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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00554619
First received: November 5, 2007
Last updated: November 1, 2012
Last verified: October 2012

November 5, 2007
November 1, 2012
February 2008
January 2011   (final data collection date for primary outcome measure)
  • Number of Participants With Any Adverse Event [ Time Frame: For 140.57 weeks at maximum, starting from Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: For 140.57 weeks at maximum, starting from Week 24 ] [ Designated as safety issue: No ]
    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.
The following check at every 4 weeks -Physical examination -Adverse event -Clinical laboratory examination -Urinalysis -Vital signs The following check at every 12 weeks -Electrocardiography [ Time Frame: 24 Weeks ]
Complete list of historical versions of study NCT00554619 on ClinicalTrials.gov Archive Site
  • 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 [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 Frame: Up to 164.14 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 153) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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).
-Changes from baseline of the Phase II/III study in 6MWD, WHO Functional Classification, and Borg Dyspnea Index measured immediately after the 6MWT -Time to clinical worsening of PAH at Week 12 and 24 [ Time Frame: 24 Weeks ]
Not Provided
Not Provided
 
A Study to Evaluate GSK1325760A - a Long-Term Extension Study
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 -

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)
Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Pulmonary Arterial Hypertension
  • Hypertension, Pulmonary
Drug: GSK1325760A
2.5mg, 5mg or 10mg/day, po, GSK1325760A treatment will be continued until its approval by the MHLW.
Other Name: GSK1325760A
Experimental: GSK1325760A
Intervention: Drug: GSK1325760A
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
January 2011
January 2011   (final data collection date for primary outcome measure)

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.
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00554619
AMB107818
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP