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To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00430716
Recruitment Status : Terminated (This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns.)
First Posted : February 2, 2007
Results First Posted : May 17, 2011
Last Update Posted : December 22, 2020
Sponsor:
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: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Intervention Drug: Sildenafil citrate
Enrollment 130
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Period Title: Double Blind Phase
Started 42 43 45
Treated 41 43 45
Completed 36 38 39
Not Completed 6 5 6
Reason Not Completed
Death             1             0             0
No longer willing to participate             2             1             1
Other             0             2             0
Study terminated by sponsor             1             1             2
Adverse Event             1             1             3
Not treated             1             0             0
Period Title: Open Label Phase
Started 36 38 39
Completed 27 31 32
Not Completed 9 7 7
Reason Not Completed
Lost to Follow-up             1             0             1
No longer willing to participate             0             1             1
Other             3             1             1
Protocol Violation             1             0             0
Study terminated by sponsor             4             5             4
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg Total
Hide Arm/Group Description Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase). Total of all reporting groups
Overall Number of Baseline Participants 41 43 45 129
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 43 participants 45 participants 129 participants
42.5  (16.5) 44.4  (17.4) 46.4  (17.7) 44.5  (17.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 43 participants 45 participants 129 participants
Female
28
  68.3%
33
  76.7%
26
  57.8%
87
  67.4%
Male
13
  31.7%
10
  23.3%
19
  42.2%
42
  32.6%
1.Primary Outcome
Title Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12
Hide Description 6 MWT was 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 Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT population) included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, last observation carried forward (LOCF) method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 41 40 42
Mean (95% Confidence Interval)
Unit of Measure: Meters
14.21
(0.41 to 28.00)
40.75
(25.16 to 56.34)
38.36
(23.77 to 52.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments An analysis of variance (ANOVA) model followed by the Williams trend test (one-sided, at the 2.5% level of significance) was used. The Williams trend test firstly determined if there was a significant downward trend in response for the descending doses, and then subsequently determined the highest dose that was statistically inferior to 20 mg (known to be an effective dose of sildenafil). A corresponding 97.5% lower confidence limit for the difference was presented.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 24.15
Confidence Interval (1-Sided) 97.5%
3.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments ANOVA model followed by the Williams trend test (one-sided, at the 2.5% level of significance) was used. The Williams trend test firstly determined if there was a significant downward trend in response for the descending doses, and then subsequently determined the highest dose that was statistically inferior to 20 mg (known to be an effective dose of sildenafil). A corresponding 97.5% lower confidence limit for the difference was presented.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.545
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.17
Confidence Interval (1-Sided) 97.5%
-21.48
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12
Hide Description mPAP was measured using a pressure transducer positioned at the mid-axillary line.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 33 33 34
Mean (95% Confidence Interval)
Unit of Measure: mmHg
-1.73
(-5.99 to 2.54)
-3.44
(-5.87 to -1.00)
-3.29
(-6.05 to -0.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments The analysis of change from baseline in week 12 mean PAP used Analysis of Covariance (ANCOVA), with etiology and baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.51
Confidence Interval (2-Sided) 95%
-7.07 to 2.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments The analysis of change from baseline in week 12 mean PAP used ANCOVA, with etiology and baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.846
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-4.98 to 4.09
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Clinical Worsening
Hide Description Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population for clinical worsening included all participants who had been randomized to study treatment and received at least 1 dose of study medication.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 41 43 45
Measure Type: Count of Participants
Unit of Measure: Participants
death
1
   2.4%
1
   2.3%
0
   0.0%
lung transplantation
0
   0.0%
0
   0.0%
0
   0.0%
hospitalisation due to pulmonary hypertension
1
   2.4%
0
   0.0%
2
   4.4%
PAH deterioration requiring therapy
0
   0.0%
0
   0.0%
0
   0.0%
receptor antagonist therapy
0
   0.0%
1
   2.3%
0
   0.0%
4.Secondary Outcome
Title Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12
Hide Description Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 41 43 45
Measure Type: Number
Unit of Measure: Participants
Worsened 2 Classes 0 0 0
Worsened 1 Class 1 3 2
No Change 35 27 35
Improved 1 Class 4 10 6
Improved 2 Classes 1 0 0
Missing 0 3 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments The analysis of the week 12 PAH functional class was done with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates.The odds ratio and corresponding two-sided 95% CI for the odds ratio for the treatment comparisons was presented along with the p-value for the tests.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.448
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
0.50 to 4.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments The analysis of the week 12 PAH functional class was done with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates.The odds ratio and corresponding two-sided 95% CI for the odds ratio for the treatment comparisons was presented along with the p-value for the tests.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.897
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.35 to 3.32
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12
Hide Description BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 38 39 42
Mean (95% Confidence Interval)
Unit of Measure: pg/mL
-6.28
(-80.75 to 68.19)
-53.46
(-99.98 to -6.94)
-97.42
(-161.45 to -33.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments ANCOVA method was used with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -104.80
Confidence Interval (2-Sided) 95%
-177.44 to -32.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments ANCOVA method was used with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.496
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -25.00
Confidence Interval (2-Sided) 95%
-97.50 to 47.50
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Pro-BNP at Week 12
Hide Description Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 39 40 43
Mean (95% Confidence Interval)
Unit of Measure: pg/mL
-111.53
(-507.68 to 284.63)
-306.76
(-523.82 to -89.70)
-428.54
(-676.74 to -180.34)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments ANCOVA method was used with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -462.12
Confidence Interval (2-Sided) 95%
-807.53 to -116.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments ANCOVA method was used with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.414
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -141.45
Confidence Interval (2-Sided) 95%
-483.48 to 200.58
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in TAPSE Measurement at Week 12
Hide Description

Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction.

