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Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension (FREEDOM-C2)

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: NCT00887978
Recruitment Status : Completed
First Posted : April 24, 2009
Results First Posted : January 15, 2013
Last Update Posted : January 15, 2013
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Hypertension
Interventions Drug: UT-15C SR
Drug: Placebo
Enrollment 310
Recruitment Details The recruitment period for this study was June 2009 to July 2011. Sites were located in North America, Europe and Asia.
Pre-assignment Details The 310 subjects who received a dose of study drug are presented here.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description Doses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID. Identical placebo tablets to UT-15C, doses were titrated in the same manner
Period Title: Overall Study
Started 157 153
Completed 132 138
Not Completed 25 15
Reason Not Completed
Adverse Event             18             5
Clinical Worsening             4             4
Death             2             3
Withdrawal by Subject             1             2
Lost to Follow-up             0             1
Arm/Group Title UT-15C SR Placebo Total
Hide Arm/Group Description Doses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID. Identical placebo tablets to UT-15C, doses were titrated in the same manner Total of all reporting groups
Overall Number of Baseline Participants 157 153 310
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 153 participants 310 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
119
  75.8%
122
  79.7%
241
  77.7%
>=65 years
38
  24.2%
31
  20.3%
69
  22.3%
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 157 participants 153 participants 310 participants
51.5
(18 to 76)
50.4
(20 to 75)
51.0
(18 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 153 participants 310 participants
Female
119
  75.8%
122
  79.7%
241
  77.7%
Male
38
  24.2%
31
  20.3%
69
  22.3%
PAH Etiology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 153 participants 310 participants
Idiopathic or familial 104 99 203
Collagen vascular disease 48 49 97
HIV infection 2 4 6
Repaired congenital heart disease 3 1 4
World Health Organization (WHO) Functional Class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 153 participants 310 participants
Class II 43 37 80
Class III 110 115 225
Class IV 3 0 3
Unknown 1 1 2
[1]
Measure Description: Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
Baseline Six-minute walk distance  
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 157 participants 153 participants 310 participants
329.4  (69.2) 336.8  (63.5) 333  (66.4)
Background PAH therapy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 153 participants 310 participants
PDE-5i 67 65 132
ERA 25 28 53
PDE-5i + ERA 65 60 125
[1]
Measure Description: Eligible subjects were receiving background PAH therapy of either a phosphodiesterase-5 inhibitor (PDE-5i) and/or endothelin receptor antagonist (ERA)
Time since PAH diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 157 participants 153 participants 310 participants
2.5  (2.6) 3.3  (4.1) 2.9  (3.4)
1.Primary Outcome
Title 6-minute Walk Distance (6MWD)
Hide Description

Placebo-corrected change in 6MWD from Baseline to Week 16, correlates with the current clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS).

The 6MWD was to be assessed between 3 and 6 hours after the morning dose of study drug and background therapy(ies).

Time Frame Baseline and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 157 153
Median (Inter-Quartile Range)
Unit of Measure: meters
Week 16 Values
370
(292 to 419)
365
(300 to 405)
Change from Baseline
15
(-12 to 55)
11
(-14 to 39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments Using an allocation ratio of 1:1 between UT-15C SR and placebo, a fixed sample size of approximately 266 subjects would provide at least 90% power at a significance level of 0.05 (two-sided hypothesis) to detect a 30 meter between-treatment difference in the change from Baseline in distance traversed during the 6-Minute Walk, assuming a standard deviation of 75 meters. A total sample size of approximately 300 subjects was determined to account for discontinuations during the enrollment period.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.089
Comments [Not Specified]
Method non-parametric ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann (H-L)
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-2.0 to 22.0
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Clinical Worsening Assessment
Hide Description

Definition of clinical worsening included patients who met at least one of the following criteria during the 16 weeks of study:

  1. Death (all causes excluding accident)
  2. Transplantation
  3. Atrial septostomy
  4. Hospitalization as a result of right heart failure
  5. Greater than or equal to a 20% decrease in 6MWD from Baseline (or too ill to walk) AND addition of an inhaled prostacyclin analogue, ERA, or PDE-5i
  6. Initiation of parenteral prostacyclin therapy (i.e., epoprostenol, iloprost, or treprostinil) for the treatment of PAH
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 157 153
Measure Type: Number
Unit of Measure: number of clinical worsening events
11 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Borg Dyspnea Score
Hide Description The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects with a Baseline Borg Score were included in the analysis. One subject in the placebo group did not have a Baseline Borg Score recorded.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 157 152
Median (Inter-Quartile Range)
Unit of Measure: score
Week 16 Value
3.0
(2.0 to 5.0)
4.0
(2.0 to 5.0)
Change from Baseline
0
(-1.0 to 1.0)
0
(-1.0 to 1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann (H-L) Estimate
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 0.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title World Health Organization (WHO) Functional Class
Hide Description Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with a WHO functional class assessment at Week 16
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 131 136
Measure Type: Number
Unit of Measure: participants
WHO Class I 1 3
WHO Class II 58 47
WHO Class III 70 83
WHO Class IV 2 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments Imputation strategies were implemented for the 26 UT-15C subjects and 17 placebo subjects without values reported at Week 16.
