Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension

• ClinicalTrials.gov Identifier: NCT00323297
• Recruitment Status: Completed
• First Posted: May 9, 2006
• Results First Posted: November 19, 2013
• Last Update Posted: February 1, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Pulmonary Arterial Hypertension
• Interventions: Drug: Bosentan; Other: Placebo; Drug: Sildenafil Citrate
• Enrollment: 105

Participant Flow

Recruitment Details	This study was conducted at 29 active centers in 10 countries (10 centers in Germany, 5 centers in the United States of America [USA], 3 centers in France, 2 centers in Australia, Czech Republic, Italy, and Israel, and 1 center in Greece, Taiwan and United Kingdom [UK])
Pre-assignment Details	Participants were on bosentan therapy for 3 months prior. Participants were randomized to sildenafil or placebo. Part A study was double-blind phase (12 weeks) and Part B was 12 months open-label phase. 53 and 51 participants were randomized to placebo and sildenafil arm respectively. One participant in sildenafil arm did not receive any treatment

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Period Title: Part A (Double Blind Randomized)
Started	53	50
Completed	48	43
Not Completed	5	7
Reason Not Completed
Reason unspecified	0	1
Death	0	1
Protocol Violation	1	3
Unrelated adverse event	1	0
Related and Unrelated adverse event	1	0
Related adverse event	2	2
Period Title: Part B (Open-label)
Started	48	43
Completed	39	31
Not Completed	9	12
Reason Not Completed
Death	0	1
Reason unspecified	0	1
Withdrawal by Subject	1	3
Lack of Efficacy	3	1
Adverse Event	5	5
Protocol Violation	0	1

Baseline Characteristics

Arm/Group Title		Placebo	Sildenafil	Total
Arm/Group Description		In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.	Total of all reporting groups
Overall Number of Baseline Participants		53	50	103
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	53 participants	50 participants	103 participants
		56.9 (14.14)	55.2 (15.10)	56.0 (14.57)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	53 participants	50 participants	103 participants
	Female	41 77.4%	37 74.0%	78 75.7%
	Male	12 22.6%	13 26.0%	25 24.3%
Six Minute Walk Test (6MWT) [1]; Mean (Standard Deviation); Unit of measure: Meters
	Number Analyzed	53 participants	50 participants	103 participants
		350.38 (87.587)	354.44 (73.121)	352.35 (80.520)
		[1] Measure Description: 6MWT is the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.
Mean Pulmonary Artery Pressure (mPAP); Mean (Standard Deviation); Unit of measure: Millimeter(mm) of mercury(Hg)
	Number Analyzed	53 participants	50 participants	103 participants
		44.9 (13.33)	46.9 (12.47)	45.8 (12.89)
World Health Organization Functional Class in Participants with Pulmonary Arterial Hypertension [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	53 participants	50 participants	103 participants
Class I		0	0	0
Class II		15	20	35
Class III		38	29	67
Class IV		0	1	1
		[1] Measure Description: Pulmonary Arterial Hypertension criteria for WHO Class: Class I (Participants with no limitation of physical activity); Class II (Participants with slight limitation of physical activity); Class III (Participants with marked limitation of physical activity); Class IV (Participants with inability to carry out any physical activity).

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Total Distance Walked During 6 Minute Walk Time (6MWT) at Week 12
Description	6MWT is the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population (Full Analysis Set) consisted of all participants who had been randomly assigned to study drug and received at least one dose of study medication. Missing values were replaced according to the last observation carried forward (LOCF) approach. Statistical analysis was carried out on LOCF values.