The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 32 29 28
Mean (95% Confidence Interval)
Unit of Measure: cm
0.08
(-0.04 to 0.19)
0.17
(0.05 to 0.29)
-0.02
(-0.15 to 0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments ANCOVA method was used with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (1 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.890
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.17 to 0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments ANCOVA method was used with etiology, baseline walking distance category (<325m or >=325m) and baseline score as the covariates. The mean difference and corresponding two-sided 95% CI for the comparisons of sildenafil 20 mg against the lower sildenafil dose (5 mg) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.29 to 0.04
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in BORG Dyspnoea Score at Week 12
Hide Description BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum] and 10 (maximum).
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.
Arm/Group Title Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description:
Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
Overall Number of Participants Analyzed 41 40 42
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-0.28
(-0.76 to 0.20)
-0.89
(-1.35 to -0.43)
-0.43
(-0.94 to 0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil 1 mg, Sildenafil 20 mg
Comments A stratified Wilcoxon test (Van-Elteren) was used. The stratified median difference and corresponding two-sided 95% CI (calculated using the Hodges-Lehmann estimator) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.382
Comments [Not Specified]
Method Wilcoxon (Van-Elteren)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-1.00 to 0.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sildenafil 5 mg, Sildenafil 20 mg
Comments A stratified Wilcoxon test (Van-Elteren) was used. The stratified median difference and corresponding two-sided 95% CI (calculated using the Hodges-Lehmann estimator) was presented along with the p-value for the test.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.141
Comments [Not Specified]
Method Wilcoxon (Van-Elteren)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
0.00 to 1.00
Estimation Comments [Not Specified]
Time Frame 24 Weeks
Adverse Event Reporting Description The same event may appear as both an AE and an 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 Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Hide Arm/Group Description Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID. Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
All-Cause Mortality
Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/41 (2.44%)   1/43 (2.33%)   0/45 (0.00%) 
Hide Serious Adverse Events
Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/41 (14.63%)   3/43 (6.98%)   5/45 (11.11%) 
Blood and lymphatic system disorders       
Anaemia * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Anaemia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Cardiac disorders       
Atrial flutter * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Cor pulmonale * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Right ventricular failure * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Atrial flutter * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Cardiac failure * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Cor pulmonale * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Right ventricular failure * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  2/45 (4.44%) 
Gastrointestinal disorders       
Gastrointestinal haemorrhage * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Gastrointestinal haemorrhage * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Gastrooesophageal reflux disease * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Hepatobiliary disorders       
Hepatitis * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Hepatitis * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Immune system disorders       
Drug hypersensitivity * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Drug hypersensitivity * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Infections and infestations       
Lower respiratory tract infection * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Pneumonia * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Lower respiratory tract infection * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Pneumonia * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Respiratory tract infection * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Injury, poisoning and procedural complications       
Ankle fracture * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Ankle fracture * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Investigations       
Blood electrolytes abnormal * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
International normalised ratio increased * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Weight increased * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Nervous system disorders       
Syncope * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary fibrosis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Pulmonary infarction * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Cough * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Pulmonary arterial hypertension * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Pulmonary fibrosis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Pulmonary hypertension * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Pulmonary infarction * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
1
Term from vocabulary, MedDRA 13.1
*
Indicates events were collected by non-systematic assessment
[1]
Double Blind Phase
[2]
Open Label Phase
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sildenafil 1 mg Sildenafil 5 mg Sildenafil 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/41 (51.22%)   22/43 (51.16%)   22/45 (48.89%) 
Blood and lymphatic system disorders       
Anaemia * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  2/45 (4.44%) 
Leukocytosis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Lymphadenopathy * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Anaemia * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  2/45 (4.44%) 
Leukocytosis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Lymphadenopathy * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Cardiac disorders       
Cyanosis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Right ventricular failure * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Tachyarrhythmia * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Tachycardia * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Angina pectoris * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Atrial fibrillation * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Cyanosis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Right ventricular failure * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Sinus bradycardia * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Tachyarrhythmia * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Tachycardia * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Congenital, familial and genetic disorders       
