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)

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

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.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: Sandostatin LAR; Drug: pegvisomant; Drug: cabergoline

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Brest Cedex, France, 29609
    • Novartis Investigative Site
  • Bron Cedex, France, 69677
    • Novartis Investigative Site
  • Kremlin-Bicetre, France, 94275
    • Novartis Investigative Site
  • Nice, France, 06202
    • Novartis Investigative Site
  • Nimes, France, 30029
    • Novartis Investigative Site
  • Pessac, France, 33604
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
• Italy
  • Genova, Italy, 16132
    • Novartis Investigative Site
  • Naples, Italy
    • Novarts Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • Padova, Italy
    • Novartis Investigative Site
  • Perugia, Italy, 06126
    • Novartis Investigative Site
  • Pisa, Italy, 56124
    • Novartis Investigative Site
  • Torino, Italy, 10126
    • Novartis Investigative Site
• Poland
  • Lodz, Poland, 91-425
    • Novartis Investigative Site
  • Warszawa, Poland
    • Novartis Investigative Site
  • Wroclaw, Poland
    • Novartis Investigative Site
  • Zabrze, Poland, 41-800
    • Novartis Investigative Site
• Portugal
  • Porto, Portugal, 4200-319
    • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, CH-1011
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Sandostatin LAR; 40 mg intramuscular (i.m.) every 28 days for 3 months; Other Names: octreotide acetate
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	Drug: Sandostatin LAR; 40 mg intramuscular (i.m.) every 28 days for 3 months; Other Names: 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
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)	Drug: Sandostatin LAR; 40 mg intramuscular (i.m.) every 28 days for 3 months; Other Names: octreotide acetate; 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); Other Names: Dostinex; octreotide acetate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 14, 2011
• First Submitted That Met QC Criteria: January 14, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: High Dose; Sandostatin LAR; cabergoline; pegvisomant; GH-receptor antagonist; combination with dopamine-agonist; acromegalic patients; octreotide acetate; Somavert; Dostinex; not adequately controlled; active acromegaly
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Octreotide; Cabergoline
• Other Study ID Numbers: CSMS995BIC03; 2005-005852-42 (Registry Identifier: EudraCT)