Imatinib (QTI571) in Pulmonary Arterial Hypertension

NCT00902174 | Completed Phase 3 Results

• 1 other identifier: CQTI571A2301
• Study Type: interventional
• Target: 202
• Locations: 14 countries
• Sites: 95

Brief Summary

A multinational, multicenter, double blind, placebo-controlled study evaluating the efficacy and safety of imatinib as an add-on therapy in the treatment of patients with severe pulmonary arterial hypertension (PAH).

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension; Imatinib; 6MWD; Borg scale; Pulmonary hypertension

Outcome Measures

Primary Outcomes (1)

• Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks

  This standardized walk course was 30 meters in length. During the walk the participant was connected to a portable pulse oximeter via a finger probe. Participants were instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. The total distance walked (in meters) was recorded. Results were compared between the 2 groups.

  24 weeks

Secondary Outcomes (15)

• Clinical Worsening Comparing Imatinib Versus Placebo for Adjudicated Cases

  24 weeks

• Change From Baseline in Right Atrial Pressure

  baseline and week 24

• Change From Baseline in Mean Pulmonary Arterial Pressure

  baseline and week 24

• Change From Baseline in Mean Pulmonary Capillary Wedge Pressure

  baseline and week 24

• Change From Baseline in Systemic Vascular Resistance

  baseline and week 24

Study Arms (2)

imatinib mesylate

EXPERIMENTAL

Imatinib mesylate (QTI571) 200 mg once daily for two weeks, increased to 400 mg once daily if well tolerated. If 400 mg dose was not well tolerated, a down titration to 200 mg once daily was permitted.

Drug: imatinib mesylate

Placebo

PLACEBO COMPARATOR

Placebo to imatinib mesylate taken once daily. Participants receiving placebo were allowed to receive already approved PAH treatments.

Drug: Placebo

Interventions

imatinib mesylate DRUG

Two or 4 imatinib mesylate (QTI571) 100 mg film coated tablets once daily.

imatinib mesylate

Placebo DRUG

Placebo to imatinib 100 mg film coated tablets

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥18 years of age with a current diagnosis of pulmonary arterial hypertension (PAH) according to the Dana Point 2008 Meeting: World Health Organization (WHO) Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect \[Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD) or Posterior Descending Artery (PDA)\], or PAH associated with diet therapies or other drugs
• A Pulmonary Vascular Resistance (PVR) ≥ 800 dynes.sec.cm-5 (as assessed by Right Heart Catheterization (RHC) at screening or in the 3 months preceding the screening visit) despite treatment with two or more specific PAH therapies, including Endothelin Receptor Antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE5), or subcutaneous, inhaled, intravenous or oral prostacyclin analogues for ≥ 3 months. Background therapy doses were to be stable for ≥ 30 days except for warfarin and prostacyclin analogues ( ≥ 30 days but doses could vary even within the month before enrollment).
• World Health Organization functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies were to be an inhaled, subcutaneous, intravenous or oral prostacyclin analogue, unless the subject showed intolerance of prostacyclin analogues.
• MWD ≥ 150 meters and ≤ 450 meters at screening. Distances of two consecutive 6MWTs were to be within 15% of one another.

You may not qualify if:

• With a pulmonary capillary wedge pressure \> 15 mm Hg to rule out PAH secondary to left ventricular dysfunction.
• With a diagnosis of pulmonary artery or vein stenosis
• Left ventricular ejection fraction (LVEF) \< 45%
• With Disseminated Intravascular Coagulation (DIC)
• With evidence of major bleeding or intracranial hemorrhage
• With a history of elevated intracranial pressure
• With a history of latent bleeding risk such as diabetic retinopathy, gastrointestinal bleeding due to gastric or duodenal ulcers, or colitis ulcerosa
• With a QTcF \> 450 msec for males and \> 470 msec for females at screening and baseline in the absence of right bundle branch block.
• With a history of ventricular tachycardia, ventricular fibrillation or ventricular flutter
• With a history of Torsades de Pointes
• With a history of long QT syndrome
• Having undergone atrial septostomy in the 3 months prior to the screening visit

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (95)

Novartis Investigative Site

Birmingham, Alabama, 35294, United States

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Novartis Investigative Site

Phoenix, Arizona, 85013, United States

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Novartis Investigative Site

Los Angeles, California, 90024, United States

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Novartis Investigative Site

San Francisco, California, 94143, United States

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Aurora, Colorado, 80045, United States

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Novartis Investigative Site

Clearwater, Florida, 33756, United States

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Novartis Investigative Site

Miami Beach, Florida, 33140, United States

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Novartis Investigative Site

Weston, Florida, 33331, United States

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Novartis Investigative Site

Atlanta, Georgia, 30342, United States

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Novartis Investigative Site

Chicago, Illinois, 60637, United States

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Novartis Investigative Site

Baltimore, Maryland, 21205, United States

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Novartis Investigative Site

Boston, Massachusetts, 02111, United States

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Novartis Investigative Site

Boston, Massachusetts, 02114, United States

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Novartis Investigative Site

Boston, Massachusetts, 02118, United States

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Novartis Investigative Site

Rochester, Minnesota, 55905, United States

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Novartis Investigative Site

St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68131, United States

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Novartis Investigative Site

Minneola, New York, 11501-3893, United States

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New York, New York, 10029, United States

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Novartis Investigative Site

New York, New York, 10032, United States

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Novartis Investigative Site

Durham, North Carolina, 27710, United States

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Novartis Investigative Site

Cincinnati, Ohio, 45219, United States

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Novartis Investigative Site

Cleveland, Ohio, 44106, United States

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Novartis Investigative Site

Cleveland, Ohio, 44195, United States

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Oklahoma City, Oklahoma, 73104, United States

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Portland, Oregon, 97210, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Novartis Investigative Site

Pittsburgh, Pennsylvania, 15213, United States

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Novartis Investigative Site

Knoxville, Tennessee, 37934, United States

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Dallas, Texas, 75390, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

Milwaukee, Wisconsin, 53215, United States

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Innsbruck, Austria

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Vienna, Austria

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Brussels, Belgium

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Leuven, Belgium

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Calgary, Canada

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Edmonton, Canada

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London, Canada

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Montreal, Canada

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Ottawa, Canada

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Toronto, Canada

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Vancouver, Canada

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Clamart, France

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Berlin, Germany

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Cologne, Germany

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Dresden, Germany

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Giessen, Germany

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Greifswald, Germany

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Hamburg, Germany

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Hanover, Germany

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Heidelberg, Germany

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Homburg, Germany

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Löwenstein, Germany

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München, Germany

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Regensberg, Germany

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Würzberg, Germany

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Bologna, Italy

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Pavia, Italy

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Pisa, Italy

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Roma, Italy

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Bunkyō City, Japan

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Hamamatsu, Japan

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Mitaka, Japan

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Okayama, Japan

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Sendai, Japan

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Suita, Japan

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Amsterdam, Netherlands

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Seoul, South Korea

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A Coruña, Spain

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Barcelona, Spain

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Caceras, Spain

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Las Palmas de Gran Canarias, Spain

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Madrid, Spain

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Málaga, Spain

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San Cristóbal de La Laguna, Spain

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Santa Cruz de Tenerife, Spain

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Santander, Spain

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Seville, Spain

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Valencia, Spain

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Valladolid, Spain

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Lund, Sweden

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Stockholm, Sweden

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Umeå, Sweden

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Novartis Investigative Site

Uppsala, Sweden

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University Hospital Basel

Basel, Switzerland

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Novartis Investigative Site

Bern, Switzerland

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Lausanne, Switzerland

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Novartis Investigative Site

Sankt Gallen, Switzerland

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Cambridge, United Kingdom

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Novartis Investigative Site

Clydebank, United Kingdom

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London, United Kingdom

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Novartis Investigative Site

Newcastle upon Tyne, United Kingdom

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Novartis Investigative Site

Sheffield, United Kingdom

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Related Publications (4)

• Querejeta Roca G, Campbell P, Claggett B, Solomon SD, Shah AM. Right Atrial Function in Pulmonary Arterial Hypertension. Circ Cardiovasc Imaging. 2015 Nov;8(11):e003521; discussion e003521. doi: 10.1161/CIRCIMAGING.115.003521.

  PMID: 26514759 DERIVED

• Querejeta Roca G, Campbell P, Claggett B, Vazir A, Quinn D, Solomon SD, Shah AM. Impact of lowering pulmonary vascular resistance on right and left ventricular deformation in pulmonary arterial hypertension. Eur J Heart Fail. 2015 Jan;17(1):63-73. doi: 10.1002/ejhf.177. Epub 2014 Nov 4.

  PMID: 25367310 DERIVED

• Shah AM, Campbell P, Rocha GQ, Peacock A, Barst RJ, Quinn D, Solomon SD; IMPRES Investigators. Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension. Eur Heart J. 2015 Mar 7;36(10):623-32. doi: 10.1093/eurheartj/ehu035. Epub 2014 Feb 23.

  PMID: 24566799 DERIVED

• Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, Gomez-Sanchez MA, Grimminger F, Grunig E, Hassoun PM, Morrell NW, Peacock AJ, Satoh T, Simonneau G, Tapson VF, Torres F, Lawrence D, Quinn DA, Ghofrani HA. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013 Mar 12;127(10):1128-38. doi: 10.1161/CIRCULATIONAHA.112.000765. Epub 2013 Feb 12.

  PMID: 23403476 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular 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

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2009
• First Posted: May 15, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: February 17, 2016
• Results First Posted: July 16, 2013

Record last verified: 2013-06

Locations

JP (6); GB (5); FR (1); NL (1); BE (2); AU (2); KR (1); US (33); IT (4); ES (12); DE (13); SE (4); CH (4); CA (7)