Pulmonary Arterial HypertensionPhase 3NCT00554619

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

A Phase 3 study testing GSK1325760A in people with Pulmonary Arterial Hypertension and Hypertension, Pulmonary, run by GlaxoSmithKline at 11 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Any age
Conditions the study is for: Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What is being tested?: GSK1325760A
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 11 sitesJapan
Study dates: Feb 2008to Jan 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

Subjects who have been withdrawn from the Phase II/III study.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.

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

Japan11 sites

GSK Investigational Site
Aichi, 470-1192
GSK Investigational Site
Hokkaido, 060-8543
GSK Investigational Site
Hokkaido, 060-8648
GSK Investigational Site
Ishikawa, 920-8641
GSK Investigational Site
Kanagawa, 252-0375
GSK Investigational Site
Kyoto, 606-8507
GSK Investigational Site
Okayama, 701-1192
GSK Investigational Site
Okinawa, 901-0243
GSK Investigational Site
Osaka, 565-8565
GSK Investigational Site
Tokyo, 113-8655
GSK Investigational Site
Tokyo, 160-8582

Other trials in Japan

About this 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 -

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)

Conditions: Pulmonary Arterial Hypertension, Hypertension, Pulmonary
Being tested: GSK1325760A
Keywords: Pulmonary Arterial Hypertension, Ambrisentan
Medical subject headings: Pulmonary Arterial Hypertension, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK1325760ADrug
2.5mg, 5mg or 10mg/day, po, GSK1325760A treatment will be continued until its approval by the MHLW.

Study groups in NCT00554619
Study group	Role	What they receive
GSK1325760A	Experimental	Not described Receives: Drug: GSK1325760A

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: For 140.57 weeks at maximum, starting from Week 24
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.
Measured: For 140.57 weeks at maximum, starting from Week 24

Secondary outcomes (7)

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.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156
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).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 159.85)
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).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 164.14)
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.
Measured: 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).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 153)
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).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 156.14)
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).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 164.14)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Jan 2011

First posted7 Nov 2007 (estimated)
Study startFeb 2008
Primary completionJan 2011
Study completionJan 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00554619
Sponsor's protocol ID: AMB107818
Status last verified: Oct 2012
First submitted: 5 Nov 2007
Last updated: 5 Nov 2012
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 22506623

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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 -
ClinicalTrials.gov ID: NCT00554619
Acronym / sponsor ID: AMB107818
Conditions: Pulmonary Arterial Hypertension, Hypertension, Pulmonary
Keywords: Pulmonary Arterial Hypertension, Ambrisentan
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: Feb 2008
Primary completion: Jan 2011 (actual)
Study completion: Jan 2011 (actual)
First posted: 7 Nov 2007 (estimated)
Results: Posted 13 Feb 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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)

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
GSK1325760A	Experimental	Drug: GSK1325760A

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (7 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK1325760A2.5mg, 5mg or 10mg/day, po, GSK1325760A treatment will be continued until its approval by the MHLW.	Drug	GSK1325760A

Primary outcome

Number of Participants With Any Adverse Event
Time frame: For 140.57 weeks at maximum, starting from Week 24
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
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.

7 secondary outcomes

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
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)
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)
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
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)
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)
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)

Results and safety

Results posted to the registry on 13 Feb 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GSK1325760A	21	18

Primary outcome: Number of Participants With Any Adverse Event

Time frame: For 140.57 weeks at maximum, starting from Week 24. Number. Unit: participants

Measure	GSK1325760A n = 21
Value	21

Population analysed: Safety Population: Participants who had received at least one dose of the investigational product

Primary outcome: Number of Participants With Adverse Events Categorized by Severity

Time frame: For 140.57 weeks at maximum, starting from Week 24. Number. Unit: participants

Measure	GSK1325760A n = 21
Mild	12
Moderate	5
Severe	4

Population analysed: Safety Population

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious AEs were collected for 140.57 weeks at maximum, starting from Week 24.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GSK1325760A	8 of 21 (38.1%)	21 of 21 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22506623Yoshida 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GSK1325760A in people with Pulmonary Arterial Hypertension and Hypertension, Pulmonary, run by GlaxoSmithKline at 11 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Adverse Event (time frame: For 140.57 weeks at maximum, starting from Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00554619, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2012.