Phase 3
N=150
Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
Cushing's Disease
Bottom Line
View on ClinicalTrials.gov: NCT01374906 ↗Enrolled (actual)
150
Serious AEs
27.3%
Results posted
Apr 2018
Primary outcome: Primary: Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration — 41.9; 40.8 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- pasireotide LAR (Drug); SOM230 LAR 30 mg (Drug); SOM230 LAR 10 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Dec 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration |
41.9; 40.8 | — |
| SECONDARY Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4 |
28.4; 31.6 | — |
| SECONDARY Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline |
-192.4; -234.3; -195.1; -247.6; -236.2; -265.2 | — |
| SECONDARY Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline |
-29.3; -33.2; -30.3; -31.1; -50.9; -51.2 | — |
| SECONDARY Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN |
39.2; 40.8; 35.1; 25.0; 39.7; 21.3 | — |
| SECONDARY Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC |
44.6; 53.9; 45.9; 42.1; 46.0; 27.9 | — |
| SECONDARY 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. |
25.7; 31.6; 25.7; 25.0 | — |
| SECONDARY 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 |
60.6; 60.6; 61.3; 65.5; 69.7; 69.7 | — |
| SECONDARY Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points |
86.2; 83.4; 90.1; 94.5 | — |
| SECONDARY Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points |
78.0; 72.9; 84.0; 82.8; 84.0; 87.1 | — |
| SECONDARY Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time |
2.7; -13.5; -10.2; -14.5; -12.1; 2.5 | — |
| SECONDARY Percentage Change From Baseline on Serum Cortisol Over Time |
-8.2; -5.1; -12.1; -0.4; -15.6; -7.4 | — |
| SECONDARY Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure |
-6.8; -4.6; -4.8; -3.0 | — |
| SECONDARY Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI) |
-0.7; -1.8 | — |
| SECONDARY Actual Change From Baseline in Clinical Signs Over Time: Weight |
-1.8; -4.6 | — |
| SECONDARY Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region |
-1.0; -1.8 | — |
| SECONDARY Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference |
-1.6; -7.1 | — |
| SECONDARY Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides |
-0.5; -0.4; -0.1; 0; 0; -0.2 | — |
| SECONDARY Percentage Change From Baseline in Clinical Signs Over Time |
-4.3; -3.0; -4.7; -2.6; -2.6; -6.1 | — |
| SECONDARY Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs |
32.7; 53.6; 22.2; 32.6; 23.1; 23.6 | — |
| SECONDARY 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. |
52.0; 52.0; 36.7; 35.3 | — |
| SECONDARY Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline |
35.1; 43.4; 35.1; 38.2; 83.3; 57.1 | — |
| SECONDARY Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points |
80.5; 73.4; 84.4; 80.7 | — |
| SECONDARY Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points |
78.4; 77.8; 84.9; 83.7; 84.9; 83.7 | — |
| SECONDARY Pharmacokinetic (PK) Parameter: Ctrough |
2.03; 7.63; 2.35; 7.82; 0.83; 2.39 | — |
| SECONDARY Pharmacokinetic (PK) Parameter: Cmax |
3.0; 8.2; 3.3; 9.4; 1.7; 4.0 | — |
| SECONDARY Actual Change in Standardized Score of Cushing's Disease HRQoL (CushingQOL) Score From Baseline |
5.7; 7.8; 6.4; 6.8; 5.9; 8.7 | — |
| SECONDARY Actual Change in SF-12v2 Score From Baseline - Mental Component Summary |
4.1; 4.3; 2.3; 3.3; 3.3; 6.4 | — |
| SECONDARY Actual Change in SF-12v2 Score From Baseline - Physical Component Summary |
1.9; -0.8; 4.9; -0.5; 5.3; -1.1 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT01374906). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.