PHARMACEUTICAL FORMULATIONS OF ABIRATERONE ACETATE AND NIRAPARIB

Abstract

This disclosure relates to a combination of abiraterone acetate and niraparib, to free-dose and fixed-dose combinations of abiraterone acetate and niraparib, and to methods of treating prostate cancer with such combinations.

Description

PHARMACEUTICAL FORMULATIONS OF ABIRATERONE ACETATE AND NIRAPARIB TECHNICAL FIELD OF THE INVENTION The present disclosure relates to combinations of antineoplastic drugs, to methods of treating prostate cancer with said combinations and to pharmaceutical formulations comprising said combinations. BACKGROUND OF THE INVENTION Prostate cancer is the most common non-cutaneous malignancy in men and the second cause of cancer death in men in the Western world. Prostate cancer is the result of uncontrolled growth of abnormal cells in the prosthetic gland. Once a prostate cancer tumor develops, androgens, such as testosterone, promote its growth. In its early stages, localized prostate cancer is often curable with local therapy including, for example, surgical removal of the prosthetic gland and radiation therapy. However, when local therapy fails to cure prostate cancer, as occurs in up to a third of men, the disease progresses to an incurable metastatic disease (that is, a disease in which the cancer has spread from one part from the body to other parts). Current therapeutic options for men with metastatic castration-resistant prostate cancer (mCRPC) that improve survival and limit progression include taxane-based chemotherapy and androgen receptor-targeted agents such as apalutamide (ERLEADA®). and enzalutamide (XTANDI®). Platinum-based chemotherapy has been tested in several clinical studies in patients with molecularly unselected prostate cancer, with limited results and significant toxicities. More recently, abiraterone acetate (ZYTIGA®) plus prednisone has been approved for the treatment of metastatic castration-resistant prostate cancer. Niraparib is an orally available, highly selective poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor with activity against the deoxyribonucleic acid (DNA) repair polymerases PARP-1 and PARP-2. Jones P, Wilcoxen K, Rowley M, Toniatti C. Niraparib: A Poly(ADP-ribose) Po / ymerase (PARP) Inhibitor for the Treatment ofTumors with Defective Homologous Recombination. J Med Chem. April 23, 2015; 58(8): 3302-3314. PARP are enzymes responsible for the repair of single strand breaks cnni? ίη / ζζηζ / Ε / γίΛΐ of DNA (SCR) through a process called base excision repair. Inhibition of PARP leads to an accumulation of unrepaired RCS, resulting in stalling and collapse of replication forks and, consequently, double-strand breaks (RCDs). Typically, RCDs are repaired through homologous recombination (HR). If left unrepaired, RCDs cause cell death. When tumor cells with DNA repair defects involving the HR pathway (e.g., breast cancer genes [BRCAJ-1 / 2) are treated with a PARP inhibitor, they are unable to repair efficiently and accurately. RCDs, creating a lethal synthesis condition. In men with metastatic castration-resistant prostate cancers (mCRPC), tumors with DNA repair abnormalities account for approximately 20% to 30% of sporadic cancers. Therapeutic options are needed for patients with prostate cancer who do not initially respond or become refractory to existing treatments. Importantly, there is an unmet need for therapeutic options for patients with prostate cancer. BRIEF DESCRIPTION OF THE INVENTION The present disclosure relates to a combination of abiraterone acetate and niraparib, which can be administered to a mammal, in particular a human, suffering from a disease or condition related to the androgen receptor (AR), in particular cancer, more particularly prostate cancer. These pharmaceutical formulations are fixed-dose combinations of abiraterone acetate and niraparib. An objective of the present invention is to provide therapies against prostate cancer, including, but not limited to, hormone-sensitive prostate cancer, high-risk hormone-unexposed prostate cancer, castration-resistant prostate cancer, metastatic castration-resistant prostate cancer (mCRPC), metastatic castration-sensitive prostate cancer (mSCPC), non-metastatic castration-resistant prostate cancer (nmCRPC), biochemically recurrent prostate cancer (BQR) and localized prostate cancer (LCC). An object of the present invention is to provide free dose combinations (CDL) of abiraterone acetate and niraparib tosylate monohydrate; or fixed-dose combinations (FDCs) comprising abiraterone acetate and niraparib tosylate monohydrate. An objective of the present invention is to provide pharmaceutical formulations that support patient compliance, therapy adherence, and therapy efficacy. An objective of the present invention is to provide pharmaceutical formulations that reduce patients' tablet burden, for example, from six or four cnni? tablets. ίη / ζζηζ / Ε / γίΛΐ abiraterone acetate and niraparib tosylate monohydrate daily to three tablets a day, or preferably two or one. An objective of the present invention is to provide fixed dose combination pharmaceutical formulations (FDC) with comparable or improved stability or shelf life over separately formulated drug dosage forms. An objective of the present invention is to provide fixed dose combination pharmaceutical formulations that are bioequivalent to the drug dosage forms when administered in separate dosage forms. An objective of the present invention is to provide fixed dose combination pharmaceutical formulations with an immediate release profile for both abiraterone acetate and niraparib. An objective of the present invention is to provide fixed dose combination pharmaceutical formulations with good content uniformity or homogeneous distribution of abiraterone acetate and niraparib tosylate monohydrate. In some aspects, abiraterone acetate and niraparib tosylate monohydrate are homogeneously distributed within an intragranular phase. In some aspects, abiraterone acetate and niraparib tosylate monohydrate are homogeneously distributed within the dosage form, for example, a tablet. In some aspects, when abiraterone acetate and niraparib tosylate monohydrate are prepared in separate granules, the respective granules are homogeneously distributed in a mixture of granules. The active substances abiraterone acetate and niraparib tosylate monohydrate have different particle sizes (dso of 4-5 pm and dso approximately 50 pm, respectively), different apparent densities and different contents (33% and 5-10% (w / p), respectively) in the fixed dose combinations of the present invention. When these two active ingredients are mixed as is, they are prone to segregation, which causes problems with homogeneity in the mixture and, therefore, with control of the dosage in individual tablets. The administration of a FDC with precise and constant amounts of the two active ingredients is essential to ensure safety and effectiveness. Content uniformity can be affected by formulation manufacturing conditions, such as inlet air temperature, spray rate, inlet air flow during granulation, and drying loss during granulation. An object of the present invention is to provide granules comprising abiraterone acetate and niraparib tosylate monohydrate with good layered content uniformity. An object of the present invention is to provide granules comprising abiraterone acetate and niraparib tosylate monohydrate with a size distribution of cnni? ίη / ζζηζ / Ε / γίΛΐ desired particle, which can be expressed in dio, dso and / or dgo values. If the granules are too small, this could result in problems during compression when preparing tablets. If the granules are too large, this could result in differences in content uniformity and unwanted segregation, problems with compression during tableting, and problems with dissolution and bioavailability of PAFs. An objective of the present invention is to provide an immediate release film-coated fixed-dose combination pharmaceutical formulation for oral administration, the ingredients of which do not cause oxidative degradation of abiraterone acetate, a PAF known to be sensitive to such degradation. . The presence of organic or inorganic impurities and / or degradants and / or metabolites, if they are out of trend, may affect patient safety or the effectiveness of the therapy. An objective of the present invention is to provide fixed dose combination pharmaceutical formulations with comparable dissolution profiles for abiraterone acetate and niraparib tosylate monohydrate with respect to each other. Such a dissolution profile may support the use of a fixed-dose combination because both agents would be suitable for administration in the same schedule. Another objective of the present invention is to provide fixed dose combination formulations with comparable or improved dissolution profiles for one or both, and preferably both, active ingredients compared to one or both respective drugs formulated separately, for example, in their formulations currently marketed on the market (such as abiraterone acetate tablets and niraparib tosylate monohydrate capsules). Dissolution profiles can be affected by manufacturing conditions, such as inlet air temperature, spray rate, inlet air flow during granulation, and by tablet hardness. An objective of the present invention is to provide fixed-dose combination pharmaceutical formulations with comparable or improved bioavailability for each drug compared to drugs dosed as separate formulations (for example, in their currently marketed formulations, which are tablets of abiraterone acetate and niraparib tosylate monohydrate capsules). Another objective of the present invention is to provide fixed dose combination pharmaceutical formulations in which the two active ingredients have one or more comparable pharmacokinetic parameters with respect to the separate formulations (for example, Tmax and / or ti / 2, or % of Cmax, similar or improved). Reduced bioavailability with respect to single agent dosing, or bioavailability parameters that do not allow the same dosing schedule for both agents, would lead to low plasma levels and affect the efficacy of the therapy and could require increasing the frequency of dosage, the number of doses, or both. cnni? ίη / ζζηζ / Ε / γίΛΐ An object of the present invention is to provide an immediate-release film-coated fixed-dose combination pharmaceutical formulation for oral administration comprising 500 mg of abiraterone acetate and 50 mg or 100 mg of niraparib free base, in monohydrate form. of tosylate. An object of the present invention is to provide an immediate-release film-coated fixed-dose combination pharmaceutical formulation for oral administration comprising 375 mg of abiraterone acetate and 50 mg or 100 mg of niraparib free base, in monohydrate form. of tosylate. An object of the present invention is to provide an immediate-release film-coated fixed-dose combination pharmaceutical formulation for oral administration comprising 250 mg of abiraterone acetate and 50 mg or 100 mg of niraparib free base, in monohydrate form. of tosylate. An objective of the present invention is to provide fixed dose combination pharmaceutical formulations with comparable or improved efficacy (for example, due to greater bioavailability at the same doses) compared to separately dosed drugs. In view of the divergent physicochemical properties of abiraterone acetate (lipophilic and poorly bioavailable) and niraparib tosylate monohydrate (hydrophilic and moderate to high bioavailability), it is also an objective of the present invention to provide a technical solution to formulators when Compounds of the two drugs are prepared together. The present disclosure relates to a method for treating prostate cancer in a male human patient comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described herein. , plus a glucocorticoid, for example, prednisone, hydrocortisone, dexamethasone, prednisolone, including methylprednisolone. The present disclosure relates to a method for the treatment of mCRPC in a male human patient with mCRPC, the method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described in the present document, plus prednisone. In one aspect, the mCRPC treatment is a first-line (Ll) mCRPC treatment. In one aspect, the patient has not been treated with abiraterone acetate plus prednisone for more than 5 months. In one aspect, the patient is positive for a homologous recombination deficiency (HRD) or the patient is not positive for a HRD. In one aspect, DRH status is detected by monoallelic or biallelic alterations in one or more DNA repair genes, including, without limitation, BRCA1 (breast cancer gene 1), BRCA2 (breast cancer gene 2), ATM (ataxia-telangiectasia mutated), FANCA (Fanconi anemia complementation group A gene), PALB2 (cnni partner and localizer gene? Ln / zznz / E / YiAi BRCA2), CHEK2 (checkpoint kinase 2 gene), BRIP1 (BRCA1-interacting protein C-terminal helicase 1 gene), HDAC2 (histone deacetylase 2), or CDK12 (cyclin-dependent kinase 12) . In one aspect, the patient has received gonadotropin-releasing hormone agonist (GnRHa) therapy or has undergone a bilateral orchiectomy, prior to treatment with the pharmaceutical formulation, plus prednisone. In one aspect, GnRHa therapy continues during treatment with the pharmaceutical formulation, plus prednisone, if there is no surgical castration. The present disclosure relates to a method for treating mCPSC in a male human patient with mCPSC, said mCPSC patient having a deleterious somatic or germ line homologous recombination repair (RRH) gene mutation, said method comprising administering to the patient a effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described herein, plus prednisone. In one aspect, the deleterious somatic or germline RRH gene mutation is in one or more genes, including, without limitation, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B (RAD51 paralog B) and RAD54L (similar to RAD54). In one aspect, the patient has undergone ADT (androgen deprivation therapy) prior to treatment with the pharmaceutical formulation, plus prednisone. In one aspect, said TPA is a medical or surgical castration. In one aspect, said ADT began within 6 months, preferably at least 14 days, prior to treatment with the pharmaceutical formulation, plus prednisone. In one aspect, the patient undergoes ADT during treatment with the pharmaceutical formulation, plus prednisone. In one aspect, the patient has not undergone prior therapy with a new generation androgen signaling inhibitor therapy (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide, nilutamide, flutamide, bicalutamide, and the like). In one aspect, the patient has received docetaxel or cabazitaxel prior to treatment with the pharmaceutical formulation, plus prednisone. In one aspect, the patient has received radiation or surgery prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has received abiraterone acetate plus prednisone, prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has received abiraterone acetate plus prednisone for one month prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has received treatments for localized prostate cancer, prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, such treatments for localized prostate cancer have been completed at least 1 year prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, such treatments for localized prostate cancer are up to 3 years of ADT, including radiation therapy, prostatectomy, lymph node dissection, or systemic therapies. The present disclosure relates to a method for the treatment of mCRPC in a cnni? ίη / ζζηζ / Ε / γίΛΐ male human patient with mCRPC, with or without DNA repair gene defects (DRA) or HRD and, optionally, with pathogenic alterations of cyclin-dependent kinase 12 (CDK12), said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described herein, plus prednisone. In one aspect, the patient continues GnRHa therapy during treatment with the pharmaceutical formulation plus prednisone, if there is no surgical castration. In one aspect, the patient has been exposed to antiandrogens selected from nilutamide, flutamide, bicalutamide, enzalutamide, apalutamide, darolutamide and abiraterone acetate; before treatment with the pharmaceutical formulation plus prednisone. In one aspect, a pharmacological rest of said antiandrogens is performed before treatment with the pharmaceutical formulation plus prednisone. The present disclosure relates to a method for treating high-risk and / or lymph node-positive prostate cancer in a male human patient with high-risk and / or lymph node-positive prostate cancer, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described herein, plus prednisone and leuprorelin acetate, before, during and after radiotherapy. In one aspect, said radiotherapy is stereotactic body radiotherapy (SBRT) or ultrahypofractionated radiotherapy, with a total dose of about 37.5 to 40 gray (Gy). The present disclosure relates to a method for the treatment of non-castration-exposed prostate cancer in a male human patient with non-castration-exposed prostate cancer, with or without metastasis, said method comprising administering to the patient an effective amount of a formulation pharmaceutical comprising abiraterone acetate and niraparib tosylate monohydrate as described herein, plus prednisone. In one aspect, the patient continues GnRHa therapy during treatment with the pharmaceutical formulation plus prednisone, if there is no surgical castration. The present disclosure relates to a method for the treatment of biochemically recurrent prostate cancer in a male human patient with biochemically recurrent prostate cancer, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and abiraterone monohydrate. niraparib tosylate as described herein, plus prednisone. In one aspect, said biochemically recurrent prostate cancer is detected by: i) an increase in prostate-specific antigen (PSA) of > 2.0 ng / ml above the nadir; or i) next-generation imaging (NGI) including prostate-specific membrane antigen positron emission tomography (PSMA-PET). In one aspect, the patient is positive for DRH biomarkers, high risk, and / or has oligometastatic disease. In one aspect, the positive DRH biomarker is one or more of, without limitation, BRCA1, BRCA2, ATM, BRIP1, CDK12, CDK17, CHEK2, FANCA, HDAC2, PALB2, PPP2R2A, RAD51B and RAD54L. The present disclosure relates to a method for the treatment of locally advanced prostate cancer in a male human patient with locally advanced prostate cancer and who is a candidate for primary radiotherapy, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described herein, plus prednisone. The present disclosure relates to a method for the treatment of mCRPC in a male human mCRPC patient who has optionally received prior chemotherapy comprising docetaxel or cabazitaxel, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate. and niraparib tosylate monohydrate, as described herein, plus prednisone. The present disclosure relates to a method for the treatment of nmCRPC in a male human patient with nmCRPC, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate as described in the present document, plus prednisone. In one aspect, the patient has a PSA doubling time equal to or less than 10 months and is DRH positive. In one aspect, the patient is DRH positive. In one aspect, the patient has high-risk BKR. In the treatment methods disclosed herein, said pharmaceutical formulation may be a free dose combination (CDL) of abiraterone acetate and niraparib tosylate monohydrate; or a fixed-dose combination (FDC) comprising abiraterone acetate and niraparib tosylate monohydrate. In one aspect, the CDL or the CDF each independently comprise about 50 mg of eq. of niraparib and approximately 500 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 500 mg of abiraterone acetate; approximately 50 mg eq. of niraparib and approximately 375 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 375 mg of abiraterone acetate; approximately 50 mg eq. of niraparib and approximately 250 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 250 mg of abiraterone acetate; approximately 33 mg eq. of niraparib and approximately 333 mg of abiraterone acetate; or approximately 67 mg eq. of niraparib and approximately 333 mg of abiraterone acetate. In one aspect, CDL or CDF are oral dosage forms. In one aspect, the oral dosage form is a tablet, capsule or sachet. In the treatment methods disclosed herein, the cnni? ίη / ζζηζ / Ε / γίΛΐ fixed dose combination (FDC) comprising abiraterone acetate and niraparib, preferably niraparib tosylate monohydrate, is as defined throughout the present disclosure. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combined preparation for use simultaneously, separately or sequentially with prednisone, in the treatment of prostate cancer in a patient, such as mCRPC, such as first-line mCRPC (Ll). In one aspect, the patient has not been treated with abiraterone acetate and prednisone for more than 5 months. In one aspect, the patient is positive for a homologous recombination deficiency (HRD) or the patient is not positive for a HRD. In one aspect, DRH status is detected by monoallelic or biallelic alterations in one or more DNA repair genes, including, without limitation, BRCA1 (breast cancer gene 1), BRCA2 (breast cancer gene 2), ATM (ataxia-telangiectasia mutated), FANCA (Fanconi anemia complementation group A gene), PALB2 (BRCA2 partner and localizer gene), CHEK2 (checkpoint kinase 2 gene), BRCA1-interacting protein C-terminal helicase 1), HDAC2 (histone deacetylase 2) or CDK12 (cyclin-dependent kinase 12). In one aspect, the patient has received gonadotropin-releasing hormone agonist (GnRHa) therapy or has undergone a bilateral orchiectomy, prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, GnRHa therapy continues during treatment with the pharmaceutical formulation plus prednisone, if there is no surgical castration. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combination preparation for simultaneous, separate or sequential use with prednisone, in the treatment of mCPSC in patients who have mCPSC with deleterious somatic or germline homologous recombination repair (HRR) gene mutation. In one aspect, the deleterious somatic or germline RRH gene mutation is in one or more genes, including, without limitation, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B and RAD54L. In one aspect, the patient has undergone ADT prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, said ADT is medical or surgical castration. In one aspect, said ADT began within 6 months, preferably at least 14 days, prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient undergoes ADT during treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has not undergone prior therapy with a new generation androgen signaling inhibitor therapy (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide, nilutamide, flutamide, bicalutamide, and the like). In one aspect, the patient has received docetaxel or cabazitaxel prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, has the patient received radiation or cnni? ίη / ζζηζ / Ε / γίΛΐ underwent surgery, before treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has received abiraterone acetate plus prednisone, prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has received abiraterone acetate plus prednisone for one month prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, the patient has received treatments for localized prostate cancer, prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, such treatments for localized prostate cancer have been completed at least 1 year prior to treatment with the pharmaceutical formulation plus prednisone. In one aspect, such treatments for localized prostate cancer are up to 3 years of ADT, including radiation therapy, prostatectomy, lymph node dissection, or systemic therapies. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combination preparation for simultaneous, separate or sequential use plus prednisone, in the treatment of mCRPC in patients with mCRPC, with or without DNA repair gene defects (DRA) or DRH and, optionally, with pathogenic alterations of cyclin-dependent kinase 12 (CDK12). In one aspect, the patient continues GnRHa therapy during treatment with the pharmaceutical formulation plus prednisone, if there is no surgical castration. In one aspect, the patient has been exposed to antiandrogens selected from nilutamide, flutamide, bicalutamide, enzalutamide, apalutamide, darolutamide and abiraterone acetate; before treatment with the pharmaceutical formulation plus prednisone. In one aspect, a pharmacological rest of said antiandrogens is performed before treatment with the pharmaceutical formulation plus prednisone. