Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension
Primary Purpose
Hypertension, Pulmonary
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
GSK1325760A
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring Ambrisentan, Pulmonary Arterial Hypertension, 6MWD
Eligibility 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
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GSK1325760A
Arm Description
Single arm safety and efficacy
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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).
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).
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).
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00540436
Brief Title
Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension
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>
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
Ambrisentan, Pulmonary Arterial Hypertension, 6MWD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK1325760A
Arm Type
Experimental
Arm Description
Single arm safety and efficacy
Intervention Type
Drug
Intervention Name(s)
GSK1325760A
Other Intervention Name(s)
Ambrisentan
Intervention Description
Primary evaluation period: 5 mg/day, po, 12 weeks. Dose adjustment period: 2.5 mg, 5 mg or 10 mg/day, po, 12 weeks.
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 12
Description
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.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 24/Withdrawal
Description
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.
Time Frame
Baseline and Week 24/Withdrawal
Title
Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24
Description
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.
Time Frame
Baseline and Weeks 12 and 24
Title
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24
Description
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.
Time Frame
Weeks 12 and 24
Title
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
Description
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.
Time Frame
Week 24
Title
Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24
Description
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).
Time Frame
Baseline and Weeks 12 and 24
Title
Mean Change From Baseline in Cardiac Index (CI) at Weeks 12 and 24
Description
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).
Time Frame
Baseline and Weeks 12 and 24
Title
Mean Change From Baseline in Cardiac Output (CO) at Weeks 12 and 24
Description
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).
Time Frame
Baseline and Weeks 12 and 24
Title
Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) at Weeks 12 and 24
Description
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).
Time Frame
Baseline and Weeks 12 and 24
Title
Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 12 and 24
Description
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).
Time Frame
Baseline and Weeks 12 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
470-1192
Country
Japan
Facility Name
GSK Investigational Site
City
Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
060-8543
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
GSK Investigational Site
City
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
228-8555
Country
Japan
Facility Name
GSK Investigational Site
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Facility Name
GSK Investigational Site
City
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Facility Name
GSK Investigational Site
City
Okinawa
ZIP/Postal Code
901-0243
Country
Japan
Facility Name
GSK Investigational Site
City
Osaka
ZIP/Postal Code
565-8565
Country
Japan
Facility Name
GSK Investigational Site
City
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
143-8541
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
160-8582
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
21812736
Citation
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.
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Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension
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