ECE2016 Eposter Presentations Pituitary - Clinical (83 abstracts)
Trial design of a phase III, multicentre, randomised, double-blind, placebo-controlled, 48-week study to evaluate the safety and efficacy of osilodrostat in patients with Cushing’s disease
Richard A Feelders 1 , Anthony Heaney 2 , Karen McBride 3 , Annie Hilliard 3 , Chuan Tian 3 , Nicholas Sauter 3 & Richard J Auchus 4
1Department of Internal Medicine, Endocrine Section, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands; 2Department of Medicine, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 4MEND/Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Background: Osilodrostat is an oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step in cortisol biosynthesis. In a 22-week, phase II study, osilodrostat treatment normalised mean urinary free cortisol (mUFC) in 78.9% (15/19) of patients with uncontrolled Cushing’s disease and was well tolerated. The present phase 3 study is designed to confirm the safety and efficacy of osilodrostat in patients with uncontrolled Cushing’s disease.
Methods: Patients: Adults with Cushing’s disease (persistent, recurrent or de novo Cushing’s disease, if not surgical candidates) with mUFC > 1.3 times upper limit of normal (ULN). Design: A pivotal, phase III, global, multicentre, randomised study to enrol 69 patients. Period 1 (week 0–12): double-blind, placebo-controlled; patients will start receiving either osilodrostat 2 mg bid or placebo 2 mg bid (2:1 randomisation). Dose adjustments to normalise UFC or address safety issues, ranging between 1 mg qod and 20 mg bid are allowed. Period 2 (week 13-48): single-arm, open-label; patients on placebo or osilodrostat dose ≥ 2 mg bid during week 12 will begin period 2 with osilodrostat 2 mg bid, those on < 2 mg bid will continue with their most recent dose. Dose escalation is permitted up to 30 mg bid. Endpoints: Primary: Proportion of randomised patients with a complete response (mUFC ≤ULN) at week 12. Key secondary: Proportion of patients with mUFC≤ULN at week 36 for patients who have received osilodrostat treatment at any time. Others: Safety and tolerability; changes in cardiovascular and metabolic parameters, bone mineral density, and quality of life.
Conclusion: The present study design combines a 12-week placebo-controlled period, which allows blinded, placebo-controlled assessments with an open-label period to allow long-term evaluation of efficacy and safety of osilodrostat in patients with Cushing’s disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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