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combined preparation for simultaneous, separate or sequential use plus prednisone and leuprorelin acetate, in the treatment of prostate cancer. high-risk and / or lymph node-positive prostate cancer in patients with high-risk, lymph node-positive prostate cancer, before, during and after radiotherapy. In one aspect, said radiotherapy is stereotactic body radiotherapy (SBRT) or ultrahypofractionated radiotherapy, with a total dose of about 37.5 to 40 Gy. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combination preparation for simultaneous, separate or sequential use plus prednisone, in the treatment of non-castration-exposed prostate cancer. in patients who have non-castration-exposed prostate cancer, with or without metastasis. In one aspect, GnRHa therapy continues during treatment with the pharmaceutical formulation plus prednisone, if there is no surgical castration. The present disclosure refers to a pharmaceutical formulation comprising cnni? ίη / ζζηζ / Ε / γίΛΐ abiraterone acetate and niraparib tosylate monohydrate, in the form of a combination preparation for simultaneous, separate or sequential use plus prednisone, in the treatment of biochemically recurrent prostate cancer in patients who have prostate cancer. biochemically recurrent prostate. In one aspect, said biochemically recurrent prostate cancer is detected by: i) an increase in prostate specific antigen (PSA) of > 2.0 ng / ml above the nadir; or i) next-generation imaging (NGI) including prostate-specific membrane antigen positron emission tomography (PSMA-PET). In one aspect, patients are positive for DRH biomarkers, high risk, and / or have oligometastatic disease. In one aspect, the positive DRH biomarker is one or more of, without limitation, BRCA1, BRCA2, ATM, BRIP1, CDK12, CDK17, CHEK2, FANCA, HDAC2, PALB2, PPP2R2A, RAD51B and RAD54L. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combination preparation for simultaneous, separate or sequential use plus prednisone, in the treatment of locally advanced prostate cancer in patients who have locally advanced prostate cancer and who are candidates for primary radiotherapy. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, as a combination preparation for simultaneous, separate or sequential use, plus prednisone, in the treatment of mCRPC in patients having mCRPC who optionally have received prior chemotherapy comprising docetaxel or cabazitaxel. The present disclosure relates to a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, in the form of a combination preparation for simultaneous, separate or sequential use, plus prednisone, in the treatment of nmCRPC in patients having nmCRPC . In one aspect, the patients have a PSA doubling time equal to or less than 10 months and are DRH positive. In one aspect, patients are DRH positive. In one aspect, patients have high-risk BQR. The pharmaceutical formulation for the uses disclosed herein may be a free dose combination (CDL) of abiraterone acetate and niraparib; or a fixed-dose combination (FDC) comprising abiraterone acetate and niraparib. The pharmaceutical formulation for the uses disclosed herein may be a CDL of abiraterone acetate and niraparib tosylate monohydrate; or a FDC comprising abiraterone acetate and niraparib tosylate monohydrate. In one aspect, the CDL or the CDF each independently comprise about 50 mg of eq. of niraparib (niraparib free base equivalent) and approximately 500 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 500 mg of abiraterone acetate; approximately 50 mg eq. cnni? ίη / ζζηζ / Ε / γίΛΐ of niraparib and approximately 375 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 375 mg of abiraterone acetate; approximately 50 mg eq. of niraparib and approximately 250 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 250 mg of abiraterone acetate; approximately 33 mg eq. of niraparib and approximately 333 mg of abiraterone acetate; or approximately 67 mg eq. of niraparib and approximately 333 mg of abiraterone acetate. In one aspect, CDL or CDF are oral dosage forms. In one aspect, the oral dosage form is a tablet, capsule or capsule. The fixed dose combination (FDC) comprising abiraterone acetate and niraparib tosylate monohydrate (or niraparib) is as defined throughout the present disclosure. The present disclosure relates to a granule composition comprising abiraterone acetate, niraparib and a pharmaceutically acceptable carrier. The present disclosure relates to a pharmaceutical formulation, such as an oral dosage form, comprising the composition in granules. In one aspect, the granules consist essentially of abiraterone acetate, niraparib and a pharmaceutically acceptable carrier. In one aspect, said granules have a particle size distribution with a dso of about 200 to about 500 pm, or about 231 to about 396 pm; with a dio of about 50 to about 250 pm, or about 93 to about 192 pm; and / or with a doo of about 500 to about 900 pm, or from about 616 to about 723 pm. In one aspect, a first portion of the granules consists essentially of abiraterone acetate and a pharmaceutically acceptable carrier; and a second portion of the granules consists essentially of niraparib and a pharmaceutically acceptable carrier. In one aspect, niraparib is in the form of a salt of tosylate monohydrate, sulfate, benzenesulfate, fumarate, succinate, camphorate, mandelate, camsylate, lauryl sulfate, or a mixture of tosylate monohydrate and lauryl sulfate. In one aspect, niraparib tosylate monohydrate is in crystalline form. In one aspect, the abiraterone acetate is in crystalline form. In one aspect, the present disclosure relates to a pharmaceutical formulation comprising niraparib lauryl sulfate and a pharmaceutically acceptable carrier. In one aspect, the present disclosure relates to a pharmaceutical formulation comprising a mixture of niraparib tosylate monohydrate and niraparib lauryl sulfate, and a pharmaceutically acceptable carrier. In one aspect, the pharmaceutically acceptable carrier of the granule composition comprises a wetting agent, a diluent, a disintegrant, optionally a cnni? ίη / ζζηζ / Ε / γίΛΐ sliding, optionally a lubricant and optionally a binder. In one aspect, the diluent is lactose, and said lactose is also used as a binder. In one aspect, the disintegrant is crospovidone. The present disclosure further relates to a pharmaceutical formulation, for example, an oral dosage form, comprising the granule composition described herein. In one aspect, the oral formulation or dosage form comprises approximately 50 mg eq. of niraparib and approximately 500 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 500 mg of abiraterone acetate; approximately 50 mg eq. of niraparib and approximately 375 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 375 mg of abiraterone acetate; approximately 50 mg eq. of niraparib and approximately 250 mg of abiraterone acetate; approximately 100 mg eq. of niraparib and approximately 250 mg of abiraterone acetate; approximately 33 mg eq. of niraparib and approximately 333 mg of abiraterone acetate; or approximately 67 mg eq. of niraparib and approximately 333 mg of abiraterone acetate. In one aspect, the oral dosage form is a tablet, wherein the pharmaceutically acceptable carrier comprises a wetting agent, a diluent, a disintegrant, a glidant, a lubricant, optionally a binder and optionally a coating material. In one aspect, the wetting agent is sodium lauryl sulfate (SLS) and is present in the dosage form in a percentage of about 3 to 6% (w / w). In one aspect, the wetting agent is SLS and is present in the final dosage forms in a weight ratio to abiraterone acetate of about 0.05:1 to 0.2:1 (SLS:abiraterone acetate), preferably about 0.1:1. , more preferably about 0.11:1, about 0.12:1 or about 0.123:1. In one aspect, the SLS is present in both the intragranular and extragranular phases of the tablet. In one aspect, the disintegrant is crospovidone and is present in both the intragranular and extragranular phases of the tablet. In one aspect, the extragranular phase diluent is silicified microcrystalline cellulose. In one aspect, the tablet has a hardness of 250 to 350 N. In one aspect, the tablet has a layered content uniformity of 75% to 125% or 90% to 110%. In one aspect, the tablet has a blend uniformity with a relative standard deviation of up to 3%. In one aspect, the tablet comprises about 500 mg of abiraterone acetate and about 50 mg of eq. of niraparib; and wherein (i) more than 40%, or about 50%, of abiraterone acetate dissolves after 5 minutes, (i) more than 75%, or about 80 or 81%, of abiraterone acetate dissolves dissolves after 10 minutes, (iii) more than 85%, or approximately 89 or 90% of abiraterone acetate dissolves after 15 minutes, (iv) more than 87%, or approximately 92%, of abiraterone acetate Does abiraterone dissolve cnni? ίη / ζζηζ / Ε / γίΛΐ after 20 minutes; (v) more than 90%, or approximately 95%, of the abiraterone acetate dissolves after 30 minutes, (vi) more than 91%, or approximately 96%, of the abiraterone acetate dissolves after 45 minutes, (vii) more than 92%, or approximately 97%, of the abiraterone acetate dissolves after 60 minutes, (viii) more than 93%, or approximately 98%, of the abiraterone acetate dissolves after 90 minutes, or (ix) more than 93%, or approximately 98%, of abiraterone acetate dissolves after 120 minutes; when measured by the USP Paddle method at 75 rpm in 900 ml of an aqueous solution comprising 0.05 mM sodium phosphate buffer with 0.25% (w / v) sodium lauryl sulfate at pH 4.5 and a temperature of 37.0 ± 0.5 °C. In one aspect, the tablet comprises about 500 mg of abiraterone acetate and about 100 mg of eq. of niraparib; and wherein (i) more than 36%, or about 41%, of abiraterone acetate dissolves after 5 minutes, (i) more than 67%, or about 72%, of abiraterone acetate dissolves after of 10 minutes, (i¡) more than 76%, or approximately 81% of abiraterone acetate dissolves after 15 minutes, (iv) more than 81%, or approximately 86%, of abiraterone acetate dissolves after 20 minutes, (v) more than 85 or 86%, or approximately 90 or 91%, of the abiraterone acetate dissolves after 30 minutes, (vi) more than 90%, or approximately 95% of the abiraterone acetate dissolves after 45 minutes, (vii) more than 90 or 91%, or approximately 95 or 96%, of the abiraterone acetate dissolves after 60 minutes, (viii) more than 93%, or about 98% of abiraterone acetate dissolves after 90 minutes, or (ix) more than 94%, or about 99%, of aribaterone acetate dissolves after 120 minutes; when measured by the USP Paddle method at 75 rpm in 900 ml of an aqueous solution comprising 0.05 mM sodium phosphate buffer with 0.25% (w / v) sodium lauryl sulfate at pH 4.5 and a temperature of 37.0 ± 0.5 °C. In one aspect, the tablet comprises about 500 mg of abiraterone acetate and about 50 mg of eq. of niraparib; and wherein (i) more than 30 or 35%, or approximately 39 or 40%, of niraparib dissolves after 5 minutes, (ii) more than 79 or 80%, or approximately 84 or 85% , of niraparib dissolves after 10 minutes, (iii) more than 90%, or approximately 95% of niraparib dissolves after 15 minutes, (iv) more than 92%, or approximately 97%, of niraparib dissolves after 20 minutes, (v) more than 93%, or approximately 98%, of niraparib dissolves after 30 minutes, (vi) more than 93%, or approximately 98%, of niraparib dissolves after 45 minutes , (vii) more than 93%, or approximately 98%, of the niraparib dissolves after 60 minutes, (viii) more than 93%, or approximately 98%, of the niraparib dissolves after 90 minutes, or (ix ) more than 93%, or approximately 98%, of niraparib dissolves after 120 minutes; When is cnni measured? ίη / ζζηζ / Ε / γίΛΐ by the USP Paddle method at 75 rpm in 900 ml of an aqueous solution comprising 0.05 mM sodium phosphate buffer with 0.25% (w / v) sodium lauryl sulfate at pH 4.5 and a temperature of 37.0 ± 0.5 °C. In one aspect, the tablet comprises about 500 mg of abiraterone acetate and about 100 mg of eq. of niraparib; and wherein (i) more than 23%, or approximately 28%, of niraparib dissolves after 5 minutes, (ii) more than 64%, or approximately 69%, of niraparib dissolves after 10 minutes, (iii) more than 80 or 81%, or approximately 85 or 86% of niraparib dissolves after 15 minutes, (iv) more than 87%, or approximately 92%, of niraparib dissolves after 20 minutes , (v) more than 90%, or approximately 95%, of the niraparib dissolves after 30 minutes, (vi) more than 91%, or approximately 96%, of the niraparib dissolves after 45 minutes, (vii) more than 92%, or approximately 97%, of niraparib dissolves after 60 minutes, (viii) more than 92%, or approximately 97%, of niraparib dissolves after 90 minutes, or (ix) more than 92% %, or approximately 97%, of niraparib dissolves after 120 minutes; when measured by the USP Paddle method at 75 rpm in 900 ml of an aqueous solution comprising 0.05 mM sodium phosphate buffer with 0.25% (w / v) sodium lauryl sulfate at pH 4.5 and a temperature of 37.0 ± 0.5 °C. In one aspect, the tablet dosage forms are bioequivalent, when administered orally on a dose equivalent basis, to the free dose combinations of abiraterone acetate and niraparib (for example, wherein one or more pharmacokinetic parameters are within 20% or within 10% or within 5% of the respective values ​​after dosing with free dose combinations or single agents). In one aspect, the oral dosage form is a capsule or sachet, optionally further comprising a diluent. In one aspect, the oral dosage form is a fixed dose combination (FDC). The present disclosure also relates to the pharmaceutical formulation or oral dosage form described herein, for use in the treatment of prostate cancer in a patient. Similarly, the present disclosure also relates to a method of treating prostate cancer in a patient, said method comprising administering said pharmaceutical formulation or oral dosage form to the patient. In one aspect, prostate cancer is metastatic prostate cancer, advanced prostate cancer, regional prostate cancer, locally advanced prostate cancer, localized prostate cancer, non-metastatic prostate cancer, advanced non-metastatic prostate cancer, non-metastatic regional prostate, non-metastatic locally advanced prostate cancer, hormone-unexposed prostate cancer, chemotherapy-unexposed prostate cancer, cnni? ίη / ζζηζ / Ε / γίΛΐ castration-unexposed with or without metastasis, radiation-naïve prostate cancer, castration-resistant prostate cancer (CRPC), non-metastatic CRPC (nmCRPC), localized CRPC, locally advanced CRPC, CRPC regional, advanced CRPC, metastatic CRPC (mCRPC), mCRPC in patients who have DNA repair gene defect (DRA) or DRH; mCRPC in patients who have monoallelic AKI or DRH; mCRPC in patients who do not have AKI or DRH; mCRPC in patients who have AKI or DRH and who have received taxane and / or androgen receptor-directed therapy, mCRPC in patients who have received docetaxel or cabazitaxel, CRPC in patients who have received hormonal therapy (e.g., enzalutamide, darolutamide, apalutamide ), CRPC in patients who have received taxane therapy (e.g., docetaxel, mitoxantrone, cabazitaxel), chemotherapy-naive CRPC, chemotherapy-unexposed mCRPC, hormone-unexposed CRPC, hormone-unexposed mCRPC, progression, CRPC with visceral metastases, CRPC with visceral metastases in patients who have received hormonal therapy (for example, enzalutamide, darolutamide, apalutamide), CRPC with visceral metastases in patients who have received taxane therapy (for example, docetaxel, mitoxantrone, cabazitaxel), CRPC with visceral metastases and progression, castration-sensitive prostate cancer (CSPC), non-metastatic CPSC (nmCPSC), localized CPSC, locally advanced CPSC, regional CPSC, advanced CPSC, metastatic CPSC (mCPSC), chemotherapy-naïve CPSC, mSCPC not exposed to chemotherapy, CPSC not exposed to hormones, mSCPC not exposed to hormones, hormone-sensitive prostate cancer (HSPC), hormone-dependent prostate cancer, androgen-dependent prostate cancer, androgen-sensitive prostate cancer, HSPC biochemically recurrent, metastatic CPRH (mCPRH), hormone-resistant prostate cancer (HRCPC), non-metastatic CPRH (nmCPRH), localized CPRH, locally advanced CPRH, regional CPRH, advanced CPRH, metastatic CPRH (mCPRH), recurrent prostate cancer, prostate cancer with persistence or reappearance of prostate-specific antigen (PSA) after prostatectomy with or without distant metastasis, radiation-resistant prostate cancer, and any combination of these. In one aspect, the patient has first-line mCRPC (Ll) and is positive for DRA or DRH. In one aspect, the patient has mCSPC with deleterious somatic or germline homologous recombination repair (HRR) gene mutation. In one aspect, the patient has mCRPC or CRPC with visceral metastases, with or without DNA repair gene defects (DRA) and, optionally, with pathogenic alterations of cyclin-dependent kinase 12 (CDK12). In one aspect, the patient has high risk localized prostate cancer. In one aspect, the patient belongs to a risk group selected from very low, low, favorable intermediate, unfavorable intermediate, high, very high and regional. In one aspect, the medical use or treatment method comprises administering about 666 to about 1500 mg / day of abiraterone acetate; administering about 999 to about 1500 mg / day of abiraterone acetate; administer approximately 666 mg / day cnni? Abiraterone acetate ίη / ζζηζ / Ε / γίΛΐ; or administer approximately 1000 mg / day of abiraterone acetate. In one aspect, the medical use or treatment method comprises administering about 33 to about 300 mg / day of eq. of niraparib; administer approximately 100 to approximately 200 mg / day eq. of niraparib; administer approximately 66 mg / day eq. of niraparib; administer approximately 100 mg / day of eq. of niraparib; administer approximately 134 mg / day eq. of niraparib; or administer approximately 200 mg / day of eq. of niraparib. In one aspect, the medical use or treatment method comprises administering 1, 2 or 3 oral dosage forms per day. In one aspect, the medical use or treatment method comprises administering the one or more oral dosage forms once a day (u.v.d.) or twice a day (d.v.d.); preferably once a day at least 1 hour before a meal or at least two hours after a meal. In one aspect, the medical use or method of treatment comprises separately administering about 1 to about 60 mg / day of prednisone; about 5 to about 15 mg / day prednisone; about 9 to about 11 mg / day prednisone; approximately 10 mg / day of prednisone; approximately 5 mg / day of prednisone; or approximately 5 mg / day of prednisone. The present disclosure also relates to a process for preparing some of the granular compositions disclosed herein, comprising the steps of: (a) preparing a binder solution comprising a wetting agent; (b) mixing the binder solution from step (a) with abiraterone acetate, niraparib and a diluent, optionally in the presence of a disintegrant; (c) wet granulate the mixture obtained in step (b); (d) drying the product obtained in step (c). In one aspect, the binder solution comprises a binder, the wetting agent and a solvent. In one aspect, the inlet air temperature during the wet granulation of step (c) is 25°C to 65°C. In one aspect, the spray rate during the wet granulation of step (c) is 190 to 300 g / min. In one aspect, the inlet air flow during the wet granulation of step (c) is 800 to 1300 m3 / h. The present disclosure also relates to a process for preparing some of the granule compositions disclosed herein, comprising the steps of: (a) mixing abiraterone acetate, niraparib, a wetting agent and a diluent, optionally in the presence of a disintegrant and a lubricant; (b) dry granulate the mixture obtained in step (a); (c) grinding the dry granulated product obtained in step (b); (d) optionally mixing the product obtained in step (c) with a wetting agent, a diluent, a disintegrant and a glidant. cnni? ίη / ζζηζ / Ε / γίΛΐ The present disclosure also relates to a process for preparing some of the granule compositions disclosed herein, comprising the steps of: a) mix niraparib with a diluent, optionally in the presence of a disintegrant, a glidant and a lubricant; b) dry granulate the mixture obtained in step (a); c) grinding the dry granulated mixture obtained in step (b); d) preparing a binder solution comprising a wetting agent; e) mixing the binder solution of step (d) with abiraterone acetate and a diluent, optionally in the presence of a disintegrant; f) wet granulate the mixture obtained in step (e); g) drying the product obtained in step (f); h) mixing the granule mixtures obtained in steps (c) and (g), optionally in the presence of a wetting agent, a diluent, a disintegrant, a lubricant and a glidant; where steps d)-g) can be carried out before, or in parallel to, steps a)-c). In one aspect, the obtained granule composition is further compressed into a tablet, optionally with a lubricant. In one aspect, the process further comprises preparing a coating suspension and coating the tablet with said suspension. In one aspect, the granule composition obtained is further dispensed into a capsule or sachet, optionally with a diluent. BRIEF DESCRIPTION OF THE FIGURES Fig. 1: Flowchart of a manufacturing process and in-process controls for wet cogranulation of abiraterone acetate and niraparib tosylate monohydrate. Fig. 2: Flow diagram of a manufacturing process and in-process controls for the coating of tablets comprising abiraterone acetate and niraparib tosylate monohydrate. Fig. 3: Flow diagram of a manufacturing process with dry cogranulation of abiraterone acetate and niraparib tosylate monohydrate and compression into tablets. Fig. 4: Flow diagram of a manufacturing process and in-process controls for the dry granulation of niraparib tosylate monohydrate, and the mixture with abiraterone acetate granules, the latter prepared by wet granulation. Fig. 5A: In vitro dissolution curves of abiraterone acetate of i) a cnni combination? ίη / ζζηζ / Ε / νίΛΐ of single agents which are one capsule of 100 mg eq. of niraparib, in the form of tosylate monohydrate, and 2 tablets of 250 mg of abiraterone acetate; i) one CDF tablet with the composition of Table 2 (50 mg eq. of niraparib, in its tosylate monohydrate form, and 500 mg of abiraterone acetate); and iii) a CDF tablet with the composition of Table 4 (100 mg eq. of niraparib, in its tosylate monohydrate form, and 500 mg of abiraterone acetate). Fig. 5B: In vitro dissolution curves. niraparib from i) a combination of single agents which are 100 mg capsule eq. of niraparib, in its tosylate monohydrate form, and 2 tablets of 250 mg of abiraterone acetate; ii) one CDF tablet with the composition of Table 2 (50 mg eq. of niraparib, in its tosylate monohydrate form, and 500 mg of abiraterone acetate); and i¡) a CDF tablet with the composition of Table 4 (100 mg of niraparib eq., in its tosylate monohydrate form, and 500 mg of abiraterone acetate). Fig. 6: Loss on drying (PPD) profiles for the granules of the compositions of Table 1 and Table 3. Fig. 7: Screening analysis of the granules in Table 1. Fig. 8: Screening analysis of the granules in Table 3. DETAILED DESCRIPTION OF THE INVENTION The present inventions may be more easily understood by reference to the following detailed description taken in conjunction with the accompanying examples, which form a part of the present disclosure. It is to be understood that these inventions are not limited to the specific products, methods, conditions or parameters described and / or shown herein, and that the terminology used herein is intended to describe particular embodiments to by way of example only and is not intended to be a limitation of the claimed inventions. The entire disclosures of each patent, patent application and publication mentioned or described herein are hereby incorporated by reference. Definitions It should be understood that, as used above and throughout the disclosure, the following terms and abbreviations, unless otherwise indicated, have the following meanings. In the present disclosure, the singular forms a, an, the and the include plural reference, and reference to a given numerical value includes at least that value, unless the cnni? Ln / zznz / E / YiAi context clearly indicates otherwise. Therefore, for example, a reference to an ingredient is a reference to one or more of said ingredients and to equivalents of these known to those skilled in the art, etc. Furthermore, when it is indicated that a certain element can be X, Y or Z, such use is not intended to exclude in all cases other options for the element. When values ​​are expressed as approximations, by using the antecedent approximately, the particular value will be understood to form another realization. As used herein, approximately X (where X is a numerical value) preferably refers to ±10% of the cited value, inclusive. For example, the expression about 8 refers to a value from 7.2 to 8.8, inclusive; As another example, the expression approximately 8% refers to a value of 7.2% to 8.8%, inclusive. When present, all intervals are inclusive and combinable. For example, when a range of 1 to 5 is cited, the quoted range should be interpreted to include ranges 1 to 4, 1 to 3, 1-2, 1-2 and 4-5, 1-3 and 5, and the like. . Furthermore, where a list of alternatives is positively provided, such a list may also include embodiments in which any of the alternatives may be excluded. For example, when describing a range from 1 to 5, such a description can accommodate situations in which any of 1, 2, 3, 4, or 5 is excluded; therefore, a mention of 1 to 5 may admit 1 and 3-5, but not 2, or simply where 2 is not included. The term immediate release, when used in the context of dosage forms (such as pharmaceutical formulations, free dose combinations, fixed dose combinations, granules, tablets, capsules and the like), refers to the rapid disintegration and dissolution of such dosage forms. dosage forms to release the active pharmaceutical ingredients included in said dosage forms. Immediate-release dosage forms dissolve or disintegrate in the stomach within a short period of time and provide rapid dissolution and absorption of active pharmaceutical ingredients, which can produce a rapid onset of action. As used herein, and unless otherwise defined, the terms treat, treat and treatment include the eradication, removal, modification, management or control of a tumor or primary cancer cells or tissues, regional or metastatic, in particular prostate cancer cells or tissues, and minimizing or delaying the spread of cancer, in particular prostate cancer. Minimizing or delaying the spread of cancer includes inhibiting the progression of cancer, a reduction in the rate of cancer progression, or a halt in the rate of cancer progression. As used herein, and unless otherwise defined, the term therapeutically effective amount or effective amount means an amount of the therapeutic agent effective in treating a prostate cancer. As used herein, and unless otherwise defined, the cnni? ίη / ζζηζ / Ε / γίΛΐ safe therapeutic term means an amount of the therapeutic agent that is safe to treat prostate cancer. The term "pharmaceutically acceptable" means that which is generally safe, non-toxic and is neither biologically nor otherwise undesirable and includes that which is acceptable for human pharmaceutical use as well as for veterinary use. The terms formulation and composition may be used interchangeably in the present disclosure. Both formulation and composition refer to the combination of two or more components, either as fixed dose combinations or as free dose combinations. As such, the term a pharmaceutical formulation refers to fixed dose combinations and free dose combinations. The two or more components herein encompass at least 1) abiraterone acetate; and 2) niraparib, and any pharmaceutically acceptable salt, solvate and hydrate forms thereof, for example, niraparib tosylate monohydrate. Additional components are usually excipients. As used herein, a fixed dose combination (FDC) are formulations or compositions that include two or more active ingredients combined in a single dosage form. In this document, the two active substances are 1) abiraterone acetate; and 2) niraparib, and any pharmaceutically acceptable salt, solvate and hydrate forms, for example, niraparib tosylate monohydrate. In contrast, a free dose combination (CDL) are formulations or compositions that include two or more active ingredients combined in separate dosage forms. In this document, the two active substances are 1) abiraterone acetate; and 2) niraparib, and any pharmaceutically acceptable salt, solvate and hydrate forms, for example, niraparib tosylate monohydrate. The terms excipient and carrier are used interchangeably in the present disclosure. The European Pharmacopoeia (Ph. Eur.) defines an excipient as any component, other than one or more active substances, present in a medicinal product or used in its manufacture. The intended function of an excipient is to act as the carrier (vehicle or base) or as a carrier component of the one or more active substances and, in doing so, contribute to product attributes, such as stability, biopharmaceutical profile, the appearance and acceptability by the patient, as well as the ease with which the product can be manufactured. Usually, more than one excipient is used in the formulation of a drug. The terms vehicle and base are further defined in the same pharmacopoeia: A vehicle is the carrier, composed of one or more excipients, for the one or more active substances in a liquid preparation and A base is the carrier, composed of one or more excipients. , for one or more active substances in semisolid and solid preparations. cnni? ίη / ζζηζ / Ε / γίΛΐ Granules, granules or granulated particles are defined herein as particles containing one or more active pharmaceutical ingredients (PAFs) and at least one pharmaceutically acceptable carrier, which are formed by granulation. A granule composition according to the present disclosure comprises two PAFs and at least one pharmaceutically acceptable carrier. A portion of the granule composition, i.e., a first granule portion, may consist essentially of a PAF and at least one pharmaceutically acceptable carrier, and another portion of the granule composition, i.e., a second granule portion, It may consist essentially of another PAF and at least one pharmaceutically acceptable carrier. In another aspect, each and every portion of the granule composition, that is, each and every granule, comprises two PAFs and at least one pharmaceutically acceptable carrier. Abiraterone acetate Abiraterone acetate is a compound of formula: cnni? ίη / ζζηζ / Ε / γίΛΐ and is a prodrug of abiraterone, which is a potent, selective, orally active inhibitor of the key enzyme in testosterone synthesis, 17a-hydroxylase-C17,20-lyase. , also known as steroid 17a-monooxygenase inhibitor or Human Cytochrome P45017a. Suppression of testosterone synthesis has been demonstrated with abiraterone acetate in patients with prostate cancer. The compound was disclosed in WO 93 / 20097 (Al). In some aspects, abiraterone acetate is used herein in crystalline form. Abiraterone acetate plus prednisone is approved for use in metastatic castration-resistant prostate cancer (mCRPC) and metastatic hormone-sensitive prostate cancer (mCRPC). Abiraterone acetate tablets are currently marketed as 250 or 500 mg oral tablets. Niraparib Niraparib, or 2-[4-[(3S)-piper¡din-3-yl]phen¡l]-2H-indazole-7-carboxamide, is a poly(adenosine diphosphate [ADP]) inhibitor. -ribose) polymerase (PARP) highly selective and orally available, with activity against the deoxyribonucleic acid (DNA) repair polymerases PARP-1 and PARP-2. The preparation of niraparib is described in US Pat. Nos. 8,071,623 and 8,436,185, both incorporated herein by reference. The currently marketed capsule formulation (ZEJULA) contains 159.4 mg of niraparib tosylate monohydrate (equivalent (eq.) to 100 mg of niraparib free base) as the active ingredient. Inactive ingredients in the capsule fill include magnesium stearate and lactose monohydrate. cnni? ίη / ζζηζ / Ε / γίΛΐ As used herein, the term niraparib means any of the free base compound (2-[4-[(3S)-p¡pend¡n-3-¡l]phenyl]-2H-¡ndazol- 7-carboxamide), a salt form, including pharmaceutically acceptable salts, of 2-[4-[(3S)-pipenden-3-yl]phenyl]-2Hindazol-7-carboxamide (e.g., 4-carboxamide -methylbenzenesulfonic acid; 2-[4-[(3S)-p¡per¡din-3-yl]phenyl]-2H-indazole-7-carboxamide). Such forms may be individually referred to as niraparib free base, niraparib tosylate and niraparib tosylate monohydrate, respectively. Unless otherwise specified, the term niraparib includes all crystals, polymorphs, pseudopolymorphs, hydrates, monohydrates, anhydrous forms, solvates, salt forms and combinations thereof, if applicable, of the compound 2-[4-[( 3S)-piperidin-3-yl]phenyl]-2H-ndazol-7-carboxamide. Examples of salts include, without limitation, tosylate or 4-methylbenzenesulfonate, sulfate, benzenesulfate, fumarate, succinate, camphorate, mandelate, camsylate and lauryl sulfate. In a particular aspect, the term niraparib refers to niraparib tosylate monohydrate. The term niraparib also encompasses the amorphous and crystalline polymorphs of this compound, and the hydrates, ansolvates and solvates of it. Examples of polymorphs are described in WO 2018 / 183354 Al, which is incorporated herein by reference. Crystalline Form I of 2-[4-[(3S)-peridin-3-yl]phenyl]-2H-indazole-7carboxamide tosylate monohydrate is characterized by at least one ray diffraction pattern reflection. Selected Crystalline Form II of non-stoichiometric hydrate of 2[4-[(3S)-piper¡din-3-¡l]phen¡l]-2H-ndazol-7-carboxamide tosylate is characterized by at minus a selected Crystalline Form III of anhydrous form of 2-[4-[(3S)-piperidin-3¡l]phenyl]-2H-índazol-7-carboxamide tosylate is characterized by at least one diffraction pattern reflection x-ray selected from a 2Θ value of 17.8±0.2, 19.0±0.2 or 22.8±0.2. Shape is preferred Crystalline I. More examples of polymorphs are described in WO 2020 / 072797 Al, which is incorporated herein by reference. The expression eq. of niraparib or niraparib equivalent refers to the free base dose amount of niraparib. Preparation of dosage forms The dosage forms of the present disclosure can be prepared according to the scheme of Fig. 1 and 2. A binder solution is prepared comprising purified water, binder (for example, hypromellose) and a wetting agent (for example, lauryl sodium sulfate) mixing with a stirrer / mixer. Abiraterone acetate, niraparib tosylate monohydrate, diluent (e.g., lactose monohydrate), and disintegrant (e.g., crospolividone) are sifted, mixed (mixture #1), and added to the binder solution. Wet granulation is performed, which includes heating, pulverizing and drying. Moisture content and particle size distribution are measured to meet quality requirements. Next, a mixture of diluent (e.g., silicified microcrystalline cellulose), disintegrant (e.g., crospolividone), wetting agent (e.g., sodium lauryl sulfate), and glidant (e.g., colloidal anhydrous silica) is screened and mixed with the granular material obtained previously (mixture no. 2). Lubricant (e.g. magnesium stearate) is screened and added to blend #2, which is finally blended (blend #3), compressed into tablets and conditioned. During compression, the appearance, weight, hardness, thickness, friability and disintegration of the tablets are measured to meet quality requirements. Next, a coating suspension is prepared comprising purified water and a coating powder (e.g. Opadry® AMBII, e.g. Opadry® AMBII 88A220039 yellow). The tablets obtained above comprising abiraterone acetate and niraparib tosylate monohydrate are film coated with the coating suspension. The appearance of the coated tablets obtained is measured to meet quality requirements. The tablets are then packaged, for example, in blister packs or bottles. In another aspect, the dosage forms of the present disclosure can be prepared as depicted in Fig. 3 and Fig. 2. Abiraterone acetate and niraparib tosylate monohydrate are cogranulated with suitable excipients by means of in-bed granulation fluid or by means of granulation by roller compaction. The granulated material is then compressed into monolayer tablets. Next, a coating suspension is prepared comprising purified water and a coating powder (e.g., Opadry® AMB II, e.g., Opadry® AMB II 88A220039 cnni? ίη / ζζηζ / Ε / γίΛΐ yellow). The tablets obtained above comprising abiraterone acetate and niraparib tosylate monohydrate are film coated with the coating suspension. The appearance of the coated tablets obtained is measured to meet quality requirements. The tablets are then packaged, for example, in blister packs or bottles. In yet another aspect, the dosage forms of the present disclosure can be prepared as depicted in Fig. 4 and Fig. 2. Niraparib tosylate monohydrate, a diluent (for example, lactose monohydrate and microcrystalline cellulose) are screened. , a binder (e.g., povidone K30), a disintegrant (e.g., crospovidone), a glidant (e.g., colloidal anhydrous silica), and a lubricant (e.g., magnesium stearate), are mixed, commutated, mixed again and dry granulated (dry granule composition #1). Abiraterone acetate, a diluent (e.g. lactose monohydrate) and a disintegrant (e.g. croscarmellose sodium) are mixed and optionally sieved. A binder solution comprising a binder (e.g. Hypromellose), a wetting agent (e.g. sodium lauryl sulphate) and purified water is prepared and added to the mixture of abiraterone acetate, diluent and disintegrant. Abiraterone acetate granules are then formed by fluid bed granulation and subsequently dried (wet granule composition #2). The wet granule composition No. 2, a diluent (e.g., silicified microcrystalline cellulose), a disintegrant (e.g., crospovidone), a wetting agent (e.g., sodium lauryl sulfate), and a glidant (colloidal anhydrous silica) are added to the No. 1 dry granule composition, and the resulting mixture is screened and mixed. A lubricant (for example, magnesium stearate) is added to the above mixture and the resulting mixture is screened, mixed, compressed into tablets and conditioned. During compression, tablet properties, including appearance, weight, hardness, thickness, friability and disintegration, are measured to meet quality requirements. Next, a coating suspension is prepared comprising purified water and a coating powder (e.g. Opadry® AMB II, e.g. Opadry® AMB II 88A220039 yellow). The tablets obtained above comprising abiraterone acetate and niraparib tosylate monohydrate are film coated with the coating suspension. The appearance of the coated tablets obtained is measured to meet quality requirements. The tablets are then packaged, for example, in blister packs or bottles. Granulation Granulation is a process of enlarging powder particles to form grain-like agglomerates. The granules formed from the particles of the active ingredient cnni? ίη / ζζηζ / Ε / γίΛΐ pharmaceutical or active pharmaceutical ingredients (PAF) and the mixture of excipients are further efficiently processed into solid dosage forms, such as tablets and capsules, or multiparticulates, such as granules, beads or spheroids that have loaded into capsules or packaged as dispersible formulations, for example. Abiraterone acetate and niraparib may cogranulate. Alternatively, granules of each of 1) abiraterone acetate and 2) niraparib, can be prepared separately and subsequently mixed or combined, and processed further. Cogranulation is practically achieved by bringing the two drugs into contact with each other, and with one or more excipients such as a binder solution, and subjecting the entire mixture to granulation. Alternatively, each of the drugs is contacted with one or more excipients creating separate mixtures, each of the mixtures is then brought together and contacted with a binder solution. Abiraterone acetate and niraparib can be dry granulated or wet granulated prior to further processing such as tableting or encapsulation. In one aspect, abiraterone acetate and niraparib can be cogranulated by wet granulation and further processed. In one aspect, abiraterone acetate and niraparib can be cogranulated by dry granulation and further processed. In one aspect, abiraterone acetate is wet granulated and niraparib is dry granulated and the resulting granules are mixed and further processed. In one aspect, abiraterone acetate is dry granulated and niraparib is wet granulated and the resulting granules are mixed and further processed. Wet granulation As used herein, the term wet granulation refers to the general process of using a granulation liquid in the granulation process to subsequently form granules, as discussed in Remington: The Science and Practice of Pharmacy, 20th edition ( 2000), chapter 45, which is hereby incorporated by reference. Wet granulation usually includes the stages of mixing, wetting and kneading, that is, wet kneading; granulation; drying; and sifting. These stages are discussed in more detail below. The wet granulation process begins with the formation of a powder mixture of the therapeutic compound or therapeutic compounds and at least one pharmaceutically acceptable excipient, by mixing with, for example, pharmaceutical granulation equipment, the ingredients (i.e., placing them in intimate proximity) in a suitable container, so that a mixture is formed. Examples of pharmaceutical granulation equipment include, but without cnni? ίη / ζζηζ / Ε / γίΛΐ limitation, shear granulators (e.g. Hobart, Collette, Beken) in combination with an oscillating granulator; high speed mixers / granulators (e.g., Diosna, Fielder, Collette-Gral); and fluid bed granulators (e.g. Aeromatic, Glatt) with subsequent screening equipment. Useful excipients for initial mixing with the therapeutic compound include, for example, binders, fillers, disintegrants, diluents, wetting agents and any combination of the above. The next stage is to wet knead the powder mixture by adding a granulation liquid while stirring or kneading the powder mixture until the powder mixture is moistened with the granulation liquid to form a wet dough. For example, 10-30% (w / w) granulation liquid is added to the powder mixture. Alternatively, 10-25% (w / w), for example 20-25%, of granulation liquid can be added to the powder mixture. The granulation liquid, for example, is pharmaceutically acceptable and volatile. Examples of suitable granulation liquids include, but are not limited to, water, organic solvents (eg, methanol, ethanol, isopropanol, acetone) either alone or in combination. An example of a combination granulation liquid includes water, ethanol and isopropanol together. Alternatively, the wet granulation process can begin with the therapeutic compound(s) itself in powder form. During wet kneading, the granulation liquid introduced into the powder is a solvent containing a dissolved excipient, for example a binder. Regardless of how wet kneading occurs, a pharmaceutical composition containing the therapeutic compound and at least one pharmaceutically acceptable excipient is wetted by the granulation liquid. In one example, water is used as the granulation liquid. The wet mass is optionally sieved forming wet or wet granules. The wet mass, for example, can be sieved through a mesh, such as a 5, 4, 3, 2 or 1 mm sieve, preferably a 1 to 2 mm sieve. A person skilled in the art can select the appropriate size of the screen to form the most suitable granule size. Alternatively, a grinding mill can be used instead of the sieve or sieve. Examples of a grinding mill include, but are not limited to, a Stokes oscillator, a Colton rotary granulator, a Fitzpatrick grinding mill, a Stokes tornado mill. Furthermore, as an alternative, a high-speed mixer equipped, for example, with a chopping blade, can be used to replace either the screen or the grinding mill. This, for example, allows wet kneading, granulation and grinding to be combined in a single step. Other wet granulation methods that can be employed include high shear granulation and twin screw granulation. High shear granulation involves adding a binder solution to a powder, which is often a mixture of one or more PAF and cnni? ίη / ζζηζ / Ε / γίΛΐ one or more excipients, and granulate the resulting mixture with mixing tools and a chopper. The powder agglomerates into larger granules, which are held together by the binder. Twin-screw granulation can be achieved with commercially available twin-screw extruders, such as those manufactured by Leistritz Extrusionstechnik GmbH — NANO 16, Thermo Fisher Scientific — Pharma 16 TSG). GEA Pharma Systems' ConsiGma™ system is a complete continuous package comprising some or all of mixing, twin screw granulation, drying (semi-continuous), milling and tableting. Wet granules, for example, are subsequently dried. For example, wet granules can be collected on trays and transferred to a drying oven. Alternatively, the wet granules can be placed in a drying cabinet with circulating air flow and thermostatic heat control. Yet another option is to dry the wet granules in a fluid bed dryer. In this example, the wet granules are suspended and agitated in a stream of hot air so that the wet granules are kept in motion. For example, the temperature may be from about room temperature to about 90°C, for example, 70°C. The wet granules are dried to a loss on drying (PPD) value preferably less than or equal to about 3% or 2%, for example, less than 2.6%, less than 2%, for example, 1-2 %, by weight of the composition. Drying can take place inside or outside the pharmaceutical granulation equipment. Granules comprising abiraterone acetate and niraparib tosylate monohydrate, prepared by wet granulation of the present invention, achieve an improved PPD of between 1 and 2%. If the PPD were too low, the granules could subsequently cause compression problems during tableting. If it is too high, the granules could have stability problems. After drying, the granules can be additionally sieved, that is, they can be dry screened, alone or in combination with at least one excipient. This typically results in a more uniform particle size of the granules, preparing the granules for further processing into a solid oral dosage form. Conventional equipment such as Quadro cornil at a fixed rotation speed (rpm) can be used to screen the dry granules and produce material with the desired particle size and without agglomerates. The rotation speed may be 5 to 15 rpm, preferably 8 to 10 rpm. In one form of wet granulation preparation, for example, fluid bed granulation, a binder solution is created by dissolving a binder, a wetting agent and purified water until a clear solution is obtained. The therapeutic compounds, optionally mixed with a diluent and a disintegrant, are transferred to suitable wet granulation equipment, and the resulting mass is heated while fluidizing. The cnni solution? Ln / zznz / E / YiAi binder is completely sprayed onto the dough using wet granulation technique. The resulting granules are dried after spraying while fluidizing. The dry powder is collected and packaged in bags, for example, aluminum bags. In another form of preparation, the therapeutic compound or therapeutic compounds can be wet granulated in a fluid bed granulator, such as, for example, a GEA Sirocco 300 or a Niro Aeromatic D600, resulting in drug granules. The fluid bed inlet air temperature may vary from 25°C to 80°C or from 25°C to 70°C, preferably from 25°C to 65°C; the outlet air temperature can vary from 25°C to 50°C, from 20°C to 50°C or from 25°C to 80°C; the inlet air flow can vary from 500 to 2200 m3 / h, from 2000 to 3000 m3 / h, from 800 to 1300 m3 / h or from 500 to 4500 m3 / h; The flow rate or spray speed of the solution may vary, depending on the batch size and the capacity of the equipment, from 170 to 4200 g / min, from 190 to 300 g / min, from 400 to 900 g / min or from 0.200 to 2 kg / min; The atomization air pressure can vary from 0.2-0.6 MPa (2-6 bar), from 0.3 to 0.4 MPa (3 to 4 bar) or from 0.1 to 0.5 MPa (1.00 to 5.00 bar). In one example, abiraterone acetate and niraparib or niraparib tosylate monohydrate can be wet granulated with a binder solution comprising a solvent, such as, for example, water, a binder, such as, for example, a polymer , for example, hypromellose, and a wetting agent, such as, for example, sodium lauryl sulfate. In one example, prior to granulation with a binder solution, abiraterone acetate may be mixed with a suitable diluent, such as, for example, lactose monohydrate, and a suitable disintegrant, such as, for example, crospovidone. dry granulation The term dry granulation refers to the process of mixing one or more therapeutic compounds