Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing's Disease

Cushing Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00171951
• Other study ID #: CSOM230B2208E1
• Secondary ID: 2004-002407-32
• Status: Completed
• Phase: Phase 2
• Start date: August 13, 2004
• Est. completion date: July 8, 2013

Study information

• Verified date: May 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 8, 2013
• Est. primary completion date: July 8, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pasireotide
Pasireotide 600 µg or 900 µg was administered as an SC injection.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Muenchen
Italy	Novartis Investigative Site	Ancona	AN
United Kingdom	Novartis Investigative Site	Belfast
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Responders With Mean Urinary Free Cortisol (UFC) Within Normal Limits	A participant was considered a responder if the mean UFC from the two 24-hour urine samples collected at Month 6 was within normal limits. The normal range for UFC is 55 to 276 nmol/day.	Month 6
Primary	Change From Baseline in Mean Urinary Free Cortisol (UFC)	24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.	Core Baseline, Days 14/15 (Core study), Months 6, 12, 24 and 102
Secondary	Number of Participants Who Had At Least One Adverse Event (AE)	An AE was any undesirable sign, symptom or medical condition occurring after starting study drug even if the event is not considered to be related to study drug. AEs were assessed according to incident dose group: Pasireotide 1200 µg sc total daily dose (TDD), Pasireotide 1800 µg SC TDD and Pasireotide SC Any Dose. The incident dose for an AE was the last total daily dose administered on or prior to the AE onset date.	Up to approximately 106 months
Secondary	Change From Baseline in Serum Cortisol Levels	Blood samples were withdrawn to obtain the serum cortisol levels. A negative change from baseline indicates improvement.	Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)
Secondary	Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders	Participants with Cushing's disease were considered responders if mean UFC levels from the 24-hour urine collections at Day 15 (Core study) and at extension Month 6, were within normal limits. Ctrough levels of pasireotide were measured at Day 15 of Core study and Month 6.	Day 15 (Core study) and Month 6
Secondary	Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels	Blood samples were withdrawn to obtain the ACTH levels. A negative change from baseline indicates improvement.	Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)
Secondary	Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development		Baseline to end of the study