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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2009

Interventions

  • Drug: Sandostatin LAR
    • 40 mg intramuscular (i.m.) every 28 days for 3 months
  • Drug: pegvisomant
    • 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
  • Drug: cabergoline
    • 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)

Arms, Groups and Cohorts

  • Active Comparator: Sandostatin LAR high dose Alone
    • 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.
  • Experimental: Sandostatin LAR high dose + Pegvisomat
    • 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
  • Experimental: Sandostatin LAR high dose + Cabergoline
    • 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)

Clinical Trial Outcome Measures

Primary Measures

  • The Percentage of Participants With Complete Response (CR) at 8 Months
    • Time Frame: From Baseline to 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).

Secondary Measures

  • The Percentage of Participants With Complete Response (CR) At 3 Months
    • Time Frame: From Baseline to 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)
  • The Percentage of Participants With Partial Response (PR) at 8 Months
    • Time Frame: From Baseline to 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • External Affairs, Novartis Pharmaceuticals
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals

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