BR-112022022534-B1 - Granule composition, preparation process, pharmaceutical formulation or oral dosage form, kit and uses.

Abstract

PROSTATE CANCER TREATMENTS WITH ABIRATERONE ACETATE AND NIRAPARIB COMBINATIONS. The present invention relates to a combination of abiraterone acetate and niraparib, fixed-dose and free-dose combinations of abiraterone acetate and niraparib, and methods of treating prostate cancer with said combinations.

Inventors

• THOMAS RONALD A. QUINTEN
• URBAIN ALFONS C. DELAET
• PHILIP ERNA H. HEYNS
• Tatiana MARCOZZI
• Johny BERTELS
• Katrien LUYTEN
• KAUSTUBH RAMESH TAMBWEKAR
• Angela LOPEZ-GITLITZ
• PAUL J. A. HARTMAN KOK

Assignees

• JANSSEN PHARMACEUTICA N.V

Dates

Publication Date

20260317

Application Date

20210507

Priority Date

20200508

Claims (9)

1. 1. Granule composition, characterized in that it comprises abiraterone acetate, niraparib tosylate monohydrate and a pharmaceutically acceptable carrier; wherein said pharmaceutically acceptable carrier comprises sodium lauryl sulfate (SLS).
2. 2. Granule composition according to claim 1, characterized in that the granule composition is compressed into a tablet.
3. 3. Granule composition according to claim 2, characterized in that SLS is present in the tablet in a weight ratio versus abiraterone acetate of 0.05:1 to 0.2:1 (SLS:abiraterone acetate).
4. 4. Granule composition according to claim 2 or 3, characterized in that SLS is present in the tablet at a percentage of 3 to 6% (w/w).
5. 5. Granule composition, according to any one of claims 2 to 4, characterized in that the tablet further comprises a diluent, a disintegrant, a glidant, a lubricant, a binder and a coating material.
6. 6. Granule composition according to any one of claims 2 to 5, characterized in that said tablet comprises 100 mg eq. niraparib and 500 mg abiraterone acetate; or 50 mg eq. niraparib and 500 mg abiraterone acetate.
7. 7. Granule composition according to claim 1, characterized in that it comprises:
8. 8. Granule composition according to claim 1, characterized in that it comprises:
9. 9. Use of abiraterone acetate and niraparib, characterized by the fact that it is in the manufacture of pharmaceutical formulations, free dose combinations (FDCs), fixed dose combinations (FDCs), granule compositions, kits or products to treat cancer, more particularly, prostate cancer.

Description

TECHNICAL FIELD OF THE INVENTION [0001] The present invention relates to combinations of anticancer drugs, methods of treating prostate cancer with said combinations, and pharmaceutical formulations comprising said combinations. BACKGROUND OF THE INVENTION [0002] Prostate cancer is the most common non-cutaneous malignant neoplasm in men and the second leading cause of cancer death in men in the Western world. [0003] Prostate cancer results from the uncontrolled growth of abnormal cells in the prostate. Once a prostate cancer tumor develops, androgens such as testosterone promote the growth of the prostate cancer. In its early stages, localized prostate cancer is often curable with local therapy, including, for example, surgical removal of the prostate and radiation therapy. However, when local therapy does not cure prostate cancer, as happens in up to one-third of men, the disease progresses to incurable metastatic disease (i.e., disease in which the cancer has spread from one part of the body to other parts). [0004] 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®). [0005] Platinum-based chemotherapy has been tested in several clinical studies in molecularly unselected prostate cancer patients with limited results and significant toxicities. [0006] More recently, abiraterone acetate (ZYTIGA®) plus prednisone has been approved for the treatment of metastatic castration-resistant prostate cancer. [0007] Niraparib is a highly selective, orally available 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) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. J Med Chem., April 23, 2015; 58(8):3302-3314. [0008] PARPs are enzymes responsible for repairing single-strand breaks (SSBs) of DNA through a process called base excision repair. Inhibition of PARP leads to an accumulation of unrepaired SSBs, resulting in the arrest and collapse of replication forks and, consequently, double-strand breaks (DSBs). Normally, DSBs are repaired through homologous recombination (HR). If not repaired, DSBs result in cell death. When tumor cells with DNA repair defects involving the HR pathway (e.g., breast cancer genes [BRCA]-1/2) are treated with a PARP inhibitor, they are unable to repair DSBs efficiently and accurately, creating a synthetic lethal condition. In men with metastatic castration-resistant prostate cancer (mCRPC), tumors with DNA repair anomalies account for approximately 20% to 30% of sporadic cancers. [0009] There is a need for therapeutic options for prostate cancer patients who do not initially respond to, or become refractory to, existing treatments. It is important to emphasize that there is an unmet need for therapeutic options for patients with prostate cancer. SUMMARY OF THE INVENTION [0010] This disclosure relates to a combination of abiraterone acetate and niraparib, which may be administered to a mammal, in particular a human being, suffering from a disease or condition related to the androgen receptor (AR), in particular cancer, more particularly prostate cancer. [0011] These pharmaceutical formulations are fixed-dose combinations of abiraterone acetate and niraparib. [0012] One objective of the present invention is to provide therapies against prostate cancer, including, but not limited to, hormone-sensitive prostate cancer, hormone-free high-risk prostate cancer, castration-resistant prostate cancer, metastatic castration-resistant prostate cancer (mCRPC), metastatic castration-sensitive prostate cancer (mCSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), biochemically recurrent prostate cancer (BCR), and localized prostate cancer (LPC). [0013] An object of the present invention is to provide free-dose combinations (FrDC) of abiraterone acetate and niraparib tosylate monohydrate; or fixed-dose combinations (FDC) comprising abiraterone acetate and niraparib tosylate monohydrate. [0014] One objective of the present invention is to provide pharmaceutical formulations that support patient adherence, adherence to therapy, and therapy efficiency. [0015] An objective of the present invention is to provide pharmaceutical formulations that reduce the tablet burden for patients, for example, from six or four tablets of abiraterone acetate and niraparib tosylate monohydrate per day to three, or preferably two or one tablet (or tablets) per day. [0016] One objective of the present invention is to provide fixed-dose combination (FDC) pharmaceutical formulations with stability or shelf life comparable to or improved upon separately formulated drug dosage for