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

NCT00171951 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CSOM230B2208E12004-002407-32
• Study Type: interventional
• Target: 19
• Locations: 5 countries
• Sites: 8

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.

Conditions

Cushing Disease

Keywords

Cushing's disease; ACTH; Cortisol; ACTH dependent Cushing's disease

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Number of Participants Who Had At Least One Adverse Event (AE)

  Up to approximately 106 months

• Change From Baseline in Serum Cortisol Levels

  Core Baseline, Day 15 (Core study), Months 6, 12, 24, and Month 105 (end of the study)

• Plasma Trough Concentrations (Ctrough) of Pasireotide in UFC Responders

  Day 15 (Core study) and Month 6

• Change From Baseline in Plasma Adrenocorticotropic Hormone (ACTH) Levels

  Core Baseline, Day 15 (Core study), Months 6, 12, 24 and Month 105 (end of the study)

• Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development

  Baseline to end of the study

Study Arms (1)

Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC

EXPERIMENTAL

Participants received pasireotide 600 micrograms (μg) twice daily (BID) subcutaneously (SC) to achieve or maintain urinary free cortisol (UFC) normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given.

Drug: Pasireotide

Interventions

Pasireotide DRUG

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

Also known as: SOM230

Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104-6149, United States

Location

Novartis Investigative Site

Paris, 75006, France

Location

Novartis Investigative Site

Essen, 45122, Germany

Location

Novartis Investigative Site

München, 80336, Germany

Location

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Belfast, BT12 6BA, United Kingdom

Location

Related 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. 2014 Aug;17(4):320-6. doi: 10.1007/s11102-013-0503-3.

  PMID: 23943009 RESULT

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion

Interventions

pasireotide

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticlas

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: August 13, 2004
• Primary Completion: July 8, 2013
• Study Completion: July 8, 2013
• Last Updated: June 2, 2021
• Results First Posted: June 2, 2021

Record last verified: 2021-05

Locations

DE (2); IT (1); US (3); FR (1); GB (1)