A Study to Assess the Efficacy and Safety of 20, 40, and 80mg of Sildenafil Three Times a Day in the Treatment of Pulmonary Arterial Hypertension

Sponsor

Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00644605

Collaborator

(none)

275

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the effect of three doses of oral sildenafil (20, 40 and 80 mg three times a day [TID]) on exercise capacity, as measured by the 6-Minute Walk test, as well as the safety and tolerability, after 12 weeks of treatment in subjects with pulmonary arterial hypertension who are aged 18 years and over. To investigate the plasma concentration-effect relationship and to determine the population pharmacokinetic (PK) parameters.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Pulmonary	Drug: sildenafil Drug: sildenafil Drug: placebo Drug: sildenafil	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

275 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Multinational, Multi-centre, Randomised, Double-blind, Double-dummy, Placebo-controlled Study to Assess the Efficacy and Safety of 20, 40, and 80mg TID Sildenafil in the Treatment of Pulmonary Arterial Hypertension in Subjects Aged 18 Years and Over

Study Start Date :

Oct 1, 2002

Actual Study Completion Date :

Nov 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1	Drug: sildenafil sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Active Comparator: Arm 2	Drug: sildenafil sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Active Comparator: Arm 3	Drug: sildenafil sildenafil 80 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks; initially, patients received 40mg TID for one week and were then up-titrated to 80mg TID
Placebo Comparator: Arm 4	Drug: placebo placebo by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks

Outcome Measures

Primary Outcome Measures

Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test). [Week 12]

Secondary Outcome Measures

Change from baseline in mean pulmonary arterial pressure [Week 12]
Time from randomisation to the first occurrence of clinical worsening (death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy) [Week 0 to 12]
Change from baseline in the BORG dyspnoea score [Week 12]
Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class [Week 12]
Change from baseline in the 8 dimensions of SF-36 (Physical functioning, Role functioning, Bodily pain, General health, Vitality, Social functioning, Mental health and Reported health transition) [Week 4 and Week 12]
Change from baseline at Weeks 4 and 12 in the 5 dimensions of ED5Q (Mobility, Self care, Usual Activities, Pain/Discomfort and Anxiety/Depression) [Week 4 and Week 12]
Patient overall preference assessment [Week 12]
Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension [throughout the study]
Change from baseline in hemodynamic parameters [Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Included patients had primary pulmonary arterial hypertension, pulmonary hypertension secondary to connective tissue disease, or pulmonary hypertension with surgical repair at least 5 years previously; a mean pulmonary artery pressure greater than or equal to 25 mmHg and a pulmonary artery wedge pressure of less than or equal to 15 mmHg at rest, via right heart catheterisation within 21 days prior to randomisation; and a baseline 6-Minute Walk test distance of 100 m to 450 m.

Exclusion Criteria:

Subjects with congenital heart disease, pulmonary hypertension due to thromboembolism, HIV, chronic obstructive airway disease, congestive heart failure or schistosomiasis; subjects with significant (ie > 2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation; and acutely decompensated heart failure within the previous 30 days; subjects with pulmonary hypertension secondary to any other etiology other than those specified in the inclusion criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Birmingham	Alabama	United States	35233
2	Pfizer Investigational Site	Birmingham	Alabama	United States	35294-0006
3	Pfizer Investigational Site	Birmingham	Alabama	United States	35294
4	Pfizer Investigational Site	La Jolla	California	United States	92037
5	Pfizer Investigational Site	La Jolla	California	United States	92093
6	Pfizer Investigational Site	Los Angeles	California	United States	90024
7	Pfizer Investigational Site	Los Angeles	California	United States	90033
8	Pfizer Investigational Site	Los Angeles	California	United States	90095
9	Pfizer Investigational Site	San Diego	California	United States	92037
10	Pfizer Investigational Site	Torrance	California	United States	90502
11	Pfizer Investigational Site	Torrance	California	United States	90509
12	Pfizer Investigational Site	Aurora	Colorado	United States	80010
13	Pfizer Investigational Site	Denver	Colorado	United States	80262
14	Pfizer Investigational Site	Chicago	Illinois	United States	60612
15	Pfizer Investigational Site	Shreveport	Louisiana	United States	71103
16	Pfizer Investigational Site	Baltimore	Maryland	United States	21205
17	Pfizer Investigational Site	Boston	Massachusetts	United States	02111
18	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48109
19	Pfizer Investigational Site	Rochester	Minnesota	United States	55905
20	Pfizer Investigational Site	New York	New York	United States	10032
21	Pfizer Investigational Site	Durham	North Carolina	United States	27710
22	Pfizer Investigational Site	Nashville	Tennessee	United States	37232
23	Pfizer Investigational Site	Houston	Texas	United States	77030
24	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53215
25	Pfizer Investigational Site	Darlinghurst	New South Wales	Australia	2010
26	Pfizer Investigational Site	Melbourne	Victoria	Australia	3004
27	Pfizer Investigational Site	Bruxelles		Belgium	1070
28	Pfizer Investigational Site	Leuven		Belgium	3000
29	Pfizer Investigational Site	Sao Paulo	SP	Brazil	05403-900
30	Pfizer Investigational Site	Prague 4		Czechia	140 00
31	Pfizer Investigational Site	Prague 4		Czechia	140 21
32	Pfizer Investigational Site	Kobenhavn		Denmark	2100
33	Pfizer Investigational Site	Clamart		France	92141
34	Pfizer Investigational Site	Berlin		Germany	13353
35	Pfizer Investigational Site	Giessen		Germany	35385
36	Pfizer Investigational Site	Giessen		Germany	35392
37	Pfizer Investigational Site	Hannover		Germany	30625
38	Pfizer Investigational Site	Leipzig		Germany	04103
39	Pfizer Investigational Site	Shatin N T		Hong Kong
40	Pfizer Investigational Site	Budapest	Pest	Hungary	1529
41	Pfizer Investigational Site	Zalaegerszeg	Zala	Hungary	8900
42	Pfizer Investigational Site	Petach Tikva		Israel	49100
43	Pfizer Investigational Site	Tel Hashomer		Israel	52621
44	Pfizer Investigational Site	Bologna		Italy	40138
45	Pfizer Investigational Site	Pisa		Italy	56124
46	Pfizer Investigational Site	Pisa		Italy	56126
47	Pfizer Investigational Site	Suwon		Korea, Republic of	442-721
48	Pfizer Investigational Site	Kuala Lumpur		Malaysia	59100
49	Pfizer Investigational Site	Tlalpan		Mexico
50	Pfizer Investigational Site	Amsterdam		Netherlands	1081 HV
51	Pfizer Investigational Site	Oslo		Norway	NO-0027
52	Pfizer Investigational Site	Katowice		Poland	40-057
53	Pfizer Investigational Site	Warszawa		Poland	01-138
54	Pfizer Investigational Site	Warszawa		Poland	03-709
55	Pfizer Investigational Site	Zabrze		Poland	41-800
56	Pfizer Investigational Site	Singapore		Singapore	168752
57	Pfizer Investigational Site	Cape Town		South Africa	7700
58	Pfizer Investigational Site	Johannesburg		South Africa	2193
59	Pfizer Investigational Site	Parow		South Africa
60	Pfizer Investigational Site	Barcelona		Spain	08035
61	Pfizer Investigational Site	Barcelona		Spain	08036
62	Pfizer Investigational Site	Madrid		Spain	28041
63	Pfizer Investigational Site	Goteborg		Sweden	413 45
64	Pfizer Investigational Site	Molndal		Sweden	431 80
65	Pfizer Investigational Site	Papworth Everard	Cambridgeshire	United Kingdom	CB3 8RE
66	Pfizer Investigational Site	Sheffield	South Yorkshire	United Kingdom	S10 2JF
67	Pfizer Investigational Site	Glasgow		United Kingdom	G11 6NT
68	Pfizer Investigational Site	HIGH Heaton, Newcastle-upon-tyne		United Kingdom	NE7 7DW