Open Label Study of Sildenafil in Patients With Pulmonary Arterial Hypertension

Pulmonary Hypertension Clinical Trial

Official title:

A Phase 3, Multi-Center, Open-Label Study to Assess Safety and Efficacy of Sildenafil Citrate 20 mg TID in Subjects With Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00454207
• Other study ID #: A1481252
• Secondary ID: JapicCTI-070381
• Status: Completed
• Phase: Phase 3
• Start date: April 2007
• Est. completion date: February 2009

Study information

• Verified date: January 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

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

Locations

Country	Name	City	State
Japan	Pfizer Investigational Site	Bunkyo-ku	Tokyo
Japan	Pfizer Investigational Site	Chiba-shi	Chiba
Japan	Pfizer Investigational Site	Hamamatsu-shi	Shizuoka
Japan	Pfizer Investigational Site	Kanazawa	Ishikawa
Japan	Pfizer Investigational Site	Okayama City	Okayama
Japan	Pfizer Investigational Site	Shinjuku-ku	Tokyo
Japan	Pfizer Investigational Site	Tokyo
Japan	Pfizer Investigational Site	Tsu-shi	Mie

Sponsors (1)

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

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, Week 12
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.	Baseline, Week 12
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	Baseline, Week 12
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	Baseline, week 12
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.	Baseline, Week 8
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	baseline, Week 12
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.	Baseline, Week 12
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).	Baseline, Week 12
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.	Baseline, Week 8, Week 12
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	Baseline, Week 4, Week 8, Week 12
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.	Baseline, Week 12
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).	Baseline, Week 12
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.	Baseline, Week 12
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	Baseline, Week 12
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	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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).	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
Secondary	Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	The total number of participants with laboratory test abnormalities without regard to baseline abnormality.	Baseline up to 1.3 years

External Links

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