Open Label Study of Sildenafil in Patients With Pulmonary Arterial Hypertension

Phase 3

Completed

Conditions: Pulmonary Hypertension

Interventions: Drug: sildenafil citrate (UK-92,480)

Registration Number: NCT00454207

Lead Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
sildenafil citrate (UK-92,480)	sildenafil citrate (UK-92,480)	sildenafil citrate 20 mg TID

Primary Outcome Measures

Name	Time	Method
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 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 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 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 Outcome Measures

Name	Time	Method
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 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 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 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.
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.
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 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.
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
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.
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).
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
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.
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.
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 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 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).
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 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).
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.
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