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A Study to Evaluate GSK1325760A - a Long-Term Extension Study

Primary Purpose

Pulmonary Arterial Hypertension, Hypertension, Pulmonary

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
GSK1325760A
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Arterial Hypertension, Ambrisentan

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects who complete the 24-week administration of the Phase II/III study (Study No.AMB107816)
  • Subjects who are assessed that the long-term extension administration of GSK1325760A is appropriate in the judgement of the investigator or subinvestigator
  • Subjects who request the long-term extension administration of GSK1325760A, and agree to newly sign the informed consent form

Exclusion Criteria:

  • Subjects who have been withdrawn from the Phase II/III study.
  • Female subjects who wish to become pregnant.
  • Treatment with other PAH medication is needed.
  • A worsening of 2 or more levels of the WHO Functional Classification (see Appendix 2.1) comparing with the baseline of Phase II/III study (Study No.AMB107816).
  • Worsening of right ventricular failure (e.g. as indicated by increased jugular venous pressure, new/worsened hepatomegaly, ascites, or peripheral edema) during Phase II/III study (Study No.AMB107816).
  • Rapidly progressing cardiac, hepatic or renal failure during Phase II/III study (Study No.AMB107816).
  • Participation to the long-term extension study is considered as inappropriate in the judgment of the investigator or subinvestigator.

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GSK1325760A

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Any Adverse Event
An adverse event was defined as any untoward medical occurrence in a participant, temporally associated with the use of an investigational product, whether or not considered related to the investigational product.
Number of Participants With Adverse Events Categorized by Severity
The severity of adverse events was assessed by the investigator; events were assigned to one of the following categories: mild, an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate, an event that was sufficiently discomforting to interfere with normal everyday activities; and severe, an event that prevented normal everyday activities.

Secondary Outcome Measures

Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156
Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 minus the baseline value. 6MWD was measured by a 6-minute walk test. This test measures the distance that a participant can walk in a period of 6 minutes. Imputation technique was last observation carried forward, which was used in an attempt to compensate for missing data. For each participant, missing values were replaced with the last observed value.
Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. The BDI scale was assessed by each participant. Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. Observed data analysis (no imputation technique).
Number of Participants With the Indicated Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
There are four grades for the 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. Observed data analysis (no imputation technique).
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH), Assessed as the First Occurrence of a Particular Event
Time to clinical worsening was defined as the time from baseline to the first occurrence of death, lung transplantation, hospitalization for PAH treatment, atrial septostomy (a surgical procedure in which a small hole is made in the wall between the left and right atria of the heart), or study discontinuation due to change to other PAH treatment. Time to clinical worsening was measured as the number of participants who experienced these events up to 164.14 weeks.
Mean Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
mPAP is a measure of cardiopulmonary hemodynamics (echocardiography). Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. Observed data analysis (no imputation technique).
Mean Change From Baseline in Cardiac Output (CO) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
CO is a measure of cardiopulmonary hemodynamics (echocardiography). Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. Observed data analysis (no imputation technique).
Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. BNP is a surrogate marker of heart failure and was measured by a central laboratory. Observed data analysis (no imputation techniques).

