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)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT01278342
First received: January 14, 2011
Last updated: April 20, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Acromegaly
Drug: Sandostatin LAR
Drug: pegvisomant
Drug: cabergoline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Percentage of Participants With Complete Response (CR) at 8 Months [ Time Frame: From Baseline to 8 months ] [ Designated as safety issue: No ]

    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:
  • 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.


Enrollment: 70
Study Start Date: September 2006
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 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
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)
Drug: Sandostatin LAR
40 mg intramuscular (i.m.) every 28 days for 3 months
Other Name: 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:

  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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01278342

Locations
France
Novartis Investigative Site
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
Italy
Novartis Investigative Site
Genova, Italy, 16132
Novarts Investigative Site
Naples, Italy
Novartis 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
Poland
Novartis Investigative Site
Lodz, Poland, 91-425
Novartis Investigative Site
Warszawa, Poland
Novartis Investigative Site
Wroclaw, Poland
Novartis Investigative Site
Zabrze, Poland, 41-800
Portugal
Novartis Investigative Site
Porto, Portugal, 4200-319
Switzerland
Novartis Investigative Site
Lausanne, Switzerland, CH-1011
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01278342     History of Changes
Other Study ID Numbers: CSMS995BIC03, 2005-005852-42
Study First Received: January 14, 2011
Results First Received: January 22, 2011
Last Updated: April 20, 2011
Health Authority: France: National Consultative Ethics Committee for Health and Life Sciences
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Portugal: Health Ethic Committee
Switzerland: Swissmedic
Poland: Ministry of Health

Keywords provided by Novartis:
Sandostatin LAR
High Dose
GH-receptor antagonist
combination with dopamine-agonist
acromegalic patients
octreotide acetate
Somavert
Dostinex
pegvisomant
cabergoline
not adequately controlled
active acromegaly

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Dopamine
Dopamine Agents
Cabergoline
Octreotide
Dopamine Agonists
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 18, 2014