Hypertension, Pulmonary
Conditions
Keywords
sitaxentan sodium hypertension
Brief summary
The safety and efficacy at 100 mg once daily for oral dose of sitaxentan sodium were demonstrated in the STRIDE clinical trial program. Sitaxentan sodium was approved in the EU, Canada and Australia. In this study, the safety and efficacy after administrations of sitaxentan sodium at a dose of 100 mg alone or in combination with another medication will be investigated in Japanese PAH patients.
Interventions
DRUGSitaxentan
sitaxentan sodium 100 mg
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Has a current diagnosis of symptomatic PAH * Has 6MWT distances from 150 to 450 meters and distance
Exclusion criteria
* Previous exposure to an endothelin receptor antagonist * Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure \>160 mm Hg or sitting diastolic blood pressure \>100 mm Hg at Screening. * Has hypotension defined as systolic arterial pressure \<90 mm Hg after sitting for 5 minutes at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 12 weeks | Number of participants with any adverse events, severe adverse events, serious adverse events |
| Change From Baseline in 6-minute Walk Distance | 12 weeks | Change from baseline in 6-minute walk distance is calculated as the value at Week 12 minus value at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in N-amino Terminal Fragment of the Prohormone Brain Natriuretic Peptide (NT-pro BNP) | 12 weeks | Change from baseline in NT-pro BNP is calculated as the value at Week 12 minus value at baseline. |
| Change From Baseline in WHO Functional Class | 12 weeks | The change from baseline in WHO functional class was classified into Improved, No change and Worsened. The change from baseline in WHO functional class at Week 12 was to be summarized with frequency count and percentage in each category based on imputed data for missing values at Week 12. |
| Number of Participants With Pharmacokinetic (PK) Parameters at Steady State | pre-dose at Week 2, 4, 8, and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose at Week 12 or study termination | The following PK parameters at the steady state were evaluated: maximum observed concentration during the dosing interval (Cmax), time for maximum observed concentration during the dosing interval (Tmax), area under the plasma concentration-time curve over dosing interval tau for multiple dose (AUCtau), terminal elimination half-life (t1/2), apparent clearance (CL/F) and apparent volume of distribution during the terminal elimination phase (Vz/F) at Week 12/Termination (as data permit), and concentration predose during multiple dosing (Ctrough) at Week 2, 4, 8 and 12/Termination. |
| Clinical Worsening | 12 weeks | Clinical worsening is defined as 1) Hospitalization for worsening pulmonary arterial hypertension, 2) On-study death, 3) Heart-lung or lung transplantation, 4) Atrial septostomy, 5) Addition of the chronic medications for the treatment of worsening pulmonary arterial hypertension, and 6) Initiation of oxygen. |
| Number of Participants With Haemodynamics Parameters | 12 weeks | The following haemodynamic measurements were assessed: right arterial pressure, pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left ventricular-end diastolic pressure, cardiac output, systemic arterial blood pressure (systolic, diastolic and mean), and heart rate. Change from baseline in haemodynamics parameters is calculated as the value at Week 12 minus value at baseline. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitaxentan Treatment All participants received one 100 mg film-coated tablet of sitaxentan daily for 12 weeks. Participants who had already received a stable dose of pulmonary arterial hypertension (PAH)-specific drug (sildenafil or beraprost) for at least 3 month prior to screening, continued to receive the PAH-specific drug during study period. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Sitaxentan Treatment |
|---|---|
| Age, Customized <=18 years | 0 Participant |
| Age, Customized 19-64 years | 1 Participant |
| Age, Customized >=65 years | 1 Participant |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Change From Baseline in 6-minute Walk Distance
Change from baseline in 6-minute walk distance is calculated as the value at Week 12 minus value at baseline.
Time frame: 12 weeks
Population: Efficacy analysis set is defined as all participants who receive at least one dose of the study drug and had efficacy observations at baseline in any efficacy assessments.~Descriptive statistics for change from baseline in 6-minute walk distance were not calculated due to a small number of participants.
