Safety and Efficacy of Imatinib Mesylate in Patients With Pulmonary Arterial Hypertension

NCT00477269 | Completed Phase 2 Results DMC

• 2 other identifiers: CSTI571E22032005-005569-12
• Study Type: interventional
• Target: 59
• Locations: 4 countries
• Sites: 13

Brief Summary

This study will evaluate the safety, tolerability, and efficacy of imatinib mesylate in patients with pulmonary arterial hypertension

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension, tyrosine kinase inhibitor, STI571

Outcome Measures

Primary Outcomes (5)

• Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Core

  In this analysis patients with all (serious and non -serious) adverse events, and death were reported. See Safety Section.

  6 months

• Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Death During the Extension

  In this analysis patients with all (serious and non -serious) adverse events, and death were reported. See Safety Section.

  72 months

• Change From Baseline of Six Minute Walk Test - Total Distance Walked at Different Time Periods

  The Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Distance \<500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance \>800 meters (with no rests) suggests mild or no limitation.

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

• Change From Baseline of Six Minute Walk Test - Number of Stops at Different Time Periods

  The Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. Number of stops were recorded for each patient.

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

• Change From Baseline of Six Minute Walk Test - Total Duration of Stops at Different Time Periods

  The Six Minute Walk test was carried out along a course, such as a hospital corridor, measuring at least 20 meters delineated by markers. Patients were instructed to walk at a comfortable speed as far as they could manage in six minutes, resting whenever they needed to. If the patient stopped the duration of each stop was recorded.

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Secondary Outcomes (19)

• Number of Patients With Pulmonary Hypertension (PAH) Assessd by World Health Organization (WHO) Classification on Physical Activity

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion

• Borg Score-Oxygen Saturation(SaO2) During the Six Minutes Walk Test at Different Time Periods

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

• Borg Score-Systolic Blood Pressure During the Six Minutes Walk Test at Different Time Periods

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

• Borg Score-Diastolic Blood Pressure During the Six Minutes Walk Test at Different Time Periods

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

• Borg Score-Heart Rate (HR) During the Six Minutes Walk Test at Different Time Periods

  Baseline, Day 32, Week 8, Week 12, Week 16, Week 20 and Study completion (Week 24)

Study Arms (3)

STI571

EXPERIMENTAL

STI571

Drug: Imatinib mesylate

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

All Patients

EXPERIMENTAL

Open label extension

Drug: Imatinib mesylate

Interventions

Imatinib mesylate DRUG

Also known as: Imatinib, Glivec, Gleevec, STI571, QTI571

All Patients; STI571

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis of PAH of either primary (idiopathic), familial or secondary to systemic sclerosis (excluding those with marked pulmonary fibrosis) according to World Conference on Pulmonary Hypertension classification (Venice, 2003).
• Symptoms with a WHO class of II-IV

You may not qualify if:

• Use of unspecific phosphodiesterase inhibitors (for example, pentoxyfillin, enoximon, milrinone or pimobendan) during the study
• Chronic inhaled nitric oxide therapy from start to study completion
• Treatment with catecholamines (for example, adrenalin, noradrenalin, dopamine),
• Pre-existing lung diseases, including parasitic diseases affecting lungs, asthma, congenital abnormalities of the lungs, chest, and diaphragm.
• Pulmonary artery or valve stenosis; pulmonary venous hypertension; chronic thromboembolic pulmonary hypertension
• Acute heart failure or chronic left sided heart failure; congenital or acquired valvular or myocardial disease

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Novartis Investigative Site

Los Angeles, California, 90073, United States

Location

Novartis investigative site

Newark, New Jersey, 07112, United States

Location

Novartis Investigative Site

New York, New York, 10032, United States

Location

Novartis Investigative Site

Graz, Austria, A-8036, Austria

Location

Novartis Investigative site

Graz, Austria

Location

Novartis Investigative Site

Hanover, Germany, 30625, Germany

Location

Novartis Investigative Site

Giessen, 35385, Germany

Location

Novartis Investigative site

Giessen, Germany

Location

Novartis Investigative site

Hanover, Germany

Location

Novartis Investigative Site

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

Location

Novartis Investigative Site

Glasgow, G11 6NT, United Kingdom

Location

Novartis Investigative site

Glasgow, United Kingdom

Location

Novartis Investigative site

Papworth Everard, United Kingdom

Location

Related Publications (1)

• Ghofrani HA, Morrell NW, Hoeper MM, Olschewski H, Peacock AJ, Barst RJ, Shapiro S, Golpon H, Toshner M, Grimminger F, Pascoe S. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med. 2010 Nov 1;182(9):1171-7. doi: 10.1164/rccm.201001-0123OC. Epub 2010 Jun 25.

  PMID: 20581169 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis

  Investigative site

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2007
• First Posted: May 23, 2007
• Study Start: April 1, 2006
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: March 23, 2015
• Results First Posted: March 23, 2015

Record last verified: 2015-03

Locations

GB (4); AU (2); US (3); DE (4)