Trial Outcomes & Findings for Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension (NCT NCT00540436)

NCT ID: NCT00540436

Last Updated: 2012-10-15

Results Overview

Mean change from baseline was calculated as the Week 12 value minus the baseline value. 6MWD was measured by a 6 minute walk test. This test measures the distance that a subject can walk in a period of 6 minutes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2012-10-15

Participant Flow

Participant milestones

Measure	GSK1325760A First Treatment Period: GSK1325760A 5 mg once a day. Second Treatment Period: GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition).
First 12-Week Treatment Period STARTED	25
First 12-Week Treatment Period COMPLETED	22
First 12-Week Treatment Period NOT COMPLETED	3
Second 12-Week Treatment Period STARTED	22
Second 12-Week Treatment Period COMPLETED	21
Second 12-Week Treatment Period NOT COMPLETED	1

Reasons for withdrawal

Measure	GSK1325760A First Treatment Period: GSK1325760A 5 mg once a day. Second Treatment Period: GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition).
First 12-Week Treatment Period Adverse Event	1
First 12-Week Treatment Period Withdrawal by Subject	1
First 12-Week Treatment Period Initiation of prohibited medication	1
Second 12-Week Treatment Period Adverse Event	1

Baseline Characteristics

Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition).
Age Continuous	45.5 years STANDARD_DEVIATION 13.66 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Japanese Heritage	25 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Full Analysis Set (FAS): all participants registered, with the exception of those who had not received any dose of the investigational product and those who had no efficacy assessment after administration of the investigational product. Imputation technique was last observation carried forward.

Mean change from baseline was calculated as the Week 12 value minus the baseline value. 6MWD was measured by a 6 minute walk test. This test measures the distance that a subject can walk in a period of 6 minutes.

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 12	33.49 Meters Standard Deviation 43.236

SECONDARY outcome

Timeframe: Baseline and Week 24/Withdrawal

Population: Full Analysis Set

Change from baseline was calculated as the Week 24/Withdrawal value minus the basline value. 6MWD was measured by a 6 minute walk test. This test measures the distance that a subject can walk in a period of 6 minutes. Imputation technique was last observation carried forward.

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 24/Withdrawal	46.82 Meters Standard Deviation 52.705

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 24

Population: Full Analysis Set

The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum). Change from baseline was calculated as the Week 12 and 24 values minus the baseline values. The BDI indicates the degree of breathlessness after completion of the 6 minute walk test. The BDI scale was assessed by each participant. Imputation technique was last observation carried forward.

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 Week 12	-0.60 Points on a scale Standard Deviation 2.157
Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 Week 24	-0.69 Points on a scale Standard Deviation 1.904

SECONDARY outcome

Timeframe: Weeks 12 and 24

Population: Full Analysis Set

There are four grades for 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. Imputation technique was last observation carried forward.

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Improved at Week 12	9 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 No change at Week 12	16 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Deteriorated at Week 12	0 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Improved at Week 24	10 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 No change at Week 24	14 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Deteriorated at Week 24	1 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Full Analysis Set: : all participants registered, with the exception of those who had not received any dose of the investigational product and those who had no efficacy assessment after administration of the investigational product

Time to clinical worsening is defined as the time from baseline to the first occurrence of death, lung transplantation, hospitalization for PAH treatment, atrial septostomy, or study discontinuation due to change to other PAH treatment. Time to clinical worsening is measured as the number of participants who experienced these events during 24 weeks.

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event Death	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event Lung transplantation	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event Hospitalization for PAH treatment	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event Atrial Septostomy	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event Study discontinuation (additional medication)	1 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 24

Population: Full Analysis Set: Analysis was conducted using observed data only. Some participants were withdrawn before Week 24, or some participants could not be measured at Week 24 in this study.

mPAP and mRAP are measures of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24 mRAP (mmHg) at Week 24, n=16	-0.69 mmHg Standard Deviation 3.683
Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24 mPAP (mmHg) at Week 12, n=21	-6.29 mmHg Standard Deviation 11.201
Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24 mRAP (mmHg) at Week 12, n=21	-1.12 mmHg Standard Deviation 3.761
Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24 mPAP (mmHg) at Week 24, n=16	-8.69 mmHg Standard Deviation 13.903

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 24

Population: Full Analysis Set: Analysis was conducted using observed data only. Some participants were withdrawn before Week 24, or some participants could not be measured at Week 24 in this study.

