Primary outcomeNumber· Month 7
Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration
| Group | Value (percentage of participants) |
|---|---|
| 10 mg Pasireotide LAR Dose | 41.9 |
| 30 mg Pasireotide LAR Dose | 40.8 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataEfficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
NCTNCT01374906 (opens ClinicalTrials.gov in a new tab)Other idCSOM230G2304Other id2009-011128-70Other id2009
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 150 participants (actual)
- Sponsor
- Novartis Pharmaceuticals · Industry
- Design
- Randomized · Triple masking
- Countries
20 countries
United States, Argentina, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Netherlands, Peru, Poland, Russia, Spain, Thailand, Turkey (Türkiye), United Kingdom
- Start
- 4 Nov 2011
- Primary completion
- 21 Dec 2016
- Completion
- 21 Dec 2016
- First posted
- 16 Jun 2011 (estimated)
- Last update posted
- 22 May 2018
- Conditions
- Cushing's Disease
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2011201220132014201520162017
- Ph 3
Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
NCT013749064 Nov 2011 to 21 Dec 2016
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- pasireotide LARDrug
- SOM230 LAR 30 mgDrug
- SOM230 LAR 10 mgDrug
Arms2
Experimental
10 mg LAR dose
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Experimental
30 mg LAR dose
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms.
Primary outcomes1
Outcomes the sponsor listed as primary.
Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration
Time frame · Month 7
Registry description
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(20)
Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4
Time frame · Month 7
Registry description
Percentage of participants that attain a mUFC ≤ 1.0×ULN at Month 7 and had not had a dose increase at Month 4. Patients who had a dose increase prior to Month 7 were counted as non-responders in this analysis. 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. A responder was defined as a patient who attains mUFC ≤1.0 X ULN and had not had a dose increase at Month 4.
Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline
Time frame · baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)
Registry description
Actual change in mUFC (nmol/24h) from baseline by randomized groups.
Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline
Time frame · M7, M12, M24, M36
Registry description
Percentage change in mUFC (nmol/24h) from baseline by randomized groups.
Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN
Time frame · M7, M12, M24, M36
Registry description
Controlled responder: mUFC ≤ 1.0×ULN by randomized groups.
Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC
Time frame · M7, M12, M24, M36
Registry description
Controlled responder: mUFC ≤ 1.0×ULN. Partially controlled responder: at least 50% reduction in mUFC from Baseline, and mUFC \>1.0×ULN.
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.
Time frame · Month 7, Month 12
Registry description
Percentage of patients with mUFC ≤ 1.0 x ULN at a minimum of 4 months up to and including Month 7, and at a minimum of 7 months up to and including Month 12 by randomized groups.
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
Time frame · Month 7, Month12
Registry description
Percentage of patients with mUFC \> 1.0 xULN at Month 7 and Month 12 within the subset of patients who were uncontrolled at a) Months 1 \& 2, b) Months 1, 2, \& 3 by randomized groups.
Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points
Time frame · Momth 7, Month 12
Registry description
Time to first achievement of attaining a mUFC ≤ 1.0 x ULN or at least a 50% reduction in mUFC from baseline by randomized groups.
Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points
Time frame · Month 6, 12, 18
Registry description
Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC \>1.0 x ULN and the reduction from baseline falls to less than 50% for the first time.
Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time
Time frame · Months 7, 12, 24 & 36
Registry description
Percentage change in ACTH (pmol/L) from Baseline by randomized groups.
Percentage Change From Baseline on Serum Cortisol Over Time
Time frame · Months 7, 12, 24 & 36
Registry description
Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups.
Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure
Time frame · Month 7
Registry description
Change in blood pressure measurements from Baseline
Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI)
Time frame · Month 7
Registry description
Change in BMI measurements from Baseline
Actual Change From Baseline in Clinical Signs Over Time: Weight
Time frame · Month 7
Registry description
Change in weight measurements from Baseline
Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region
Time frame · Month 7
Registry description
Change in body composition: region measurements from Baseline
Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference
Time frame · Month 7
Registry description
Change in waist circumference measurements from Baseline
Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides
Time frame · Month 7
Registry description
Change in parameter measurements: cholesterol \& triglycerides from Baseline
Percentage Change From Baseline in Clinical Signs Over Time
Time frame · Month 7
Registry description
Percentage change in parameter measurements: blood pressure, body mass index, waist circumference, fasting serum lipid profile, weight, bone density and body composition (examined by DXA scan) from Baseline
Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs
Time frame · Month 7
Registry description
This includes patients with improvements in symptoms from baseline. Clinical signs over time include: facial rubor, fat pads, hirsutism, striae, (via photographs by a second local physician who was blinded to the treatment dose and time point of the photograph) and muscle strength.
