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

NCT01278342 | Completed Phase 4 Results

• 2 other identifiers: CSMS995BIC032005-005852-42
• Study Type: interventional
• Target: 70
• Locations: 5 countries
• Sites: 20

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.

Conditions

Acromegaly

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• The Percentage of Participants With Complete Response (CR) At 3 Months

  From Baseline to 3 months

• The Percentage of Participants With Partial Response (PR) at 8 Months

  From Baseline to 8 months

Study Arms (3)

Sandostatin LAR high dose Alone

ACTIVE COMPARATOR

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

Sandostatin LAR high dose + Pegvisomat

EXPERIMENTAL

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; Drug: pegvisomant

Sandostatin LAR high dose + Cabergoline

EXPERIMENTAL

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; Drug: cabergoline

Interventions

Sandostatin LAR DRUG

40 mg intramuscular (i.m.) every 28 days for 3 months

Also known as: octreotide acetate

Sandostatin LAR high dose + Cabergoline; Sandostatin LAR high dose + Pegvisomat; Sandostatin LAR high dose Alone

pegvisomant DRUG

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

Also known as: Somavert, octreotide acaetate

Sandostatin LAR high dose + Pegvisomat

cabergoline DRUG

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)

Also known as: Dostinex, octreotide acetate

Sandostatin LAR high dose + Cabergoline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Novartis Investigative Site

Brest, 29609, France

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Nice, 06202, France

Location

Novartis Investigative Site

Nîmes, 30029, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Genova, 16132, Italy

Location

Novarts Investigative Site

Naples, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Padua, Italy

Location

Novartis Investigative Site

Perugia, 06126, Italy

Location

Novartis Investigative Site

Pisa, 56124, Italy

Location

Novartis Investigative Site

Torino, 10126, Italy

Location

Novartis Investigative Site

Lodz, 91-425, Poland

Location

Novartis Investigative Site

Warsaw, Poland

Location

Novartis Investigative Site

Wroclaw, Poland

Location

Novartis Investigative Site

Zabrze, 41-800, Poland

Location

Novartis Investigative Site

Porto, 4200-319, Portugal

Location

Novartis Investigative Site

Lausanne, CH-1011, Switzerland

Location

MeSH Terms

Conditions

Acromegaly

Interventions

Octreotide; pegvisomant; Cabergoline

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 14, 2011
• First Posted: January 17, 2011
• Study Start: September 1, 2006
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: March 3, 2017
• Results First Posted: February 17, 2011

Record last verified: 2017-02

Locations

PT (1); CH (1); IT (7); FR (7); PL (4)