Clinical trial NCT00434148: Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cushing's Disease
Keywords: Cushing's Disease
pasireotide
SOM230
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-02-12
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group
timeFrame: 6 months
Secondary outcomes:
measure: Change From Baseline in mUFC
timeFrame: baseline, 3 months, 12 months
measure: Time to First UFC Response
timeFrame: 12 months
measure: Percent Change From Baseline in Serum Cortisol
timeFrame: 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
measure: Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)
timeFrame: 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
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP)
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI)
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score
timeFrame: baseline, month 3, month 6, month 12, month 18, month 24
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD)
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
measure: Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition
timeFrame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
measure: Change From Baseline in Tumor Volume
timeFrame: baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months
measure: Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score
timeFrame: baseline, 3 months, 6 months, 12 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center Stanford Cancer Center (3)
state: California
city: Chicago
country: United States
facility: University Chicago Hospital Dept. of Univ of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute The Melanoma Program
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center- New York Presbyterian Columbia University DeptofMed
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation Dept. of Cleveland Clinic (6)
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.
state: Oregon
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Clinical-TranslationalRes.Ctr.
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(8)
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center Dept.ofSeattle Neuroscience(2)
state: Washington
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Ribeirao Preto
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Arhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Angers
country: France
facility: Novartis Investigative Site
city: Grenoble Cédex 9
country: France
facility: Novartis Investigative Site
city: LILLE Cedex
country: France
facility: Novartis Investigative Site
city: Limoges cedex
country: France
facility: Novartis Investigative Site
city: Marseille cedex 05
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: St Priest en Jarez Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Heifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Orbassano
country: Italy
facility: Novartis Investigative Site
state: TO
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: México
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: México
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Balcova / Izmir
country: Turkey
facility: Novartis Investigative Site
city: Fatih / Istanbul
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.