with at least one excipient. The mixture is then compressed, or compacted, to form a compressed or compacted material. This material is then broken down by crushing, grinding or cutting into dry granulated particles. Optionally, the particles may be further processed, such as by further mixing with additional excipients. The crushing, grinding or cutting processes involve an operation that reduces the size of the compressed material, such as that achieved by grinding or by other operations known to those skilled in the art. A compact is a compressed material formed by processing the therapeutic compound(s) and optional excipients by precompression or by roller compaction. To prepare the mixture, the components are weighed and placed in a mixing container. Mixing is done over a period of time to produce a homogeneous mixture cnni? Ln / zznz / E / YiAi using suitable mixing equipment. Optionally, the mixture is passed through a mesh screen to remove agglomerates from the mixture. The screened mixture can be returned to the mixing container and mixed for an additional period of time. Lubricant can then be added and the mixture mixed for an additional period of time. The mixture is then compressed, or compacted, to form a compact. Prior to compression, the mixture may undergo a precompression step, such as in a rotary tablet press. Compression of the mixture to form granules can be achieved by techniques known in the art, including precompression, in which the mixture is introduced into dies comprising one or more perforation faces that are installed in a press, such as a press. compressed, and pressure is applied to the mixture by moving one or more punch faces in the die. Dry granulation can also be carried out by means of a roller compactor. A roller compactor generally incorporates two or more rollers adjacent and parallel to each other with a fixed or adjustable spacing between the rollers. A hopper or other feeding device deposits the mixture between moving rollers which act to compact the mixture into a compacted material. Roller compactors are typically equipped with dividers that cut or otherwise divide the compacted material emerging from the roller compactor into ribbons. An example of a roller compactor is the TF-Mini Roller Compactor (Vector Corporation, Marion, IA, Freund). The compact is then comminuted to form granules, usually by a suitable mechanical means such as crushing, grinding or cutting. For example, granules can be formed from a compact by grinding. Milling involves subjecting the granules to a shear force so that the desired particle size of the granulation is achieved. The grinding step can vary from an aggressive process in which the particle size is significantly reduced to a non-aggressive process in which the particle size is not significantly reduced, but is done simply to remove agglomerates or break up lumps. larger granulation. In the pharmaceutical industry, milling is frequently used to reduce the particle size of solid materials. There are many types of mills available, including needle mills, hammer mills and jet mills. One of the most commonly used types of mills is the hammer mill. The hammer mill uses a high-speed rotor to which several fixed or oscillating hammers are attached. Hammers can be attached so that the blade face or hammer face contacts the material. As the material is fed to the mill, it hits against the rotating hammers and breaks into smaller particles. Below the hammers is a sieve that allows smaller particles to pass through the openings of the sieve. The largest particles are retained in the cnni mill? ίη / ζζηζ / Ε / γίΛΐ and the hammers continue to break them until the particles are fine enough to flow through the screen. The material can be optionally screened. In screening, the material is passed through a mesh screen or a series of mesh screens to obtain the desired particle size. Excipients The formulations of the disclosure, including granules and final dosage forms such as tablets, may comprise one or more conventional excipients (pharmaceutically acceptable carrier) such as disintegrants, diluents, binders, buffering agents, lubricants, glidants, thickening agents, agents. sweeteners, flavors and colors. Some excipients can perform several functions. In one aspect, the formulations of the present disclosure include a disintegrant, a diluent or filler, a lubricant and a glidant. In one aspect, the formulations of the present disclosure include a disintegrant, a diluent or filler, a lubricant, a glidant, a wetting agent and a binder. In one aspect, the formulations of the present disclosure include a disintegrant, a diluent or filler, a lubricant, a glidant, a wetting agent and a binder, wherein the wetting agent or part thereof, and the binder are present in the granules. of abiraterone acetate and niraparib. In one aspect, the formulations of the present disclosure include a disintegrant, a diluent or filler, a lubricant, a glidant, a wetting agent and a binder, wherein the wetting agent or part thereof, the binder, and the disintegrant or part of it, are present in abiraterone acetate and niraparib granules. In one aspect, the formulations of the present disclosure include a disintegrant, a diluent or filler, a lubricant, a glidant, a wetting agent and a binder, wherein the wetting agent or part thereof, the binder, the diluent, and the disintegrant or part of it, are present in abiraterone acetate and niraparib granules. In one aspect, the formulations of the present disclosure include a disintegrant, a diluent or filler, a lubricant, a glidant and a wetting agent, wherein the wetting agent or part thereof is present in the abiraterone acetate and niraparib granules. In one aspect, the formulations of the present disclosure comprise an intragranular phase and an extragranular phase. In one aspect, the intragranular phase comprises the PAFs, a diluent or filler, a disintegrant, a wetting agent and a binder. In one aspect, the intragranular phase comprises the PAFs, a diluent or filler, a disintegrant, a wetting agent, a glidant and a lubricant. In one aspect, the extragranular phase comprises a diluent or filler, a disintegrant, a wetting agent, a glidant and a lubricant. In one aspect, the intragranular and extragranular phases comprise a disintegrant, cnni? ίη / ζζηζ / Ε / γίΛΐ for example, crospovidone. The presence of disintegrants in both the intragranular and extragranular phases enhances the disintegration of the tablet and granules, thereby increasing the dissolution of PAFs in the body, ultimately increasing the bioavailability of PAFs. Suitable wetting agents may be selected from anionic, cationic or nonionic surfactants or surfactants. Suitable anionic surfactants include those containing carboxylate, sulfonate and sulfate ions, such as sodium lauryl sulfate (SLS), sodium laurate, sodium dialkyl sulfosuccinates, in particular, sodium bis-(2-ethylhexyl) sulfosuccinate, sodium stearate. sodium, potassium stearate, sodium oleate and the like. Suitable cationic surfactants include those containing long chain cations, such as benzalkonium chloride, bis-2-hydroxyethyl oleyl amine or the like. Suitable nonionic surfactants include polyoxyethylene sorbitan fatty acid esters, fatty alcohols such as lauryl, cetyl and stearyl alcohols; glyceryl esters such as the natural mono, di and triglycerides; fatty acid esters of fatty alcohols and other alcohols such as propylene glycol, polyethylene glycol, sorbitan, sucrose and cholesterol. In one aspect, the wetting agent is sodium lauryl sulfate. The amount of wetting agent in the tablets or pharmaceutical formulations according to the present disclosure may conveniently vary from about 0.5 to about 8% (w / w) and preferably from about 1 to 7% (w / w) or approximately 2 to 6% (w / w) or approximately 3 to 6% (w / w). In one aspect, the wetting agent is sodium lauryl sulfate and is present in the final dosage forms in a percentage of about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, approximately 3.8, approximately 3.85, approximately 3.9, approximately 4.00, approximately 4.07, approximately 4.1, approximately 4.2, approximately 4.3, approximately 4.4, approximately 4.5, approximately 4.6, approximately 4.7 , approximately 4.8, approximately 4.9, approximately 5.0, approximately 5.1, approximately 5.2, approximately 5.3, approximately 5.4, approximately 5.5, approximately 5.6, approximately 5.7, approximately 5.8 or approximately 5.9% in weight. In one aspect, the wetting agent is sodium lauryl sulfate and is present in the granule composition in a weight ratio to abiraterone acetate of about 0.005:1 to 0.02:1 (SLS:abiraterone acetate), preferably about 0.01. :1, more preferably about 0.0112:1. In one aspect, the wetting agent is sodium lauryl sulfate and is present in the final dosage forms in a weight ratio to abiraterone acetate of about 0.05:1 to 0.2:1 (SLS:abiraterone acetate), preferably about cnni? ίη / ζζηζ / Ε / γίΛΐ 0.1:1, more preferably about 0.11:1, about 0.12:1 or about 0.123:1. Suitable disintegrants are those that have a large expansion coefficient. Examples of pharmaceutically acceptable disintegrants include, but are not limited to, starches, clays, celluloses, alginates, gums, hydrophilic, insoluble or poorly water-soluble cross-linked polymers such as crospovidone (cross-linked polyvinylpyrrolidone, for example, commercially available as Kollidon CL-F and Polyplasdone XL-10) and croscarmellose sodium (cross-linked sodium carboxymethylcellulose). The disintegrant may be present in the tablets or pharmaceutical formulations in an amount of about 1 to about 20% (w / w), preferably about 2 to about 10% (w / w), in particular about 3 to 9% or approximately 5 to 9% (w / w). For the granule compositions of the present invention and the oral dosage forms comprising these granule compositions, excipients that can dissociate into ions are less preferred, although an exception is made for sodium lauryl sulfate (wetting agent) and magnesium stearate (lubricant), in the formulations disclosed herein. In particular embodiments, the disintegrant is a non-ionizable disintegrant, such as crospovidone. A variety of materials can be used as a diluent or filler. Examples are lactose monohydrate, lactose anhydrous, sucrose, dextrose, mannitol, sorbitol, starch, cellulose (e.g., microcrystalline cellulose (Avicel™), silicified microcrystalline cellulose), calcium phosphate. dibasic dihydrate or anhydrous and others known in the art, and mixtures thereof (for example, a spray-dried mixture of lactose monohydrate (75%) with microcrystalline cellulose (25%), which is commercially available as MicroceLac®) . Preferred are microcrystalline cellulose, silicified microcrystalline cellulose or lactose monohydrate. Lactose monohydrate is usually characterized as a diluent or filler, but it also has binding properties that are particularly useful for granulation of the intragranular phase. The amount of diluent or filler in the tablets or pharmaceutical formulations according to the present disclosure may conveniently range from about 20% to about 70% (w / w) and preferably ranges from about 20% to about 60% ( w / w) or from about 25% to about 35% (w / w) or from about 25% to about 30% (w / w). Preferably, the silicified microcrystalline cellulose diluent is used in the extragranular phase. Preferably, a CDF tablet comprises an extragranular phase containing about 25% to about 30% (w / w) silicified MCC HD90. This content of silicified MCC HD90 provides an optimal compression profile of the tablet, reducing its friability and abrasion. cnni? ίη / ζζηζ / Ε / γίΛΐ Examples of pharmaceutically acceptable binders include, but are not limited to, starches; celluloses and derivatives thereof, for example, microcrystalline cellulose, for example, AVICEL PH from FMC (Philadelphia, PA), hydroxypropyl cellulose, hydroxyethyl cellulose and hydroxypropylmethyl cellulose, for example, METHOCEL from Dow Chemical Corp. (Midland, MI); saccharose; dextrose; corn syrup; polysaccharides; and gelatin. The binder, for example, may be present in an amount of about 0.5% to about 5%, for example, 0.5 to 3% by weight of the formulation. Preferably, the binder is low viscosity grade hypromellose, for example, HPMC 2910 15 mPa.s. Lubricants and glidants can be used in the manufacture of certain dosage forms and will usually be used in the production of tablets. Examples of lubricants and glidants are hydrogenated vegetable agents, for example, hydrogenated cottonseed oil, magnesium stearate, stearic acid, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silica, colloidal anhydrous silica talc, mixtures of these. and others known in the art. Magnesium stearate and mixtures of magnesium stearate with colloidal anhydrous silica are interesting lubricants. Magnesium stearate is a preferred lubricant. Colloidal anhydrous silica is a preferred slider. The glidants generally comprise 0.2 to 5.0% of the total weight of the composition, in particular the total weight of the tablet, in particular 0.25 to 1.5%, more particularly 0.3 to 1.0% (w / w). Lubricants, such as magnesium stearate, generally comprise 0.2 to 5.0% of the total weight of the tablet, in particular 0.5 to 2.5%, more particularly 0.5 to 2.0%, for example about 1.0%, about 1.25 % or approximately 1.5% (w / w). Final pharmaceutical formulations The granules can be formulated with excipients in oral dosage forms, solid oral dosage forms, tablets, pills, lozenges, hard or soft capsules, sachets, troches, aqueous or oily suspensions, powders or disperse granules, granules. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and said compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preservative agents. in order to provide pharmaceutically elegant and palatable preparations. The tablets contain the active ingredients in admixture with pharmaceutically acceptable non-toxic excipients that are suitable for the manufacture of tablets. These excipients can be, for example, inert diluents, such as calcium carbonate, cnni carbonate? ίη / ζζηζ / Ε / γίΛΐ sodium, lactose monohydrate, silicified microcrystalline cellulose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, crospovidone, microcrystalline cellulose, croscarmellose sodium, corn starch or alginic acid; binding agents, for example starch, gelatin, polyvinylpyrrolidone or gum arabic; lubricating agents, for example magnesium stearate, stearic acid or talc; and slippers such as colloidal anhydrous silica. To manufacture, for example, a tablet, the granules are combined or mixed with at least one excipient, for example a lubricant, to form a mixture. Mixing can be achieved using any conventional pharmaceutical equipment, for example, a V-mixer. Furthermore, any additional excipients used can be screened separately from the granules or simultaneously with the screening of the granules, as described in the dry screening step mentioned above. One of ordinary skill in the art will appreciate the necessary particle size of each component that is necessary for the particular pharmaceutical composition being formulated. The combined mixture, for example, may be subsequently compacted into a tablet (e.g., using a tablet press) or may be encapsulated in a capsule. The hardness of the tablets is preferably in a range of 250 to 350 N. Solid oral dosage forms can be subjected to additional conventional processes known to one skilled in the art, for example, printing, embossing or coating. The tablets may be uncoated or may be coated by known techniques. The tablets of the present disclosure may be additionally film coated, for example, to improve taste, to facilitate swallowing and to provide an elegant appearance. Many suitable polymeric film coating materials are known in the art. In one aspect, the film coating material is OPADRY® AMB II 88A170010 BEIGE, OPADRY® AMB II 88A210027 GREEN, OPADRY® AMB II 88A620004 YELLOW, OPADRY® AMB II 88A220039 YELLOW, OPADRY® QX 321A220006 YELLOW OPADRY II The film coating material is usually mixed with Ph. Eur purified water to form a coating suspension. Preferred coating suspensions are those in which the film coating material is Opadry® AMB II 88A170010 beige, Opadry® AMB II 88A210027 green and Opadry® AMB II 88A620004 yellow, because the resulting coated tablets do not show markings. Other film-forming polymers may also be used herein, including hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), especially HPMC 2910 5 mPa.s, and acrylate-methacrylate copolymers. A preferred film coating material is a water permeable film coating material, such as, for example, Opadry 32F220009 HPMC coating. In addition to a film-forming polymer, the film coating may further comprise a plasticizer (e.g., propylene glycol) and, optionally, a pigment (e.g., titanium dioxide). The film coating suspension may also contain talc as an anti-adhesive. In tablets according to the present disclosure, the film coating in terms of weight preferably represents about 5% (w / w) or less of the total weight of the tablet. In order to facilitate the swallowing of said formulation by a mammal, it is advantageous to give the formulation, in particular the tablets, an appropriate shape. A film coating on the tablet may contribute to the ease with which it can be swallowed. In one aspect of the present disclosure, the tablet may be an oblong-shaped tablet, in particular an oblong-shaped tablet with a length of <19 mm. Other excipients, such as coloring agents and pigments, may also be added to the formulations of the present disclosure. Coloring agents and pigments include titanium dioxide and food-grade colorants. A coloring agent is an optional ingredient in the formulation of the present disclosure, but when used, the coloring agent may be present in an amount of about 1 to about 6% by weight based on the total weight of the tablet, e.g. , from about 2 to about 5%, from about 3 to about 4% or up to 3.5% by weight based on the total weight of the tablet. Flavors are optional in the formulation and you can choose between synthetic flavoring and flavoring oils or natural oils, extracts of leaves, flowers, fruits and so on and combination of these. These may include cinnamon oil, wintergreen oil, peppermint oils, bay leaf oil, anise oil, eucalyptus or thyme oil. Also useful as flavors are vanilla, citrus oil, including lemon, orange, grape, lime and grapefruit, and fruit essences, including apple, banana, pear, peach, strawberry. , raspberry, cherry, plum, pineapple, apricot and so on. The amount of flavor may depend on several factors, including the desired organoleptic effect. Generally, the flavor will be present in an amount of about 0% to about 3% (w / w). Formulations for oral use may also be presented as hard gelatin or HPMC capsules where the active ingredients are mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules where The active ingredients are mixed with a water-soluble carrier or an oil medium, for example, peanut oil, liquid paraffin or olive oil. The aqueous suspensions contain the granules with the therapeutic compounds in a mixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum arabic; cnni? ίη / ζζηζ / Ε / γίΛΐ the dispersing or wetting agents may be a naturally occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example, polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example, heptadecaethyleneoxycetanal, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol, such as polyoxyethylenesorbitol monooleate, or condensation products of ethylene oxide with esters partial derivatives of fatty acids and hexitol anhydrides, for example, polyethylene sorbitan monooleate. Aqueous suspensions may also contain one or more preservatives, for example, ethyl or n-propyl phydroxybenzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, saccharin or aspartame. Oil suspensions can be formulated by suspending the granules with the therapeutic compounds in a vegetable oil, for example, peanut oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. Oily suspensions may contain a thickening agent, for example beeswax, solid paraffin or cetyl alcohol. Sweetening agents such as those mentioned above and flavoring agents may be added to provide a palatable oral preparation. These compositions can be preserved by the addition of an antioxidant such as butylated hydroxyanisole or alpha-tocopherol. Dispersible powders and granules suitable for the preparation of an aqueous suspension by the addition of water provide the active ingredients in admixture with a dispersing or wetting agent, a suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are, for example, those already mentioned above. There may also be additional excipients, for example sweetening, flavoring and coloring agents. These compositions can be preserved by adding an antioxidant such as ascorbic acid. In the first instance, the pharmaceutical formulations of the present disclosure are intended for oral administration such as tablets and capsules, but the pharmaceutical formulations of the present disclosure may also be used for rectal administration. Preferred formulations are those adapted for oral administration in tablet form. They can be produced by conventional tableting techniques with conventional ingredients or excipients (pharmaceutically acceptable carrier) and with conventional tableting machines. Treatment methods and medical uses The methods of treating prostate cancer or the medical uses of pharmaceutical formulations comprise, consist and / or essentially consist of administering to a patient that cnni? ίη / ζζηζ / Ε / γίΛΐ requires a therapeutically effective amount of the PARP inhibitor niraparib, a therapeutically effective amount of the CYP17 inhibitor abiraterone acetate, and, optionally, a therapeutically effective amount of another drug, e.g., a glucocorticoid, e.g. , prednisone. The methods of treating prostate cancer or the medical uses of pharmaceutical formulations comprise, consist of and / or essentially consist of administering to a patient in need a combination of free doses (CDL) or a combination of fixed doses (CDF) of niraparib and abiraterone acetate. The methods for treating prostate cancer or the medical uses of pharmaceutical formulations comprise, consist and / or essentially consist of administering to a patient in need the combination of free doses or the combination of fixed doses mentioned above, plus a glucocorticoid, for example, prednisone. The treatment methods and medical uses disclosed herein comprise administering to a patient in need oral dosage forms as defined in the present disclosure, said oral dosage forms comprising a granule composition comprising abiraterone acetate , niraparib and a pharmaceutically acceptable carrier. These oral dosage forms and granule compositions constitute FDCs. Also disclosed are dosage regimens of the oral dosage forms disclosed herein, said dosage regimens comprising, consisting and / or essentially consisting of administering the FDC of niraparib and abiraterone acetate, and optionally plus a glucocorticoid, for For example, prednisone, in a total amount that is therapeutically effective for the treatment of prostate cancer in a human patient. The present disclosure also discloses kits comprising, consisting of, and / or essentially consisting of a free-dose combination or a fixed-dose combination comprising niraparib and abiraterone acetate, and an instruction form for administering the free-dose combination or the combination. of fixed doses to a human patient who has prostate cancer. The kits may comprise, consist of, and / or essentially consist of a free dose combination or a fixed dose combination comprising niraparib and abiraterone acetate, a separate composition comprising a glucocorticoid, for example, prednisone; and an instruction form for administering the free dose combination or the fixed dose combination to a human patient having prostate cancer. Where particular reference is made to prednisone in the present disclosure, one of ordinary skill in the art will recognize that prednisone may be substituted by a different glucocorticoid, such as prednisolone, hydrocortisone, methyl prednisolone or dexamethasone. The expert in the field will know how to interchange prednisone with these other drugs and adjust their dosage, if necessary. cnni? ίη / ζζηζ / Ε / γίΛΐ Particular suitable glucocorticoids include, but are not limited to, (1) dexamethasone (e.g., Decadron, oral; Decadron-LA injection, etc.), (2) prednisolone (e.g., Delta-CORTEF®, prednisolone