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Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00540436
First received: October 5, 2007
Last updated: October 11, 2012
Last verified: October 2012
History of Changes
  Purpose

The primary objective of this study is to evaluate the effect of GSK1325760A on improvement in exercise capacity in subjects with pulmonary arterial hypertension (PAH).

The secondary objectives of this study are to evaluate administration of GSK1325760A on:

  • The safety and tolerability
  • Improvement of PAH
  • The steady-state plasma pharmacokinetics of GSK1325760A

Condition Intervention Phase
Hypertension, Pulmonary
 Drug: GSK1325760A
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study AMB107816, Clinical Evaluation of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension (PAH)- An Open-Label Phase II/III Study to Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A -<Classification: Exploratory and Confirmatory Clinical Trial>

Resource links provided by NLM:

Drug Information available for: Ambrisentan
U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Mean change from baseline was calculated as the Week 12 value minus the baseline value. 6MWD was measured by a 6 minute walk test. This test measures the distance that a subject can walk in a period of 6 minutes.


Secondary Outcome Measures:
  • Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 24/Withdrawal [ Time Frame: Baseline and Week 24/Withdrawal ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 24/Withdrawal value minus the basline value. 6MWD was measured by a 6 minute walk test. This test measures the distance that a subject can walk in a period of 6 minutes. Imputation technique was last observation carried forward.

  • Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum). Change from baseline was calculated as the Week 12 and 24 values minus the baseline values. The BDI indicates the degree of breathlessness after completion of the 6 minute walk test. The BDI scale was assessed by each participant. Imputation technique was last observation carried forward.

  • Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 [ Time Frame: Weeks 12 and 24 ] [ Designated as safety issue: No ]
    There are four grades for WHO FC (class I = none, Class IV = most severe). The WHO FC indicates the severity of Pulmonary Arterial Hypertension and is an adaptation of the New York Heart Association classification. It was assessed by the investigator. Imputation technique was last observation carried forward.

  • Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Time to clinical worsening is defined as the time from baseline to the first occurrence of death, lung transplantation, hospitalization for PAH treatment, atrial septostomy, or study discontinuation due to change to other PAH treatment. Time to clinical worsening is measured as the number of participants who experienced these events during 24 weeks.

  • Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    mPAP and mRAP are measures of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

  • Mean Change From Baseline in Cardiac Index (CI) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    CI is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

  • Mean Change From Baseline in Cardiac Output (CO) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    CO is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

  • Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    PVR is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

  • Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. BNP is a surrogate maker of heart failure and was measured by a central laboratory. Observed data analysis (no imputation techniques).


Enrollment: 25
Study Start Date: August 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1325760A
Single arm safety and efficacy
 Drug: GSK1325760A
Primary evaluation period: 5 mg/day, po, 12 weeks. Dose adjustment period: 2.5 mg, 5 mg or 10 mg/day, po, 12 weeks.
Other Name: Ambrisentan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) in clinical classification of Pulmonary Hypertension Group1
  • The mean right heart catheterization parameters measured from 6 months prior to the administration of the investigational drug must meet the criteria below:
  • Mean pulmonary arterial pressure (mPAP) of >25 mmHg
  • Pulmonary vascular resistance (PVR) of >3 mmHg/L/min
  • Mean pulmonary capillary wedge pressure or left ventricular end diastolic pressure of <15 mmHg (if measurable)
  • The measured six minutes walk distance (6MWD) at screening visit is in the range of =>150m and <=450m
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00540436

Locations
Japan
GSK Investigational Site
Aichi, Japan, 470-1192
GSK Investigational Site
Fukuoka, Japan, 830-0011
GSK Investigational Site
Hokkaido, Japan, 060-8543
GSK Investigational Site
Hokkaido, Japan, 060-8648
GSK Investigational Site
Ishikawa, Japan, 920-8641
GSK Investigational Site
Kanagawa, Japan, 228-8555
GSK Investigational Site
Kyoto, Japan, 606-8507
GSK Investigational Site
Okayama, Japan, 701-1192
GSK Investigational Site
Okinawa, Japan, 901-0243
GSK Investigational Site
Osaka, Japan, 565-8565
GSK Investigational Site
Shizuoka, Japan, 431-3192
GSK Investigational Site
Tokyo, Japan, 113-8431
GSK Investigational Site
Tokyo, Japan, 143-8541
GSK Investigational Site
Tokyo, Japan, 113-8655
GSK Investigational Site
Tokyo, Japan, 160-8582
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00540436     History of Changes
Other Study ID Numbers: AMB107816
Study First Received: October 5, 2007
Results First Received: August 10, 2009
Last Updated: October 11, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Ambrisentan
Pulmonary Arterial Hypertension
6MWD

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
 Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on May 16, 2013