Extension to QTI571A2301 to Evaluate the Long-term Safety, Tolerability and Efficacy of Imatinib in Severe Pulmonary Arterial Hypertension (PAH)

NCT01117987 | Terminated Phase 3 Results DMC

• 2 other identifiers: CQTI571A2301E12009-018167-26
• Study Type: interventional
• Target: 144
• Locations: 13 countries
• Sites: 59

Brief Summary

This is a multinational, multi center extension study. This study will provide data on the long-term safety, tolerability, and efficacy of imatinib in the treatment of severe pulmonary arterial hypertension.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension, imatinib, 6MWD, pulmonary hypertension

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events, Serious Adverse Events and Deaths

  Adverse event monitoring was conducted throughout the study.

  204 weeks

Secondary Outcomes (2)

• Change From Core Study Baseline in Six-Minute Walk Distance (6MWD)

  core study baseline, extension baseline, 12 weeks, 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 156 weeks, 204 weeks

• Percentage of Participants With Incidence of Clinical Worsening Events

  204 weeks

Study Arms (2)

Core imatinib

EXPERIMENTAL

Depending on the participants' randomized treatment in the core study, CQTI571A2301 (NCT00902174), and their completion status in the core study, participants received imatinib at 200 mg qd, 400 mg qd, or 200 mg qd with an increase to 400 mg qd after 2 weeks, if tolerated.

Drug: Imatinib; Drug: Placebo

Core placebo

EXPERIMENTAL

Depending on the participants' randomized treatment in the core study, CQTI571A2301 (NCT00902174), and their completion status in the core study, participants received imatinib at 200 mg qd, 400 mg qd, or 200 mg qd with an increase to 400 mg qd after 2 weeks, if tolerated.

Drug: Imatinib; Drug: Placebo

Interventions

Imatinib DRUG

Participants, who received imatinib 200 mg in the core study, CQTI571A2301 (NCT00902174), and completed the core study, received imatinib 200 mg every day (qd) in the extension. Participants, who were randomized to receive imatinib 400 mg in the core study and completed the core study, received imatinib 400 mg qd in the extension. Participants, who terminated early from the core study or who were randomized to placebo and completed the core study, started the extension with imatinib 200 mg qd. After 2 weeks, the dose was increased to 400 mg qd if tolerated.

Core imatinib; Core placebo

Placebo DRUG

To preserve the blind of the core study until the core study, CQTI571A2301 (NCT00902174), was completed, participants received a blinded study drug package containing a 70-tablet bottle of imatinib and a 70-tablet bottle of matching placebo.

Core imatinib; Core placebo

Eligibility Criteria

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

You may qualify if:

• Patients who participated in CQTI571A2301 clinical trial and completed the week 24 visit of the study protocol, including all Study Completion assessments
• Patients who withdrew from the CQTI571A2301 study prematurely for reasons not related to study drug or not related to a safety issue but performed all Study Completion assessments

You may not qualify if:

• Patients with a pulmonary capillary wedge pressure \> 15 mmHg at time of Study Completion assessments in core protocol CQTI571A2301. If pulmonary capillary wedge pressure is not attainable, then a left atrial pressure measurement may be used in its place.
• LVEF \< 45%
• Patients with thrombocytopenia, platelet count \< 50E9/L (50E3/µL)
• Patients with uncontrolled systemic arterial hypertension, systolic \> 160 mmHg or diastolic \> 90 mmHg
• Patients with a QTcF \> 450 ms for males and \> 470 ms for females in the absence of right branch bundle block (based on Visit 1 ECG if required to be performed)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (59)

Novartis Investigative Site

Birmingham, Alabama, 35294-0006, United States

Location

Novartis Investigative Site

Phoenix, Arizona, 85013, United States

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Novartis Investigative Site

Los Angeles, California, 90095, United States

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Novartis Investigative Site

San Francisco, California, 94143, United States

Location

Novartis Investigative Site

Weston, Florida, 33331, United States

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Novartis Investigative Site

Chicago, Illinois, 60637, 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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Novartis Investigative Site

Omaha, Nebraska, 68131, United States

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Novartis Investigative Site

Mineola, New York, 11501, United States

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Novartis Investigative Site

New York, New York, 10029, 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, 44195, United States

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Novartis Investigative Site

Oklahoma City, Oklahoma, 73104, United States

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Novartis Investigative Site

Tualatin, Oregon, 97062, United States

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Novartis Investigative Site

Pittsburgh, Pennsylvania, 15213, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

Milwaulkee, Wisconsin, 53215, United States

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Novartis Investigative Site

Vienna, A-1090, Austria

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Calgary, Alberta, T1Y 6J4, Canada

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Novartis Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

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Novartis Investigative Site

London, Ontario, N6A 4G5, Canada

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Novartis Investigative Site

Clamart, 92141, France

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Novartis Investigative Site

Berlin, 12552, Germany

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Novartis Investigative Site

Berlin, 12683, Germany

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Novartis Investigative Site

Cologne, 50937, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Hamburg, 20246, Germany

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Novartis Investigative Site

Hanover, 30625, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Homburg, 66421, Germany

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Novartis Investigative Site

Marburg, 35039, Germany

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Novartis Investigative Site

München, 81377, Germany

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Novartis Investigative Site

Regensburg, 93053, Germany

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Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Pavia, (pv), 27100, Italy

Location

Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Sendai, Miyagi, 980-8574, Japan

Location

Novartis Investigative Site

Okayama, Okayama-ken, 701-1192, Japan

Location

Novartis Investigative Site

Hamamatsu, Shizuoka, 431-3192, Japan

Location

Novartis Investigative Site

Bunkyo-ku, Tokyo, 113-8655, Japan

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Novartis Investigative Site

Mitaka, Tokyo, 181-8611, Japan

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Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

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Novartis Investigative Site

Seoul, Korea, 110 744, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 120-752, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 135-710, South Korea

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28041, Spain

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

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Novartis Investigative Site

Newcastle upon Tyne, Newcastle, NE7 7DN, United Kingdom

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Novartis Investigative Site

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Novartis Investigative Site

London, NW3 3QG, United Kingdom

Location

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

Limitations and Caveats

Within primary outcome measure (OM) #1, an additional death (\>30 days post study completion) was included in the imatinib arm. The participant flow and secondary OM #2 reflect deaths that occurred up to and including 30 days post study completion.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Trialandresults.registries@novartis.com

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2010
• First Posted: May 6, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: August 13, 2015
• Results First Posted: May 21, 2015

Record last verified: 2015-07

Locations

IT (2); DE (12); NL (1); ES (6); FR (1); GB (4); CA (3); BE (1); JP (5); KR (3); AU (1); CH (1); US (19)