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

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>

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

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Drug: GSK1325760A

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 470-1192
    • GSK Investigational Site
  • Fukuoka, Japan, 830-0011
    • GSK Investigational Site
  • Hokkaido, Japan, 060-8648
    • GSK Investigational Site
  • Hokkaido, Japan, 060-8543
    • 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, 160-8582
    • GSK Investigational Site
  • Tokyo, Japan, 113-8655
    • GSK Investigational Site
  • Tokyo, Japan, 113-8431
    • GSK Investigational Site
  • Tokyo, Japan, 143-8541
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Ambrisentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 12	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.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 24/Withdrawal	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.	Baseline and Week 24/Withdrawal
Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24	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.	Baseline and Weeks 12 and 24
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24	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.	Weeks 12 and 24
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 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.	Week 24
Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24	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).	Baseline and Weeks 12 and 24
Mean Change From Baseline in Cardiac Index (CI) at Weeks 12 and 24	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).	Baseline and Weeks 12 and 24
Mean Change From Baseline in Cardiac Output (CO) at Weeks 12 and 24	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).	Baseline and Weeks 12 and 24
Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) at Weeks 12 and 24	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).	Baseline and Weeks 12 and 24
Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 12 and 24	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).	Baseline and Weeks 12 and 24

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Yoshida S, Shirato K, Shimamura R, Nakahara N, Iwase T, Nakajima H. Efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension. Curr Med Res Opin. 2011 Sep;27(9):1827-34. doi: 10.1185/03007995.2011.605440. Epub 2011 Aug 4.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: October 5, 2007
• First Submitted That Met QC Criteria: October 5, 2007
• First Posted (Estimate): October 8, 2007

Study Record Updates

• Last Update Posted (Estimate): October 15, 2012
• Last Update Submitted That Met QC Criteria: October 11, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; 6MWD; Ambrisentan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Ambrisentan
• Other Study ID Numbers: AMB107816