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

Tracking Information
First Submitted Date ICMJE	May 3, 2010
First Posted Date ICMJE	May 6, 2010
Results First Submitted Date	April 2, 2015
Results First Posted Date	May 21, 2015
Last Update Posted Date	August 13, 2015
Study Start Date ICMJE	April 2010
Actual Primary Completion Date	April 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 5, 2015)	Number of Participants With Adverse Events, Serious Adverse Events and Deaths [ Time Frame: 204 weeks ]; Adverse event monitoring was conducted throughout the study.
Original Primary Outcome Measures ICMJE; (submitted: May 4, 2010)	Number of patients with Adverse Events as a measure of the safety and tolerability of QTI571 [ Time Frame: 672 days ]
Change History	Complete list of historical versions of study NCT01117987 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 5, 2015)	Change From Core Study Baseline in Six-Minute Walk Distance (6MWD) [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures ICMJE; (submitted: May 4, 2010)	Change in Six-Minute Walk Distance (6MWD) from baseline [ Time Frame: 672 days ]; Time to clinical worsening (TTCW) endpoints [ Time Frame: 672 days ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Extension to QTI571A2301 to Evaluate the Long-term Safety, Tolerability and Efficacy of Imatinib in Severe Pulmonary Arterial Hypertension (PAH)
Official Title ICMJE	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
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 Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Pulmonary Arterial Hypertension
Intervention ICMJE	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.
Study Arms	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. Interventions: Drug: Imatinib Drug: 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. Interventions: Drug: Imatinib Drug: Placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: May 5, 2015)	144
Original Estimated Enrollment ICMJE; (submitted: May 4, 2010)	160
Actual Study Completion Date	April 2014
Actual Primary Completion Date	April 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Austria, Belgium, Canada, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Spain, Switzerland, United Kingdom, United States
Removed Location Countries	Sweden
Administrative Information
NCT Number ICMJE	NCT01117987
Other Study ID Numbers ICMJE	CQTI571A2301E1; 2009-018167-26
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Novartis ( Novartis Pharmaceuticals )
Study Sponsor ICMJE	Novartis Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account	Novartis
Verification Date	July 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP