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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

Phase 4
Completed
Conditions
Acromegaly
Interventions
Registration Number
NCT01278342
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sandostatin LAR high dose + PegvisomatpegvisomantAll 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
Sandostatin LAR high dose AloneSandostatin LARAll 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.
Sandostatin LAR high dose + PegvisomatSandostatin LARAll 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
Sandostatin LAR high dose + CabergolineSandostatin LARAll 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: 1. st week: 0.25 mg twice a week (0.50 mg/week) 2. nd week: 0.50 mg/week twice a week (1 mg/week) 3. rd week: 0.50 mg four times a week (2 mg/week) 4. th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Sandostatin LAR high dose + CabergolinecabergolineAll 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: 1. st week: 0.25 mg twice a week (0.50 mg/week) 2. nd week: 0.50 mg/week twice a week (1 mg/week) 3. rd week: 0.50 mg four times a week (2 mg/week) 4. th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Primary Outcome Measures
NameTimeMethod
The Percentage of Participants With Complete Response (CR) at 8 MonthsFrom 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 Outcome Measures
NameTimeMethod
The Percentage of Participants With Complete Response (CR) At 3 MonthsFrom 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 MonthsFrom 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.

Trial Locations

Locations (2)

Novarts Investigative Site

🇮🇹

Naples, Italy

Novartis Investigative Site

🇨🇭

Lausanne, Switzerland

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