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
  Purpose

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)

Condition Intervention Phase
Pulmonary Arterial Hypertension
Hypertension, Pulmonary
Drug: GSK1325760A
Phase 3

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 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 -

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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.


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 [ 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).


Enrollment: 21
Study Start Date: February 2008
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1325760A Drug: GSK1325760A
2.5mg, 5mg or 10mg/day, po, GSK1325760A treatment will be continued until its approval by the MHLW.
Other Name: GSK1325760A

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554619

Locations
Japan
GSK Investigational Site
Aichi, Japan, 470-1192
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, 252-0375
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
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: NCT00554619     History of Changes
Other Study ID Numbers: AMB107818
Study First Received: November 5, 2007
Results First Received: October 20, 2011
Last Updated: November 1, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Pulmonary Arterial Hypertension
Ambrisentan

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

ClinicalTrials.gov processed this record on August 28, 2014