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann (H-L) estimate
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
0.0 to 0.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Symptoms of PAH
Hide Description Symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea were assessed by the physician at Baseline and Week 16. Severity grade values (i.e., 0, 1, 2 or 3) for each symptom were provided each subject. A severity of 0 indicated no symptoms, the maximum severity was 3, indicating severe symptoms. Mean change in symptom severity from Baseline to Week 16 is described.
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects without Baseline assessments of PAH symptoms were not included in the analysis.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 156 150
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change in Fatigue Symptoms 0.0  (0.9) 0.0  (1.0)
Change in Dyspnea Symptoms -0.1  (0.9) -0.2  (0.9)
Change in Edema Symptoms 0.0  (1.0) 0.0  (0.9)
Change in Dizziness Symptoms 0.1  (1.0) 0.0  (1.0)
Change in Syncope Symptoms 0.2  (0.8) 0.2  (0.7)
Change in Chest Pain Symptoms 0.1  (1.0) 0.1  (1.0)
Change in Orthopnea Symptoms 0.2  (1.0) 0.1  (0.9)
6.Secondary Outcome
Title Dyspnea Fatigue Index
Hide Description The dyspnea-fatigue index was assessed at Baseline and Week 16. Each of the three components of the dyspnea-fatigue index were rated on a scale 0 to 4, with 0 being the worst condition and 4 being the best condition for each component. The dyspnea-fatigue index is computed by summing the three component scores.
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects without a Dyspnea Fatigue Index score at Baseline were not included in the analysis.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 154 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.7  (2.6) 6.0  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann (H-L) estimate
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
0.0 to 1.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title N-terminal proBNP (NT-proBNP)
Hide Description Serum N-terminal pro-BNP concentration was assessed at Baseline and Week 16.
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who were missing Week 16 samples were not included in the analysis.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 120 135
Mean (Standard Deviation)
Unit of Measure: pg/mL
Week 16 Value 1310  (1663) 1627  (2401)
Change from Baseline 135  (913) 136  (1242)
8.Secondary Outcome
Title Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
Hide Description Change in CAMPHOR Scores from Baseline to Week 16. The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in countries where the CAMPHOR has not been validated in the local language were not included in these analyses. Additionally, only subjects with completed questionnaires at Baseline and Week 16 were analyzed.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 102 85
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Symptom Score
10.0
(6.0 to 16.0)
9.0
(4.0 to 14.0)
Activity Score
10.0
(7.0 to 14.0)
10.0
(6.0 to 13.0)
Quality of Life Score
9.0
(4.0 to 15.0)
5.0
(1.5 to 13.0)
Total Score
28.0
(19.0 to 43.0)
24.5
(12.0 to 40.5)
9.Post-Hoc Outcome
Title 6-minute Walk Distance by PAH Etiology: Idiopathic PAH (IPAH) / Heritable PAH(HPAH)
Hide Description Covariate analysis of change in 6MWD by PAH etiology, specifically idiopathic or heritable PAH
Time Frame Baseline and 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with IPAH/HPAH
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 104 99
Median (Inter-Quartile Range)
Unit of Measure: meters
21.5
(-0.5 to 64.5)
13
(-14 to 39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehman Estimate
Estimated Value 14.0
Confidence Interval (2-Sided) 95%
0.0 to 28.0
Estimation Comments [Not Specified]
10.Post-Hoc Outcome
Title 6-minute Walk Distance by Background PAH Therapy: PDE-5i Only
Hide Description [Not Specified]
Time Frame 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects receiving only a PDE-5i at Baseline
