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

An Extension to QTI571A2301 to Evaluate the Long-term Safety, Tolerability and Efficacy of Oral QTI571 (Imatinib) in the Treatment of Severe Pulmonary Arterial Hypertension: IMPRES Extension

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Imatinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T6G 2B7
      • Novartis Investigative Site
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
• France
  • Clamart Cedex, France, 92141
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 12683
    • Novartis Investigative Site
  • Berlin, Germany, 12552
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Köln, Germany, 50937
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Regensburg, Germany, 93053
    • Novartis Investigative Site
  • Würzburg, Germany, 97080
    • Novartis Investigative Site
• Italy
  • (pv)
    • Pavia, (pv), Italy, 27100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
• Japan
  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 701-1192
      • Novartis Investigative Site
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • Novartis Investigative Site
    • Mitaka-city, Tokyo, Japan, 181-8611
      • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 120-752
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 110 744
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 135-710
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• Switzerland
  • St. Gallen, Switzerland, 9007
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, NW3 3QG
    • Novartis Investigative Site
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Novartis Investigative Site
  • Newcastle
    • Newcastle Upon Tyne, Newcastle, United Kingdom, NE7 7DN
      • Novartis Investigative Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90095
      • Novartis Investigative Site
    • San Francisco, California, United States, 94143
      • Novartis Investigative Site
  • Florida
    • Weston, Florida, United States, 33331
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Novartis Investigative Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Novartis Investigative Site
  • New York
    • Mineola, New York, United States, 11501
      • Novartis Investigative Site
    • New York, New York, United States, 10029
      • Novartis Investigative Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Novartis Investigative Site
    • Cleveland, Ohio, United States, 44195
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novartis Investigative Site
  • Oregon
    • Tualatin, Oregon, United States, 97062
      • Novartis Investigative Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
  • Wisconsin
    • Milwaulkee, Wisconsin, United States, 53215
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Core imatinib; 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; 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.; Drug: Placebo; 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.
Experimental: Core placebo; 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; 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.; Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events, Serious Adverse Events and Deaths	Adverse event monitoring was conducted throughout the study.	204 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Core Study Baseline in Six-Minute Walk Distance (6MWD)	A six minute walk test (6MWT) was performed in accordance with the guidleines of the American Thoracic Society (2002).	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	Clinical worsening events included death, overnight hospitalization for worsening of PAH, worsening of World Health Organization (WHO) functional class by at least one level (drop in WHO ), 15% decrease in the 6MWD as compared to baseline confirmed by two 6MWTs at two consecutive study visits (6MWD reduction), and drop in WHO & 6MWD reduction. Some participants have fulfilled more than one criterion. Therefore, the sum of individual components may be higher than the total number of participants with clinical worsening.	204 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: May 3, 2010
• First Submitted That Met QC Criteria: May 4, 2010
• First Posted (Estimate): May 6, 2010

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: July 24, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Pulmonary arterial hypertension, imatinib, 6MWD, pulmonary hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CQTI571A2301E1; 2009-018167-26