acetate (ECONOPRED® ), prednisolone sodium phosphate (HYDELTRASOL®), prednisolone tebutate (HYDELTRA-TBA®, etc.), (3) prednisone (DELTASONE®, etc.) or (4) methylprednisolone (e.g., MEDROL®) and combinations thereof. See, for example, Goodman & Gi / man's The PharmacologicalBasis of Therapeutics, 10th edition 2001. The formulations described herein can be used in methods of treating prostate cancer patients with negative biomarker status. The formulations described herein can be used in methods of treating prostate cancer patients with positive biomarker status. The formulations described herein can be used in methods of treating prostate cancer patients with homologous recombination deficiency (HRD) positive biomarker status. DRH is also called homologous recombination repair defects (HRD) and can result from DNA repair gene defects (DRA). Such positive DRH status – or RRH defects – can be detected by assessing somatic or germline alterations, or by assessing genome-wide loss of heterozygosity (PDH) or homozygous deleterious changes in DNA repair genes. Positive DRH status – or RRH defects – is also synonymous with positive PARP biomarker status. Positive biomarker status may be a positive DRH status. Negative biomarker status may be a negative HRD status. DRH status can be assessed by a plasma (Resolution Bioscience) or tissue assay (Foundation Medicine), particularly by detection of circulating plasma DNA or circulating tumor cells. DRH positive status can be defined by the presence of monoallelic or biallelic alterations in one or more DNA repair genes, including, without limitation, BRCA1 (breast cancer gene 1), BRCA2 (breast cancer gene 2), ATM (ataxia-telangiectasia mutated), FANCA (Fanconi anemia complementation group A gene), PALB2 (BRCA2 partner and localizer gene), CHEK2 (checkpoint kinase 2 gene), BRIP1 (mutated ataxia-telangiectasia gene), BRCA1-interacting protein C-terminal helicase 1), HDAC2 (histone deacetylase 2), CDK12 (cyclin-dependent kinase 12), RAD51B (RAD51 paralog B), RAD54L (RAD54-like), CDK17 (cyclin-dependent kinase 17) or PPP2R2A (protein phosphatase 2 regulatory subunit B alpha). Gene expression profiling analysis and protein biomarkers can also be used to risk stratify patients with prostate cancer to guide treatment decisions. Commercially available assays include Prolaris® (Myriad Genetics, Salt Lake City, UT); OncotypeDx® Prostate Cancer Assay (Genomic Health, Redwood cnni? ίη / ζζηζ / Ε / γίΛΐ City, CA); ProMark™ Protein Biomarker Assay / ProMark™ Risk Score (Metamark Genetics, Cambridge, MA); CDx FoundationOne® (Foundation Medicine, Cambridge, MA); FoundationOne® Liquid CDx (Foundation Medicine, Cambridge, MA); Caris Molecular Intelligence (Caris Life Sciences, Irving, TX); Guardant360 (Guardant Health Inc., Redwood City, CA); ProstateNext® (Ambry Genetics, Aliso Viejo, CA); Hereditary Cancer Color Assay (Color Genomics, Burlingame, CA); Invitae Prostate Cancer Panel (Invitae Corp., San Francisco, CA); prostate gene (GeneHealth, Cambridge, UK); Myriad myRisk® Hereditary Cancer Assay (Myriad Genetics Inc., Salt Lake City, UT) and Decipher® Prostate Cancer Assay (GenomeDx Biosciences, San Diego, CA), the latter based on the expression pattern of 22 RNA markers in biopsy or radical prostatectomy samples. Prolaris®, OncotypeDx® and Decipher® are tissue-based gene expression assays. The formulations described herein can be used in methods of treating patients with biochemically recurrent (BQR) or biochemically failing (FB) prostate cancer. BQR or FB can be defined by an increase in prosthetic specific antigen (PSA) without evidence of disease on imaging. For patients who have received primary radiation therapy, BQR is currently defined as an increase in PSA of > 2.0 ng / ml above the nadir (Phoenix criteria). For patients who have received primary surgery, BQR is currently defined as a confirmed PSA rise of > 2.0 ng / mL above nadir. Next-generation imaging (NGI), for example, prostate-specific membrane antigen positron emission tomography (PSMA-PET), can be used to detect lesions not visible on conventional or subthreshold imaging. of Phoenix, that is, an increase in PSA < 2.0 ng / ml. IGN may, for example, classify some patients with localized prostate cancer, BKR, nmCRPC, or nmCRPC as having metastatic prostate cancer. The formulations described herein can be used in methods of treating patients with prostate cancer with BQR or FB, and who are positive for HRD biomarkers and / or high risk. The positive DRH biomarker can be at least one of BRCA1, BRCA2, ATM, BRIP1, CDK12, CDK17, CHEK2, FANCA, HDAC2, PALB2, PPP2R2A, RAD51B and RAD54L. The formulations described herein can be used in methods of treating BKR or FB, oligometastatic disease or localized prostate cancer in a patient, which can be detected by conventional imaging. The formulations described herein can be used in methods of treating BQR or FB, oligometastatic disease or localized prostate cancer cnni? ίη / ζζηζ / Ε / γίΛΐ in a patient, which can be detected by IGN. The formulations described herein can be used in methods of treating patients with locally advanced prostate cancer who are candidates for primary radiotherapy. The formulations described herein can be used in methods of treating cancer patients, in particular CRPC patients, with circulating tumor cells that test negative for androgen receptor splice variant 7 (AR-V7). ). The formulations described herein can be used in methods of treating cancer patients, in particular CRPC patients, with circulating tumor cells that test positive for androgen receptor splice variant 7 (AR-V7). ). The formulations described herein can be used in methods of treating prostate cancer in patients with detectable circulating tumor cells (CTCs), circulating DNA or reduced plasma DNA. The formulations described herein can be used in methods of treating metastatic prostate cancer in patients with detectable CTCs and / or median and non-medial bone diseases or lesions. CTC elimination in patients with metastatic prostate cancer can be established when >5 cells are detected per 7.5 ml of starting blood, detecting <5 cells per 7.5 ml of blood at the lowest point, further confirmed by a second consecutive value ooted 4 or more weeks later. The lower dose combinations or the fixed dose combinations of aoiraterone acetate and niraparió and, optionally, a separate composition comprising a glucocorticoid, for example, prednisone, can be administered to a subject, a patient, a mammal, in particular a being. human, suffering from prostate cancer, primary peritoneal cancer, breast cancer or ovarian cancer. In one aspect, the human being suffering from breast cancer or ovarian cancer is a biomarker-positive patient. Prostate cancer can be metastatic prostate cancer, advanced prostate cancer, regional prostate cancer, locally advanced prostate cancer, localized prostate cancer, non-metastatic prostate cancer, non-metastatic advanced prostate cancer, non-regional prostate cancer. metastatic, locally advanced non-metastatic prostate cancer, hormone-unexposed prostate cancer, chemotherapy-unexposed prostate cancer, castration-unexposed cancer with or without metastasis, radiation-unexposed prostate cancer, refractory prostate cancer castration (CRPC), CRPC with AKI, non-metastatic CRPC (nmCRPC), nmCRPC in a population of patients with a PSA doubling time equal to or less than 10 months and who are DRH positive (or enriched for biomarkers), nmCRPC in patients who have AKI or DRH, cnni? ίη / ζζηζ / Ε / γίΛΐ nmCRPC in patients without AKI, nmCRPC in patients with high-risk BRK (e.g. in an AKI+ population), nmCRPC in patients monitored with next-generation imaging (NGI), localized CRPC, locally advanced CRPC, regional CRPC , advanced CRPC, metastatic CRPC (mCRPC), mCRPC in patients who have biallelic DNA repair gene defect (ARD); mCRPC in patients who have monoallelic AKI; mCRPC in patients without AKI; mCRPC in patients who have AKI and who have received taxane and / or androgen receptor-directed therapy, CRPC in patients who have received hormonal therapy (e.g., enzalutamide, darolutamide, apalutamide), CRPC in patients who have received therapy with taxanes (e.g., docetaxel, mitoxantrone, cabazitaxel), chemotherapy-naïve CRPC, chemotherapy-unexposed mCRPC, hormone-unexposed CRPC, hormone-unexposed mCRPC, progression, CRPC with visceral metastases, CRPC with visceral metastases in patients who have received hormonal therapy (e.g., enzalutamide, darolutamide, apalutamide), CRPC with visceral metastases in patients who have received taxane therapy (e.g., docetaxel, mitoxantrone, cabazitaxel), CRPC with visceral metastases and progression, prostate cancer castration sensitive (CPSC), non-metastatic CPSC (nmCPSC), localized CPSC, locally advanced CPSC, regional CPSC, advanced CPSC, metastatic CPSC (mCPSC), chemotherapy-naïve CPSC, chemotherapy-naïve mCPSC, hormones, hormone-naive mSCPC, hormone-sensitive prostate cancer (HSPC), hormone-dependent prostate cancer, androgen-dependent prostate cancer, androgen-sensitive prostate cancer, biochemically recurrent HSPC, metastatic HSPC (mHSPC), cancer hormone-resistant prostate cancer (CPRH), non-metastatic CPRH (nmCPRH), localized CPRH, locally advanced CPRH, regional CPRH, advanced CPRH, metastatic CPRH (mCPRH), recurrent prostate cancer, prostate cancer with persistence or reappearance of prostate antigen specific (PSA) after prostatectomy with or without distant metastasis, radiation-resistant prostate cancer, and any combination of these. The subject or patient may be in a selected risk group of very low risk, low risk, intermediate favorable risk, intermediate unfavorable risk, high risk, very high risk and regional risk. The subject can be castrated surgically or chemically. Most, but not all, prostate cancers are adenocarcinomas, and the patient may have adenocarcinoma- or sarcoma-based prostate cancer. In any of these cases, the prostate cancer may be metastatic. The patient may have undergone one or more types of treatment for prostate cancer before the first dose of the free-dose combination or the fixed-dose combination of niraparib and abiraterone acetate. For example, the patient may have undergone CNI? ίη / ζζηζ / Ε / γίΛΐ taxane-based chemotherapy before administering the free-dose combination or the fixed-dose combination of niraparib and abiraterone acetate. Additionally or alternatively, the patient may have undergone at least one line of androgen receptor-directed therapy, such as apalutamide (ERLEADA®) and / or enzalutamide (XTANDI®), prior to administering the free-dose combination or the fixed-dose combination of niraparib and abiraterone acetate. In one aspect, the patient initially does not respond or becomes refractory to previous treatments, before administering the free-dose or fixed-dose combination of niraparib and abiraterone acetate. Optionally, the glucocorticoid, for example prednisone, may also be administered in addition to the free-dose or fixed-dose combination of niraparib and abiraterone acetate. The period of time between the end of the other treatment and the administration of the combination of free doses or fixed doses of niraparib and abiraterone acetate, and optionally plus a glucocorticoid, for example, prednisone, according to the present disclosure may be of years, months, weeks, days, a single day or less than 24 hours. Administration of the combination of free or fixed doses of niraparib and abiraterone acetate, and optionally plus a glucocorticoid, for example, prednisone, may be once, twice or three times a day. Daily administration includes administering a single fixed-dose combination (FDC) of niraparib and abiraterone acetate to the patient one, two, or three times daily. Any dosage regimen included in the above description is contemplated. In one aspect, 1 tablet or capsule comprising the FDC of niraparib and abiraterone acetate is administered once a day. In one aspect, 2 tablets or capsules comprising the FDC of niraparib and abiraterone acetate are administered once a day. In one aspect, 3 tablets or capsules comprising the FDC of niraparib and abiraterone acetate are administered once a day. In one aspect, 1 tablet or capsule comprising the FDC of niraparib and abiraterone acetate is administered once a day, at least 1 hour before a meal or at least two hours after a meal. In one aspect, 2 tablets or capsules comprising the FDC of niraparib and abiraterone acetate are administered once a day, at least 1 hour before a meal or at least two hours after a meal. In one aspect, 3 tablets or capsules comprising the FDC of niraparib and abiraterone acetate are administered once a day, at least 1 hour before a meal or at least two hours after a meal. In one aspect, 1 tablet or capsule comprising the FDC of niraparib and abiraterone acetate is administered once a day, with water or on an empty stomach, at least 1 hour before a meal or at least two hours after a meal. . In one aspect, 2 tablets or capsules comprising the FDC of niraparib and abiraterone acetate are administered once a day, with water or on an empty stomach, at least 1 hour before a meal or at least two hours after a meal. . In one aspect, 3 tablets or capsules comprising the cnni FDC are administered? ίη / ζζηζ / Ε / γίΛΐ niraparib and abiraterone acetate once daily, with water or on an empty stomach, at least 1 hour before a meal or at least two hours after a meal. In one aspect, a glucocorticoid is administered once or twice a day. In one aspect, prednisone tablets or capsules are administered once or twice a day. In one aspect, 1 or 2 tablets or capsules comprising the FDC of niraparib and abiraterone acetate are administered once a day and 1 tablet or capsule of a glucocorticoid, for example, prednisone, is administered twice a day. The amount of niraparib equivalent administered to the patient may be about 30 to about 400 mg / day, about 50 to about 350 mg / day, about 66 to about 325 mg / day, about 100 to about 300 mg / day, from about 100 to about 275 mg / day, from about 125 to about 250 mg / day, from about 150 to about 225 mg / day, from about 175 to about 225 mg / day, or from about 190 to about 210 mg / day, or, approximately 30, approximately 33, approximately 40, approximately 50, approximately 60, approximately 66, approximately 67, approximately 70, approximately 80, approximately 90, approximately99, approximately 100, approximately 110, approximately 120, approximately130, approximately 132, approximately 134, approximately 140, approximately150, approximately 160, approximately 170, approximately 180, approximately190, approximately 200, approximately 201, approximately 210, approximately220, approximately 230, approximately 240, approximately 250, approximately260, approximately 270, approximately 280, approximately 290, approximately 300, approximately 310, approximately 320, approximately 330, approximately 340 or approximately 350 mg / day. The amount of abiraterone acetate administered to the patient may be about 300 to about 2000 mg / day, about 500 to about 1500 mg / day, about 700 to about 1200 mg / day, about 800 to about 1200 mg / day. day, from about 900 to about 1100 mg / day, from about 950 to about 1050 mg / day, or may be about 300, about 333, about 500, about 600, about 666, about 700, about 750, about 800, about 850, approximately 875, approximately 900, approximately 925, approximately 950, approximately 999, approximately 1000, approximately 1025, approximately 1050, approximately 1075, approximately 1100, approximately 1125 or approximately 1500 mg / day. cnni? ίη / ζζηζ / Ε / γίΛΐ The amount of prednisone administered to the patient may be from about 1 to about 25 mg / day, from about 2 to about 23 mg / day, from about 3 to about 20 mg / day, from about 4 to about 18 mg / day. , from about 5 to about 15 mg / day, from about 6 to about 12 mg / day, from about 7 to about 11 mg / day, from about 8 to about 11 mg / day, from about 9 to cnni? ίη / ζζηζ / Ε / γίΛΐ about 11 mg / day, or may be about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24 or about 25 mg / day. In some aspects, the patient has mCPSC and the amount of prednisone is 5 mg / day. In some aspects, the patient has mCRPC and the amount of prednisone is 10 mg / day. When the FDC of niraparib and abiraterone acetate is administered to a patient, the dosage level selected for each drug will depend on a variety of factors including, but not limited to, the activity of the particular compound, the severity of the individual's symptoms, the route of administration, time of administration, rate of excretion of the compound, duration of treatment, other drugs, compounds and / or materials used in combination, and age, sex, weight, condition, general health and the patient's previous medical history. The amount of niraparib, the amount of abiraterone acetate and, optionally, the amount of prednisone, will ultimately be at the discretion of the doctor, although generally the dosage will be to achieve local concentrations at the site of action that achieve the desired effect without causing significant harmful or harmful side effects. The FDCs may comprise, for example, from about 33 to about 350 mg of the niraparib, from about 100 to about 1500 mg of the abiraterone acetate. For example, the present compositions may include niraparib equivalent in an amount, for example, from 33 to about 350 mg, from about 33 to about 300 mg, from about 50 to about 200 mg, from about 50 to about 150 mg, about 50 to about 100 mg, about 33 to about 100 mg, or may be about 30, about 33, about 50, about 67, about 100, about 110, about 120, about 130, about 140, about 150, about 160, approximately 170, approximately 180, approximately 190, approximately 200, approximately 210, approximately 220, cnni? ίη / ζζηζ / Ε / γίΛΐ about 230, about 240, about 250, about 260, about 270, about 280, about 290, about 300, about 310, about 320, about 330, about 340 or about 350 mg. The present compositions may include niraparib equivalent in an amount of about 33, about 50, about 67 or about 100 mg. The present compositions may also include abiraterone acetate in an amount, for example, from about 100 to about 1500 mg, from about 125 to about 1400 mg, from about 150 to about 1300 mg, from about 175 to about 1200 mg, from about 200 to about 1175 mg, about 225 to about 1150 mg, about 250 to about 1100 mg, about 250 to about 1075 mg, about 250 to about 1050 mg, about 250 to about 1000 mg, about 300 to about 950 mg, about 350 to about 900 mg, about 400 to about 850 mg, about 450 to about 800 mg or about 500 to about 700 mg, or can be i about 200, about 300, about 400, about 600, about 800, e about 100 about 225, about 325, about 450, about 650, about 850, about 150, about 250, about 350, about 500, about 700, about 900, about 175, about 275, about 375, about 550, about 750, about 950, about 1000, about 1050, about 1100, about 1150, about 1200, about 1250, about 1300, about 1350 , approximately 1400, approximately 1450 or approximately 1500 mg. The present compositions may include abiraterone in an amount of about 333 or about 500 mg. The present compositions may include niraparib equivalent in an amount of about 33 mg and abiraterone in an amount of 333 mg. The present compositions may include niraparib equivalent in an amount of about 67 mg and abiraterone in an amount of 333 mg. The present compositions may include niraparib equivalent in an amount of about 50 mg and abiraterone in an amount of 500 mg. The present compositions may include niraparib equivalent in an amount of about 100 mg and abiraterone in an amount of 500 mg. The present treatment guidelines may also include administration by cnni? ίη / ζζηζ / Ε / γίΛΐ separated from a glucocorticoid, for example, prednisone, in an amount, for example, from about 2 to about 15 mg, from about 2 to about 14, from about 3 to about 5 to about 6 a about 13, about 11, about 11, about 4 to about 5 to about 7 to about 12, about 10, about 11, about 8 to about 11, about 9 to about 11 or may be about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14 or about 15 mg. The present methods may include administering the FDC of niraparib and abiraterone acetate and, optionally, the glucocorticoid or prednisone separately, to the patient over several days, weeks, months or years. Preferably, administration of the FDC of niraparib and abiraterone acetate is performed one, two or three times a day and, optionally, the separate administration of prednisone is performed one, two or three times a day. The amount of niraparib, abiraterone acetate, and optionally prednisone administered separately may be constant over time (i.e., from day to day), or may increase or decrease over time. For example, the amount of niraparib, abiraterone acetate and, optionally, separately administered prednisone, or two of these, or all three, administered per day may be increased or decreased after one day of administration, after a few days of administration, after a week of administration, and the new dosage amount can be maintained for any desired period of time, for example, days, weeks or months, or can be subsequently increased or reduced after the desired interval. Thus, the present methods may include increasing or decreasing the FDC dosage of niraparib and abiraterone acetate (e.g., the amount of niraparib and abiraterone acetate, respectively, administered daily) at least once with the time. The present methods may also include, or alternatively, increasing or decreasing the prednisone dosage (e.g., the total amount of prednisone administered daily) at least once over time. The amount of increase or decrease may be expressed in terms of a percentage and, in such circumstances, the amount of a single episode of increase or decrease may be about 5%, about 10%, about 15%, about 20%. %, approximately 25%, approximately 30%, approximately 35%, approximately 40%, approximately 45%, approximately 50%, approximately 55%, approximately 60%, approximately 65%, approximately 70% %, approximately 80%, approximately 85%, approximately 90%, approximately 95%, approximately 100% or more than approximately 100%. Described herein are methods of treating a cancer in which a patient is administered a therapeutically effective amount of niraparib, abiraterone acetate and, optionally, the separately administered glucocorticoid, such as prednisone, a prednisolone, hydrocortisone, methylprednisolone and dexamethasone. , for example, to a patient in need thereof, in combination with a therapeutically effective amount of at least one additional therapeutic agent including, but not limited to, an anticancer agent (for example, docetaxel, mitoxantrone, cabazitaxel, cisplatin, carboplatin, oxaliplatin and etoposide), an immunotherapeutic agent (e.g., pembrolizumab, sipuleucel-T), bone-directed therapies (e.g., denosumab, zoledronic acid, alendronate, radium-223, strontium-89, samarium-153), gonadotropin-releasing hormone (GnRHa, including, but not limited to, triptorelin, nafarelin, goserelin, leuprorelin or leuprolide, histrelin, gonadorelin and buserelin) and hormonal therapies (for example, nilutamide, flutamide, bicalutamide, goserelin, histrelin, leuprolide, triptorelin, degarelix, enzalutamide, apalutamide, darolutamide, ketoconazole, diethylstilbestrol, estrogens). Such methods may also provide effective treatment for individuals with a refractory cancer, including individuals who are currently undergoing cancer treatment. Therefore, the methods may be directed to treating a chemotherapy-resistant prostate cancer in a patient, wherein a therapeutically effective amount of niraparib and abiraterone acetate is administered to a patient currently receiving an antineoplastic agent. Additionally, the methods of treating a cancer described herein can be combined with androgen deprivation therapy (ADT). The methods of treating a cancer described herein can be combined with radiation therapy, preferably in a DRH+ population. In one aspect, the methods of treating a cancer described herein can be combined with ADT and external beam radiation therapy (EBRT). The methods of treating cancer described herein can be combined with alternative energy sources, such as high intensity focused ultrasound (UFAI), cryosurgery and laser treatments. The FDC of the present invention and a separately administered glucocorticoid (for example, prednisone, a prednisolone, hydrocortisone, methylprednisolone or dexamethasone; preferably prednisone or a prednisolone) can be administered to