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.
Time frame · Month 7
Registry description
All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants 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. Analysis split by screening strata of mUFC Stratum 1: mUFC 1.5x to \< 2.0 x ULN Stratum 2: mUFC 2.0x to \<= 5.0 x ULN
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeNumber· Month 7
Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4
| Group | Value (percentage of participants) |
|---|---|
| 10 mg Pasireotide LAR Dose | 28.4 |
| 30 mg Pasireotide LAR Dose | 31.6 |
Secondary outcomeMean· baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)
Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline
| Group | Value (nmol/24h) | Spread |
|---|---|---|
| 10 mg Pasireotide LAR Dose | -192.4 | 271.59 |
| 30 mg Pasireotide LAR Dose | -234.3 | 362.86 |
Secondary outcomeMean· M7, M12, M24, M36
Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline
| Group | Value (percentage change) | Spread |
|---|---|---|
| 10 mg Pasireotide LAR Dose | -29.3 | 102.76 |
| 30 mg Pasireotide LAR Dose | -33.2 | 61.37 |
Secondary outcomeNumber· M7, M12, M24, M36
Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN
| Group | Value (percentage of participants) |
|---|---|
| 10 mg Pasireotide LAR Dose | 39.2 |
| 30 mg Pasireotide LAR Dose | 40.8 |
Secondary outcomeNumber· M7, M12, M24, M36
Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC
| Group | Value (percentage of participants) |
|---|---|
| 10 mg Pasireotide LAR Dose | 44.6 |
| 30 mg Pasireotide LAR Dose | 53.9 |
Secondary outcomeNumber· Month 7, Month 12
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.
| Group | Value (percentage of participants) |
|---|---|
| 10 mg Pasireotide LAR Dose | 25.7 |
| 30 mg Pasireotide LAR Dose | 31.6 |
Secondary outcomeNumber· Month 7, Month12
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
| Group | Value (percentage of participants) |
|---|---|
| 10 mg Pasireotide LAR Dose | 60.6 |
| 30 mg Pasireotide LAR Dose | 60.6 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| 10 mg Pasireotide LAR DoseRandomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. | – | 22 / 74 | 73 / 74 |
| 30 mg Pasireotide LAR DoseRandomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. | – | 19 / 76 | 76 / 76 |
| All PatientsAll Patients from both the 10 mg and 30 mg groups. | – | 41 / 150 | 149 / 150 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies4
Studies that cite this trial.
Studies with results
3 studies on this page
Indexing hint: Randomized controlled trial · 2020
5 results
Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.
Newell-Price et al. 2020European journal of endocrinologycited by 54
PMID 31804965PMC7003692DOI 10.1530/eje-19-0695PUB-31804965
CC BY5 results
Indexing hint: Clinical trial · 2020
6 results
Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study.
Lacroix et al. 2020Journal of endocrinological investigationcited by 17
PMID 32385851DOI 10.1007/s40618-020-01246-0PUB-32385851
Full text at the publisher6 results
Indexing hint: Randomized controlled trial · 2019
11 results
Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study.
Fleseriu et al. 2019Clinical endocrinologycited by 30
PMID 31465533PMC6899900DOI 10.1111/cen.14081PUB-31465533
Free to read · publisher termsCC BY-NC11 results
More studies
1 study on this page
Indexing hint: Randomized controlled trial · 2018
Corrected
Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial.
Lacroix et al. 2018The lancet. Diabetes & endocrinologycited by 127
PMID 29032078DOI 10.1016/s2213-8587(17)30326-1PUB-29032078
Full text at the publisher
Other registry references
References listed at the registry that are not in PepBank. They link to PubMed.
- DerivedSilverstein JM. Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly. Pituitary. 2016 Oct;19(5):536-43. doi: 10.1007/s11102-016-0734-1. PMID 27405306
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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
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