OPR reviewer comment: Notwithstanding the evaluation of the nonclinical and clinical aspects of the SS, this was considered acceptable. Pharmacovigilance plan The sponsor proposes routine pharmacovigilance activities for important identified and potential risks and missing information (as stated above). Furthermore, additional activities are planned for some of the risks. These activities are summarised in Table 8. Table 8. Activities additional to routine planned by the sponsor regarding certain safety concerns. Table continued across2 pages. Additional activity Assigned safety concern Actions/outcome proposed Planned submission of final data Trial (QTc) A QT/QTc and multi-dose PK Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients with Metastatic Castration- Resistant Prostate Cancer Protocol available Cardiac disorders Primary Objective: To evaluate the effects of abiraterone acetate plus prednisone on cardiac QT/QTc interval by using pharmacokinetic and ECGs in patients with metastatic castration resistant prostate cancer (CRPC) Secondary Objectives: To evaluate the pharmacokinetics (PK) of abiraterone acetate and abiraterone after multiple doses of abiraterone acetate To evaluate the effects of abiraterone acetate and prednisone To evaluate the effects of abiraterone acetate and prednisone on adrenal function as measured by the Cortrosyn stimulation test at baseline and after abiraterone acetate/prednisone administration 2013 Targeted follow-up with reporter through a guided questionnaire Hepatotoxicity Osteoporosis including fractures
Trial 212082PCR2008 An Open-Label Study to Determine the Short-Term Safety of Continuous Dosing of Abiraterone Acetate and Prednisone in Modified Fasting and Fed States to Subjects With Metastatic Prostate Cancer. Protocol available Increased exposure with food Primary Objective: To establish the safety profile of oral abiraterone acetate and oral prednisone following short-term administration after standardized low-fat or high-fat meals to subjects with metastatic prostate cancer (mCRPC) Secondary Objective: To evaluate the exposure to abiraterone following administration of oral abiraterone acetate in the modified fasting state and after standardized low-fat or high-fat meals to subjects with mCRPC August 2013 Trial 212082PCR1004 Severe hepatic impairment (single dose PK trial). Protocol not available Use in patients with moderate/severe hepatic impairment and chronic liver disease Protocol not available but study is nearly complete. March 2013 Trials: 212082PCR3001 212082JPN102 212082PCR2007 ABI-PRO-3001 ABI-PRO-3002 Use in non-White patients Multiple (see individual study protocols) Q4, 2014 Dec 2012 Jun 2014 Dec 2015 Sep 2013 OPR reviewer’s comments in regard to the pharmacovigilance plan (PP) and the appropriateness of milestones The sponsor mainly plans routine pharmacovigilance activities. Only some safety concerns have been assigned an additional activity. The sponsor’s proposed pharmacovigilance activities and milestones were considered to be acceptable. All relevant studies were ongoing at the time of this evaluation. The available study protocols submitted were considered to be acceptable in regard to the assigned safety concern for RMP purposes.