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 (HOSCAR)

• The Percentage of Participants With Complete Response (CR) At 3 Months [ Time Frame: From Baseline to 3 months ] [ Designated as safety issue: No ]

  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 ] [ Designated as safety issue: No ]

  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.

• biochemical control on high dose SandostatinLAR in mono treatment [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• partial biochemical control under combination of high dose of Sandostatin + combination partner [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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.

• Drug: Sandostatin LAR
  40 mg intramuscular (i.m.) every 28 days for 3 months
  Other Name: octreotide acetate
• 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
  Other Names:

  • Somavert
  • octreotide acaetate
• 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:

  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)
  Other Names:

  • Dostinex
  • octreotide acetate

• 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.
  Intervention: Drug: Sandostatin LAR
• 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
  Interventions:

  • Drug: Sandostatin LAR
  • Drug: pegvisomant
• 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:

  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)
  Interventions:

  • Drug: Sandostatin LAR
  • Drug: cabergoline

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