Hereditary haemorrhagic telangiectasia * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Hereditary haemorrhagic telangiectasia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Ear and labyrinth disorders       
Ear pain * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Vertigo * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Ear pain * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Vertigo * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Endocrine disorders       
Goitre * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Eye disorders       
Conjunctivitis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Periorbital oedema * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Photophobia * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Vision blurred * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Blindness transient * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  1/45 (2.22%) 
Conjunctivitis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Periorbital oedema * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Photophobia * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Vision blurred * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Visual impairment * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Gastrointestinal disorders       
Abdominal distension * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Abdominal pain * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Diarrhoea * 1 [1]  0/41 (0.00%)  2/43 (4.65%)  1/45 (2.22%) 
Dyspepsia * 1 [1]  1/41 (2.44%)  1/43 (2.33%)  1/45 (2.22%) 
Dysphagia * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Flatulence * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Gastrooesophageal reflux disease * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Nausea * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Abdominal distension * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Abdominal pain * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Abdominal pain lower * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Constipation * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Diarrhoea * 1 [2]  1/41 (2.44%)  2/43 (4.65%)  1/45 (2.22%) 
Dyspepsia * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  1/45 (2.22%) 
Dysphagia * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Faecal incontinence * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Flatulence * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Gastrooesophageal reflux disease * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Gingival bleeding * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Glossodynia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Nausea * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
General disorders       
Asthenia * 1 [1]  1/41 (2.44%)  1/43 (2.33%)  1/45 (2.22%) 
Exercise tolerance decreased * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Fatigue * 1 [1]  2/41 (4.88%)  1/43 (2.33%)  0/45 (0.00%) 
Feeling hot * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Medical device pain * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Oedema peripheral * 1 [1]  1/41 (2.44%)  1/43 (2.33%)  2/45 (4.44%) 
Pyrexia * 1 [1]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Asthenia * 1 [2]  1/41 (2.44%)  2/43 (4.65%)  2/45 (4.44%) 
Chest pain * 1 [2]  0/41 (0.00%)  2/43 (4.65%)  0/45 (0.00%) 
Exercise tolerance decreased * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Fatigue * 1 [2]  3/41 (7.32%)  1/43 (2.33%)  0/45 (0.00%) 
Feeling hot * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Medical device pain * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Oedema * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Oedema peripheral * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  2/45 (4.44%) 
Pyrexia * 1 [2]  2/41 (4.88%)  2/43 (4.65%)  0/45 (0.00%) 
Infections and infestations       
Bronchitis * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Conjunctivitis bacterial * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Herpes zoster * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Nasopharyngitis * 1 [1]  2/41 (4.88%)  1/43 (2.33%)  1/45 (2.22%) 
Otitis externa * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Rhinitis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Sinusitis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Tinea barbae * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Bronchitis * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  1/45 (2.22%) 
Conjunctivitis bacterial * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Gastroenteritis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Herpes zoster * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Infected bites * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Influenza * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Lower respiratory tract infection * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Nasopharyngitis * 1 [2]  2/41 (4.88%)  1/43 (2.33%)  3/45 (6.67%) 
Otitis externa * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Rhinitis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Sinusitis * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Subcutaneous abscess * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Tinea barbae * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Urinary tract infection * 1 [2]  0/41 (0.00%)  2/43 (4.65%)  1/45 (2.22%) 
Investigations       
Blood potassium decreased * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Prostatic specific antigen increased * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Weight decreased * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Weight increased * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
White blood cell count decreased * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Blood potassium decreased * 1 [2]  2/41 (4.88%)  0/43 (0.00%)  0/45 (0.00%) 
Blood pressure increased * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Blood urea increased * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Prostatic specific antigen increased * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Weight decreased * 1 [2]  1/41 (2.44%)  2/43 (4.65%)  0/45 (0.00%) 
Weight increased * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
White blood cell count decreased * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Metabolism and nutrition disorders       
