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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease

NCTNCT00434148 (opens ClinicalTrials.gov in a new tab)Other idCSOM230B2305Other id2006-004111-22
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
162 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Randomized · Quadruple masking
Countries
18 countries

United States, Argentina, Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Israel, Italy, Mexico, Poland, Portugal, Spain, Turkey (Türkiye)

Start
Dec 2006
Primary completion
Mar 2010
Completion
May 2014
First posted
12 Feb 2007 (estimated)
Last update posted
8 Mar 2016 (estimated)
Conditions
Cushing's Disease

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20062008201020122014
  1. Ph 3

    Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease

    NCT00434148

    Dec 2006 to May 2014

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This study will evaluate the safety and efficacy of two different doses of Pasireotide in patients with de novo or recurrent/persistent Cushing's Disease.

Interventions

  • PasireotideDrug

Arms2

  • Experimental

    Pasireotide 600 ug

    At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.

  • Experimental

    Pasireotide 900 ug

    At randomization, participants received 900 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group

    Time frame · 6 months

    Registry description

    A responder in the primary efficacy analysis was a patient with a mUFC≤ULN at Month 6 and whose dose was not increased prior to Month 6.

Secondary outcomes(14)

  1. Change From Baseline in mUFC

    Time frame · baseline, 3 months, 12 months

    Registry description

    Twenty four hour urine samples were collected to obtain mUFC measurements. A negative change from baseline indicates improvement.

  2. Time to First UFC Response

    Time frame · 12 months

    Registry description

    Time to first UFC response is defined as the number of months from baseline to first attainment of UFC response.

  3. Percent Change From Baseline in Serum Cortisol

    Time frame · baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months

    Registry description

    Blood samlpes were drawn to obtain serum cortisol levels. A negative change from baseline indicates improvement.

  4. Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)

    Time frame · baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months

    Registry description

    Blood samples were drawn to obtain ACTH levels. A negative change from baseline indicates improvement.

  5. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP)

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

    Registry description

    Sitting blood pressure assessments were performed at every study visit. A negative change from baseline indicates improvement.

  6. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI)

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60

    Registry description

    BMI was determined by using height and weight measurements. A negative change from baseline indicates improvement.

  7. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

    Registry description

    Waist circumference was measured with a measuring tape correctly positioned. A negative change from baseline indicates improvement.

  8. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

    Registry description

    Blood samples were drawn to obtain total cholesterol and triglycerides' levels. A negative change from baseline indicates improvement.

  9. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score

    Time frame · baseline, month 3, month 6, month 12, month 18, month 24

    Registry description

    The BDI-II is a 21 item self-report rating inventory measuring characteristic attitudes and symptoms of depression. The BDI-II contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The scores range as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; and 29-63: severe depression. A negative change from baseline indicates imrpovement.

  10. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

    Registry description

    The Ferriman Gallwey scoring system is used to score the degree of excess male pattern body hair. The scorecard of every body location under survey begins from 0 (no excessive terminal hair growth) to 4 (extensive terminal hair growth) and the numbers are added up to a maximum count of 36. A score \>= 6 indicates the hirsutism. A negative change from baseline indicates imrpovement.

  11. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD)

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

    Registry description

    BMD was measured using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done in the lumbar vertebrae (L1-L4), proximal femur (total hip) and proximal femur (femur neck). A negative change from baseline indicates imrpovement.

  12. Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition

    Time frame · baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

    Registry description

    Body composition as in percentage of body fat by region was assessed by total body scan. A negative change from baseline indicates improvement.

  13. Change From Baseline in Tumor Volume

    Time frame · baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months

    Registry description

    Pituitary magnetic resonance imaging (MRI) was performed to determine tumor volume. A negative change from baseline indicates imrpovement.

  14. Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score

    Time frame · baseline, 3 months, 6 months, 12 months

    Registry description

    A Cushing's syndrome health related quality of life (HRQL) questionnaire was completed. The Cushing's Syndrome HRQL questionnaire contains 12 sentences with 5 possible answers each. The answers are based on Likert scales, with 5 response categories: Always, Often, Sometimes, Rarely and Never; or Very much, Quite a bit, Somewhat, Very little, and Not at all. The answers to each of the items are rated on a scale of 1 to 5. "1" corresponds to the response category "Always" or "Very much" and "5" corresponds to the category "Never" or "Not at all". The score is the sum of all item responses and can range from 12 to 60 points. The lower the score, the greater the Cushing's Syndrome impacts on HRQoL. A positive change from baseline indicates improvement.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 6 months

Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group

GroupValue (Responders)
Pasireotide 600 ug12
Pasireotide 900 ug21
Secondary and other outcome results(7)
Secondary outcomeMean· baseline, 3 months, 12 months

Change From Baseline in mUFC

GroupValue (nmol/24h)Spread
Pasireotide 600 ug-375.8631.07
Pasireotide 900 ug-343.4485.48
Secondary outcomeMedian· 12 months

Time to First UFC Response

GroupValue (months)
Pasireotide 600 ug1.0
Pasireotide 900 ug1.0
Secondary outcomeMean· baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months

Percent Change From Baseline in Serum Cortisol

GroupValue (Percent change)Spread
Pasireotide 600 ug-4.028.23
Pasireotide 900 ug-10.830.57
Secondary outcomeMean· baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months

Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)

GroupValue (percent change)Spread
Pasireotide 600 ug9.3181.17
Pasireotide 900 ug-15.930.75
Secondary outcomeMean· baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP)

GroupValue (mmHg)Spread
Pasireotide 600 ug-7.417.37
Pasireotide 900 ug-9.917.01
Secondary outcomeMean· baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60

Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI)

GroupValue (kg/m^2)Spread
Pasireotide 600 ug-1.01.26
Pasireotide 900 ug-1.41.29
Secondary outcomeMean· baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference

GroupValue (cm)Spread
Pasireotide 600 ug-1.010.47
Pasireotide 900 ug-2.25.23

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Pasireotide 600 ugAt randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.–23 / 8278 / 82
Pasireotide 900 ugAt randomization, participants received 900 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.–25 / 8079 / 80

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

Studies5

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2020

5 results

Pasireotide treatment significantly reduces tumor volume in patients with Cushing's disease: results from a Phase 3 study.

Lacroix et al. 2020Pituitarycited by 20

PMID 31875276PMC7181422DOI 10.1007/s11102-019-01021-2PUB-31875276

CC BY5 results
Download PDFSee results (5)

Indexing hint: Randomized controlled trial · 2015

10 results

Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing's disease: results from an open-ended, open-label extension trial.

Schopohl et al. 2015Pituitarycited by 43

PMID 25537481PMC4560758DOI 10.1007/s11102-014-0618-1PUB-25537481

CC BY10 results
Download PDFSee results (10)

More studies

3 studies on this page

Indexing hint: Case report · 2017

Medical Therapy with Pasireotide in Recurrent Cushing's Disease: Experience of Patients Treated for At Least 1 Year at a Single Center.

Yedinak et al. 2017Frontiers in endocrinologycited by 5

PMID 28289402PMC5327352DOI 10.3389/fendo.2017.00035PUB-28289402

CC BY
Download PDF

Indexing hint: Randomized controlled trial · 2014

Pasireotide monotherapy in Cushing's disease: a single-centre experience with 5-year extension of phase III Trial.

MacKenzie Feder et al. 2014Pituitarycited by 29

PMID 24287689DOI 10.1007/s11102-013-0539-4PUB-24287689

Full text at the publisher
Publisher page

Indexing hint: Randomized controlled trial · 2012

Corrected

A 12-month phase 3 study of pasireotide in Cushing's disease.

Colao et al. 2012The New England journal of medicinecited by 411

PMID 22397653DOI 10.1056/nejmoa1105743PUB-22397653

Full text at the publisher
Publisher pageRead the notice

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedPetersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Sen K, Salgado LR, Colao A, Biller BM; Pasireotide B2305 Study Group. High variability in baseline urinary free cortisol values in patients with Cushing's disease. Clin Endocrinol (Oxf). 2014 Feb;80(2):261-9. doi: 10.1111/cen.12259. Epub 2013 Jul 15. PMID 23746264

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria * 18 years or greater * Confirmed diagnosis of ACTH-dependent Cushing's disease * Not considered candidate for pituitary surgery Exclusion criteria * History of pituitary irradiation in the last 10 years * Cushing's syndrome not caused by pituitary tumor * Patients with active malignant disease (cancer) in the last 5 years * Women who are pregnant or lactating Other protocol-defined inclusion/exclusion criteria apply.

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