Pulmonary Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, PAH
Brief summary
To assess the safety of sildenafil 20 mg TID orally given to Japanese pulmonary arterial hypertension patients (Part 1 and 2) To assess the efficacy after 12 weeks of treatment of sildenafil 20 mg TID orally given to Japanese pulmonary arterial hypertension patients (Part 1)
Interventions
DRUGsildenafil citrate (UK-92,480)
sildenafil citrate (UK-92,480)
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects aged 16 and over, and classified as having pulmonary arterial hypertension * Subjects who meet the following conditions on right heart catheterization at screening or baseline: mean pulmonary arterial pressure of ≥ 25mmHg and pulmonary capillary wedge pressure of ≤ 15mmHg at rest * Subjects whose baseline 6-Minute Walk test distance is \>100 m and \<450 m
Exclusion criteria
* Significant Hepatic and/or renal disorder * Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic ischemic optic neuropathy (NAION) * Subjects who are currently receiving nitrates or nitric oxide donors in any form, ritonavir, ketoconazole and itraconazole
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:total distance walked during the 6-minute walk test. |
| Change in the Mean Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change:Mean pulmonary arterial pressure at Week 12 minus mean pulmonary arterial pressure at baseline. |
| Change in the Pulmonary Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Pulmonary vascular resistance at Week 12 minus pulmonary vascular resistance at baseline |
| Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, week 12 | Change：Cardiac output at Week 12 minus cardiac output at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Systolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Systolic systemic blood pressure at Week 12 minus systolic systemic blood pressure at baseline. |
| Change in the Mean Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Mean systemic blood pressure:diastolic blood pressure+(systolic blood pressure-diastolic blood pressure)/3. Change：Mean systemic blood pressure at Week 12 minus mean systemic blood pressure at baseline. |
| Change in the Pulmonary Capillary Wedge Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Pulmonary capillary wedge pressure at Week 12 minus pulmonary capillary wedge pressure at baseline. |
| Change in the Right Atrial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Right atrial pressure at Week 12 minus right atrial pressure at baseline. |
| Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Cardiac index at Week 12 minus cardiac index at baseline. |
| Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Heart rate at Week 12 minus heart rate at baseline. |
| Change in the Pulmonary Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change:Pulmonary vascular resistance index at Week 12 minus pulmonary vascular resistance index at baseline. |
| Change in the Systemic Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Systemic vascular resistance at Week 12 minus systemic vascular resistance at baseline. |
| Change in the Systemic Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I | baseline, Week 12 | Change：Systemic vascular resistance index at Week 12 minus systemic vascular resistance index at baseline. |
| Change in the Mixed Venous Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Mixed venous oxygen saturation at Week 12 minus mixed venous oxygen saturation at baseline. |
| Change in the Arterial Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Arterial oxygen saturation at Week 12 minus arterial oxygen saturation at baseline. |
| Change in the Arterial Oxygen Partial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | baseline, Week 12 | Change：Arterial oxygen partial pressure at Week 12 minus arterial oxygen partial pressure at baseline. |
| Change in the Partial Pressure of Mixed Venous Oxygen From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Partial pressure of mixed venous oxygen at Week 12 minus partial pressure of mixed venous oxygen at baseline. |
| Change in the Diastolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Diastolic systemic blood pressure at Week 12 minus diastolic systemic blood pressure at baseline. |
| Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 8, Week 12 | Change：BORG dyspnoea score at Week 8 and Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance. |
| Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 4, Week 8, Week 12 | Change：Plasma brain natriuretic peptide level at Week 4, Week 8 and Week 12 minus plasma brain natriuretic peptide level at baseline |
| Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Baseline, Week 12 | Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test. |
| Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Baseline, Week 12 | The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms). |
| Changes in the BORG Dyspnoea Score From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Baseline, Week 12 | Change：BORG dyspnoea score at Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance. |
| Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 12 in Participants Who Newly Enterd the Study From Part II | Baseline, Week 12 | Change：Plasma brain natriuretic peptide level at Week 12 minus plasma brain natriuretic peptide level at baseline |
| Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing | Maximum plasma concentrations was calculated from the observed value of plasma concentrations in each participant |
| Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing | Time to first occurrence of maximum plasma concentrations were calculated from the observed value of plasma concentrations in each participant. |
| The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing | The area under the curve from time 0 to time 8 hour was calculated from area under the curve in each perticipant on the date of blood sampling using the linear/log trapezoidal rule |
| The Average Plasma Concentration (Css,av) of Sildenafil at Steady State | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing | The average plasma concentration of sildenafil at steady state was calculated from the area under the curve from time 0 to 8 hour/dosing interval (8 hours). |
| The Average Plasma Trough Concentration (Ctrough) of Sildenafil | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing | The average plasma trough concentration of sildenafil was calculated from the observed value before administration of the drug in each participants. |
| Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Baseline up to 1.3 years | The total number of participants with laboratory test abnormalities without regard to baseline abnormality. |
| Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms). |
| Change in the 6-minute Walk Distance From Baseline at Week 8 in Participants Who Entered the Study From Part I | Baseline, Week 8 | Change：6-minute walk distance at Week 8 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test. |
| Change in the Systolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Systolic pulmonary arterial pressure at Week 12 minus Systolic pulmonary arterial pressure at baseline. |
| Change in the Diastolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | Baseline, Week 12 | Change：Diastolic pulmonary arterial pressure at Week 12 minus diastolic pulmonary arterial pressure at baseline. |
Countries
Japan
Participant flow
Recruitment details
Eight centers in Japan
Pre-assignment details
Twenty-one pulmonary arterial hypertension patients who have never received sildenafil therapy entered the study from Part I period and could continue to study part II period. Twenty-three patients who were continuously using sildenafil entered the study from Part II period.
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil: Participant Who Entered the Study From Part I Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension). | 21 |
| Sildenafil: Participants Who Entered the Study From Part II Consists of participants who newly entered the study from Part II period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to subjects after approval for the indication of pulmonary arterial hypertension). | 23 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Sildenafil: Participant Who Entered the Study From Part I | Sildenafil: Participants Who Entered the Study From Part II | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 20 Participants | 39 Participants |
| Region of Enrollment Japan | 21 participants | 23 participants | 44 participants |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 38 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 44 |
| serious Total, serious adverse events | 7 / 44 |
Outcome results
Primary
Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:total distance walked during the 6-minute walk test.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Entered the Study From Part I | 84.2 meters | Standard Deviation 74.9 |
Primary
Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Cardiac output at Week 12 minus cardiac output at baseline
Time frame: Baseline, week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I | 0.556 liter/minute | Standard Deviation 1 |
Primary
Change in the Mean Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change:Mean pulmonary arterial pressure at Week 12 minus mean pulmonary arterial pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Mean Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -4.7 mmHg | Standard Deviation 8.2 |
Primary
Change in the Pulmonary Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Pulmonary vascular resistance at Week 12 minus pulmonary vascular resistance at baseline
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Pulmonary Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I | -246.49 dyne·second/centimeter^5 | Standard Deviation 301.17 |
Secondary
Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | -23.5 meters | Standard Deviation 34.1 |
Secondary
Change in the 6-minute Walk Distance From Baseline at Week 8 in Participants Who Entered the Study From Part I
Change：6-minute walk distance at Week 8 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test.
Time frame: Baseline, Week 8
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the 6-minute Walk Distance From Baseline at Week 8 in Participants Who Entered the Study From Part I | 87.5 meters | Standard Deviation 75.3 |
Secondary
Change in the Arterial Oxygen Partial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Arterial oxygen partial pressure at Week 12 minus arterial oxygen partial pressure at baseline.
