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

Purpose

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.

Condition	Intervention	Phase
Cushing's Disease	Drug: Pasireotide	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind Study to Assess the Safety and Efficacy of Different Dose Levels of Pasireotide (SOM230) sc Over a 6 Month Treatment Period in Patients With de Novo, Persistent or Recurrent Cushing's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Cushing disease

MedlinePlus related topics: Cushing's Syndrome

Drug Information available for: Pasireotide

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Proportion of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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 Outcome Measures:

Reduction of UFC at Months 3 and 12 [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
Time to First Response [ Time Frame: Month 1, 2, 3, 4, 5, 6, 12 and every 3 months to study end. ] [ Designated as safety issue: No ]
Assessment of Plasma ACTH and Serum Cortisol Level [ Time Frame: Month 1, 2, 3, 4, 5, 6, 12 and every 3 months to study end. ] [ Designated as safety issue: No ]
Assessment of Clinical Signs and Symptoms [ Time Frame: Month 1, 2, 3, 4, 5, 6, 12 and every 3 months to study end. ] [ Designated as safety issue: No ]

Enrollment:	165
Study Start Date:	December 2006
Estimated Study Completion Date:	June 2013
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 600ug b.i.d All patients received a double blind dose of 600 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment if their Month 3 mUFC was a ≤2 X ULN and b) below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblinded and were required to increase their dose to 900 µg b.i.d, given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 900 µg b.i.d dose were to be discontinued from the study.	Drug: Pasireotide All patients received Pasireotide subcutaneously (s.c.) twice a day (b.i.d) at either 600 µg or 900 µg doses. Patients self administered the drug (subcutaneous injections) after they received instruction from the site staff or investigator on the correct procedures.
Experimental: 900ug b.i.d All patients received a double blind dose of 900 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment) if their Month 3 mUFC was a) ≤ 2 x ULN and b)below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblended and were offered to increase their dose to 1200 µg b.i.d., given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 1200 µg b.i.d dose were to be discontinued from the study. [China only: Patients in the 900 µg b.i.d dose group were not offered to have their dose increased to 1200 µg b.i.d but had to be discontinued.	Drug: Pasireotide All patients received Pasireotide subcutaneously (s.c.) twice a day (b.i.d) at either 600 µg or 900 µg doses. Patients self administered the drug (subcutaneous injections) after they received instruction from the site staff or investigator on the correct procedures.

Arms

Assigned Interventions

Experimental: 600ug b.i.d

All patients received a double blind dose of 600 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment if their Month 3 mUFC was a ≤2 X ULN and b) below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblinded and were required to increase their dose to 900 µg b.i.d, given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 900 µg b.i.d dose were to be discontinued from the study.

Drug: Pasireotide

All patients received Pasireotide subcutaneously (s.c.) twice a day (b.i.d) at either 600 µg or 900 µg doses. Patients self administered the drug (subcutaneous injections) after they received instruction from the site staff or investigator on the correct procedures.

Experimental: 900ug b.i.d

All patients received a double blind dose of 900 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment) if their Month 3 mUFC was a) ≤ 2 x ULN and b)below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblended and were offered to increase their dose to 1200 µg b.i.d., given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 1200 µg b.i.d dose were to be discontinued from the study. [China only: Patients in the 900 µg b.i.d dose group were not offered to have their dose increased to 1200 µg b.i.d but had to be discontinued.

Drug: Pasireotide

All patients received Pasireotide subcutaneously (s.c.) twice a day (b.i.d) at either 600 µg or 900 µg doses. Patients self administered the drug (subcutaneous injections) after they received instruction from the site staff or investigator on the correct procedures.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00434148

Show 67 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

Additional Information:

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers. This link exits the ClinicalTrials.gov site

Related Info This link exits the ClinicalTrials.gov site

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Dipl-Biol, 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.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00434148 History of Changes
Other Study ID Numbers:	CSOM230B2305, 2006-004111-22
Study First Received:	February 9, 2007
Results First Received:	January 3, 2013
Last Updated:	February 5, 2013
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Brazil: National Health Surveillance Agency Canada: Health Canada China: Ministry of Health Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: German Institute of Medical Documentation and Information Greece: National Organization of Medicines Italy: The Italian Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: National Pharmacy and Medicines Institute Spain: Ministry of Health and Consumption Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:

Cushing's Disease
pasireotide
SOM230

Additional relevant MeSH terms:

Cushing Syndrome
Pituitary ACTH Hypersecretion
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Hyperpituitarism

Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on May 22, 2013