Clinical Trials/NCT01374906

NCT01374906

Completed

Phase 3

A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Pasireotide LAR in Patients With Cushing's Disease

Novartis Pharmaceuticals13 sites in 2 countries150 target enrollmentNovember 4, 2011

ConditionsCushing's Disease

Interventionspasireotide LAR SOM230 LAR 10 mg SOM230 LAR 30 mg

Drugspasireotide LAR SOM230 LAR 30 mg SOM230 LAR 10 mg

Overview

Phase: Phase 3
Intervention: pasireotide LAR
Conditions: Cushing's Disease
Sponsor: Novartis Pharmaceuticals
Enrollment: 150
Locations: 13
Primary Endpoint: Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a randomized, double-blind, multicenter, phase III study to evaluate the safety and efficacy of 2 dosing regiments of Pasireotide long acting release (LAR) in patients with Cushing's disease.

Registry

clinicaltrials.gov

Start Date

November 4, 2011

End Date

December 21, 2016

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Karnofsky performance status ≥ 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs)
•For patients on medical treatment for Cushing's disease the following washout periods must be completed before screening assessments are performed
•Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week
•Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and PPARγ agonists (rosiglitazone or pioglitazone): 4 weeks
•Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks
•Octreotide (immediate release formulation): 1 week

Exclusion Criteria

•Patients who are considered candidates for surgical treatment at the time of study entry
•Patients who have received pituitary irradiation within the last ten years prior to visit 1
•Patients who have had any previous pasireotide treatment
•Patients who have been treated with mitotane during the last 6 months prior to Visit 1
•Diabetic patients on antihyperglycemic medications with poor glycemic control as evidenced by HbA1c \>8%
•Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF \>470 ms, hypokalemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval
•Female patients who are pregnant or lactating, or are of childbearing potential (defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control. Sexually active males must use a condom during intercourse while taking the drug and for 2 months after the last dose of study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid

Arms & Interventions

10 mg LAR dose

Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.

Intervention: pasireotide LAR

10 mg LAR dose

Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.

Intervention: SOM230 LAR 10 mg

30 mg LAR dose

Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.

Intervention: pasireotide LAR

30 mg LAR dose

Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.

Intervention: SOM230 LAR 30 mg

Outcomes

Primary Outcomes

Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration

Time Frame: Month 7

Percentage of participants that attained a mean urinary free cortisol (mUFC) \<= 1.0 x upper limit of normal (ULN) at Month 7 regardless of dose up-titration at Month 4. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.

Secondary Outcomes

Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4(Month 7)
Percentage Change From Baseline in Clinical Signs Over Time(Month 7)
Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs(Month 7)
Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline(baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36))
Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline(M7, M12, M24, M36)
Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN(M7, M12, M24, M36)
Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC(M7, M12, M24, M36)
Percentage of Patients Who Are Controlled Responders (mUFC ≤ 1.0 xULN) on at Least 4 of the 7 mUFC Assessments by Month 7 & on at Least 7 of the 12 mUFC Assessments by Month 12.(Month 7, Month 12)
Percentage of Patients With Uncontrolled Response at Month 7 & Month 12 Within the Subset of Patients Who Had Uncontrolled Response at a) Months 1 and 2; b) Months 1, 2, and 3(Month 7, Month12)
Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points(Momth 7, Month 12)
Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points(Month 6, 12, 18)
Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time(Months 7, 12, 24 & 36)
Percentage Change From Baseline on Serum Cortisol Over Time(Months 7, 12, 24 & 36)
Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure(Month 7)
Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI)(Month 7)
Actual Change From Baseline in Clinical Signs Over Time: Weight(Month 7)
Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region(Month 7)
Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference(Month 7)
Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides(Month 7)
Percentage of Participants That Attained a Mean Urinary Free Cortisol (mUFC) <= 1.0 x Upper Limit of Normal (ULN) at Month 7 Regardless of Dose Up-titration at Month 4.(Month 7)
Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline(Months 7, 12, 24 & 36)
Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points(every month in the core phase and every 3 months in the extension phase) up to and including the cut-off date for the Month 12 CSR (10-Nov-2015))
Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points(Months 6, 12 & 18)
Pharmacokinetic (PK) Parameter: Ctrough(Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337)
Pharmacokinetic (PK) Parameter: Cmax(Days 22, 106, 190)
Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline(Months 7, 12, 24 & 36)
Actual Change in SF-12v2 Score From Baseline - Mental Component Summary(Months 7, 12 & 24)
Actual Change in SF-12v2 Score From Baseline - Physical Component Summary(Months 7, 12 & 24)