Clinical trial NCT00171951: Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease
Official title: Extension to a Multicenter, Open-label Study to Assess the Safety and Efficacy of 600 μg SOM230, Administered Subcutaneously, Bid in Patients With Cushing's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cushing Disease
Keywords: Cushing's disease
ACTH
Cortisol
ACTH dependent Cushing's disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Cushing's disease is a rare serious condition that is caused by an adrenocorticotropic hormone (ACTH) secreting pituitary adenoma. This study assessed the long-term safety and efficacy of pasireotide in participants with Cushing's disease.


Eligibility criteria: Inclusion Criteria:

* Participants who have completed the 15 days of Pasireotide treatment in the CSOM230B2208 study and have achieved normalization of 24-hour urinary free cortisol. Participants who did not achieve normalization of 24 -hour urinary free cortisol may be enrolled if in the opinion of the investigator the participant is getting significant clinical benefits from treatment with Pasireotide .
* The participant did not experience any unacceptable adverse events of tolerability issues during the original 15 day treatment.
* Female participants of childbearing potential who have not undergone clinically documented total hysterectomy and/or ovariectomy or tubal ligation must agree to use barrier contraception throughout the course of the extension study, and for one month after the study has ended.

Exclusion Criteria:

* Participant who have developed poorly controlled diabetes mellitus as indicated by ketoacidosis or hemoglobin (Hgb) A1C (HgbA1C) \> 10 since starting \[study CSOM230B2208\].
* Participant with persistent alanine aminotransferase (ALT)/ aspartate transaminase (AST) or alkaline phosphatase levels more than 2.5X upper limit of normal (ULN), serum creatinine \> 2.0 X ULN, serum bilirubin \> 2 X ULN.
* Participant with abnormal coagulation (Prothrombin time (PT) and partial thromboplastin time (PTT) elevated by 30% above normal limits), white blood cells (WBC) \<3.0x1'000'000'000/L; Hgb \<12.0g/dL for females, Hgb \<13.0g/dL for males; PLT \<100x1'000'000'000/L.

Other protocol-defined inclusion / exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits
timeFrame: Month 6
measure: Change From Baseline in Mean Urinary Free Cortisol (UFC)
timeFrame: Core Baseline, Days 14/15 (Core study), Months 6, 12, 24 and 102
Secondary outcomes:
measure: Number of Participants Who Had At Least One Adverse Event (AE)
timeFrame: Up to approximately 106 months
measure: Change From Baseline in Serum Cortisol Levels
timeFrame: Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)
measure: Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders
timeFrame: Day 15 (Core study) and Month 6
measure: Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels
timeFrame: Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)
measure: Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development
timeFrame: Baseline to end of the study
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Paris
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticlas
role: STUDY_DIRECTOR
References:
citation: Boscaro M, Bertherat J, Findling J, Fleseriu M, Atkinson AB, Petersenn S, Schopohl J, Snyder P, Hughes G, Trovato A, Hu K, Maldonado M, Biller BM. Extended treatment of Cushing's disease with pasireotide: results from a 2-year, Phase II study. Pituitary. 2014 Aug;17(4):320-6. doi: 10.1007/s11102-013-0503-3.