Hypertension, Pulmonary, Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Ambrisentan
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)
Interventions
DRUGGSK1325760A
2.5mg, 5mg or 10mg/day, po, GSK1325760A treatment will be continued until its approval by the MHLW.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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* Subjects who have been withdrawn from the Phase II/III study.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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Event | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 164.14) | 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 | Up to 164.14 weeks | 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 Six Minutes Walk Distance (6MWD) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 | Baseline and 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 Cardiac Output (CO) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion | Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 156.14) | 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 | Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 164.14) | 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). |
| 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 | Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 153) | 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 the Borg Dyspnea Index (BDI) at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion | Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 159.85) | 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). |
Countries
Japan
Participant flow
Pre-assignment details
Study AMB107818 was an extension study of Study AMB107816 (NCT00540436).
Participants by arm
| Arm | Count |
|---|---|
| GSK1325760A Dose of GSK1325760A could be adjusted up to 10 milligrams, once daily, as appropriate according to a participant's condition. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Liver Function Test Abnormality | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | GSK1325760A |
|---|---|
| Age Continuous | 45.6 Years STANDARD_DEVIATION 12.62 |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 21 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 8 / 21 |
Outcome results
Primary
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.
Time frame: For 140.57 weeks at maximum, starting from Week 24
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1325760A | Number of Participants With Adverse Events Categorized by Severity | Mild | 12 participants |
| GSK1325760A | Number of Participants With Adverse Events Categorized by Severity | Moderate | 5 participants |
| GSK1325760A | Number of Participants With Adverse Events Categorized by Severity | Severe | 4 participants |
Primary
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.
Time frame: For 140.57 weeks at maximum, starting from Week 24
Population: Safety Population: Participants who had received at least one dose of the investigational product
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK1325760A | Number of Participants With Any Adverse Event | 21 participants |
Secondary
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).
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)
Population: FAS. Participants were followed for different lengths of time; thus, not all participants were analyzed at all study weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1325760A | 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 | Week 84, n=19 | -118.78 nanograms per liter (ng/L) | Standard Deviation 160.738 |
| GSK1325760A | 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 | Week 96, n=19 | -115.73 nanograms per liter (ng/L) | Standard Deviation 146.038 |
| GSK1325760A | 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 | Week 24, n=20 | -109.54 nanograms per liter (ng/L) | Standard Deviation 170.495 |
| GSK1325760A | 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 | Week 36, n=21 | -96.98 nanograms per liter (ng/L) | Standard Deviation 167.736 |
| GSK1325760A | 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 | Week 48, n=21 | -70.40 nanograms per liter (ng/L) | Standard Deviation 211.457 |
| GSK1325760A | 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 | Week 60, n=21 | -79.89 nanograms per liter (ng/L) | Standard Deviation 232.876 |
| GSK1325760A | 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 | Week 72, n=20 | -81.36 nanograms per liter (ng/L) | Standard Deviation 204.379 |
| GSK1325760A | 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 | Week 108, n=19 | -117.07 nanograms per liter (ng/L) | Standard Deviation 183.77 |
| GSK1325760A | 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 | Week 120, n=18 | -113.23 nanograms per liter (ng/L) | Standard Deviation 164.368 |
| GSK1325760A | 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 | Week 132, n=13 | -140.93 nanograms per liter (ng/L) | Standard Deviation 215.436 |
| GSK1325760A | 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 | Week 144, n=10 | -138.17 nanograms per liter (ng/L) | Standard Deviation 226.688 |
| GSK1325760A | 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 | Week 156, n=6 | -146.52 nanograms per liter (ng/L) | Standard Deviation 218.553 |
| GSK1325760A | 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 | Withdrawal/Completion, n=20 | -62.72 nanograms per liter (ng/L) | Standard Deviation 260.373 |
Secondary
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).
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)
Population: FAS. Participants were followed for different lengths of time; thus, not all participants were analyzed at all study weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1325760A | 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 | Week 24, n=20 | 0.425 Liters per minute (L/min) | Standard Deviation 1.6453 |
| GSK1325760A | 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 | Week 36, n=20 | 0.291 Liters per minute (L/min) | Standard Deviation 1.6786 |
| GSK1325760A | 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 | Week 48, n=20 | 0.227 Liters per minute (L/min) | Standard Deviation 1.5546 |
| GSK1325760A | 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 | Week 60, n=20 | 0.430 Liters per minute (L/min) | Standard Deviation 1.2865 |
| GSK1325760A | 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 | Week 72, n=19 | -0.002 Liters per minute (L/min) | Standard Deviation 1.4237 |
| GSK1325760A | 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 | Week 84, n=18 | 0.151 Liters per minute (L/min) | Standard Deviation 1.5211 |
| GSK1325760A | 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 | Week 96, n=18 | 0.025 Liters per minute (L/min) | Standard Deviation 1.3813 |
| GSK1325760A | 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 | Week 108, n=17 | 0.175 Liters per minute (L/min) | Standard Deviation 1.6398 |
| GSK1325760A | 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 | Week 120, n=17 | 0.285 Liters per minute (L/min) | Standard Deviation 1.2126 |
| GSK1325760A | 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 | Week 132, n=13 | 0.068 Liters per minute (L/min) | Standard Deviation 1.4774 |
| GSK1325760A | 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 | Week 144, n=10 | 0.391 Liters per minute (L/min) | Standard Deviation 1.1643 |
| GSK1325760A | 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 | Week 156, n=5 | 0.458 Liters per minute (L/min) | Standard Deviation 0.5779 |
| GSK1325760A | 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 | Withdrawal/Completion, n=7 | 0.257 Liters per minute (L/min) | Standard Deviation 1.1571 |
Secondary
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).
