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

Purpose

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.

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: Imatinib Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

Drug Information available for: Imatinib Imatinib mesylate

Genetic and Rare Diseases Information Center resources: Pulmonary Arterial Hypertension

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Number of Participants With Adverse Events, Serious Adverse Events and Deaths [ Time Frame: 204 weeks ] [ Designated as safety issue: Yes ]
Adverse event monitoring was conducted throughout the study.

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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.


Enrollment:	144
Study Start Date:	April 2010
Study Completion Date:	April 2014
Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01117987

Show 59 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01117987 History of Changes
Other Study ID Numbers:	CQTI571A2301E1 2009-018167-26
Study First Received:	May 3, 2010
Results First Received:	April 2, 2015
Last Updated:	July 24, 2015
Health Authority:	United States: Food and Drug Administration Austria: Federal Office for Safety in Health Care Belgium: Federal Agency for Medicinal Products and Health Products France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Italy: The Italian Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Spain: Spanish Agency of Medicines Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency Switzerland: Swissmedic Korea: Food and Drug Administration Japan: Pharmaceuticals and Medical Devices Agency Canada: Health Canada

Keywords provided by Novartis:


Pulmonary arterial hypertension, imatinib, 6MWD, pulmonary hypertension

Additional relevant MeSH terms:


Hypertension Familial Primary Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Hypertension, Pulmonary Lung Diseases	Respiratory Tract Diseases Imatinib Mesylate Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016

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