Phase 3
Completed N=150
Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
Cushing's Disease
Source: ClinicalTrials.gov NCT01374906 ↗
Enrolled (actual)
150
Serious AEs
27.3%
Results posted
Apr 2018
Primary outcomePrimary: Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration — 41.9; 40.8 percentage of participants
◆ Published Evidence
Highly cited
165citations · ~21 / year
Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial.
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.
Linked Publications (5)
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Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial.
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Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly.
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Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.
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Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study.
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Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study.
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 | — |
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) and the linked publication. 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. Informational only — not medical advice.