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and Withdrawal/Completion (up to Week 153)
Population: FAS. Participants were followed for different lengths of time; thus, not all participants were analyzed at all study weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1325760A | 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 | Week 24, n=19 | -9.96 millimeters of mercury (mmHg) | Standard Deviation 7.419 |
| GSK1325760A | 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 | Week 36, n=19 | -8.16 millimeters of mercury (mmHg) | Standard Deviation 8.969 |
| GSK1325760A | 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 | Week 48, n=19 | -7.06 millimeters of mercury (mmHg) | Standard Deviation 10.064 |
| GSK1325760A | 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 | Week 60, n=18 | -5.44 millimeters of mercury (mmHg) | Standard Deviation 14.839 |
| GSK1325760A | 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 | Week 72, n=18 | -10.68 millimeters of mercury (mmHg) | Standard Deviation 10.661 |
| GSK1325760A | 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 | Week 84, n=15 | -9.23 millimeters of mercury (mmHg) | Standard Deviation 14.241 |
| GSK1325760A | 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 | Week 96, n=16 | -13.33 millimeters of mercury (mmHg) | Standard Deviation 13.108 |
| GSK1325760A | 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 | Week 108, n=16 | -10.87 millimeters of mercury (mmHg) | Standard Deviation 10.786 |
| GSK1325760A | 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 | Week 120, n=15 | -10.56 millimeters of mercury (mmHg) | Standard Deviation 10.011 |
| GSK1325760A | 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 | Week 132, n=10 | -13.30 millimeters of mercury (mmHg) | Standard Deviation 10.592 |
| GSK1325760A | 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 | Week 144, n=8 | -12.04 millimeters of mercury (mmHg) | Standard Deviation 9.364 |
| GSK1325760A | 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 | Week 156, n=6 | -13.85 millimeters of mercury (mmHg) | Standard Deviation 8.9 |
| GSK1325760A | 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 | Withdrawal/Completion, n=6 | -10.72 millimeters of mercury (mmHg) | Standard Deviation 14.972 |
Secondary
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.
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156
Population: Full Analysis Set (FAS): All participants registered, with the exception of those who did not receive any dose of the investigational product and those who had no efficacy assessment after treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1325760A | 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 | Week 24 | 53.55 meters | Standard Deviation 52.951 |
| GSK1325760A | 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 | Week 36 | 51.90 meters | Standard Deviation 61.141 |
| GSK1325760A | 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 | Week 48 | 59.61 meters | Standard Deviation 53.415 |
| GSK1325760A | 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 | Week 60 | 46.38 meters | Standard Deviation 56.871 |
| GSK1325760A | 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 | Week 72 | 59.86 meters | Standard Deviation 59.667 |
| GSK1325760A | 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 | Week 84 | 58.11 meters | Standard Deviation 64.244 |
| GSK1325760A | 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 | Week 96 | 49.84 meters | Standard Deviation 57.571 |
| GSK1325760A | 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 | Week 108 | 56.38 meters | Standard Deviation 67.131 |
| GSK1325760A | 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 | Week 120 | 58.66 meters | Standard Deviation 66.633 |
| GSK1325760A | 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 | Week 132 | 54.42 meters | Standard Deviation 66.402 |
| GSK1325760A | 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 | Week 144 | 54.83 meters | Standard Deviation 67.739 |
| GSK1325760A | 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 | Week 156 | 49.19 meters | Standard Deviation 78.369 |
Secondary
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).