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description:	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Overall Number of Participants Analyzed	53	50
Mean (Standard Deviation); Unit of Measure: Meters
Change from baseline at Week 12 (n=46,44)	17.42 (57.270)	14.08 (63.679)
Change from baseline at Week 12 LOCF (n=53,49)	14.08 (57.557)	13.62 (60.950)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sildenafil
	Comments	The estimated sample size was based upon the primary endpoint. A sample size of 51 subjects per treatment group was required to detect a difference of 30 meters between treatments with 80% power at a one-sided significance level of 0.05, assuming a standard deviation of 60 meters. This primary statistical analysis was carried for Week 12 data.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5802
	Comments	A sequential closed-testing procedure was implemented for all secondary endpoints. If no statistically significant treatment effect was found for the primary endpoint then statistical tests were not to be performed on the secondary endpoints.
	Method	ANCOVA
	Comments	The mean difference in method of estimation is the difference between Sildenafil - placebo.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.38
	Confidence Interval	(2-Sided) 90%; -21.843 to 17.087
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.722
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Week 12 LOCF
Description	WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (can not perform a physical activity without any symptoms, dyspnea at rest). Improvement=reduction in functional class; deterioration = increase in functional class, no change = no change in functional class.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT Population (Full Analysis Set) consisted of all participants who had been randomly assigned to study drug and received at least one dose of study medication. Missing values were replaced according to the LOCF approach.

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description:	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Overall Number of Participants Analyzed	53	50
Measure Type: Number; Unit of Measure: Participants
Worsened 2 Classes	0	0
Worsened 1 Class	1	0
No Change	45	39
Improved 1 Class	7	10
Improved 2 Classes	0	0
Discontinued	0	0
Died	0	1
Missing	0	0

3. Secondary Outcome

Title	Clinical Worsening Events
Description	No survival analysis was carried out for the study due to very few events of clinical worsening. Hence, we present a summary of clinical worsening events instead. Events of clinical worsening were categorized as (A). Death, (B). Heart/lung transplantation, (C). Hospitalization due to pulmonary arterial hypertension (PAH), and (D). Clinical deterioration of PAH requiring additional therapy.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT Population (Full Analysis Set) consisted of all participants who had been randomly assigned to study drug and received at least one dose of study medication.

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description:	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Overall Number of Participants Analyzed	53	50
Measure Type: Number; Unit of Measure: Participants
None	51	47
(A)	0	1
(B)	0	0
(C)	2	2
(D)	0	0

4. Secondary Outcome

Title	Change From Baseline in Borg Dyspnea Score at Week 12
Description	Borg dyspnea scale is a 10-point scale where following scores stands for severity of dyspnea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); (very slight);; (slight breathlessness);; (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum]); and 10 (maximum).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT Population (Full Analysis Set) consisted of all participants who had been randomly assigned to study drug and received at least one dose of study medication. Missing values were replaced according to the last observation carried forward LOCF approach.

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description:	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Overall Number of Participants Analyzed	53	50
Mean (Standard Deviation); Unit of Measure: Units on a scale
Change from Baseline at Week 12 (n=46,43)	0.16 (1.637)	-0.73 (1.656)
Change from Baseline at Week 12 LOCF (n=53,49)	0.24 (1.709)	-0.62 (1.583)

5. Secondary Outcome

Title	One Year Survival Probability From the Start of Sildenafil Treatment.
Description	The survival probability of all participants up to 1-year post start of Sildenafil treatment; for participants who were randomized to Sildenafil, this was the week 52 from randomization, and for participants who were originally randomized to Placebo group, this was the Week 64 from Baseline (Week 52 from Week 12, when the first dose of Sildenafil was administered to these participants). Those participants who discontinued from the study prior to 1 year after start of sildenafil were considered as censored at the time of discontinuation and those who discontinued from the study post 1-year after start of sildenafil were considered as censored at the time of 1-year post start of sildenafil.
Time Frame	One year from the time of starting sildenafil

Outcome Measure Data

Analysis Population Description

ITT Population (Full Analysis Set) consisted of all participants who had been randomly assigned to study drug and received at least one dose of study medication. Missing values were replaced according to the last observation carried forward LOCF approach. The participants in placebo arm have received Sildenafil on or after Week 12.

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description:	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Overall Number of Participants Analyzed	48	50
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Probability of death
	0.042; (0.013 to 0.127)	0.040; (0.013 to 0.124)

6. Secondary Outcome

Title	One Year Survival From the Start of Sildenafil Treatment.
Description	The survival status of all participants who discontinued from the study, including those participants who discontinued during the double-blind phase, was to be assessed at one year post their Week 12 visit/ End of treatment visit.
Time Frame	One year from the time of starting sildenafil

Outcome Measure Data

Analysis Population Description

ITT Population (Full Analysis Set) consisted of all participants who had been randomly assigned to study drug and received at least one dose of study medication. Missing values were replaced according to the last observation carried forward LOCF approach. The participants in placebo arm have received Sildenafil on or after Week 12.

Arm/Group Title	Placebo	Sildenafil
Arm/Group Description:	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months	In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
Overall Number of Participants Analyzed	48	50
Measure Type: Number; Unit of Measure: Participants who died
	2	2

Adverse Events

Time Frame	From the time that the participant provides informed consent through and including 28 calendar days after the last administration of the investigational product
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Placebo		Sildenafil
Arm/Group Description	In Part A of the study: the participants received placebo three times a day (TID), in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.		In Part A of the study: the participants received sildenafil 20 mg TID, in addition to their existing stable bosentan treatment (62.5 mg BID or 125 mg BID for minimum 3 months prior to randomization), for 12-Week Double-Blind Phase of the study. In Part B of the study: All the participants received sildenafil 20 mg TID for 12 months.
All-Cause Mortality
	Placebo		Sildenafil
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Placebo		Sildenafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/53 (43.40%)		22/50 (44.00%)
Blood and lymphatic system disorders
Anaemia * 1	2/53 (3.77%)	2	1/50 (2.00%)	1
Cardiac disorders
Acute coronary syndrome * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Right ventricular failure * 1	1/53 (1.89%)	1	3/50 (6.00%)	3
Cardiac failure * 1	1/53 (1.89%)	1	1/50 (2.00%)	1
Cardiovascular disorder * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Coronary artery disease * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Mitral valve incompetence * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Pericardial effusion * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Gastrointestinal disorders
Abdominal pain * 1	2/53 (3.77%)	2	0/50 (0.00%)	0
Inguinal hernia * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
General disorders
Asthenia * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Death * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Chest discomfort * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
General physical health deterioration * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Oedema peripheral * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Immune system disorders
Contrast media allergy * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Infections and infestations
Bronchopneumonia * 1	1/53 (1.89%)	1	2/50 (4.00%)	2
Erysipelas * 1	2/53 (3.77%)	2	0/50 (0.00%)	0
Gastritis viral * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Abscess * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Gangrene * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Osteomyelitis * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Pneumonia * 1	2/53 (3.77%)	2	0/50 (0.00%)	0
Respiratory syncytial virus infection * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Respiratory tract infection * 1	1/53 (1.89%)	1	1/50 (2.00%)	1
Sepsis * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Urinary tract infection * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Injury, poisoning and procedural complications
Post procedural haematoma * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Investigations
