Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing’s disease

• DOI: 10.1007/s11102-015-0692-z
• Publication Date: 2015-11-05T10:23:14Z
• Authors: Maria Fleseriu; Rosario Pivonello; Jacques Young; Amir H. Hamrahian; Mark E. Molitch; Chikara Shimizu; Tomoaki Tanaka; Akira Shimatsu; Tracy White; Annie Hilliard; Chuan Tian; Nicholas Sauter; Beverly MK Biller; Xavier Bertagna
• Keywords: Cushing's disease

In a 10-week proof-of-concept study (LINC 1), the potent oral 11β-hydroxylase inhibitor osilodrostat (LCI699) normalized urinary free cortisol (UFC) in 11/12 patients with Cushing's disease. The current 22-week 2; NCT01331239) further evaluated Phase II, open-label, prospective of two patient cohorts. Follow-up cohort: 4/12 previously enrolled LINC 1, offered re-enrollment if baseline mean UFC was above ULN. Expansion 15 newly > 1.5 × follow-up cohort, initiated twice daily at penultimate efficacious/tolerable dose 1; adjusted as needed. expansion 4 mg/day (10 3 ULN), escalated every 2 weeks to 10, 20, 40, and 60 until ≤ Main efficacy endpoint proportion responders (UFC ULN or ≥50 % decrease from baseline) 10 22. Overall response rate 89.5 (n/N = 17/19) 78.9 15/19) 22 weeks; week 22, all responding had most common AEs observed during treatment were nausea, diarrhea, asthenia, adrenal insufficiency (n 6 for each). New worsening hirsutism 2) and/or acne 3) reported among four female patients, whom increased testosterone levels. Osilodrostat reduced patients; normal Treatment generally well tolerated.