a patient who has metastatic prostate cancer. In particular, the FDC of the present invention and a separately administered glucocorticoid (for example, prednisone, a prednisolone, hydrocortisone, methylprednisolone or dexamethasone; preferably prednisone or a prednisolone) can cnni? Ln / zznz / E / YiAi be administered to a patient who has mCRPC, such as first-line (Ll) mCRPC (e.g., subjects who have not been treated with any therapy in the metastatic castration-resistant setting, except castration-resistant therapy. androgen deprivation (ADT) and limited exposure to abiraterone acetate plus prednisone). The patient may be DRH positive or DRH non-positive. Preferably, the patient is DRH positive. Metastatic prostate cancer can be confirmed by a positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI). The patient may have castration testosterone levels < 50 ng / dl and may be undergoing GnRHa therapy or have undergone bilateral orchiectomy. The patient can continue GnRHa therapy during treatment if there is no surgical castration. The patient may have an Eastern Cooperative Oncology Group Performance Score (ECOG PS) Grade of 0 or 1. ADT uses surgery or medications to reduce the levels of androgens produced in the testicles, preventing them from feeding prostate cancer cells. ADT includes, without limitation, surgical castration or orchiectomy; and medical castration such as luteinizing hormone-releasing hormone (LHRH) agonists, for example, leuprolide, goserelin, triptorelin, histrelin; LHRH antagonists; abiraterone acetate; ketoconazole; antiandrogens such as flutamide, bicalutamide, nilutamide, enzalutamide, apalutamide, darulotamide; or estrogens. The FDC of the present invention and a separately administered glucocorticoid (for example, prednisone, a prednisolone, hydrocortisone, methylprednisolone or dexamethasone; preferably prednisone or a prednisolone) can be administered to a patient who has mCSPC, for example, mCSPC with gene mutation of deleterious somatic or germline homologous recombination repair (HRR). The deleterious somatic or germline RRH gene mutation may be at least one of, without limitation, BRCA1, BRCA2, ATM, BRIP1, CDK12, CDK17, CHEK2, FANCA, HDAC2, PALB2, PPP2R2A, RAD51B and RAD54L. mCPSC can be confirmed by at least one or more bone lesions on bone scan; bone metastasis is also preferably confirmed by CT or MRI. mCPSC can be detected by IGN as PET-PSMA. The patient may have an Eastern Cooperative Oncology Group Performance Score (ECOG PS) grade less than or equal to 2. The patient may be undergoing androgen deprivation therapy (medical or surgical castration) and this therapy may have been initiated within the 6 months prior to treatment with CDF plus prednisone (or a prednisolone), preferably it may have been started at least 14 days before treatment with CDF plus prednisone (or a prednisolone). Such androgen deprivation therapy may continue throughout treatment with FDC plus prednisone (or a prednisolone). Those patients who have started GnRHa therapy less than 28 days before treatment with CDF plus prednisone (or a prednisolone) are preferably administered a cnni? Ln / zznz / E / YiAi first-generation antiandrogen, preferably for at least 14 days before treatment with FDC plus prednisone (or a prednisolone). This antiandrogen should be discontinued before starting treatment with FDC plus prednisone (or a prednisolone). The patient may have received prior treatment with docetaxel or cabazitaxel; preferably, the patient has received a maximum of 6 cycles of docetaxel therapy; preferably, the patient has received the last dose of docetaxel or cabazitaxel within 2 months prior to treatment with FDC plus prednisone (or prednisolone). Before treatment with FDC plus prednisone (or a prednisolone), the patient may have received radiation or surgery to control the symptoms of prostate cancer. Prior to CDF plus prednisone (or a prednisolone) therapy, the patient may have received abiraterone acetate plus glucocorticoid (e.g., prednisone, a prednisolone, hydrocortisone, methylprednisolone, or dexamethasone), preferably for one month prior to CDF therapy. plus prednisone (or a prednisolone). Prior to therapy with CDF plus prednisone (or a prednisolone), the patient may have received treatments for localized prostate cancer, preferably these treatments should have been completed at least 1 year before treatment with CDF plus prednisone (or a prednisolone); For example, the patient may have undergone up to 3 years of androgen deprivation therapy; For example, the patient may have received radiation therapy, prostatectomy, lymph node dissection, or systemic therapies. The FDC of the present invention and a separately administered glucocorticoid (for example, prednisone, a prednisolone, hydrocortisone, methylprednisolone or dexamethasone; preferably prednisone or a prednisolone) can be administered to a patient who has metastatic castration-resistant prostate cancer (mCRPC). ), with or without homologous recombination deficiency (HRD) or AKI and, optionally, with pathogenic alterations of cyclin-dependent kinase 12 (CDK12). The CDF can be of low concentration: 100 mg eq. of niraparib / 1000 mg abiraterone acetate, provided as 2 x CDF tablets (50 mg niraparib eq. / 500 mg abiraterone acetate), administered orally as a single dose under modified fasting conditions. The CDF can be of normal concentration: 200 mg eq. of niraparib / 1000 mg abiraterone acetate, provided as 2 x CDF tablets (100 mg niraparib eq. / 500 mg abiraterone acetate), administered orally once daily under modified fasting conditions. The patient may continue GnRHa therapy during treatment with CDF plus prednisone (or a prednisolone) if there is no surgical castration (i.e., subjects who have not undergone a bilateral orchiectomy). The patient may have an Eastern Cooperative Oncology Group Performance Score Status (ECOG PS) less than or equal to 1. Prior to treatment with CDF plus prednisone (or a prednisolone), the patient may have been exposed to antiandrogens, including, but not limited to, limitation, nilutamide, flutamide, bicalutamide, enzalutamide, apalutamide, darolutamide or abiraterone acetate; Preferably, a cnni is carried out? ίη / ζζηζ / Ε / γίΛΐ adequate pharmacological rest from said previous antiandrogen therapy before administering the first dose of FDC plus prednisone or a prednisolone. In the case of bicalutamide, flutamide and nilutamide, the drug withdrawal time is approximately 2 weeks. For enzalutamide, the washout time is approximately 8 weeks. For apalutamide, the washout time is approximately 6 weeks. The FDC of the present invention and a separately administered glucocorticoid (for example, prednisone, a prednisolone, hydrocortisone, methylprednisolone or dexamethasone; preferably prednisone or a prednisolone) can also be administered in combination with leuprorelin acetate (also known as leuprolide acetate). , before, during and after radiotherapy, to a patient who has high-risk prostate cancer and positive lymph nodes. Radiation therapy may be stereotactic body radiation therapy (SBRT) or ultrahypofractionated radiation therapy, with a total dose of approximately 37.5 to 40 Gy. The FDC of the present invention and a separately administered glucocorticoid (for example, prednisone, a prednisolone, hydrocortisone, methylprednisolone or dexamethasone; preferably prednisone or a prednisolone) can be administered to a patient who has prostate cancer not exposed to castration, with or no metastasis. The patient may continue GnRHa therapy during treatment with CDF plus prednisone (or a prednisolone) if there is no surgical castration (i.e., subjects who have not undergone a bilateral orchiectomy). In the compositions disclosed, niraparib may be present in an amount that is therapeutically effective by itself, abiraterone acetate may be present in an amount that is therapeutically effective by itself, and, optionally, prednisone administered separately may be present in an amount that is therapeutically effective by itself. be present in an amount that is therapeutically effective by itself, or two or more of these conditions may apply. In other examples, the total amount of niraparib, abiraterone acetate and, optionally, prednisone administered separately, when considered together, may represent a therapeutically effective amount, that is, the amount of niraparib would not be therapeutically effective by itself. , the amount of abiraterone acetate would not be therapeutically effective by itself and, if present, the amount of prednisone would not be therapeutically effective by itself. Also disclosed herein are kits that include a composition comprising niraparib and abiraterone acetate and, optionally, a composition comprising prednisone, and, a printout of instructions for administering the compositions to a human patient having prostate cancer. The instruction form may provide instructions for administering the respective compositions once a day, twice a day, or several times a day. For example, the instruction form may provide instructions for administering the composition comprising niraparib and abiraterone acetate to a human patient having cnni cancer? ίη / ζζηζ / Ε / γίΛΐ of prostate once a day and, optionally, to administer the composition comprising prednisone to the human patient twice a day. The present disclosure further relates to a method for determining the bioequivalence of a trial fixed dose combination formulation (CDF) of niraparib and abiraterone acetate, with respect to an oral dosage form of the present disclosure, said method comprising i ) measure a bioequivalence parameter of the test CDF formulation and optionally measure a bioequivalence parameter of the oral dosage form of the present disclosure, and i) compare the bioequivalence parameter of the test CDF formulation with the corresponding bioequivalence parameter of the oral dosage form of the present disclosure. In one aspect, the bioequivalence parameter is selected from AUQo-t), AUQo-oo), residual area, Cmax and tmax, AUC(o-?2 h), terminal rate constant (λζ), ti / 2, AUQo -t), Cmax,ee, tmax,ee, Ae(o-t) and Rmax, bioequivalence parameters that are well known to those skilled in the fields of bioequivalence and pharmacokinetics. The present invention is further defined in the following examples. It is to be understood that these examples, while indicating preferred embodiments of the invention, are provided by way of illustration only and are not to be construed as limiting the appended claims. From the previous analysis and these examples, a person skilled in the art can determine the essential characteristics of the present invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various uses. and conditions. EXAMPLES Example 1 — Formulation Compositions Table 1: Composition of abiraterone acetate core tablet: niraparib tosylate monohydrate 500 / 50 mg eq., prepared according to the procedures of Examples 2.1 and 2.2. cnni? ίη / ζζηζ / Ε / γίΛΐ Component Quality reference Function Quantity per unit (mg) Composition in granules: Binder solution: HPMC 2910 15 mPa.s Ph.Eur Binder 22.50 Sodium lauryl sulfate Ph.Eur Agent 5.60 wetting Purified Water3 Intragranular Phase: Ph.Eur Solvent3 <750.00a Abiraterone Acetate Company Specification Active P. 500.00 Narpar¡bb Tosylate Monohydrate Company Specification Active P. 79.70b Lactose Monohydrate Ph.Eur Diluent 253.20 Crospovidone Ph.Eur Disintegrant 30.00 cnni? ίη / ζζηζ / Ε / γίΛΐ Extragranular phase: Silicified microcrystalline cellulose NF Diluent 451.70 Crospovidone Ph.Eur Disintegrant 75.00 Sodium lauryl sulfate Ph.Eur Agent 56.00 humectant Colloidal anhydrous silica Ph.Eur Slider 11.30 Magnesium stearate Ph.Eur Lubricant 15.00 Weight of core tablet: 1500.00 aRemoved during processingbSalt factor = 1.594; 79.70 mg niraparib tosylate is equivalent to a dose of 50.00 mg niraparib (base) Table 2: Composition of abiraterone acetate film-coated tablet: niraparib tosylate monohydrate 500 / 50 mg eq. of Table 1, prepared according to the procedure of Example 2.3. Component Quality Reference Function Quantity per unit (mg) Abiraterone Acetate Oral Tablet: Niraparib Tosylate Monohydrate 500 / 50 mg eq. from Table 1 1500.00 Purified water3 Ph.Eur Processing agent3 <240.00a > 60.00 Powder Specification Opadry® AMB II 88A620004 Yellow coating company Component Quality reference Function Quantity per unit (mg) Total weight: 1560.00 cnni? ίη / ζζηζ / Ε / γίΛΐaWithdrawn during processing Table 3: Composition of abiraterone acetate core tablet: niraparib tosylate monohydrate 500 / 100 mg eq., prepared according to the procedures of Examples 2.1 and 2.2 Component Quality reference Function Quantity per unit (mg) Composition in granules: Binder solution: HPMC 2910 15 mPa.s Ph.Eur Binder 24.00 Sodium lauryl sulfate Ph.Eur Wetting agent 5.60 Purified water3 Intragranu / ar phase: Ph.Eur Solvent3 <800.003> Abiraterone Acetate Company Specification Asset P. 500.00 Niraparibb Tosylate Monohydrate Company Specification Asset P. 159.40b. Lactose monohydrate Ph.Eur Diluent 253.20 Crospovidone Ph.Eur Disintegrant 32.00 Extragranular phase: Silicified microcrystalline cellulose NF Diluent 461.80 Crospovidone Ph.Eur Disintegrant 80.00 Sodium lauryl sulfate Ph.Eur Wetting agent 56.00 Colloidal anhydrous silica Ph.Eur Desl izing 12.00 Magnesium stearate Ph.Eur Lubricant 16.00 Weight of core tablet: 1600.00 aRemoved during processingbSalt factor = 1.594; 159.40 mg niraparib tosylate is equivalent to a dose of 100.00 mg niraparib (base) Table 4: Composition of abiraterone acetate film-coated tablet: niraparib tosylate monohydrate 500 / 100 mg eq. of Table 3, prepared according to the procedure of Example 2.3. cnni? ίη / ζζηζ / Ε / γίΛΐ Component Quality reference Function Quantity per unit (mg) Abiraterone acetate oral tablet: tosylate monohydrate 1600.00 niraparib 500 / 100 mg eq. Table 3 Purified Water Agent3 Ph.Eur <256.003> processing3 Opadry® AMB II 88A170010 Beige Coating Powder Specification 64.00 Company Total Weight: 1664.00 aRemoved during processing Table 5: Composition of abiraterone acetate core tablet: niraparib tosylate monohydrate 333 / 33 mg eq., prepared according to the procedures of Examples 3.1, 3.2 and 3.3. Amount Component Quality reference Function per unit (mg) Internal phase: Niraparib3 tosylate monohydrate Company specification Active P. 53.13a Lactose monohydrate Ph.Eur Diluent 11.56 Microcrystalline cellulose PH101 Ph.Eur Diluent 37.25 Povidone K30 Ph.Eur Binder 2.22 Crospovidone Ph.Eur Disintegrant 1.11 Colloidal anhydrous silica Ph.Eur Glide 2.78 Magnesium stearate Abiraterone acetate granules*5 Ph.Eur Company specification Lubricant Active P. 0.56 531.99 External phase: Silicified microcrystalline cellulose (HD90) NF Diluent 533.30 Crospovidone Ph.Eur Disintegrant 65.50 Sodium lauryl sulfate Ph.Eur Wetting agent 37.30 Colloidal anhydrous silica Ph.Eur Slider 10.00 Magnesium stearate Ph.Eur Lubricant 13.30 cnni? ίη / ζζηζ / Ε / γίΛΐ Core tablet weight: 1300.00 Salt tactor = 1.594; 53.13 mg niraparib tosylate is equivalent to a dose of 33.00 mg niraparib (base) Table 6: Composition of abiraterone acetate film-coated tablet: niraparib tosylate monohydrate 333 / 33 mg eq. of Table 5, prepared according to the procedure of Example 3.4. Component Quality Reference Function Quantity per unit (mg) Abiraterone Acetate Oral Tablet: Niraparib Tosylate Monohydrate 333 / 33 mg eq. Table 5 Processing Agent 1300.00 Purified water3 Ph.Eur <221.003>3 Opadry® AMB II 88A220039 Company Coating Powder Specification 39.00 Yellow Total Weight: 1339.00 aRemoved during processing Table 7: Composition of abiraterone acetate core tablet: niraparib tosylate monohydrate 333 / 67 mg eq., prepared according to the procedures of Examples 3.1, 3.2 and 3.3. Amount Component Quality reference Function per batch (kg) Internal phase: Niraparib3 Tosylate MonohydrateSpecification of Active P. 1.063 company Lactose monohydrate Ph.Eur Diluent 0.231 Microcrystalline cellulose PH101 Ph.Eur Diluent 0.745 Povidone K30 Ph.Eur Binder 0.045 Crospovidone Ph.Eur Disintegrant 0.022 Colloidal anhydrous silica Ph.Eur Slider 0.056 Magnesium stearate Ph.Eur Lubricant Specification 0.011 Granules of abiraterone acetate company P. active 5,320 cnni? ίη / ζζηζ / Ε / γίΛΐ External phase: Silicified microcrystalline cellulose (HD90) NF Diluent 6.109 Crospovidone Ph.Eur Disintegrant 0.755 Sodium lauryl sulfate Ph.Eur Wetting agent 0.373 Colloidal anhydrous silica Ph.Eur Slider 0.116 Magnesium stearate Ph.Eur Lubricant 0.155 Weight of core tablet: 15.001 aSalt factor = 1.594 Table 8: Composition of abiraterone acetate film-coated tablet: niraparib tosylate monohydrate 333 / 67 mg eq. of Table 7, prepared according to the procedure of Example 3.4. Quantity per Component Quality reference Lot function (kg) (11539 tablets) Abiraterone acetate oral tablet: tosylate monohydrate 15.00 niraparib 333 / 67 mg eq. Table 7 Purified Water Processing Agent3 Ph.Eur <2.55a>3 Opadry® AMB II 88A220039 Yellow Powder Specification 0.45 coating company Total weight: 15.45 cnni? ίη / ζζηζ / Ε / γίΛΐaWithdrawn during processing Table 9: Composition of abiraterone acetate core tablet: niraparib tosylate monohydrate 500 / 100 mg eq., prepared according to the procedures of Examples 4.1 and 4.2. Component Quality reference Function mg / tablet Intragranular phase: Abiraterone acetate Company specification Active part 500 Niraparib tosylate monohydrate3 Company specification Active part 159.40 Lactose monohydrate Ph.Eur Diluent 110.0 Crospovidone Ph.Eur Disintegrant 40.0 Lauryl sodium sulfate Ph.Eur Wetting agent 5.6 Anhydrous colloidal silica Ph.Eur Slider 8.0 Microcrystalline cellulose PH101 NF Diluent 349.00 Magnesium stearate Ph.Eur Lubricant 4.0 Extragranular phase: Silicified microcrystalline cellulose NF Diluent 308.0 Crospovidone Ph.Eur Disintegrant 40.0 Lauryl su sodium lphate Ph.Eur Wetting agent 56.0 Colloidal anhydrous silica Ph.Eur Slider 8.0 Magnesium stearate Ph.Eur Lubricant 12.0 Weight of core tablet: 1600 Salt tactor = 1.594 Table 10: Composition of abiraterone acetate film-coated tablet: niraparib tosylate monohydrate 500 / 100 mg eq. of Table 9, prepared according to the procedure of Example 4.3. Component Quality reference Function Quantity per unit (mg) Abiraterone Acetate Oral Tablet: Niraparib Tosylate Monohydrate 500 / 100 mg eq. from Table 5 1600.00 Purified water3 Ph.Eur Processing agent3 <256.00a > Opadry® AMBII 88A170010 Beige Company specification Coating powder 64.00 Total weight: 1664.00 aRemoved during processing Table 11: Composition of abiraterone acetate core tablet : niraparib tosylate monohydrate 500 / 50 mg eq., prepared according to the procedures of Examples 4.1 and 4.2. Component Quality reference Function mg / tablet Intragranular phase: Abiraterone acetate Company specification Active part 500 Niraparib tosylate monohydrate3 Company specification Active part 79.70 Lactose monohydrate Ph.Eur Diluent 130.0 Crospovidone Ph.Eur Disintegrant 40.0 Lauryl sodium sulfate Ph.Eur Wetting agent 5.6 Anhydrous colloidal silica Ph.Eur Slider 8.0 Microcrystalline cellulose PH101 NF Diluent 408.70 Magnesium stearate Ph.Eur Lubricant 4.0 Extragranular phase: Silicified microcrystalline cellulose NF Diluent 308.0 Crospovidone Ph.Eur Disintegrant 40.0 Lauryl su sodium lphate Ph.Eur Wetting agent 56.0 Colloidal anhydrous silica Ph.Eur Slipper 8.0 cnni? ίη / ζζηζ / Ε / γίΛΐ Magnesium stearate Ph.Eur Lubricant 12.0 Core tablet weight: 1600aSalt factor = 1.594 Table 12: Composition of cnni acetate film-coated tablet ίη / ζζηζ / Ε / γίΛΐ abiraterone: niraparib tosylate monohydrate 500 / 50 mg eq. of Table 9, prepared according to the procedure of Example 4.3. Component Reference Quantity per unit (mg) quality Function Abiraterone acetate oral tablet: 1600.00 niraparib tosylate monohydrate 500 / 100 mg eq. Table 5 Purified Water Agent3 Ph.Eur <256.00a > processing3 Opadry® AMB II 88A620004 Yellow Coating Powder Specification 64.00 Company Total Weight: 1664.00 aRemoved during processing Example 2 — Preparation of a coated tablet comprising cogranules of abiraterone acetate and niraparib tosylate monohydrate, prepared by wet granulation 2.1 Wet Granulation of Abiraterone Acetate and Niraparib Tosylate Monohydrate A binder solution was prepared by dissolving HPMC 2910 15 mPa.s and sodium lauryl sulfate in purified water until a clear solution was obtained. The ingredients abiraterone acetate, niraparib tosylate monohydrate, lactose monohydrate and crospovidone were screened, premixed and transferred to a suitable wet granulation equipment, the GPCG30 fluid bed granulator. These ingredients were heated while fluidizing. The complete binder solution was sprayed onto the ingredients using the wet granulation technique. The granules were dried after spraying while fluidizing. The dry powder was collected and packaged in aluminum bags. Table 13: Granulometry results for the granules resulting from the granulation of the binder solution with the ingredients of the intragranular phase, of the composition of the Table 1 and composition of Table 3 Parameter Table 1 Table 3 PPD (%) 1.46 1.41 Angle of repose (°) 34.73 35.07 Apparent density (g / ml) 0.403 0.397 Compacted density (g / ml) 0.455 0.431 dio; dso; doo (pm) 230; 403; 726 256; 399; 695 cnni? ίη / ζζηζ / Ε / γίΛΐ The PPD profile for the granules of the compositions of Table 1 and Table 3 is provided in Figure 6. The screening analysis is provided in Figure 7 for the granules in Table 1 and in Figure 8 for the granules in Table 3. 2.2 Extraqranular phase and compression Silicified microcrystalline cellulose, crospovidone, sodium lauryl sulfate and colloidal anhydrous silica were screened and added to the fluid bed granulate. All materials were screened and mixed in a suitable mixer. Magnesium stearate was sieved and added to the container, and all materials were mixed again in a suitable mixer. The mixture was then compressed into core tablets using the Module S tablet press (KC11). The PPD, angle of repose, bulk density and compacted density of the final mixture of the compositions of Table 1 and Table 3 can be found in Table 14. Table 14: PPD, angle of repose and densities of the Final Mixture of the composition of Table 1 and the composition of Table 3 Parameter Table 1 Table 3 PPD (%) 2.57 2.37 Angle of repose (°) 43.46 41.22 Apparent density (g / ml) 0.47 0.46 Compacted density (g / ml) 0.54 0.53 The mixture uniformity (MU) results of the Final Mix of the composition of Table 1 and Table 3 are provided in Table 15 and Table 16, while the stratified content uniformity results are presented in Table 17 and Table 18, respectively. The UM results indicate that both mixtures are well mixed and that both PAFs are uniformly distributed in the mixture. The stratified content uniformity results demonstrate good and uniform distribution of abiraterone acetate and niraparib tosylate monohydrate within the core tablets throughout the manufacturing process. For the composition in Table 3, content uniformity is also determined and can be found in Table 19. Table 15: Mixing uniformity results of the composition of Table 1 cnni? ίη / ζζηζ / Ε / γίΛΐ Abiraterone Acetate Niraparib Tosylate Monohydrate Mean 100.55 100.20 Minimum 97.19 96.88 Maximum 102.72 102.70 Table 16: Mixing Uniformity Results of Table 3 Composition Abiraterone Acetate Niraparib Tosylate Monohydrate Mean 99.70 .22 Minimum 94.67 95.06 Maximum 103.42 103.84 Table 17: Stratified content uniformity results of the composition of Table 1 Abiraterone acetate Niraparib tosylate monohydrate Mean 102.61 102.17 Minimum 97.66 96.99 Maximum 109.76 108.35 Table 18: Stratified content uniformity results of the composition of Table 3 Sample Abiraterone acetate Niraparib tosylate monohydrate Tablet weight (g) Average 101.41 101.74 Minimum 97.20 97.62 Maximum 104.81 104.99 Table 19: Content uniformity results of the composition of Table 3 Abiraterone Acetate Niraparib Tosylate Monohydrate Table 15: Mix uniformity results of the composition of Table 1 Abiraterone acetate Niraparib tosylate monohydrate Mean 101.32 102.18 Std 1.94 2.07 DTR 1.91 2.03 cnni? ίη / ζζηζ / Ε / γίΛΐ The resulting tablets were tested for weight, thickness, hardness and disintegration time, and the results are shown in Table 20. The tablets were collected and packaged in a suitable container. Table 20: Weight, thickness, hardness and disintegration time of the tablet of the composition of Table 1 and the composition of Table 3 Reference Average weight (min-max) (mg, n = 10) Average thickness (min-max) (mm, n = 5) Average hardness (minmax) (N, n = 5) Average disintegration time (min-max) (min:s, n = 6) composition Sample 1504.4 7.81 267 02:59 Sample 1 (1500.2-1513.6) (7.80-7.83) (261-273) (02:39-03:13) 1506.6 7.83 273 03: 06 Sample 2 (1502.7-1516.1) (7.82-7.83) (268-278) (02:57-03:23) 1502.7 7.81 266 02:51 Table 1 Sample 3 (1496.8-1513.7) (7.80-7.83) (262- 274) (02:33-03:03) 1503.9 7.81 268 03:07 Sample 4 (1496.8-1509.8) (7.80-7.82) (260-274) (02:43-03:25) 1505.5 7.80 265 03:12 Sample 5 (1496.5-1515.8) (7.80-7.80) (258-270) (02:55-03:29) 1608.1 8.06 330 03:07 Sample 1 (1597.0-1627.2) (8.06-8.07) (320-348) (02 :47-03:23) 1601.7 8.05 321 03:02 Sample 2 (1585.3-1614.3) (8.0-8.07) (311-339) (02:41-03:31) 1595.2 8.06 306 03:36 Table 3 Sample 3 ( 1579.4-1608.2) (8.04-8.07) (293-318) (03:27-04:05) 1597.5 8.04 316 04:27 Sample 4 (1580.6-1609.7) (8.03-8.05) (309-324) (04:09 -04:45) 1597.9 8.04 316 03:39 Sample 5 (1583.8-1608.6) (8.02-8.06) (299-345) (03:12-04:06) All these results indicate that it was possible to successfully manufacture two clinical batches of abiraterone acetate / niraparib tosylate, that is, the compositions of Tables 1 and 3. 