CI is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in Cardiac Index (CI) at Weeks 12 and 24 Week 24, n=16	0.598 L/min/m2 Standard Deviation 0.6115
Mean Change From Baseline in Cardiac Index (CI) at Weeks 12 and 24 Week 12, n=21	0.623 L/min/m2 Standard Deviation 0.5980

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 24

Population: Full Analysis Set: Analysis was conducted using observed data only. Some participants were withdrawn before Week 24, or some participants could not be measured at Week 24 in this study.

CO is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in Cardiac Output (CO) at Weeks 12 and 24 Week 12, n=21	1.033 L/min Standard Deviation 0.8783
Mean Change From Baseline in Cardiac Output (CO) at Weeks 12 and 24 Week 24, n=16	1.035 L/min Standard Deviation 0.9968

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 24

Population: Full Analysis Set: Analysis was conducted using observed data only. Some participants were withdrawn before Week 24, or some participants could not be measured at Week 24 in this study.

PVR is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) at Weeks 12 and 24 Week 24, n=16	-8.349 mmHg/L/min Standard Deviation 7.6391
Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) at Weeks 12 and 24 Week 12, n=21	-7.257 mmHg/L/min Standard Deviation 7.4344

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 24

Population: Full Analysis Set: Analysis was conducted using observed data only. Some participants were withdrawn before Week 24, or some participants could not be measured at Week 24 in this study.

Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. BNP is a surrogate maker of heart failure and was measured by a central laboratory. Observed data analysis (no imputation techniques).

Outcome measures

Measure	GSK1325760A n=25 Participants GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition)
Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 12 and 24 Week 12, n=21	-76.86 Nanograms/Liter (ng/L) Standard Deviation 160.942
Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 12 and 24 Week 24, n=24	-60.15 Nanograms/Liter (ng/L) Standard Deviation 248.345

Adverse Events

GSK1325760A

Serious events: 4 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	GSK1325760A GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition).
Cardiac disorders Right ventricular failure	8.0% 2/25
Infections and infestations Bacterial infection	4.0% 1/25
Infections and infestations Pneumonia	4.0% 1/25
Infections and infestations Pyelonephritis	4.0% 1/25
Blood and lymphatic system disorders Leukopenia	4.0% 1/25
Eye disorders Vitreous hemorrhage	4.0% 1/25
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.0% 1/25
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	4.0% 1/25
Skin and subcutaneous tissue disorders Rash	4.0% 1/25

Other adverse events

Measure	GSK1325760A GSK1325760A 5 mg once a day by Week 12. After Week 12, GSK1325760A 10 mg once a day (the dosage could be increased or decreased appropriately according to a participant's condition).
Nervous system disorders Headache	40.0% 10/25
Infections and infestations Nasopharyngitis	28.0% 7/25
Respiratory, thoracic and mediastinal disorders Nasal congestion	20.0% 5/25
Vascular disorders Hot flush	16.0% 4/25
General disorders Edema peripheral	16.0% 4/25
Blood and lymphatic system disorders Anemia	12.0% 3/25
Nervous system disorders Dizziness	12.0% 3/25
Respiratory, thoracic and mediastinal disorders Epistaxis	12.0% 3/25
Vascular disorders Flushing	12.0% 3/25
Musculoskeletal and connective tissue disorders Pain in extremity	12.0% 3/25
Skin and subcutaneous tissue disorders Rash	12.0% 3/25
Investigations Blood pressure decreased	8.0% 2/25
Infections and infestations Cystitis	8.0% 2/25
General disorders Fatigue	8.0% 2/25
Psychiatric disorders Insomnia	8.0% 2/25
Blood and lymphatic system disorders Leukopenia	8.0% 2/25
Cardiac disorders Palpitations	8.0% 2/25
Nervous system disorders Somnolence	8.0% 2/25
Gastrointestinal disorders Constipation	8.0% 2/25

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER