Section B1 was used.

[0452] [Table 5]

[0453] The results are also shown in Figure 4. Figure 4: Awakened Wistar rats with an activated renin-angiotensin-aldosterone system were tested in a metabolic cage for 24 hours after oral administration of the substance, according to Section B, "Evaluation of Physiological Efficacy," above. (a) Urine volume (Figure 4a), (b) Urinary glucose concentration (Figure 4b) (c) Urinary potassium concentration (Figure 4c), and (d) Urinary sodium concentration (Figure 4d) Effects of the SGLT2 inhibitor canagliflozin (groups B-D), the MR antagonist finerenone (group E), and combinations thereof (groups F-H) on [specific organisms]. n=9-10 animals / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S means solvent (group A). ​​1 mg / kg canagliflozin (group B), 3 mg / kg canagliflozin (group C), 10 mg / kg canagliflozin (group D), 1 mg / kg finerenone (group E), 1 mg / kg canagliflozin + 1 mg / kg finerenone combination (group F), 3 mg / kg canagliflozin + 1 mg / kg finerenone combination (group G), 10 mg / kg canagliflozin + 1 mg / kg finerenone combination (group H).

[0454] From Table 4 and Figures 4a-4d, we can conclude the following: Group A (solvent only), administered with the solvent (PEG400), shows physiological urine volume, potassium, and sodium excretion in awake rats over 24 hours under RAAS activation. Groups B, C, and D (canagliflozin (SGLT2 inhibitor) monotherapy) showed that canagliflozin administration at doses of 1 and 3 mg / kg did not affect urine volume, urinary potassium, or urinary sodium, but a dose of 10 mg / kg induced an increase in urine volume and urinary sodium. All doses of canagliflozin induced a potent increase in urinary glucose. Group E (finerenone monotherapy) showed that administration of 1 mg / kg of finerenone did not affect urine volume, urinary glucose, or urinary potassium, but caused a weak increase in urinary sodium. Groups F, G, and H (combinations of finerenone and canagliflozin (SGLT2 inhibitor)) showed that administration of 1 mg / kg finerenone and 1-10 mg / kg canagliflozin combinations did not increase urinary glucose compared to individual canagliflozin administrations (finerenone alone does not affect urinary glucose) and did not increase urine volume compared to individual canagliflozin administrations. However, compared to the individual finerenone and canagliflozin (SGLT2 inhibitor) administration groups, the two higher combination groups (1 mg / kg finerenone and 3 mg / kg canagliflozin; 1 mg / kg finerenone and 10 mg / kg canagliflozin) strongly induced sodium excretion.

[0455] It should be noted that urinary sodium concentrations were statistically significantly higher in the combination groups of 3 mg / kg canagliflozin and 1 mg / kg finerenone, respectively. Urinary sodium excretion from the combination therapy was greater than the pure sum of each monotherapy. Thus, it showed an effect that outweighed the additive effect compared to each monotherapy. Therefore, the combination of finerenone and canagliflozin (SGLT2 inhibitor) under typical conditions of activated RAAS results in a significant improvement in natriuretic efficacy compared to the sum of the monotherapys. This improvement in natriuretic efficacy is a major clinical goal in the treatment of cardiovascular diseases and / or cardiorenal diseases such as heart failure and CKD.

[0456] B-7 Comparison of monotherapy (finerenone or dapagliflozin (SGLT2 inhibitor)) and combination therapy (finerenone and dapagliflozin (SGLT2 inhibitor) combination) in awakened rats with activated RAAS In this comparison, eight different administrations were performed (see groups A-H): Group A received only the solvent (PEG400). This group serves as a control group. Groups B, C, and D received only three escalating doses of dapagliflozin (SGLT2 inhibitor). This helps to detect the effect of monotherapy with an SGLT2 inhibitor. Group E received only finerenone. This helps to detect the effect of monotherapy with finerenone. Groups F, G, and H received a combination of finerenone and three doses of an SGLT2 inhibitor, respectively. This helps to detect the effect of combination therapy with finerenone and dapagliflozin (SGLT2 inhibitor) (the combination according to the present invention). The following methods (10 animals per group) described in Section B1 were used.

[0457] [Table 6]

[0458] The results are also shown in Figure 5. Figure 5: Awakened Wistar rats with an activated renin-angiotensin-aldosterone system were tested in a metabolic cage for 24 hours after oral administration of the substance, according to Section B, "Evaluation of Physiological Efficacy," above. (a) Urine volume (Figure 5a), (b) Urinary glucose concentration (Figure 5b) (c) Urinary potassium concentration (Figure 5c), and (d) Urinary sodium concentration (Figure 5d) Effects of the SGLT2 inhibitor dapagliflozin (groups B-D), the MR antagonist finerenone (E), and combinations thereof (groups F-H) on [specific organism]. n=10 animals / group. +: p<0.05 vs. combination group, ++: p<0.01 vs. combination group, +++: p<0.005 vs. combination group, "ns" means not statistically significant compared to the combination group. S represents the solvent (group A). 0.03 mg / kg dapagliflozin (Group B), 0.3 mg / kg dapagliflozin (Group C), 3 mg / kg dapagliflozin (Group D), 1 mg / kg finerenone (Group E), 0.03 mg / kg dapagliflozin + 1 mg / kg finerenone combination (Group F), 0.3 mg / kg dapagliflozin + 1 mg / kg finerenone combination (Group G), 3 mg / kg dapagliflozin + 1 mg / kg finerenone combination (Group H).

[0459] From Table 5 and Figures 5a-5d, we can conclude the following: Group A (solvent only), administered with the solvent (PEG400), shows physiological urine volume, potassium, and sodium excretion in awake rats over 24 hours under RAAS activation. Groups B, C, and D (dapagliflozin monotherapy (SGLT2 inhibitor)) showed that dapagliflozin at doses of 0.03 and 0.3 mg / kg did not affect urine volume, urinary potassium, or urinary sodium, but a dose of 3 mg / kg induced an increase in urine volume and urinary sodium. All doses of dapagliflozin induced a potent increase in urinary glucose. Group E (finerenone monotherapy) showed that administration of 1 mg / kg of finerenone did not affect urine volume, urinary glucose, or urinary potassium, but caused an increase in urinary sodium. Groups F, G, and H (combinations of finerenone and dapagliflozin (SGLT2 inhibitor)) showed that administration of 1 mg / kg finerenone and 0.03-3 mg / kg dapagliflozin did not increase urinary glucose compared to individual dapagliflozin administrations (finerenone alone does not affect urinary glucose), nor did it increase urine volume compared to individual dapagliflozin administrations. However, compared to the individual finerenone and dapagliflozin (SGLT2 inhibitor) administration groups, all combination groups (1 mg / kg finerenone and 0.03 mg / kg dapagliflozin; 1 mg / kg finerenone and 0.3 mg / kg dapagliflozin; 1 mg / kg finerenone and 3 mg / kg dapagliflozin) strongly induced sodium excretion.

[0460] It should be noted that urinary sodium concentrations were statistically significantly higher in all combination groups of 0.03–3 mg / kg dapagliflozin and 1 mg / kg finerenone, respectively. The urinary sodium excretion from the combination therapy of 0.03 mg / kg dapagliflozin and 1 mg / kg finerenone, and the combination therapy of 3 mg / kg dapagliflozin and 1 mg / kg finerenone, was greater than the pure sum of the individual monotherapies. Thus, the effect exceeded the additive effect compared to each monotherapy. Therefore, the combination of finerenone and canagliflozin (SGLT2 inhibitor) under typical activated RAAS conditions results in a significant improvement in natriuretic efficacy compared to the sum of the individual monotherapies. This improvement in natriuretic efficacy is a major clinical goal in the treatment of cardiovascular diseases and / or cardiorenal diseases such as heart failure and CKD.

Claims

1. A combination comprising 0.25 to 80 mg of finerenone or its hydrate, solvate, or a pharmaceutically acceptable salt thereof, and an SGLT2 inhibitor or its hydrate, solvate, or a pharmaceutically acceptable salt thereof, wherein the SGLT2 inhibitor is selected from the group consisting of ertugliflozin, ipragliflozin, remogliflozin, cergliflozin, sotagliflozin, and tofogliflozin.

2. The combination according to claim 1, which is selected from or is part of the group consisting of a fixed combination, a single dosage form, two distinct dosage forms, a combination pack, a parts kit, or an unfixed combination.

3. component: a. One dosage form comprising finerenone or its hydrate, solvate, or a pharmaceutically acceptable salt thereof, b. One dosage form comprising an SGLT2 inhibitor or its hydrate, solvate, or pharmaceutically acceptable salt thereof A combination according to claim 1 or 2, including the following:

4. The combination according to claim 3, wherein components a. and b. are administered separately, sequentially, simultaneously, concurrently, or alternately with a time delay.

5. A combination according to any one of claims 1 to 4, which is a single dosage form.

6. A combination according to any one of claims 1 to 5, for once-daily administration.

7. A pharmaceutical product comprising a combination according to any one of claims 1 to 6.

8. A pharmacopoeia according to claim 7 for treating and / or preventing a disease.

9. Cardiovascular disorders; • Renal and cardiorenal impairment; Edema, pulmonary edema, cerebral edema, renal edema, and heart failure-related edema; • Cirrhosis of the liver; • NASH (Non-Alcoholic Steatohepatitis); Arterial hypertension, resistant hypertension, pulmonary hypertension, essential hypertension; ·shock; Hypertensive nephropathy, peripheral artery disease (PAD) including claudication and severe limb ischemia, coronary microcirculatory disorders (CMD) including CMD types 1-4, primary and secondary Raynaud's phenomenon, microcirculatory disorders, peripheral and autonomic neuropathy, diabetic microangiopathy, diabetic retinopathy, diabetic limb ulcers, gangrene, CREST syndrome, erythematous disorders, rheumatic diseases, for promoting wound healing, inflammatory diseases, asthmatic diseases, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), acute lung injury (ALI), α1-antitrypsin deficiency (AATD), pulmonary fibrosis, emphysema and cystic fibrosis (CF); • Lung and cardiopulmonary disorders, central nervous system disorders; Fibrotic disorders and other disease symptoms; ・Sleep apnea; ·obesity; Coronary artery disease (CAD), - Acute kidney injury (AKI), Chronic kidney disease following acute kidney injury (AKIM) after major surgery - Multiple injuries A combination of any one of claims 1 to 6 or a pharmaceutical according to claim 7 for use as a pharmaceutical for treating and / or preventing a disease selected from.

10. Cardiovascular disorders are selected from congestive heart failure, acute heart failure, chronic heart failure, worsening chronic heart failure (WCHF), hospitalization for heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with mildly impaired ejection fraction (HFmrEF), and heart failure with impaired ejection fraction (HFrEF), hypertension, left ventricular dysfunction, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular arrhythmias, ventricular arrhythmias, atrial fibrillation, atrial flutter, stable angina, unstable angina, myocardial infarction and its complications, aneurysm, adverse vascular remodeling, atherosclerosis, atrial fibrillation, and stroke; - Renal and cardiorenal disorders are selected from chronic kidney disease (CKD), non-diabetic chronic kidney disease (ndCKD), diabetic nephropathy (DKD), hypertensive nephropathy, cardiorenal syndrome, nephrotic syndrome, hepatorenal syndrome, renal hypoperfusion, dialysis-induced hypotension, obstructive urinary tract disease, glomerulopathy, IgA nephropathy, glomerulonephritis, glomerulosclerosis, tubulointerstitial damage, nephropathy, nephritis, Alport syndrome, nephritis, immunological nephropathy, kidney transplant rejection, immune complex-induced nephropathy, toxic substance-induced nephropathy, contrast-induced nephropathy; minimal change glomerulonephritis (lipoid), focal segmental glomerulosclerosis (FSGS), amyloidosis, renal cysts, hypertensive nephrosclerosis, nephrotic syndrome, uremia, anemia, electrolyte abnormalities, bone and carbohydrate metabolism abnormalities, polycystic kidney disease (PCKD), and syndrome of inappropriate ADH secretion (SIADH); The type of shock is selected from cardiogenic shock, septic shock, and anaphylactic shock; - Lung damage and cardiopulmonary damage are accompanied by pulmonary hypertension; • Multiple injuries are selected from ischemia-reperfusion injury, contrast agent administration, cardiopulmonary bypass surgery, shock, and sepsis. The combination or pharmaceutical product according to claim 9.

11. Nephropathy includes primary and congenital kidney diseases; Nephrotic syndrome may be diagnostically characterized by abnormally decreased creatinine and / or fluid excretion, abnormally elevated blood concentrations of urea, nitrogen, potassium, and / or creatinine, altered urine osmolality or urine volume, increased microalbuminuria, macroalbuminuria, lesions of the glomeruli and arterioles, tubular dilation, hyperphosphatemia, and / or the need for dialysis; Electrolyte abnormalities include hyperkalemia or hyponatremia; Emphysema is smoking-induced emphysema; Other disease symptoms include end-organ damage affecting the brain, kidneys, or heart. The combination or pharmaceutical product according to claim 10.

12. The combination or pharmaceutical product according to claim 9, wherein the disease is selected from chronic kidney disease (CKD), hypertensive kidney disease, diabetic kidney disease (DKD), non-diabetic chronic kidney disease (ndCKD), chronic kidney disease in type 1 diabetes patients, chronic kidney disease in type 2 diabetes patients, diabetic retinopathy, diabetic retinopathy in type 1 diabetes patients, diabetic retinopathy in type 2 diabetes patients, worsening chronic heart disease (WCHF), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF).

Images