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 67 65
Median (Inter-Quartile Range)
Unit of Measure: meters
30
(4 to 55)
14
(-7 to 39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.054
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate
Estimated Value 15.0
Confidence Interval (2-Sided) 95%
-1.0 to 29.0
Estimation Comments [Not Specified]
11.Post-Hoc Outcome
Title 6-minute Walk Test by Background PAH Therapy: ERA Only
Hide Description [Not Specified]
Time Frame Baseline and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who were only receiving an ERA at Baseline
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 25 28
Median (Inter-Quartile Range)
Unit of Measure: meters
-5
(-43.0 to 42.0)
-2.5
(-49.0 to 30.0)
12.Post-Hoc Outcome
Title 6-minute Walk Test by Background PAH Therapy: ERA + PDE-5i
Hide Description [Not Specified]
Time Frame 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects receiving both an ERA and a PDE-5i at Baseline.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 65 60
Median (Inter-Quartile Range)
Unit of Measure: meters
14.0
(-17 to 59)
15.5
(-14.5 to 39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.674
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehman Estimate
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
-16.0 to 24.0
Estimation Comments [Not Specified]
13.Post-Hoc Outcome
Title 6-minute Walk Distance by Time to PAH Diagnosis: 0 - 0.9 Years
Hide Description [Not Specified]
Time Frame Baseline and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who have been diagnosed with PAH between 0 to 0.9 years prior to Baseline.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 40 38
Median (Inter-Quartile Range)
Unit of Measure: meters
21.5
(-12.5 to 50.5)
-6.0
(-63.0 to 26.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate
Estimated Value 28.0
Confidence Interval (2-Sided) 95%
1.0 to 59.0
Estimation Comments [Not Specified]
14.Post-Hoc Outcome
Title 6-minute Walk Distance by Time Since PAH Diagnosis: 0.9 - 1.74 Years
Hide Description [Not Specified]
Time Frame 16 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who had been diagnosed with PAH between 0.9 and 1.74 years prior to Baseline.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 40 37
Median (Inter-Quartile Range)
Unit of Measure: meters
20.1
(1.0 to 61.0)
13.0
(-2.0 to 45.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-10.0 to 31.0
Estimation Comments [Not Specified]
15.Post-Hoc Outcome
Title 6-minute Walk Distance by Years Since PAH Diagnosis: 1.8 - 3.5 Years
Hide Description [Not Specified]
Time Frame Baseline and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who were diagnosed with PAH between 1.8 and 3.5 years prior to Baseline.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 40 37
Median (Inter-Quartile Range)
Unit of Measure: meter
15.5
(-16.0 to 51.5)
4.0
(-14.0 to 42.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-23.0 to 28.0
Estimation Comments [Not Specified]
16.Post-Hoc Outcome
Title 6-minute Walk Distance by Time Since PAH Diagnosis: 3.6 - 26.4 Years
Hide Description [Not Specified]
Time Frame Baseline and 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who had been diagnosed with PAH for 3.6 to 26.4 years prior to Baseline.
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description:
At Week 16, the mean(SD) dose of UT-15C was 3.1mg (1.9).
At Week 16, the mean(SD) dose of placebo was 6.1mg (3.6).
Overall Number of Participants Analyzed 37 41
Median (Inter-Quartile Range)
Unit of Measure: meters
14.0
(-23.0 to 59.0)
16.0
(-5.0 to 36.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UT-15C SR, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate
Estimated Value -2.0
Confidence Interval 95%
-25.0 to 22.0
Estimation Comments [Not Specified]
Time Frame Adverse events were recorded throughout the 16 week study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title UT-15C SR Placebo
Hide Arm/Group Description At Week 16, the mean(SD) dose of UT-15C was 3.1 (1.9). At Week 16, the mean(SD) dose of placebo was 6.1 (3.6).
