Endocrine Abstracts

Background: Cushing’s disease is associated with high morbidity and mortality, and there are currently no approved medical therapies. Twice-daily pasireotide sc showed efficacy in patients with mostly moderate-to-severe (UFC≥2×ULN) Cushing’s disease in a large, randomized, double-blind, 12-month trial. A monthly long-acting release (LAR) formulation of pasireotide has been developed to provide a smoother pharmacokinetic profile, potentially a better efficacy/safety ratio, and to enhance convenience. The current study is designed to evaluate the efficacy and safety of pasireotide LAR in patients with Cushing’s disease.

Patients: Adult patients with persistent/recurrent or de novo (if not surgical candidates) Cushing’s disease, with baseline mean UFC≥1.5 and ≤5×ULN (mild-to-moderate Cushing’s disease). Diagnosis of Cushing’s disease will be made by: i) the mean of three 24 h urinary free cortisol (mUFC) samples; ii) morning plasma ACTH within or above the normal range; and iii) confirmation of pituitary adenoma by MRI, IPSS or histopathology. Patients will be pasireotide naïve.

Design: Global, multicenter, randomized, double-blind, Phase III trial. Target enrollment is ~148 patients; recruitment is under way. Patients will be stratified based on baseline mUFC values and randomized to receive pasireotide LAR 10 or 30 mg im every 28 days for 12 months. If mUFC>1.5×ULN and patients tolerate pasireotide LAR at month 4, dose uptitration will be performed at month 4 to either 30 or 40 mg respectively. Dose uptitration to 30 or 40 mg will also be performed at months 7, 9 and 12 in patients with mUFC>ULN and no tolerability issues. Patients achieving mUFC≤ULN or significant clinical benefit at month 12 may enter a 12-month extension.

Endpoints: Primary efficacy endpoint is the proportion of patients with UFC≤ULN at month seven, regardless of dose titration. Secondary endpoints include: proportion of patients with mUFC≤ULN at month 7 in patients who did not uptitrate at month 4; changes in UFC, plasma ACTH, and serum cortisol; changes in quality of life, and signs and symptoms of Cushing’s disease; tolerability and safety.

Conclusions: This phase III study will provide the basis for the evaluation of long-acting pasireotide as a medical therapy for patients with mild-to-moderate Cushing’s disease.

Declaration of interest: The authors declare that there is a conflict of interest.

Funding: This work was supported, however funding details are unavailable.