NCT01374906CompletedPhase 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 enrollmentStarted: November 4, 2011Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- 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
Study 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Experimental
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Intervention: pasireotide LAR (Drug)
10 mg LAR dose
Experimental
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Intervention: SOM230 LAR 10 mg (Drug)
30 mg LAR dose
Experimental
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Intervention: pasireotide LAR (Drug)
30 mg LAR dose
Experimental
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Intervention: SOM230 LAR 30 mg (Drug)
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)
Investigators
Study Sites (13)
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