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

Pulmonary Arterial Hypertension Clinical Trial

— IMPRES Extn  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01117987
• Other study ID #: CQTI571A2301E1
• Secondary ID: 2009-018167-26
• Status: Terminated
• Phase: Phase 3
• First received: May 3, 2010
• Last updated: July 24, 2015
• Start date: April 2010
• Est. completion date: April 2014

Study information

• Verified date: July 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySwitzerland: SwissmedicKorea: Food and Drug AdministrationJapan: Pharmaceuticals and Medical Devices AgencyCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 144
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	London	Ontario
France	Novartis Investigative Site	Clamart Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Würzburg
Italy	Novartis Investigative Site	Pavia	(pv)
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Hamamatsu	Shizuoka
Japan	Novartis Investigative Site	Mitaka-city	Tokyo
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Netherlands	Novartis Investigative Site	Amsterdam
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	St. Gallen
United Kingdom	Novartis Investigative Site	Cambridge	Cambridgeshire
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne	Newcastle
United Kingdom	Novartis Investigative Site	Sheffield	South Yorkshire
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Milwaulkee	Wisconsin
United States	Novartis Investigative Site	Mineola	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Rochester	Minnesota
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Tualatin	Oregon
United States	Novartis Investigative Site	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events, Serious Adverse Events and Deaths	Adverse event monitoring was conducted throughout the study.	204 weeks	Yes
Secondary	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	No
Secondary	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	No