All-Cause Mortality
UT-15C SR Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
UT-15C SR Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/157 (14.65%)      23/153 (15.03%)    
Cardiac disorders     
Right ventricular failure * 1  5/157 (3.18%)  5 2/153 (1.31%)  2
Atrial fibrillation * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Cardiac failure * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Cardio-respiratory arrest * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Palpitations * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Gastrointestinal disorders     
Diverticulum * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Lower gastrointestinal hemorrhage * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
General disorders     
Pyrexia * 1  2/157 (1.27%)  2 1/153 (0.65%)  2
Sudden death * 1  1/157 (0.64%)  1 1/153 (0.65%)  1
Peripheral edema * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Hepatobiliary disorders     
Hepatic ischemia * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Infections and infestations     
Lower respiratory tract infection * 1  3/157 (1.91%)  3 0/153 (0.00%)  0
Gastroenteritis * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Infection * 1  0/157 (0.00%)  0 1/153 (0.65%)  2
Sepsis * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Tracheobronchitis * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Upper respiratory tract infection * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Injury, poisoning and procedural complications     
Fall * 1  2/157 (1.27%)  2 0/153 (0.00%)  0
Rib fracture * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Metabolism and nutrition disorders     
Fluid overload * 1  2/157 (1.27%)  2 1/153 (0.65%)  1
Fluid retention * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Hypervolemia * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Hypoglycemia * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Hypokalemia * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain * 1  2/157 (1.27%)  2 0/153 (0.00%)  0
Bone pain * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Rheumatoid arthritis * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Nervous system disorders     
Cerebrovascular accident * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Depressed level of consciousness * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Dizziness * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Dysarthria * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Hypoesthesia * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Presyncope * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Psychiatric disorders     
Affect lability * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Reproductive system and breast disorders     
Ovarian mass * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea * 1  4/157 (2.55%)  4 2/153 (1.31%)  2
Pulmonary hypertension * 1  2/157 (1.27%)  2 4/153 (2.61%)  4
Hemoptysis * 1  1/157 (0.64%)  1 1/153 (0.65%)  1
Chronic obstructive pulmonary disease * 1  0/157 (0.00%)  0 1/153 (0.65%)  3
Cough * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Orthopnea * 1  0/157 (0.00%)  0 1/153 (0.65%)  1
Pulmonary embolism * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Respiratory failure * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Skin and subcutaneous tissue disorders     
Stasis dermatitis * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Urticaria * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Surgical and medical procedures     
Joint arthroplasty * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
Vascular disorders     
Deep vein thrombosis * 1  1/157 (0.64%)  1 0/153 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
UT-15C SR Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   157/157 (100.00%)      136/153 (88.89%)    
Cardiac disorders     
Palpitations * 1  6/157 (3.82%)  6 12/153 (7.84%)  12
Gastrointestinal disorders     
Diarrhea * 1  87/157 (55.41%)  105 38/153 (24.84%)  42
Nausea * 1  73/157 (46.50%)  77 34/153 (22.22%)  35
Vomiting * 1  33/157 (21.02%)  38 16/153 (10.46%)  20
Abdominal pain * 1  12/157 (7.64%)  13 11/153 (7.19%)  11
Abdominal pain upper * 1  12/157 (7.64%)  13 7/153 (4.58%)  7
Dyspepsia * 1  11/157 (7.01%)  12 8/153 (5.23%)  8
General disorders     
Fatigue * 1  23/157 (14.65%)  25 16/153 (10.46%)  17
Peripheral edema * 1  17/157 (10.83%)  18 10/153 (6.54%)  10
Chest Pain * 1  9/157 (5.73%)  9 10/153 (6.54%)  11
Infections and infestations     
Upper respiratory tract infection * 1  17/157 (10.83%)  18 13/153 (8.50%)  13
Metabolism and nutrition disorders     
Decreased appetite * 1  12/157 (7.64%)  14 4/153 (2.61%)  4
Musculoskeletal and connective tissue disorders     
Pain in jaw * 1  39/157 (24.84%)  39 10/153 (6.54%)  10
Pain in extremity * 1  27/157 (17.20%)  29 11/153 (7.19%)  12
Myalgia * 1  18/157 (11.46%)  18 10/153 (6.54%)  11
Arthralgia * 1  12/157 (7.64%)  13 9/153 (5.88%)  9
Back pain * 1  12/157 (7.64%)  13 6/153 (3.92%)  6
Muscle spasms * 1  12/157 (7.64%)  12 5/153 (3.27%)  5
Nervous system disorders     
Headache * 1  112/157 (71.34%)  145 61/153 (39.87%)  69
Dizziness * 1  30/157 (19.11%)  36 15/153 (9.80%)  15
Respiratory, thoracic and mediastinal disorders     
Dyspnea * 1  25/157 (15.92%)  27 10/153 (6.54%)  15
Nasal congestion * 1  10/157 (6.37%)  10 0/153 (0.00%)  0
Nasopharyngitis * 1  17/157 (10.83%)  19 25/153 (16.34%)  28
Vascular disorders     
Flushing * 1  55/157 (35.03%)  64 16/153 (10.46%)  18
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.0)
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.
Any publication of the results of this trial must be consistent with the United Therapeutics publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Results Point of Contact
Name/Title: Kevin Laliberte, PharmD
Organization: United Therapeutics Corporation
Phone: 919-425-8350
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00887978     History of Changes
Other Study ID Numbers: TDE-PH-308
First Submitted: April 23, 2009
First Posted: April 24, 2009
Results First Submitted: November 2, 2012
Results First Posted: January 15, 2013
Last Update Posted: January 15, 2013