2.3 Film coating A coating suspension was prepared by dispersing coating powder in purified water until a suspension was obtained. The core tablets were transferred to a suitable coating container. The coating solution was then sprayed onto the core tablets using the film coating technique. The film-coated tablets were dried, after spraying, in the same coating container. The coated tablets were collected and packaged in a suitable container. The resulting coated tablets in Table 2 showed no marks or other defects observed. The resulting coated tablets in Table 4 showed no marking defects or white spots on their surface. In summary, these film-coated tablets of Tables 2 and 4 were manufactured satisfactorily and without defects. Example 3 — Preparation of a coated tablet comprising abiraterone acetate granules prepared by fluid bed granulation, and niraparib tosüate monohydrate, the latter prepared by dry granulation 3.1 Niraparib Tosylate Monohydrate Dry Granulation Niraparib tosylate monohydrate, lactose monohydrate, microcrystalline cellulose, povidone K30, crospovidone, colloidal anhydrous silica and magnesium stearate were screened and mixed using a suitable mixer. The mixture was then ground and the ground material was further mixed with a suitable mixer. A dry granulate was prepared using a suitable compaction technique, for example a roller compactor, and the dry granulate was further ground using a suitable dry mill. 3.2 Abiraterone Acetate Wet Granulation Abiraterone acetate, lactose monohydrate and croscarmellose sodium were mixed and optionally sieved. A binder solution comprising hypromellose, sodium lauryl sulfate (SLS) and purified water was prepared and added to the mixture of abiraterone acetate, lactose monohydrate and croscarmellose sodium. Granules were then formed by fluid bed granulation and subsequently dried. 3.3 Extragranular phase and compression Abiraterone acetate granules and cnni tosylate monohydrate granules? ίη / ζζηζ / Ε / γίΛΐ niraparib obtained were sieved and mixed with silicified microcrystalline cellulose, crospovidone, sodium lauryl sulfate and colloidal anhydrous silica, in a suitable mixer. Magnesium stearate was sieved and added to the container, and all materials were mixed again in a suitable mixer. The mixture containing niraparib tosylate monohydrate granules and abiraterone acetate granules was then compressed into core tablets using a suitable tablet press. The tablets were collected and packaged in a suitable container. 3.4 Film coating A coating suspension was prepared by dispersing coating powder in purified water until a suspension was obtained. The core tablets were transferred to a suitable coating container. The coating solution was then sprayed onto the core tablets using the film coating technique. The film-coated tablets were dried, after spraying, in the same coating container. The coated tablets were collected and packaged in a suitable container. 4.1 Dry Granulation of Niraparib Tosylate Monohydrate and Abiraterone Acetate Abiraterone acetate, niraparib tosylate monohydrate, lactose monohydrate, crospovidone, sodium lauryl sulfate, colloidal anhydrous silica, microcrystalline cellulose and magnesium stearate were screened and mixed using a suitable mixer. The mixture was then ground and the ground material was further mixed with a suitable mixer. A dry granulate was prepared using a suitable compaction technique, for example a roller compactor, and the dry granulate was further ground using a suitable dry mill. 4.2 Extraoranular phase and compression The cogranules of abiraterone acetate and niraparib tosylate monohydrate obtained were screened and mixed with silicified microcrystalline cellulose, crospovidone, sodium lauryl sulfate and colloidal anhydrous silica, in a suitable mixer. Magnesium stearate was sieved and added to the container, and all materials were mixed again in a suitable mixer. The mixture was then compressed into core tablets using a suitable tablet press. The tablets were collected and packaged in a suitable container. 4.3 Film coating A coating suspension was prepared by dispersing coating powder in purified water until a suspension was obtained. The core tablets were transferred to a cnni? ίη / ζζηζ / Ε / γίΛΐ suitable coating container. The coating solution was then sprayed onto the core tablets using the film coating technique. The film-coated tablets were dried, after spraying, in the same coating container. The coated tablets were collected and packaged in a suitable container. Example 5 - Stability data of the dry granules prepared from Tables 1 and 3 After preparation of the dried granules of Tables 1 and 3, the stability data did not show any degradation of abiraterone acetate or niraparib tosylate monohydrate. Oxidative degradants for abiraterone acetate remain within specifications after 12 months at 5°C, 25°C / 60% RH and 30°C / 75% RH and after 6 months at 40°C / 75% RH. Example 6 - Dissolution method to test the in vitro release of the active pharmaceutical ingredients of the prepared compositions The parameters of the dissolution methods are summarized in Table 21, below. Table 21 cnni? ίη / ζζηζ / Ε / γίΛΐ Parameter Value Dissolution apparatus: Temperature of dissolution medium: Volume of dissolution medium: Dissolution medium: Paddle rotation speed: Sample filter: Analytical finish: Paddle (USP type 2, Ph.Eur, JP.) 37.0 ± 0.5 °C 900 ml 0.25% (w / v) SLS in 0.05 M sodium phosphate buffer, pH 4.5 75 rpm 0.2 pm pore size syringe filter, UHPLC regenerated cellulose membrane with UV detection at 236 nm USP= United States Pharmacopeia; JP= Japan; Ph.Eur.= European Pharmacopoeia; SLS= sodium lauryl sulfate; UHPLC= ultra-high performance liquid chromatography; UV= ultraviolet; p / v= weight / volume. • In vitro dissolution curves for abiraterone acetate and niraparib are provided in Figures 5A and 5B, respectively, for a single agent combination that is a 100 mg capsule eq. of niraparib, in its tosylate monohydrate form, and 2 tablets of 250 mg of abiraterone acetate; • one CDF tablet with the composition of Table 2 (50 mg eq. of niraparib, in its tosylate monohydrate form, and 500 mg of abiraterone acetate); and • one CDF tablet with the composition of Table 4 (100 mg eq. of niraparib, in its tosylate monohydrate form, and 500 mg of abiraterone acetate). Example 7 - Randomized, double-blind, placebo-controlled phase III study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for the treatment of subjects with metastatic prostate cancer, the MAGNITUDE study The primary objective of this study is to evaluate the efficacy of niraparib and abiraterone acetate plus prednisone (AAP) compared to abiraterone acetate plus prednisone and placebo, as determined by radiographic progression-free survival (rPFS). The study consists of 5 phases; a Prescreening Phase for biomarker assessment only, a Screening Phase, a Treatment Phase, a Follow-up Phase, and an Extension Phase (either open-label or long-term, depending on cohort assignment). A treatment cycle is defined as 28 days. Cohort 1: Subjects with mCRPC and RRH gene alteration Cohort 1 evaluates the combination of niraparib and AAP versus placebo and AAP in subjects with L1 mCRPC (i.e., who have not been treated with any therapy in the metastatic castration-resistant setting except androgen deprivation therapy ( TPA) and limited exposure to AAP) and RRH gene alteration. This cohort includes approximately 400 subjects. Cohort 2: Subjects with mCRPC and without RRH gene alteration Cohort 2 evaluates the combination of niraparib and AAP versus placebo and AAP in subjects with L1 mCRPC (i.e., who have not been treated with any therapy in the metastatic castration-resistant setting except androgen deprivation therapy ( TPA) and limited exposure to AAP) and who do not have RRH gene alteration. The cohort may include approximately 600 subjects. A prespecified futility analysis was performed after approximately 200 subjects were enrolled and approximately 125 progression events had occurred in this cohort. cnni? Ln / zznz / E / YiAi Cohort 3: mCRPC Subjects Receiving Niraparib FDC v Abiraterone Acetate To evaluate the clinical efficacy and safety of the FDC tablet formulation of niraparib and abiraterone acetate, a separate unblinded cohort (Cohort 3) has been added to the study. Up to approximately 100 subjects may be enrolled in Cohort 3 under the same inclusion / exclusion criteria and undergo the same study procedures as Cohort 1, except that subjects in Cohort 3 receive niraparib + abiraterone acetate open-label as a CDF tablet formulation rather than as single agents. Study Populations • Intent-to-treat (ITT) population: Randomized subjects from both Cohorts ly2. • Safety population: Subjects in Cohorts 1 and 2 who receive at least one dose of study drug. • CDF Population: Subjects in Cohort 3 receiving at least one dose of CDF. Evaluations • Effectiveness evaluations include the following: o Radiographic progression-free survival (rPFS; primary endpoint): assessed by tumor measurements using CT or MRI scans and whole-body bone scans (99mTc). The sweeps are collected and reviewed by a central provider. o Serum prostate-specific antigen (measurements in a central laboratory) evaluated by Prostate Cancer Working Group 3 (PCWG3) criteria. o Survival state. o Subsequent systemic therapy for prostate cancer. o Radiotherapy associated with cancer or surgical procedures. o Symptomatic progression. o Patient reported outcomes. • FC evaluations. Blood samples to measure plasma levels of niraparib and its metabolite (if considered relevant) are obtained on day 1 of cycles 2 to 7. Population PK parameters and derived exposure are also determined for niraparib. Blood samples to measure plasma abiraterone levels are obtained predose on day 1 of cycles 2 and 3. cnni? ίη / ζζηζ / Ε / γίΛΐ Biomarker Assessments: RRH gene alteration status is PS) Grade 0 or 1 6. Score of < 3 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in the last 24 hours). 7. Clinical laboratory values ​​in selection: to. Absolute neutrophil count (ANC) >1.5 x 109 / l. b. Hemoglobin >9.0 g / dl, independent of transfusions for at least 30 days. c. Platelet count >100 x 109 / l. d. Serum albumin >3.0 g / dl. and. Creatinine excretion >30 ml / min either calculated or directly measured by 24-hour urine collection. F. Serum potassium >3.5 mmol / l. g. Serum total bilirubin <1.5 times the upper limit of normal (ULN) or direct bilirubin < 1 time the ULN (Note: in subjects with Gilbert syndrome, if total bilirubin is >1.5 times the ULN, measure direct and indirect bilirubin , and if direct bilirubin is <1.5 times the ULN, the subject may be chosen as determined by the medical monitor). h. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 times the ULN. 8. Able to swallow study drug tablets and capsules whole. 9. While taking study drug and for 3 months after the last dose of study drug, a male subject must agree to use adequate contraception as deemed appropriate by the investigator and agree not to donate sperm. 10. Willing and able to adhere to the prohibitions and restrictions specified in this protocol. Exclusion criteria 1. Previous treatment with a PARP inhibitor. 2. Systemic therapy (ie, new second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy or more than 4 months of AAP before randomization) in the setting of mCRPC; or AAP outside the mCPRC establishment. 3. For subjects who received 2 to 4 months of AAP prior to randomization for mCRPC treatment, evidence of PSA progression (per PCWG3) during screening. These potential subjects must have 2 PSA values ​​during the prescreening and selection phases. The second PSA value must be within 2 weeks of randomization. If the PSA increase is believed to be due to a rebound, the investigator should cnni? ίη / ζζηζ / Ε / γίΛΐ confirm that there is no radiographic progression. 4. Symptomatic brain metastasis. 5. History or current diagnosis of myelodysplastic syndrome (MDS) / acute myeloid leukemia (AML). 6. Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other in situ cancer currently in complete remission) < 2 years prior to randomization, or malignancy currently requiring therapy active systemic. 7. Severe or unstable angina, myocardial infarction or ischemia requiring coronary artery bypass graft or stent within the previous 6 months, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, stroke , including transient ischemic attacks) or clinically significant ventricular arrhythmias within 6 months prior to randomization or New York Heart Association (NYHA) class II to IV cardiac disease. 8. Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >160 mm Hg or diastolic BP >100 mm Hg). Subjects with a history of hypertension are allowed, if BP is controlled within these limits by antihypertensive treatment. 9. Current evidence of any of the following: to. Any medical condition that could contraindicate the use of prednisone. b. Any chronic medical condition that requires a higher dose of corticosteroid than 10 mg prednisone (or equivalent) once daily. 10. Active or symptomatic viral hepatitis or chronic liver disease (evidenced by ascites, encephalopathy or bleeding disorders secondary to liver dysfunction). 11. History of adrenal dysfunction 12. Known allergies, hypersensitivity or intolerance to AA or niraparib or the corresponding excipients. 13. Subjects who are receiving opioid analgesics at the time of screening. 14. Human immunodeficiency virus (HIV) positive subjects with 1 or more of the following: to. Do not receive highly active antiretroviral therapy. b. Receiving antiretroviral therapy that may interfere with the study drug. c. A change in antiretroviral therapy within 6 months of starting screening (except if a change is made to avoid a possible drug-drug interaction with the study drug). cnni? ίη / ζζηζ / Ε / γίΛΐ d. CD4 count <350 at screening. and. An opportunistic infection that defines acquired immunodeficiency syndrome within 6 months after the start of selection. 15. Subjects who have had the following < 28 days before randomization: to. A transfusion (platelets or red blood cells). b. Hematopoietic growth factors. c. An investigational agent for prostate cancer. d. Major surgery (sponsor should be consulted regarding what constitutes major surgery). and. Radiotherapy. Example 8 - Phase III, randomized, double-blind, placebo-controlled study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for the treatment of participants with metastatic castration-sensitive prostate cancer ( CPSCm) with harmful mutation in the germ line! or somatic in the homologous recombination repair (HRR) gene, the AMPLITUDE study The objectives of this study are: • determine whether niraparib and abiraterone acetate plus prednisone, compared to abiraterone acetate plus prednisone in participants with mCSPC with deleterious germline or somatic mutation in the HRR gene, provides superior efficacy in improving radiographic progression-free survival (rPFS); • evaluate the clinical benefit of niraparib and abiraterone acetate plus prednisone compared with abiraterone acetate plus prednisone in participants with mCSPC with deleterious germline or somatic mutation in the HRR gene; To characterize the safety profile of niraparib and dre abiraterone acetate, plus prednisone, compared to abiraterone acetate plus prednisone in participants with mCSPC with deleterious germline or somatic mutation in the HRR gene. Approximately 788 participants are randomized 1:1 to 200 mg niraparib and 1000 mg abiraterone acetate plus 5 mg prednisone daily; or 1000 mg abiraterone acetate plus 5 mg prednisone daily. All participants must be receiving prior androgen deprivation therapy (ADT; i.e. gonadotropin-releasing hormone analogue or surgical castration). The study consists of 4 phases: a prescreening phase for biomarker evaluation for eligibility only, a screening phase, a treatment phase, and a follow-up phase. cnni? ίη / ζζηζ / Ε / γίΛΐ Inclusion criteria 1. Each potential participant must meet all of the following criteria to be enrolled in the study: 2. > 18 years of age (or the legal age of consent). 3. Diagnosis of prostate adenocarcinoma. 4. Metastatic disease documented by >1 bone lesion(s) on 99mTc bone scan. Participants with 5. A single bone lesion must have confirmation of bone metastasis by CT or MRI. 6. Must have at least one of the deleterious somatic or germline RRH gene alterations selected from BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B and RAD54L. 7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) Grade <2. 8. Androgen deprivation therapy (either by medical or surgical castration) must have been initiated >14 days prior to randomization and willing to continue it during the treatment phase. Participants initiating a GnRH agonist <28 days prior to randomization must take a first-generation antiandrogen for >14 days prior to randomization. Antiandrogen should be discontinued before randomization. 9. Participants who have received prior treatment with docetaxel must meet the following criteria: to. Received a maximum of 6 cycles of docetaxel therapy for mCPSC b. Received last dose of docetaxel <2 months before randomization c. Maintained a docetaxel response of stable disease or better, by investigator assessment of imaging or PSA, before randomization. 10. Other prior therapy allowed for mCPSC: to. Maximum of 1 course of radiation or surgery to control prostate cancer symptoms. Radiation with curative intent is not permitted. Radiation must be completed before randomization. b. <6 months of ADT before randomization. c. 30 days of abiraterone acetate plus prednisone if necessary are allowed. 11. Previous treatments allowed for localized prostate cancer (all treatments must have been completed > 1 year before randomization): to. <3 years total TPA cnni? ίη / ζζηζ / Ε / γίΛΐ b. All other forms of above therapies, including radiation therapy, prostatectomy, lymph node dissection, and systemic therapies. cnni? Ln / zznz / E / YiAi 12. Clinical laboratory values ​​in selection: a. Absolute neutrophil count >1.5 x 109 / l b. Hemoglobin >9.0 g / dl, independent of transfusions for at least 28 days c. Platelet count >100 x 109 / l d. Creatinine <2 times the upper limit of normal (ULN) e. Serum potassium >3.5 mmol / l f. Serum total bilirubin <1.5 times ULN or direct bilirubin <1 time ULN (Note: In participants with Gilbert syndrome, if total bilirubin is > 1.5 times ULN, measure direct and indirect bilirubin, and if direct bilirubin is <1.5 times ULN, participant may be eligible) g. AST or ALT <3 times ULN 13. Able to swallow study medication tablets whole. 14. You must sign the informed consent (written or remote / virtual) indicating that you understand the purpose and procedures required for the study and that you are willing to participate in the study, including providing a DNA sample. 15. While taking study medication and for 3 months afterward of the last dose of study medication, a male participant must agree to use adequate contraception as deemed appropriate by the investigator. 16. A male participant must agree not to donate sperm during the study treatment and for a minimum of 3 months after the last dose of study medication. Exclusion criteria Any potential participant who meets any of the following criteria is excluded from participating in the study: 1. Pathological finding compatible with small cell ductal or neuroendocrine carcinoma of the prostate. 2. Previous treatment with a PARP inhibitor. 3. Prior RA-targeted therapy (e.g., Ketoconazole for prostate cancer, apalutamide, enzalutamide, darolutamide), immunotherapy, or radiopharmaceuticals with the exception of only 30 days of abiraterone acetate plus prednisone allowed before randomization. 4. Initiation of treatment with a bisphosphonate or denosumab for the management of bone metastases <28 days before randomization. 5. History of adrenal dysfunction 6. Prolonged use of systemically administered corticosteroids (> 5 mg prednisone or equivalent) is not permitted during the study. Short-term use (< 4 weeks, including taper) and locally administered spheroids (e.g., inhaled, topical, ophthalmic, and intra-articular) are permitted if clinically indicated. 7. Active neoplasms (that is, progressing or requiring a change in treatment in the last 24 months) other than the disease being treated under study. The only exceptions allowed are: to. non-muscle invasive bladder cancer; b. skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c. breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ; d. malignant neoplasm that is considered cured with minimal risk of recurrence. 8. History or current diagnosis of MDS / AML. 9. Current evidence within 6 months prior to randomization of any of the following: severe / unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant arterial or venous thromboembolic events (e.g., pulmonary embolism), or clinically ventricular arrhythmias significant. 10. Presence of sustained uncontrolled hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled within these limits by antihypertensive treatment. 11. Known allergies, hypersensitivity or intolerance to cnni excipients? ίη / ζζηζ / Ε / γίΛΐ niraparib, abiraterone acetate or niraparib / abiraterone acetate CDF. 12. Current evidence of any medical condition that would contraindicate the use of prednisone. 13. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the first planned dose of study medication. 14. Participants who have had the following < 28 days prior to randomization: to. A transfusion (platelets or red blood cells); b. Hematopoietic growth factors; c. Major surgery (sponsor should be consulted regarding what constitutes major surgery). 15. Human immunodeficiency virus positive participants with 1 or more of the following: to. Do not receive highly active antiretroviral therapy or antiretroviral therapy for less than 4 weeks. b. Receiving antiretroviral therapy that may interfere with study medication (consult sponsor to review medication prior to enrollment). c. A change in antiretroviral therapy within 6 months of initiation of screening (except if, after consulting the sponsor regarding exclusion criteria, a change is made to avoid a potential drug-drug interaction with the study medication) . d. CD4 count <350 at screening. and. An opportunistic infection that defines acquired immunodeficiency syndrome within 6 months after the start of selection. F. Human immunodeficiency virus load > 400 copies / ml. 16. Active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites or bleeding disorders secondary to hepatic dysfunction. 17. Class C severe liver failure according to the ChildPugh classification system. It is stated that in relation to this date, the best method known to the applicant to put the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A granule composition comprising abiraterone acetate, niraparib tosylate monohydrate, and a pharmaceutically acceptable carrier; wherein the granules consist essentially of abiraterone acetate, niraparib tosylate monohydrate, and a pharmaceutically acceptable carrier; wherein the pharmaceutically acceptable carrier of the granules comprises a wetting agent, a diluent, a disintegrant, optionally a glidant, optionally a lubricant, and optionally a binder; wherein the disintegrant is crospovidone.

