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

NCT00434148 | Completed Phase 3 Results

• 2 other identifiers: CSOM230B23052006-004111-22
• Study Type: interventional
• Target: 162
• Locations: 18 countries
• Sites: 68

Brief 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.

Conditions

Cushing's Disease

Keywords

Cushing's Disease; pasireotide; SOM230

Outcome Measures

Primary Outcomes (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.

  6 months

Secondary Outcomes (14)

• Change From Baseline in mUFC

  baseline, 3 months, 12 months

• Time to First UFC Response

  12 months

• Percent Change From Baseline in Serum Cortisol

  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)

  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

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

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

Study Arms (2)

Pasireotide 600 ug

EXPERIMENTAL

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.

Drug: Pasireotide

Pasireotide 900 ug

EXPERIMENTAL

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.

Drug: Pasireotide

Interventions

Pasireotide DRUG

Pasireotide 600 ug; Pasireotide 900 ug

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (68)

Stanford University Medical Center Stanford Cancer Center (3)

Stanford, California, 94304, United States

Location

University Chicago Hospital Dept. of Univ of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute The Melanoma Program

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center- New York Presbyterian Columbia University DeptofMed

New York, New York, 10032, United States

Location

Cleveland Clinic Foundation Dept. of Cleveland Clinic (6)

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.

Portland, Oregon, 97239, United States

Location

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

Dallas, Texas, 75390-8527, United States

Location

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

Houston, Texas, 77030-4009, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Swedish Medical Center Dept.ofSeattle Neuroscience(2)

Seattle, Washington, United States

Location

Novartis Investigative Site

Buenos Aires, Buenos Aires, C1232AAC, Argentina

Location

Novartis Investigative Site

Buenos Aires, Buenos Aires, C1405BCH, Argentina

Location

Novartis Investigative Site

Capital Federal, Buenos Aires, 1425EKP, Argentina

Location

Novartis Investigative Site

Edegem, 2650, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Curitiba, Paraná, 80060-900, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90560-030, Brazil

Location

Novartis Investigative Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01401-901, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 2S2, Canada

Location

Novartis Investigative Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

Location

Novartis Investigative Site

Beijing, 100028, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Aarhus, 8000, Denmark

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Herlev, DK-2730, Denmark

Location

Novartis Investigative Site

Helsinki, FIN-00290, Finland

Location

Novartis Investigative Site

Angers, 49033, France

Location

Novartis Investigative Site

Grenoble Cédex 9, 38043, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Limoges, 87042, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Paris, 75014, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Saint-Priest-en-Jarez, 42277, France

Location

Novartis Investigative Site

Toulouse, 31000, France

Location

Novartis Investigative Site

München, Germany, 80336, Germany

Location

Novartis Investigative Site

Berlin, 10098, Germany

Location

Novartis Investigative Site

Essen, 45122, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Athens, GR, 105 52, Greece

Location

Novartis Investigative Site

Athens, GR, 115 27, Greece

Location

Novartis Investigative Site

Haifa, 3339419, Israel

Location

Novartis Investigative Site

Haifa, 35152, Israel

Location

Novartis Investigative Site

Jerusalem, 9112001, Israel

Location

Novartis Investigative Site

Petah Tikva, 49100, Israel

Location

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Cona, FE, 44100, Italy

Location

Novartis Investigative Site

Milan, MI, 20149, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Mexico City, Mexico City, 06720, Mexico

Location

Novartis Investigative Site

Mexico City, Mexico City, 14269, Mexico

Location

Novartis Investigative Site

Warsaw, 01 809, Poland

Location

Novartis Investigative Site

Porto, Portugal, 4200-319, Portugal

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Barcelona, 08041, Spain

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Balcova / Izmir, 35340, Turkey (Türkiye)

Location

Novartis Investigative Site

Fatih / Istanbul, 34098, Turkey (Türkiye)

Location

Related Publications (6)

• 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.

  PMID: 31875276 DERIVED

• 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.

  PMID: 28289402 DERIVED

• 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.

  PMID: 25537481 DERIVED

• 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.

  PMID: 24287689 DERIVED

• 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.

  PMID: 23746264 DERIVED

• 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.

  PMID: 22397653 DERIVED

Related Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion

Interventions

pasireotide

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2007
• First Posted: February 12, 2007
• Study Start: December 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: May 1, 2014
• Last Updated: March 8, 2016
• Results First Posted: February 6, 2013

Record last verified: 2016-02

Locations

ME (2); IT (9); PL (1); FI (1); CN (3); DE (4); AR (3); BR (6); FR (9); US (10); GR (2); IL (4); DK (3); PT (1); TU (3); BE (2); CA (3); ES (2)