AzTrials
AzTrials

Cushing's DiseasePhase 3NCT00434148

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

A Phase 3 study testing Pasireotide in people with Cushing's Disease, run by Novartis Pharmaceuticals at 68 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cushing's Disease
What is being tested?
Pasireotide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
68 sitesin 18 countries
Study dates
Dec 2006to May 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years or greater
  • Confirmed diagnosis of ACTH-dependent Cushing's disease
  • Not considered candidate for pituitary surgery

Who cannot join

  • 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.

Trial locations and contacts

68 sites in 18 countries.

68 sites in 18 countries

United States10 sites

  • Dana Farber Cancer Institute The Melanoma Program

    Boston, Massachusetts, 02115

  • University Chicago Hospital Dept. of Univ of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic Foundation Dept. of Cleveland Clinic (6)

    Cleveland, Ohio, 44195

  • University of Texas Southwestern Medical Center Clinical-TranslationalRes.Ctr.

    Dallas, Texas, 75390-8527

  • University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(8)

    Houston, Texas, 77030-4009

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Columbia University Medical Center- New York Presbyterian Columbia University DeptofMed

    New York, New York, 10032

  • Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.

    Portland, Oregon, 97239

  • Swedish Medical Center Dept.ofSeattle Neuroscience(2)

    Seattle, Washington

  • Stanford University Medical Center Stanford Cancer Center (3)

    Stanford, California, 94304

Other trials in United States

France9 sites

  • Novartis Investigative Site

    Angers, 49033

  • Novartis Investigative Site

    Grenoble Cédex 9, 38043

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Limoges, 87042

  • Novartis Investigative Site

    Marseille, 13385

  • Novartis Investigative Site

    Paris, 75014

  • Novartis Investigative Site

    Pessac, 33604

  • Novartis Investigative Site

    Saint-Priest-en-Jarez, 42277

  • Novartis Investigative Site

    Toulouse, 31000

Other trials in France

Italy9 sites

  • Novartis Investigative Site

    Ancona, AN, 60126

  • Novartis Investigative Site

    Cona, FE, 44100

  • Novartis Investigative Site

    Milan, MI, 20149

  • Novartis Investigative Site

    Milan, MI, 20162

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Orbassano, TO, 10043

  • Novartis Investigative Site

    Padova, PD, 35128

  • Novartis Investigative Site

    Pisa, PI, 56124

  • Novartis Investigative Site

    Torino, TO, 10126

Other trials in Italy

Brazil6 sites

  • Novartis Investigative Site

    Curitiba, Paraná, 80060-900

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90560-030

  • Novartis Investigative Site

    Ribeirão Preto, São Paulo, 14048-900

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 21941-913

  • Novartis Investigative Site

    São Paulo, São Paulo, 01401-901

  • Novartis Investigative Site

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

Germany4 sites

  • Novartis Investigative Site

    Berlin, 10098

  • Novartis Investigative Site

    Essen, 45122

  • Novartis Investigative Site

    München, Germany, 80336

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

Israel4 sites

  • Novartis Investigative Site

    Haifa, 3339419

  • Novartis Investigative Site

    Haifa, 35152

  • Novartis Investigative Site

    Jerusalem, 9112001

  • Novartis Investigative Site

    Petah Tikva, 49100

Other trials in Israel

Argentina3 sites

  • Novartis Investigative Site

    Buenos Aires, Buenos Aires, C1232AAC

  • Novartis Investigative Site

    Buenos Aires, Buenos Aires, C1405BCH

  • Novartis Investigative Site

    Capital Federal, Buenos Aires, 1425EKP

Other trials in Argentina

Canada3 sites

  • Novartis Investigative Site

    Edmonton, Alberta, T6G 2S2

  • Novartis Investigative Site

    Halifax, Nova Scotia, B3H 2Y9

  • Novartis Investigative Site

    Montreal, Quebec, H2W 1T8

Other trials in Canada

China3 sites

  • Novartis Investigative Site

    Beijing, Beijing Municipality, 100730

  • Novartis Investigative Site

    Beijing, 100028

  • Novartis Investigative Site

    Shanghai, 200025

Other trials in China

Denmark3 sites

  • Novartis Investigative Site

    Aarhus, 8000

  • Novartis Investigative Site

    Copenhagen, DK-2100

  • Novartis Investigative Site

    Herlev, DK-2730

Other trials in Denmark

Turkey (Türkiye)3 sites

  • Novartis Investigative Site

    Ankara, 06100

  • Novartis Investigative Site

    Balcova / Izmir, 35340

  • Novartis Investigative Site

    Fatih / Istanbul, 34098

Other trials in Turkey (Türkiye)