Hyperkalaemia * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Hypernatraemia * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Decreased appetite * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Diabetes mellitus * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Hyperglycaemia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Hyperkalaemia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Hypernatraemia * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Hyperuricaemia * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  2/45 (4.44%) 
Bone pain * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Flank pain * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Muscle spasms * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Myalgia * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  2/45 (4.44%) 
Pain in extremity * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  1/45 (2.22%) 
Pain in jaw * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Arthralgia * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Back pain * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  3/45 (6.67%) 
Bone pain * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Flank pain * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Muscle spasms * 1 [2]  2/41 (4.88%)  0/43 (0.00%)  1/45 (2.22%) 
Myalgia * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  2/45 (4.44%) 
Pain in extremity * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  2/45 (4.44%) 
Pain in jaw * 1 [2]  2/41 (4.88%)  0/43 (0.00%)  0/45 (0.00%) 
Nervous system disorders       
Dizziness * 1 [1]  2/41 (4.88%)  1/43 (2.33%)  1/45 (2.22%) 
Dysgeusia * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Headache * 1 [1]  1/41 (2.44%)  1/43 (2.33%)  3/45 (6.67%) 
Lethargy * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Loss of consciousness * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Paraesthesia * 1 [1]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Presyncope * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Sciatica * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Dizziness * 1 [2]  3/41 (7.32%)  2/43 (4.65%)  2/45 (4.44%) 
Dysgeusia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Head discomfort * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Headache * 1 [2]  2/41 (4.88%)  3/43 (6.98%)  3/45 (6.67%) 
Lethargy * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  1/45 (2.22%) 
Loss of consciousness * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Paraesthesia * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Presyncope * 1 [2]  0/41 (0.00%)  2/43 (4.65%)  0/45 (0.00%) 
Sciatica * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Syncope * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Psychiatric disorders       
Anxiety * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Depression * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Insomnia * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Anxiety * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Depression * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Insomnia * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Renal and urinary disorders       
Micturition urgency * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Renal failure * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Micturition urgency * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Renal failure * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea * 1 [1]  2/41 (4.88%)  3/43 (6.98%)  3/45 (6.67%) 
Epistaxis * 1 [1]  0/41 (0.00%)  2/43 (4.65%)  0/45 (0.00%) 
Nasal congestion * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Orthopnoea * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Productive cough * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Pulmonary fibrosis * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Pulmonary hypertension * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Rhinorrhoea * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Upper airway obstruction * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Wheezing * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Chronic obstructive pulmonary disease * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Cough * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Dyspnoea * 1 [2]  2/41 (4.88%)  4/43 (9.30%)  3/45 (6.67%) 
Epistaxis * 1 [2]  1/41 (2.44%)  3/43 (6.98%)  0/45 (0.00%) 
Nasal congestion * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Oropharyngeal pain * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Orthopnoea * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Productive cough * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Pulmonary fibrosis * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Pulmonary hypertension * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Rhinorrhoea * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Upper airway obstruction * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Wheezing * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Erythema * 1 [1]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Lichen planus * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Rash * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  2/45 (4.44%) 
Rash erythematous * 1 [1]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Alopecia * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Butterfly rash * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Erythema * 1 [2]  1/41 (2.44%)  1/43 (2.33%)  0/45 (0.00%) 
Increased tendency to bruise * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Lichen planus * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Palmar erythema * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Pruritus * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Rash * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  2/45 (4.44%) 
Rash erythematous * 1 [2]  0/41 (0.00%)  1/43 (2.33%)  0/45 (0.00%) 
Vascular disorders       
Flushing * 1 [1]  0/41 (0.00%)  2/43 (4.65%)  1/45 (2.22%) 
Orthostatic hypotension * 1 [1]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
Flushing * 1 [2]  0/41 (0.00%)  2/43 (4.65%)  1/45 (2.22%) 
Hypertension * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  0/45 (0.00%) 
Hypotension * 1 [2]  1/41 (2.44%)  0/43 (0.00%)  1/45 (2.22%) 
Orthostatic hypotension * 1 [2]  0/41 (0.00%)  0/43 (0.00%)  1/45 (2.22%) 
1
Term from vocabulary, MedDRA 13.1
*
Indicates events were collected by non-systematic assessment
[1]
Double Blind Phase
[2]
Open Label Phase
The trial was not designed to demonstrate the equivalence of doses and due to premature study termination, the resulting sample size was not adequately powered to show superiority.
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
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
ClinicalTrials.gov Identifier: NCT00430716    
Other Study ID Numbers: A1481244
2006-006748-76 ( EudraCT Number )
First Submitted: January 31, 2007
First Posted: February 2, 2007
Results First Submitted: April 22, 2011
Results First Posted: May 17, 2011
Last Update Posted: December 22, 2020