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)
Population: FAS. Participants were followed for different lengths of time; thus, not all participants were analyzed at all study weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1325760A | 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 | Week 24, n=21 | -0.79 scores on a scale | Standard Deviation 1.67 |
| GSK1325760A | 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 | Week 36, n=21 | -0.57 scores on a scale | Standard Deviation 2.254 |
| GSK1325760A | 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 | Week 48, n=20 | -1.00 scores on a scale | Standard Deviation 2.242 |
| GSK1325760A | 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 | Week 60, n=21 | -1.00 scores on a scale | Standard Deviation 2.372 |
| GSK1325760A | 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 | Week 72, n=18 | -1.08 scores on a scale | Standard Deviation 2.433 |
| GSK1325760A | 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 | Week 84, n=18 | -1.31 scores on a scale | Standard Deviation 2.438 |
| GSK1325760A | 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 | Week 96, n=17 | -0.74 scores on a scale | Standard Deviation 2.617 |
| GSK1325760A | 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 | Week 108, n=18 | -0.58 scores on a scale | Standard Deviation 2.574 |
| GSK1325760A | 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 | Week 120, n=16 | -0.94 scores on a scale | Standard Deviation 2.732 |
| GSK1325760A | 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 | Week 132, n=10 | 1.30 scores on a scale | Standard Deviation 2.371 |
| GSK1325760A | 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 | Week 144, n=7 | 1.21 scores on a scale | Standard Deviation 1.776 |
| GSK1325760A | 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 | Week 156, n=4 | -0.13 scores on a scale | Standard Deviation 1.436 |
| GSK1325760A | 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 | Withdrawal/Completion, n=7 | -0.36 scores on a scale | Standard Deviation 4.308 |
Secondary
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).
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)
Population: FAS. Participants were followed for different lengths of time; thus, not all participants were analyzed at all study weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1325760A | 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 | Improved at Week 24, n=21 | 10 participants |
| GSK1325760A | 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 | No change at Week 24, n=21 | 11 participants |
| GSK1325760A | 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 | Deteriorated at Week 24, n=21 | 0 participants |
| GSK1325760A | 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 | Improved at Week 36, n=21 | 10 participants |
| GSK1325760A | 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 | No change at Week 36, n=21 | 11 participants |
| GSK1325760A | 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 | Deteriorated at Week 36, n=21 | 0 participants |
| GSK1325760A | 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 | Improved at Week 48, n=21 | 11 participants |
| GSK1325760A | 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 | No change at Week 48, n=21 | 9 participants |
| GSK1325760A | 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 | Deteriorated at Week 48, n=21 | 1 participants |
| GSK1325760A | 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 | Improved at Week 60, n=21 | 11 participants |
| GSK1325760A | 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 | No change at Week 60, n=21 | 10 participants |
| GSK1325760A | 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 | Deteriorated at Week 60, n=21 | 0 participants |
| GSK1325760A | 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 | Improved at Week 72, n=20 | 8 participants |
| GSK1325760A | 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 | No change at Week 72, n=20 | 12 participants |
| GSK1325760A | 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 | Deteriorated at Week 72, n=20 | 0 participants |
| GSK1325760A | 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 | Improved at Week 84, n=19 | 9 participants |
| GSK1325760A | 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 | No change at Week 84, n=19 | 10 participants |
| GSK1325760A | 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 | Deteriorated at Week 84, n=19 | 0 participants |
| GSK1325760A | 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 | Improved at Week 96, n=19 | 9 participants |
| GSK1325760A | 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 | No change at Week 96, n=19 | 10 participants |
| GSK1325760A | 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 | Deteriorated at Week 96, n=19 | 0 participants |
| GSK1325760A | 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 | Improved at Week 108, n=19 | 9 participants |
| GSK1325760A | 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 | No change at Week 108, n=19 | 10 participants |
| GSK1325760A | 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 | Deteriorated at Week 108, n=19 | 0 participants |
| GSK1325760A | 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 | Improved at Week 120, n=18 | 8 participants |
| GSK1325760A | 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 | No change at Week 120, n=18 | 10 participants |
| GSK1325760A | 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 | Deteriorated at Week 120, n=18 | 0 participants |
| GSK1325760A | 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 | Improved at Week 132, n=13 | 5 participants |
| GSK1325760A | 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 | No change at Week 132, n=13 | 8 participants |
| GSK1325760A | 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 | Deteriorated at Week 132, n=13 | 0 participants |
| GSK1325760A | 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 | Improved at Week 144, n=10 | 3 participants |
| GSK1325760A | 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 | No change at Week 144, n=10 | 7 participants |
| GSK1325760A | 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 | Deteriorated at Week 144, n=10 | 0 participants |
| GSK1325760A | 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 | Improved at Week 156, n=6 | 2 participants |
| GSK1325760A | 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 | No change at Week 156, n=6 | 4 participants |
| GSK1325760A | 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 | Deteriorated at Week 156, n=6 | 0 participants |
| GSK1325760A | 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 | Improved at Withdrawal/Completion, n=20 | 10 participants |
| GSK1325760A | 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 | No change at Withdrawal/Completion, n=20 | 10 participants |
| GSK1325760A | 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 | Deteriorated at Withdrawal/Completion, n=20 | 0 participants |
Secondary
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.
Time frame: Up to 164.14 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK1325760A | 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 | Death | 0 participants |
| GSK1325760A | 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 | Lung transplantation | 0 participants |
| GSK1325760A | 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 | Hospitalization for PAH treatment | 0 participants |
| GSK1325760A | 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 | Atrial septostomy | 0 participants |
| GSK1325760A | 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 | Study discontinuation (additional medication) | 1 participants |