Belgium2 sites

  • Novartis Investigative Site

    Edegem, 2650

  • Novartis Investigative Site

    Ghent, 9000

Other trials in Belgium

Greece2 sites

  • Novartis Investigative Site

    Athens, GR, 105 52

  • Novartis Investigative Site

    Athens, GR, 115 27

Other trials in Greece

Mexico2 sites

  • Novartis Investigative Site

    Mexico City, Mexico City, 06720

  • Novartis Investigative Site

    Mexico City, Mexico City, 14269

Other trials in Mexico

Spain2 sites

  • Novartis Investigative Site

    Barcelona, Barcelona, 08041

  • Novartis Investigative Site

    Seville, Andalusia, 41013

Other trials in Spain

Finland1 site

  • Novartis Investigative Site

    Helsinki, FIN-00290

Other trials in Finland

Poland1 site

  • Novartis Investigative Site

    Warsaw, 01 809

Other trials in Poland

Portugal1 site

  • Novartis Investigative Site

    Porto, Portugal, 4200-319

Other trials in Portugal

About this study

Official title: A Randomized, Double-blind Study to Assess the Safety and Efficacy of Different Dose Levels of Pasireotide (SOM230) Subcutaneous (sc) Over a 6 Month Treatment Period in Patients With de Novo, Persistent or Recurrent Cushing's Disease

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.

Being tested
Pasireotide
Keywords
Cushing's Disease, pasireotide, SOM230
Medical subject headings
Pituitary ACTH Hypersecretion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PasireotideDrug

Study groups in NCT00434148
Study groupRoleWhat they receive
Pasireotide 600 ugExperimentalAt 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.
Receives: Drug: Pasireotide
Pasireotide 900 ugExperimentalAt 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.
Receives: Drug: Pasireotide

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: 6 months

Secondary outcomes (14)

  1. Change From Baseline in mUFC

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

    Measured: baseline, 3 months, 12 months

  2. Time to First UFC Response

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

    Measured: 12 months

  3. Percent Change From Baseline in Serum Cortisol

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

    Measured: 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

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

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

    Measured: 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

  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)

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

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

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

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

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60

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

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

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

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

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

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

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

    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.

    Measured: baseline, month 3, month 6, month 12, month 18, month 24

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

    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.

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

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

    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.

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

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

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

    Measured: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60

  13. Change From Baseline in Tumor Volume

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

    Measured: baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months

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

    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.

    Measured: baseline, 3 months, 6 months, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2007 (estimated)
  2. Study startDec 2006
  3. Primary completionMar 2010
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
162 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00434148
Sponsor's protocol ID
CSOM230B2305
Other IDs
2006-004111-22
Status last verified
Feb 2016
First submitted
9 Feb 2007
Last updated
8 Mar 2016
Data monitoring committee
No

Publications

  • Lacroix A, Gu F, Schopohl J, Kandra A, Pedroncelli AM, Jin L, Pivonello R. Pasireotide treatment significantly reduces tumor volume in patients with Cushing's disease: results from a Phase 3 study. Pituitary. 2020 Jun;23(3):203-211. doi: 10.1007/s11102-019-01021-2.

    PubMed 31875276

  • Yedinak CG, Hopkins S, Williams J, Ibrahim A, Cetas JS, Fleseriu M. Medical Therapy with Pasireotide in Recurrent Cushing's Disease: Experience of Patients Treated for At Least 1 Year at a Single Center. Front Endocrinol (Lausanne). 2017 Feb 27;8:35. doi: 10.3389/fendo.2017.00035. eCollection 2017.

    PubMed 28289402

  • Schopohl J, Gu F, Rubens R, Van Gaal L, Bertherat J, Ligueros-Saylan M, Trovato A, Hughes G, Salgado LR, Boscaro M, Pivonello R; Pasireotide B2305 Study Group. 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. Pituitary. 2015 Oct;18(5):604-12. doi: 10.1007/s11102-014-0618-1.

    PubMed 25537481

  • MacKenzie Feder J, Bourdeau I, Vallette S, Beauregard H, Ste-Marie LG, Lacroix A. Pasireotide monotherapy in Cushing's disease: a single-centre experience with 5-year extension of phase III Trial. Pituitary. 2014 Dec;17(6):519-29. doi: 10.1007/s11102-013-0539-4.

    PubMed 24287689

  • Petersenn 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.

    PubMed 23746264

  • Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM; Pasireotide B2305 Study Group. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med. 2012 Mar 8;366(10):914-24. doi: 10.1056/NEJMoa1105743.

    PubMed 22397653

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pasireotide in people with Cushing's Disease, run by Novartis Pharmaceuticals at 68 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 sites in United States, France, Italy, Brazil, Germany and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00434148, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in