Time frame: baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Arterial Oxygen Partial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -2.02 mmHg | Standard Deviation 11.17 |
Secondary
Change in the Arterial Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Arterial oxygen saturation at Week 12 minus arterial oxygen saturation at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Arterial Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I | 0.440 percent saturation | Standard Deviation 5.437 |
Secondary
Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Cardiac index at Week 12 minus cardiac index at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I | 0.32 liter/minute/meter^2 | Standard Deviation 0.62 |
Secondary
Change in the Diastolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Diastolic pulmonary arterial pressure at Week 12 minus diastolic pulmonary arterial pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Diastolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -3.2 mmHg | Standard Deviation 8.3 |
Secondary
Change in the Diastolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Diastolic systemic blood pressure at Week 12 minus diastolic systemic blood pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Diastolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -3.1 mmHg | Standard Deviation 9 |
Secondary
Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Heart rate at Week 12 minus heart rate at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I | -4.14 beats/minute | Standard Deviation 7.45 |
Secondary
Change in the Mean Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Mean systemic blood pressure:diastolic blood pressure+(systolic blood pressure-diastolic blood pressure)/3. Change：Mean systemic blood pressure at Week 12 minus mean systemic blood pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Mean Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -0.9 mmHg | Standard Deviation 12.9 |
Secondary
Change in the Mixed Venous Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Mixed venous oxygen saturation at Week 12 minus mixed venous oxygen saturation at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Mixed Venous Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I | 2.91 percent saturation | Standard Deviation 9.05 |
Secondary
Change in the Partial Pressure of Mixed Venous Oxygen From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Partial pressure of mixed venous oxygen at Week 12 minus partial pressure of mixed venous oxygen at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Partial Pressure of Mixed Venous Oxygen From Baseline at Week 12 in Participants Who Entered the Study From Part I | 0.57 mmHg | Standard Deviation 4.35 |
Secondary
Change in the Pulmonary Capillary Wedge Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Pulmonary capillary wedge pressure at Week 12 minus pulmonary capillary wedge pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Pulmonary Capillary Wedge Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | 0.68 mmHg | Standard Deviation 3.14 |
Secondary
Change in the Pulmonary Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change:Pulmonary vascular resistance index at Week 12 minus pulmonary vascular resistance index at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Pulmonary Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I | -382.00 dyne*second/centimeter^5/meter^2 | Standard Deviation 491.8 |
Secondary
Change in the Right Atrial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Right atrial pressure at Week 12 minus right atrial pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Right Atrial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -0.3 mmHg | Standard Deviation 4.4 |
Secondary
Change in the Systemic Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Systemic vascular resistance at Week 12 minus systemic vascular resistance at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Systemic Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I | -265.77 dyne*second/centimeter^5 | Standard Deviation 785.52 |
Secondary
Change in the Systemic Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Systemic vascular resistance index at Week 12 minus systemic vascular resistance index at baseline.
Time frame: baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Systemic Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I | -409.89 dyne*second/centimeter^5/meter^2 | Standard Deviation 1271.3 |
Secondary
Change in the Systolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Systolic pulmonary arterial pressure at Week 12 minus Systolic pulmonary arterial pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Systolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | -3.4 mmHg | Standard Deviation 13.4 |
Secondary
Change in the Systolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Change：Systolic systemic blood pressure at Week 12 minus systolic systemic blood pressure at baseline.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Change in the Systolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I | 0.7 mmHg | Standard Deviation 16.5 |
Secondary
Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms).
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sildenafil: Part I | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: I | 1 participants |
| Sildenafil: Part I | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: II | 0 participants |
| Sildenafil: Part I | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: III | 0 participants |
| Sildenafil: Part I | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: IV | 0 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: IV | 0 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: I | 0 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: III | 1 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | Functional class at Week 12: II | 5 participants |
Secondary
Changes in the BORG Dyspnoea Score From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
Change：BORG dyspnoea score at Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance.
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Changes in the BORG Dyspnoea Score From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II | 0.33 scores on a scale | Standard Deviation 1.21 |
Secondary
Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I
Change：BORG dyspnoea score at Week 8 and Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance.