Haemoglobin decreased * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Walking distance test abnormal * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Metabolism and nutrition disorders
Fluid overload * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Fluid retention * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Musculoskeletal and connective tissue disorders
Osteoporosis * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Back pain * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Pain in extremity * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Rotator cuff syndrome * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Breast cancer * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Gastric cancer * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Pancreatic neoplasm * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Nervous system disorders
Paresis * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Sciatica * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Syncope * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Psychiatric disorders
Mania * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Reproductive system and breast disorders
Uterine haemorrhage * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	2/53 (3.77%)	2	2/50 (4.00%)	2
Pleural effusion * 1	2/53 (3.77%)	2	0/50 (0.00%)	0
Pulmonary arterial hypertension * 1	6/53 (11.32%)	6	2/50 (4.00%)	2
Haemoptysis * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Hypoxia * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Pulmonary hypertension * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Skin and subcutaneous tissue disorders
Skin ulcer * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Surgical and medical procedures
Skin graft * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
Vascular disorders
Circulatory collapse * 1	0/53 (0.00%)	0	1/50 (2.00%)	1
Hypertension * 1	1/53 (1.89%)	1	0/50 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Sildenafil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/53 (71.70%)		33/50 (66.00%)
Blood and lymphatic system disorders
Anaemia * 1	4/53 (7.55%)	4	2/50 (4.00%)	2
Cardiac disorders
Palpitations * 1	3/53 (5.66%)	3	5/50 (10.00%)	5
Right ventricular failure * 1	4/53 (7.55%)	4	0/50 (0.00%)	0
Ear and labyrinth disorders
Vertigo * 1	2/53 (3.77%)	2	5/50 (10.00%)	5
Eye disorders
Vision blurred * 1	0/53 (0.00%)	0	3/50 (6.00%)	3
Gastrointestinal disorders
Diarrhoea * 1	5/53 (9.43%)	5	7/50 (14.00%)	7
Nausea * 1	5/53 (9.43%)	5	1/50 (2.00%)	1
General disorders
Oedema peripheral * 1	8/53 (15.09%)	8	7/50 (14.00%)	7
Chest pain * 1	4/53 (7.55%)	4	0/50 (0.00%)	0
Infections and infestations
Bronchitis * 1	5/53 (9.43%)	5	5/50 (10.00%)	5
Nasopharyngitis * 1	8/53 (15.09%)	8	5/50 (10.00%)	5
Upper respiratory tract infection * 1	5/53 (9.43%)	5	2/50 (4.00%)	2
Respiratory tract infection * 1	1/53 (1.89%)	1	4/50 (8.00%)	4
Sinusitis * 1	5/53 (9.43%)	5	1/50 (2.00%)	1
Investigations
Weight increased * 1	3/53 (5.66%)	3	0/50 (0.00%)	0
Metabolism and nutrition disorders
Gout * 1	3/53 (5.66%)	3	0/50 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain * 1	5/53 (9.43%)	5	1/50 (2.00%)	1
Arthralgia * 1	4/53 (7.55%)	4	0/50 (0.00%)	0
Musculoskeletal chest pain * 1	3/53 (5.66%)	3	0/50 (0.00%)	0
Nervous system disorders
Headache * 1	7/53 (13.21%)	7	7/50 (14.00%)	7
Presyncope * 1	3/53 (5.66%)	3	3/50 (6.00%)	3
Syncope * 1	3/53 (5.66%)	3	0/50 (0.00%)	0
Psychiatric disorders
Depression * 1	0/53 (0.00%)	0	3/50 (6.00%)	3
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension * 1	4/53 (7.55%)	4	2/50 (4.00%)	2
Cough * 1	3/53 (5.66%)	3	1/50 (2.00%)	1
Dyspnoea * 1	8/53 (15.09%)	8	3/50 (6.00%)	3
Pulmonary hypertension * 1	0/53 (0.00%)	0	3/50 (6.00%)	3
Vascular disorders
Flushing * 1	4/53 (7.55%)	4	5/50 (10.00%)	5
Hypertension * 1	3/53 (5.66%)	3	1/50 (2.00%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vizza CD, Jansa P, Teal S, Dombi T, Zhou D. Sildenafil dosed concomitantly with bosentan for adult pulmonary arterial hypertension in a randomized controlled trial. BMC Cardiovasc Disord. 2017 Sep 6;17(1):239. doi: 10.1186/s12872-017-0674-3.

• Responsible Party: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
• ClinicalTrials.gov Identifier: NCT00323297
• Other Study ID Numbers: A1481243; 2006-001464-23 ( EudraCT Number ); PATHWAYS ( Other Identifier: Alias Study Number )
• First Submitted: May 5, 2006
• First Posted: May 9, 2006
• Results First Submitted: August 23, 2013
• Results First Posted: November 19, 2013
• Last Update Posted: February 1, 2021