An Extension Study to Assess the Long-Term Safety and Efficacy of Pasireotide in Participants With Acromegaly

Study Overview
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Brief Summary
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Acromegaly is a rare, serious condition characterized by chronic hypersecretion of growth hormone (GH), generally caused by a GH-secreting pituitary adenoma. The study assessed the long-term safety and efficacy of pasireotide in participants with acromegaly.

Official Title
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Extension to a Multi-Center, Randomized, Crossover, Open Label, Dose Finding Study to Compare the Safety, Efficacy, and Pharmacokinetics/Pharmacodynamics (PK/PD) Relationship of Multiple Doses of Pasireotide (SOM230) (200, 400, and 600 μg Bid) and Doses of Open Label Sandostatin® (SMS) (100 μg Tid) in Acromegalic Patients

Conditions
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Acromegaly

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 all four treatment regimens in the core study CSOM230B2201 (NCT00088582) and achieved biochemical control in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels after at least one month of pasireotide administration at any of the three doses. Participants who did not experience any unacceptable adverse events or tolerability issues during the core study CSOM230B2201. Exclusion Criteria: Participants who experienced or developed compression of the optic chiasm causing any visual field defect during the core study CSOM230B2201. Participants who required a surgical intervention for relief of any sign or symptom associated with tumor compression during the core study CSOM230B2201. Participants who experienced or developed congestive heart failure, unstable angina, sustained ventricular tachycardia, ventricular fibrillation or acute myocardial infraction during the core study CSOM230B2201. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 s.c. Overall<br>Participants received pasireotide as a daily subcutaneous (s.c) injection, every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 microgram (μg)) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months). | Drug: Pasireotide<br> <br> * Other names: SOM230;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) Observed Response by Dose Class | A participant was a responder to a dose level if the mean GH level after dosing (t30, t60, t90, and t120) was below/equal to 2.5 microgram/litre (μg/L), and if the mean of IGF-1 of the two pre-dose values (t-30, t-1) was within normal limits for age-sex matched controls. If three or more of t30, t60, t90, or t120 were missing, mean GH was considered missing. If either t-30 or t-1 was missing, mean IGF-1 was considered missing. Pasireotide incident dose classes were defined by total daily doses ranges (<1200 μg/d, 1200 to <1500 μg/d, ≥ 1500 μg/d). | Month 9 (Month 9 visit is at the completion of six months in this extension study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Response | Time to tumor response was defined as time from Sandostatin baseline (core study baseline) to at least 20% decrease in tumor volume. | Core study baseline to at least a 20% decrease in pituitary tumor volume (up to approximately 114 months) | 
| Summary Magnetic Resonance Imaging (MRI) Pituitary Tumor Volumes | Pituitary Tumor Volumes were assessed by MRI. Core study baseline was defined as the last non-missing observation prior to the start of Sandostatin s.c. treatment. | Core study baseline, Months 9, 27, 63, 75 and 99 | 
| Percentage of Participants With Symptoms of Acromegaly | Participants scored the following symptoms of acromegaly: Headache, perspiration, paresthesia, fatigue, osteoarthralgia, and carpal tunnel syndrome on a 5-point scale (0 = None/absent, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe). | Core study baseline till the last assessment of the extension study (up to approximately 114 months) | 
| Percentage of Participants With Sleep Apnea Symptoms as Assessed by Epworth Sleepiness Scale by Situation | Sleep apnea symptoms were assessed using the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. It provides a measure of a person's general level of daytime sleepiness, or average sleep propensity in daily life. Percentage of participants were reported in 8 different situations: sitting and reading; watching TV; sitting, inactive in a public place; passenger in a car, an hour without break; lying down to rest in the afternoon; sitting and talking to someone; sitting quietly after a lunch without alcohol; and in a car, stopped a few minutes in the traffic. The participants were rated: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, 3 = high chance of dozing. Higher scores indicate more severe daytime sleepiness. | Core study baseline till the last assessment of the extension study (up to approximately 114 months) | 
| Percentage of Participants With One or More Adverse Events (AEs) | An AE was any undesirable sign, symptom or medical condition that occurred after starting study drug even if the event was not considered to be related to study drug. Percentage of participants with any AE were categorized by pasireotide incident dose classes, which were defined by total daily doses ranges (<1200 μg/d, 1200 to <1500 μg/d, ≥ 1500 μg/d). | From start of study drug treatment up to end of study (approximately 111 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acromegaly, Pasireotide, GH, IGF-1