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

Cushing's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00434148
• Other study ID #: CSOM230B2305
• Secondary ID: 2006-004111-22
• Status: Completed
• Phase: Phase 3
• First received: February 9, 2007
• Last updated: February 5, 2016
• Start date: December 2006
• Est. completion date: May 2014

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentBrazil: National Health Surveillance AgencyCanada: Health CanadaChina: Ministry of HealthDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: German Institute of Medical Documentation and InformationGreece: National Organization of MedicinesItaly: The Italian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteSpain: Ministry of Health and ConsumptionTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: May 2014
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Cushing's Disease
• Pituitary ACTH Hypersecretion

Intervention

Drug:
• Pasireotide

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal	Buenos Aires
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Gent
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Ribeirao Preto	SP
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Montreal	Quebec
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Shanghai
Denmark	Novartis Investigative Site	Arhus
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Herlev
Finland	Novartis Investigative Site	Helsinki
France	Novartis Investigative Site	Angers
France	Novartis Investigative Site	Grenoble Cédex 9
France	Novartis Investigative Site	LILLE Cedex
France	Novartis Investigative Site	Limoges cedex
France	Novartis Investigative Site	Marseille cedex 05
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pessac Cedex
France	Novartis Investigative Site	St Priest en Jarez Cedex
France	Novartis Investigative Site	Toulouse Cedex 9
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Würzburg
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens	GR
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Heifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Torino	TO
Mexico	Novartis Investigative Site	México	Distrito Federal
Mexico	Novartis Investigative Site	México	Distrito Federal
Poland	Novartis Investigative Site	Warszawa
Portugal	Novartis Investigative Site	Porto
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Sevilla	Andalucia
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Balcova / Izmir
Turkey	Novartis Investigative Site	Fatih / Istanbul
United States	Dana Farber Cancer Institute The Melanoma Program	Boston	Massachusetts
United States	University Chicago Hospital Dept. of Univ of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation Dept. of Cleveland Clinic (6)	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center Clinical-TranslationalRes.Ctr.	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(8)	Houston	Texas
United States	Columbia University Medical Center- New York Presbyterian Columbia University DeptofMed	New York	New York
United States	Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.	Portland	Oregon
United States	Swedish Medical Center Dept.ofSeattle Neuroscience(2)	Seattle	Washington
United States	Stanford University Medical Center Stanford Cancer Center (3)	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change From Baseline in mUFC	Twenty four hour urine samples were collected to obtain mUFC measurements. A negative change from baseline indicates improvement.	baseline, 3 months, 12 months	No
Secondary	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.	12 months	No
Secondary	Percent Change From Baseline in Serum Cortisol	Blood samlpes were drawn to obtain serum cortisol levels. A negative change from baseline indicates improvement.	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	No
Secondary	Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)	Blood samples were drawn to obtain ACTH levels. A negative change from baseline indicates improvement.	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	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60	No
Secondary	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.	baseline, month 3, month 6, month 12, month 18, month 24	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60	No
Secondary	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.	baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60	No
Secondary	Change From Baseline in Tumor Volume	Pituitary magnetic resonance imaging (MRI) was performed to determine tumor volume. A negative change from baseline indicates imrpovement.	baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months	No
Secondary	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.	baseline, 3 months, 6 months, 12 months	No

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