Phase II therapeutic equivalence study of Abiraterone Acetate Tablets (I) vs. ZYTIGA® in patients with metastatic castration-resistant prostate cancer.

Abstract

e17040 Background: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the originator abiraterone acetate (ZYTIGA) is observed to be with relatively low bioavailability and high pharmacokinetic variability. Abiraterone Acetate Tablets (I), in which Sodium N-[8-(2-hydroxy-benzoyl) amino] caprylate (SNAC) was added in the formulation as an absorption enhancer, was therefore developed by using nanocrystal technology to enhance the dissolution rate of pharmaceutical compounds, leading to the improvement of the low oral bioavailability and significant food effects. Methods: Patients with mCRPC were randomized (1:1) to receive either Abiraterone Acetate Tablets (I) 300 mg daily plus 5 mg prednisone orally twice daily, or ZYTIGA 1000 mg once daily plus 5 mg prednisone orally twice daily for 84 days. The primary endpoint was serum testosterone concentration (Day 9/10). Secondary endpoints included serum prostate-specific antigen (PSA), pharmacokinetics and adverse events. Results: 68 patients with a median age of 71 (52-84 yrs) (n = 34 in each group) were enrolled in the full analysis set (FAS). The least square geometric mean of Day 9/10 serum testosterone concentration (rounded-up by 1 ng/dl) in Abiraterone Acetate Tablets (I) and ZYTIGA groups was 1.053 (95% CI, 1.006-1.102) and 1.000 (95% CI, 0.956-1.046), respectively. The geometric mean ratio between two groups was 1.053 (90% CI, 0.998-1.110) and the 90% CI fell within 80.0% to 125.0% equivalence limits. The PSA-50 response rate was also similar on Days 28, 56 and 84 (46.9% vs 50.0%, 65.6% vs 57.6%, 71.9% vs 67.7%). Compared with ZYTIGAlabel, no new safety concerns were observed in Abiraterone Acetate Tablets (I). In addition, Abiraterone Acetate Tablets (I) group was observed to be with lower frequency of treatment-emergent adverse events (TEAEs) of any grade (76.5% vs 85.7%), grade ≥3 TEAEs (8.8% vs 22.9%), and grade ≥3 treatment-related adverse events (TRAEs) (5.9% vs 14.3%). Conclusions: Therapeutic equivalence between Abiraterone Acetate Tablets (I) 300 mg and ZYTIGA 1000 mg was confirmed by Day 9/10 serum testosterone concentration in mCRPC patients. Abiraterone Acetate Tablets (I) also showed a trend of improvement in safety profile. Clinical trial information: NCT04862091.