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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cushing Disease

Intervention / Treatment
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* Drug: Pasireotide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC<br>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<br>* Pasireotide 600 μg or 900 μg was administered as an SC injection.<br>* Other names: SOM230;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 
| 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 | 
| 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) | 
| Change From Baseline in Gene-expression and Protein in Blood and Urine for Biomarker Development |  | Baseline to end of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cushing's disease, ACTH, Cortisol, ACTH dependent Cushing's disease