Full Information

First Posted
November 5, 2007
Last Updated
November 1, 2012
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00554619
Brief Title
A Study to Evaluate GSK1325760A - a Long-Term Extension Study
Official Title
Study AMB107818, Clinical Evaluation of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension (PAH)- An Open Label Study of GSK1325760A to Evaluate the Safety and Efficacy of GSK1325760A - a Long-term Extension Study -
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (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 safety of long-term administration of GSK1325760A in patients with PAH. The secondary objectives of this study are to evaluate long-term administration of GSK1325760A on: Improvement in exercise capacity (six-minutes walk distance: 6MWD), change in WHO Functional Classification and time to clinical worsening of PAH Change in the Borg Dyspnea Index (assessed immediately following the six-minute walk test [6MWT]) Change in plasma brain natriuretic peptide (BNP) levels Cardiopulmonary hemodynamics parameters (as measured by echocardiography)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension, Hypertension, Pulmonary
Keywords
Pulmonary Arterial Hypertension, Ambrisentan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GSK1325760A
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GSK1325760A
Intervention Description
2.5mg, 5mg or 10mg/day, po, GSK1325760A treatment will be continued until its approval by the MHLW.
Primary Outcome Measure Information:
Title
Number of Participants With Any Adverse Event
Description
An adverse event was defined as any untoward medical occurrence in a participant, temporally associated with the use of an investigational product, whether or not considered related to the investigational product.
Time Frame
For 140.57 weeks at maximum, starting from Week 24
Title
Number of Participants With Adverse Events Categorized by Severity
Description
The severity of adverse events was assessed by the investigator; events were assigned to one of the following categories: mild, an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate, an event that was sufficiently discomforting to interfere with normal everyday activities; and severe, an event that prevented normal everyday activities.
Time Frame
For 140.57 weeks at maximum, starting from Week 24
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156
Description
Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 minus the baseline value. 6MWD was measured by a 6-minute walk test. This test measures the distance that a participant can walk in a period of 6 minutes. Imputation technique was last observation carried forward, which was used in an attempt to compensate for missing data. For each participant, missing values were replaced with the last observed value.
Time Frame
Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156
Title
Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
Description
The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. The BDI scale was assessed by each participant. Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. Observed data analysis (no imputation technique).
Time Frame
Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 159.85)
Title
Number of Participants With the Indicated Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
Description
There are four grades for the 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. Observed data analysis (no imputation technique).
Time Frame
Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 164.14)
Title
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH), Assessed as the First Occurrence of a Particular Event
Description
Time to clinical worsening was defined as the time from baseline to the first occurrence of death, lung transplantation, hospitalization for PAH treatment, atrial septostomy (a surgical procedure in which a small hole is made in the wall between the left and right atria of the heart), or study discontinuation due to change to other PAH treatment. Time to clinical worsening was measured as the number of participants who experienced these events up to 164.14 weeks.
Time Frame
Up to 164.14 weeks
Title
Mean Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
Description
mPAP is a measure of cardiopulmonary hemodynamics (echocardiography). Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. Observed data analysis (no imputation technique).
Time Frame
Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 153)
Title
Mean Change From Baseline in Cardiac Output (CO) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
Description
CO is a measure of cardiopulmonary hemodynamics (echocardiography). Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. Observed data analysis (no imputation technique).
Time Frame
Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 156.14)
Title
Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion
Description
Change from baseline was calculated as each value at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion minus the baseline value. BNP is a surrogate marker of heart failure and was measured by a central laboratory. Observed data analysis (no imputation techniques).
Time Frame
Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 164.14)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects who complete the 24-week administration of the Phase II/III study (Study No.AMB107816) Subjects who are assessed that the long-term extension administration of GSK1325760A is appropriate in the judgement of the investigator or subinvestigator Subjects who request the long-term extension administration of GSK1325760A, and agree to newly sign the informed consent form Exclusion Criteria: Subjects who have been withdrawn from the Phase II/III study. Female subjects who wish to become pregnant. Treatment with other PAH medication is needed. A worsening of 2 or more levels of the WHO Functional Classification (see Appendix 2.1) comparing with the baseline of Phase II/III study (Study No.AMB107816). Worsening of right ventricular failure (e.g. as indicated by increased jugular venous pressure, new/worsened hepatomegaly, ascites, or peripheral edema) during Phase II/III study (Study No.AMB107816). Rapidly progressing cardiac, hepatic or renal failure during Phase II/III study (Study No.AMB107816). Participation to the long-term extension study is considered as inappropriate in the judgment of the investigator or subinvestigator.
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
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
252-0375
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
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
160-8582
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
22506623
Citation
Yoshida S, Shirato K, Shimamura R, Iwase T, Aoyagi N, Nakajima H. Long-term safety and efficacy of ambrisentan in Japanese adults with pulmonary arterial hypertension. Curr Med Res Opin. 2012 Jun;28(6):1069-76. doi: 10.1185/03007995.2012.685930. Epub 2012 May 15. Erratum In: Curr Med Res Opin. 2012 Jun;28(6):1076.
Results Reference
derived

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A Study to Evaluate GSK1325760A - a Long-Term Extension Study

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