Time frame: Baseline, Week 8, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward (Week 12).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil: Part I | Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I | Week 8 (n=19, 0) | -0.84 scores on a scale | Standard Deviation 1.89 |
| Sildenafil: Part I | Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I | Week 12 (n=20, 6) | -0.95 scores on a scale | Standard Deviation 1.94 |
Secondary
Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 12 in Participants Who Newly Enterd the Study From Part II
Change：Plasma brain natriuretic peptide level at Week 12 minus plasma brain natriuretic peptide level at baseline
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 12 in Participants Who Newly Enterd the Study From Part II | 15.91 picograms/milliliter | Standard Deviation 55.94 |
Secondary
Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I
Change：Plasma brain natriuretic peptide level at Week 4, Week 8 and Week 12 minus plasma brain natriuretic peptide level at baseline
Time frame: Baseline, Week 4, Week 8, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward (Week 12).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil: Part I | Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I | Week 4 (n=20, 0) | -78.00 picograms/milliliter | Standard Deviation 166.41 |
| Sildenafil: Part I | Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I | Week 8 (n=19, 0) | -88.25 picograms/milliliter | Standard Deviation 178.39 |
| Sildenafil: Part I | Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I | Week 12 (n=20, 7) | -61.82 picograms/milliliter | Standard Deviation 209.96 |
Secondary
Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I
The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms).
Time frame: Baseline, Week 12
Population: Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sildenafil:Part I, Functional Class at Baseline: II | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:I | 0 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:II | 6 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:III | 1 participants |
| Sildenafil:Part I, Functional Class at Baseline: II | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:IV | 0 participants |
| Sildenafil, Part I, Functional Class at Baseline: III | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:IV | 0 participants |
| Sildenafil, Part I, Functional Class at Baseline: III | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:I | 1 participants |
| Sildenafil, Part I, Functional Class at Baseline: III | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:III | 7 participants |
| Sildenafil, Part I, Functional Class at Baseline: III | Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I | Functional class at Week 12:II | 5 participants |
Secondary
Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
The total number of participants with laboratory test abnormalities without regard to baseline abnormality.
Time frame: Baseline up to 1.3 years
Population: All subjects who received at least one dose of the study medication and had any evaluable laboratory test data after treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sildenafil: Part I | Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 35 participants |
Secondary
Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320
Maximum plasma concentrations was calculated from the observed value of plasma concentrations in each participant
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil: Part I | Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Sildenafil | 164.88 nanograms/milliliter | Standard Deviation 74.78 |
| Sildenafil: Part I | Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Sildenafil's Metabolite, UK-103,320 | 87.27 nanograms/milliliter | Standard Deviation 30.67 |
Secondary
The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320
The area under the curve from time 0 to time 8 hour was calculated from area under the curve in each perticipant on the date of blood sampling using the linear/log trapezoidal rule
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil: Part I | The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Sildenafil | 545.14 nanogram*hour/milliliter | Standard Deviation 294.88 |
| Sildenafil: Part I | The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Sildenafil's Metabolite, UK-103,320 | 365.85 nanogram*hour/milliliter | Standard Deviation 186.55 |
Secondary
The Average Plasma Concentration (Css,av) of Sildenafil at Steady State
The average plasma concentration of sildenafil at steady state was calculated from the area under the curve from time 0 to 8 hour/dosing interval (8 hours).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | The Average Plasma Concentration (Css,av) of Sildenafil at Steady State | 68.14 nanograms/milliliter | Standard Deviation 36.86 |
Secondary
The Average Plasma Trough Concentration (Ctrough) of Sildenafil
The average plasma trough concentration of sildenafil was calculated from the observed value before administration of the drug in each participants.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil: Part I | The Average Plasma Trough Concentration (Ctrough) of Sildenafil | 19.608 nanograms/milliliter | Standard Deviation 12.438 |
Secondary
Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320
Time to first occurrence of maximum plasma concentrations were calculated from the observed value of plasma concentrations in each participant.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil: Part I | Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Sildenafil | 1.102 hours | Standard Deviation 0.499 |
| Sildenafil: Part I | Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 | Sildenafil's Metabolite, UK-103,320 | 1.611 hours | Standard Deviation 1.024 |