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

• ClinicalTrials.gov Identifier: NCT01117987
• Recruitment Status: Terminated
• First Posted: May 6, 2010
• Results First Posted: May 21, 2015
• Last Update Posted: August 13, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: May 3, 2010
• First Posted Date: 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: April 2010
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: May 4, 2010): Number of patients with Adverse Events as a measure of the safety and tolerability of QTI571 [ Time Frame: 672 days ]

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Extension to QTI571A2301 to Evaluate the Long-term Safety, Tolerability and Efficacy of Imatinib in Severe Pulmonary Arterial Hypertension (PAH)
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pulmonary Arterial Hypertension

Intervention

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 5, 2015): 144
• Original Estimated Enrollment (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

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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT01117987
• Other Study ID Numbers: CQTI571A2301E1; 2009-018167-26
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: External Affairs, Novartis Pharmaceuticals
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: July 2015