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

Phase 3

Terminated

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Imatinib; Drug: Placebo

• Registration Number: NCT01117987
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-05-03
• Study First Submitted QC: 2010-05-04
• Study First Posted: 2010-05-06
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Results First Submitted: 2015-04-02
• Results First Submitted QC: 2015-05-05
• Results First Posted: 2015-05-21
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-24
• Last Update Posted: 2015-08-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 144

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Core imatinib	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.
Core placebo	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.
Core imatinib	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.
Core placebo	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events, Serious Adverse Events and Deaths	204 weeks	Adverse event monitoring was conducted throughout the study.

Secondary Outcome Measures

Name	Time	Method
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	A six minute walk test (6MWT) was performed in accordance with the guidleines of the American Thoracic Society (2002).
Percentage of Participants With Incidence of Clinical Worsening Events	204 weeks	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 London, United Kingdom