2. The granule composition of claim 1, wherein the granules have a particle size distribution with a dso of approximately 200 to approximately 500 pm, or from approximately 231 to approximately 396 pm; a dio of approximately 50 to approximately 250 pm, or from approximately 93 to approximately 192 pm; and / or a dgo of approximately 500 to approximately 900 pm, or from approximately 616 to approximately 723 pm.

3. The granule composition of claim 1 or 2, wherein the diluent is lactose, and wherein the lactose is also used as a binder.

4. The granular composition of any one of claims 1-3, wherein the slip is anhydrous colloidal silica.

5. The granular composition of any one of claims 1-4, wherein the lubricant is magnesium stearate.

6. The granule composition of any one of claims 1-5, wherein the binder is HPMC 2910 15 mPas.

7. An oral dosage form comprising the granule composition of any one of claims 1-6.

8. The oral dosage form of claim 7, wherein the oral dosage form comprises approximately 50 mg of niraparib eq. and approximately 500 mg of abiraterone acetate; approximately 100 mg of niraparib eq. and approximately 500 mg of abiraterone acetate; approximately 50 mg of niraparib eq. and approximately 375 mg of abiraterone acetate; approximately 100 mg of niraparib eq. and approximately 375 mg of abiraterone acetate; approximately 50 mg of niraparib eq. and approximately 250 mg of abiraterone acetate; approximately 100 mg of niraparib eq. and approximately 250 mg of abiraterone acetate; approximately 33 mg of niraparib eq. of niraparib and approximately 333 mg of abiraterone acetate; or approximately 67 mg eq. of niraparib and approximately 333 mg of abiraterone acetate.

9. The oral dosage form of claim 7 or 8, wherein said oral dosage form is a tablet, wherein the pharmaceutically acceptable carrier comprises a wetting agent, a diluent, a disintegrant, a gluing agent, a lubricant, optionally a binder and optionally a coating material.

10. The oral dosage form of claim 9, wherein the wetting agent is sodium lauryl sulfate (SLS) and is present in the dosage form in a percentage of approximately 3 to 6% (w / w).

11. The oral dosage form of claim 9 or 10, wherein the wetting agent is SLS and is present in the final dosage forms in a weight ratio to abiraterone acetate of approximately 0.05:1 to 0.2:1 (SLS:abiraterone acetate), preferably approximately 0.1:1, more preferably approximately 0.11:1, approximately 0.12:1 or approximately 0.123:

1.

12. The oral dosage form of any one of claims 9-11, wherein SLS is present in both the intragranular and extragranular phases of the tablet.

13. The oral dosage form of any one of claims 9-12, wherein the disintegrant is crospovidone and is present in both the intragranular and extragranular phases of the tablet.

14. The oral dosage form of any one of claims 9-13, wherein the diluent of the extragranular phase is silicified microcrystalline cellulose.

15. The oral dosage form of any one of claims 9-14, wherein the tablet has a hardness of 250 to 350 N.

16. The oral dosage form of any one of claims 9-15, wherein the tablet has a stratified content uniformity of 75% to 125%, or 90% to 110%.

17. The oral dosage form of any one of claims 9-16, wherein the tablet has a mixing uniformity with a relative standard deviation of up to 3%.

18. The oral dosage form of any one of claims 7-17, for use in the treatment of prostate cancer in a patient.