Primary
Number of Participants With Adverse Events
Number of participants with any adverse events, severe adverse events, serious adverse events
Time frame: 12 weeks
Population: Safety analysis set is defined as all participants who receive at least one dose of the study drug.~Descriptive statistics for adverse events were not calculated due to a small number of subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitaxentan Treatment | Number of Participants With Adverse Events | All-causality adverse events | 1 Participant |
| Sitaxentan Treatment | Number of Participants With Adverse Events | All-causality serious adverse events | 0 Participant |
| Sitaxentan Treatment | Number of Participants With Adverse Events | All-causality severe adverse events | 0 Participant |
Secondary
Change From Baseline in N-amino Terminal Fragment of the Prohormone Brain Natriuretic Peptide (NT-pro BNP)
Change from baseline in NT-pro BNP is calculated as the value at Week 12 minus value at baseline.
Time frame: 12 weeks
Population: Efficacy analysis set is defined as all participants who receive at least one dose of the study drug and had efficacy observations at baseline in any efficacy assessments.~Descriptive statistics for change from baseline in NT-pro BNP were not calculated due to a small number of participants.
Secondary
Change From Baseline in WHO Functional Class
The change from baseline in WHO functional class was classified into Improved, No change and Worsened. The change from baseline in WHO functional class at Week 12 was to be summarized with frequency count and percentage in each category based on imputed data for missing values at Week 12.
Time frame: 12 weeks
Population: Efficacy analysis set is defined as all participants who receive at least one dose of the study drug and had efficacy observations at baseline in any efficacy assessments.~Descriptive statistics for change from baseline in WHO functional class were not calculated due to a small number of participants.
Secondary
Clinical Worsening
Clinical worsening is defined as 1) Hospitalization for worsening pulmonary arterial hypertension, 2) On-study death, 3) Heart-lung or lung transplantation, 4) Atrial septostomy, 5) Addition of the chronic medications for the treatment of worsening pulmonary arterial hypertension, and 6) Initiation of oxygen.
Time frame: 12 weeks
Population: Efficacy analysis set is defined as all participants who receive at least one dose of the study drug and had efficacy observations at baseline in any efficacy assessments.~Descriptive statistics for clinical worsening were not calculated due to a small number of participants.
Secondary
Number of Participants With Haemodynamics Parameters
The following haemodynamic measurements were assessed: right arterial pressure, pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left ventricular-end diastolic pressure, cardiac output, systemic arterial blood pressure (systolic, diastolic and mean), and heart rate. Change from baseline in haemodynamics parameters is calculated as the value at Week 12 minus value at baseline.
Time frame: 12 weeks
Population: Efficacy analysis set is defined as all participants who receive at least one dose of the study drug and had efficacy observations at baseline in any efficacy assessments.~Descriptive statistics for change from baseline in haemodynamics parameters were not calculated due to a small number of participants.
Secondary
Number of Participants With Pharmacokinetic (PK) Parameters at Steady State
The following PK parameters at the steady state were evaluated: maximum observed concentration during the dosing interval (Cmax), time for maximum observed concentration during the dosing interval (Tmax), area under the plasma concentration-time curve over dosing interval tau for multiple dose (AUCtau), terminal elimination half-life (t1/2), apparent clearance (CL/F) and apparent volume of distribution during the terminal elimination phase (Vz/F) at Week 12/Termination (as data permit), and concentration predose during multiple dosing (Ctrough) at Week 2, 4, 8 and 12/Termination.
Time frame: pre-dose at Week 2, 4, 8, and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose at Week 12 or study termination
Population: The PK concentration set was defined as all participants who have at least 1 concentration.~The PK parameter analysis set was defined as all participants who have at least 1 of PK parameters of interest.~Descriptive statistics for PK parameters were not calculated due to a small number of participants.