Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients

Study Overview
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Brief Summary
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This study will assess the efficacy of 8 months treatment of Sandostatin® LAR® High Dose monotherapy or Sandostatin® LAR® High Dose in combination either with growth hormone antagonist or dopamine agonist to control biochemical parameters (GH and insulin-like growth factor I [IGF I]) of acromegalic patients not achieving biochemical normalization at conventional regimen.

Official Title
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An Open-label, Two-step, Multicenter European Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients Not Adequately Controlled by Conventional Regimen

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Sandostatin LAR
* Drug: pegvisomant
* Drug: cabergoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patient with a biochemically documented active acromegaly, not adequately controlled by somatostatin-analogues at conventional regimen as follow : mean 1-hour GH > 2.5 ng/mL and elevated IGF-1 (adjusted for age and gender) Patient with reduction of either mean fasting GH at least 50% or IGF-1 at least 25% from any medical pretreatment level Patient currently receiving somatostatin-analogues at conventional regimen (maximum registered dose) for at least 6 months before inclusion Exclusion Criteria: Newly diagnosed or previously medically untreated acromegalic patient Concomitant treatment with GH-receptor antagonist Concomitant treatment with dopamine-agonist Symptomatic cholelithiasis or choledocolithiasis Liver transaminases (ALT, AST) elevated, but > 3 times upper normal limit (according to local laboratory) Previous gamma-knife radiotherapy for treatment of acromegaly Compression of the optic chiasm causing visual field defect Any medical conditions contraindicated in the Summary of Product Characteristic (SPC) of all drugs 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sandostatin LAR high dose Alone<br>All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months. | Drug: Sandostatin LAR<br>* 40 mg intramuscular (i.m.) every 28 days for 3 months<br>* Other names: octreotide acetate;|
| Experimental: Sandostatin LAR high dose + Pegvisomat<br>All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and or IGF-I received Sandostatin LAR40 mg every 28 days in combination with weekly doses of pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months | Drug: Sandostatin LAR<br>* 40 mg intramuscular (i.m.) every 28 days for 3 months<br>* Other names: octreotide acetate;Drug: pegvisomant<br>* Weekly doses of pegvisomant 70 mg subcutaneously (s.c.) for 4 months given with Sandostatin LAR 40 mg intramuscular (i.m.) every 28 days for 4 months<br>* Other names: octreotide acaetate;|
| Experimental: Sandostatin LAR high dose + Cabergoline<br>All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and or IGF-I received Sandostatin LAR 40 mg every 28 days in combination with weekly cabergoline for a further 4 months, with cabergoline doses as follows: st week: 0.25 mg twice a week (0.50 mg/week) nd week: 0.50 mg/week twice a week (1 mg/week) rd week: 0.50 mg four times a week (2 mg/week) th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week) | Drug: Sandostatin LAR<br>* 40 mg intramuscular (i.m.) every 28 days for 3 months<br>* Other names: octreotide acetate;Drug: cabergoline<br>* Weekly cabergoline for 4 months, with weekly doses of Sandostatin LAR 40 mg intramuscular (i.m.) every 28 days for 4 months. Cabergoline doses as follows: st week: 0.25 mg twice a week (0.50 mg/week) nd week: 0.50 mg/week twice a week (1 mg/week) rd week: 0.50 mg four times a week (2 mg/week) th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)<br>* Other names: octreotide acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Complete Response (CR) at 8 Months | A patient was classified as a Complete Responder (CR) if both biochemical parameters were controlled at the end of 8 months of treatment: Mean 1 hour GH < 2.5µg/L (according to Central Laboratory); and IGF-I within the Central Laboratory Normal Range (for age and gender). | From Baseline to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Complete Response (CR) At 3 Months | A patient was classified as CR if both biochemical parameters were controlled at the end of 3 months of treatment: Mean 1 hour GH < 2.5µg/L (according to Central Laboratory); and IGF-I within the Central Laboratory Normal Range (for age and gender) | From Baseline to 3 months | 
| The Percentage of Participants With Partial Response (PR) at 8 Months | Patients who met one of the following criteria at the end of 8 months of treatment were defined as Partial Responders, regardless of the treatment. Mean 1 hour GH > 2.5 µg/L and < 5 µg/L and either a decrease in IGF-I of at least 50% compared to baseline or IGF-I within normal range. Mean 1 hour GH < 2.5 µg/L and a decrease in IGF-I of at least 50% compared to baseline and IGF-I outside normal range. | From Baseline to 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sandostatin LAR, High Dose, GH-receptor antagonist, combination with dopamine-agonist, acromegalic patients, octreotide acetate, Somavert, Dostinex, pegvisomant, cabergoline, not adequately controlled, active acromegaly