Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 GP22.01 | DOI: 10.1530/endoabs.37.GP.22.01

ECE2015 Guided Posters Pituitary–Therapy of Cushing's disease (7 abstracts)

Phase III, multicentre, double-blind, randomised withdrawal study of osilodrostat (LCI699) in patients with Cushing's disease: a study design

Akira Shimatsu 1 , Nicholas Sauter 2 , Roxzana Kelly 2 , Peter Unge 3 , Xin Zhi 2 & Maria Fleseriu 4


1Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; 2Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 3Novartis Pharma AG, Basel, Switzerland; 4Northwest Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA.


Introduction: Osilodrostat is a potent, oral inhibitor of 11β-hydroxylase, the enzyme that catalyses final step of cortisol biosynthesis. In a phase II study, 15/19 patients treated with osilodrostat met the primary endpoint (normal urinary free cortisol (UFC) at 22 weeks); osilodrostat was generally well tolerated. This phase III study aims to confirm the efficacy and long-term safety of osilodrostat.

Patients and methods: Adults (18–75 years) with persistent or recurrent CD post-surgery and/or post-irradiation or with de novo CD not considered surgical candidates.

Design: Phase III, multicentre, double-blind, randomised withdrawal study of osilodrostat. Period 1 (week 1–12): Osilodrostat will be initiated at 2mg bid and dose adjusted (range: 1–30 mg bid) based on UFC and patient’s safety. Period 2 (week 13–24): Stable dose. Period 3 (wk 26–34): 8-week, double-blind, placebo-controlled randomised withdrawal phase. Patients with mean UFC (mUFC) ≤ULN at week 24 and with no dose increase above dose level established at week 12, will be randomised (1:1) at week 26 to continue the same dose of osilodrostat or to receive matching placebo. Patients who are non-responders (UFC >1.5×ULN) will discontinue from randomised withdrawal and resume open-label osilodrostat. Non-randomised patients will continue to receive open-label osilodrostat. Period 4 (week 34–48): Single-arm, open-label osilodrostat treatment for all patients. Endpoints: Primary: proportion of randomised patients in each treatment group with mUFC ≤ULN at week 34. Key secondary: proportion of patients with mUFC ≤ULN at week 24 with no dose increase above the level established at week 12.

Conclusion: This study design, with a short (8-week) double-blind, placebo-controlled randomised withdrawal period, following a 24-week run-in period of open-label osilodrostat treatment allows assessment of efficacy (versus placebo) and long-term safety of osilodrostat in a larger CD population. This design is well suited to patients with rare and serious diseases such as CD as long-term placebo-controlled studies would be difficult to conduct.

Disclosure: This work was supported by Novartis.

Article tools

My recent searches

No recent searches.