Trial Outcomes & Findings for FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH) (NCT NCT00325403)
NCT ID: NCT00325403
Last Updated: 2024-01-03
Results Overview
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 12, correlates with the historical 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 six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
349 participants
Primary outcome timeframe
Baseline and Week 12
Results posted on
2024-01-03
Participant Flow
349 subjects participated in the study from 24 October 2006 to 29 April 2011 at 52 of 77 sites across the United States, Puerto Rico, Canada, Europe, Israel, India, Mexico, and China. The primary endpoint was analyzed using the primary analysis population which included 228 subjects who had access to 0.25 mg tablets at the time of randomization.
Participant milestones
| Measure |
Placebo
These subjects were randomly allocated to receive matching oral placebo twice daily (every 12 hours +/- 1 hour) and were included in the primary analysis population. Dose increases were made in the absence of dose-limiting drug-related AEs, to ensure the subject received the optimal clinical dose throughout the study.
|
UT-15C (Oral Treprostinil)
These subjects were randomly allocated to receive oral treprostinil twice daily (every 12 hours +/- 1 hour) and were included in the primary analysis population. Dose increases were made in the absence of dose-limiting drug-related AEs, to ensure the subject received the optimal clinical dose throughout the study.
|
|---|---|---|
|
Overall Study
STARTED
|
116
|
233
|
|
Overall Study
COMPLETED
|
98
|
182
|
|
Overall Study
NOT COMPLETED
|
18
|
51
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)
Baseline characteristics by cohort
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population. Baseline measures are provided for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population. Baseline measures are provided for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
Total
n=228 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
69 Participants
n=5 Participants
|
141 Participants
n=7 Participants
|
210 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 13.5 • n=5 Participants
|
37.8 years
STANDARD_DEVIATION 13.5 • n=7 Participants
|
39.4 years
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
166 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
PAH Etiology
Idiopathic or heritable PAH
|
56 participants
n=5 Participants
|
114 participants
n=7 Participants
|
170 participants
n=5 Participants
|
|
PAH Etiology
PAH associated w collagen vascular disease
|
17 participants
n=5 Participants
|
26 participants
n=7 Participants
|
43 participants
n=5 Participants
|
|
PAH Etiology
PAH associated w repaired congenital heart defect
|
3 participants
n=5 Participants
|
10 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
PAH Etiology
PAH associated w HIV infection
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Baseline Six Minute Walk Distance
|
327.6 meters
STANDARD_DEVIATION 70.7 • n=5 Participants
|
331.3 meters
STANDARD_DEVIATION 64.9 • n=7 Participants
|
330.0 meters
STANDARD_DEVIATION 66.8 • n=5 Participants
|
|
WHO Functional Classification
WHO Class I
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
WHO Functional Classification
WHO Class II
|
24 participants
n=5 Participants
|
52 participants
n=7 Participants
|
76 participants
n=5 Participants
|
|
WHO Functional Classification
WHO Class III
|
52 participants
n=5 Participants
|
98 participants
n=7 Participants
|
150 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: Analyses were conducted using the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228). All alpha was spent on this subgroup, thereby maintaining an overall type I error rate of 0.05. For sensitivity purposes, efficacy analyses were also performed on all enrolled subjects (n=349).
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 12, correlates with the historical 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 six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD)
6MWD at Baseline
|
339 meters
Interval 282.0 to 381.0
|
350 meters
Interval 283.0 to 386.0
|
|
Six Minute Walk Distance (6MWD)
6MWD at Week 12
|
343 meters
Interval 246.0 to 403.0
|
370 meters
Interval 300.0 to 418.0
|
|
Six Minute Walk Distance (6MWD)
Change in 6MWD from Baseline to Week 12
|
-5 meters
Interval -41.0 to 49.0
|
25 meters
Interval -16.0 to 63.0
|
SECONDARY outcome
Timeframe: Baseline and Week 11Population: Analyses were conducted using the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228). All alpha was spent on this subgroup, thereby maintaining an overall type I error rate of 0.05. For sensitivity purposes, efficacy analyses were also performed on all enrolled subjects (n=349).
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 11, a time expected to correlate with trough treprostinil concentration. The six minute walk test was to be conducted 8 to 13 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 11. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD)
6MWD at Baseline
|
339 meters
Interval 282.0 to 381.0
|
350 meters
Interval 283.0 to 386.0
|
|
Six Minute Walk Distance (6MWD)
6MWD at Week 11
|
335 meters
Interval 254.0 to 400.0
|
350 meters
Interval 290.0 to 400.0
|
|
Six Minute Walk Distance (6MWD)
Change in 6MWD from Baseline to Week 11
|
0 meters
Interval -54.0 to 36.0
|
8 meters
Interval -25.0 to 50.0
|
SECONDARY outcome
Timeframe: Baseline and Week 8Population: Analyses were conducted using the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228). All alpha was spent on this subgroup, thereby maintaining an overall type I error rate of 0.05. For sensitivity purposes, efficacy analyses were also performed on all enrolled subjects (n=349).
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 8, correlates with the historical 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 six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 8. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD)
6MWD at Week 8
|
347 meters
Interval 240.0 to 398.0
|
355 meters
Interval 300.0 to 408.0
|
|
Six Minute Walk Distance (6MWD)
6MWD at Baseline
|
339 meters
Interval 282.0 to 381.0
|
350 meters
Interval 283.0 to 386.0
|
|
Six Minute Walk Distance (6MWD)
Change in 6MWD from Baseline to Week 8
|
0 meters
Interval -36.0 to 35.0
|
17 meters
Interval -15.0 to 54.0
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: Analyses were conducted using the modified intention to treat (mITT), which includes subjects who had access to 0.25 mg tablets at randomization (n=228). All alpha was spent on this subgroup, thereby maintaining an overall type I error rate of 0.05. For sensitivity purposes, efficacy analyses were also performed on all enrolled subjects (n=349).
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 4, correlates with the historical 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 six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 4. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD)
6MWD at Baseline
|
339 meters
Interval 282.0 to 381.0
|
350 meters
Interval 283.0 to 386.0
|
|
Six Minute Walk Distance (6MWD)
6MWD at Week 4
|
350 meters
Interval 254.0 to 387.0
|
360 meters
Interval 285.0 to 400.0
|
|
Six Minute Walk Distance (6MWD)
Change in 6MWD from Baseline to Week 4
|
0 meters
Interval -28.0 to 17.0
|
7 meters
Interval -15.0 to 42.0
|
SECONDARY outcome
Timeframe: Baseline and Week 12Definition of clinical worsening included patients who met at least one of the following criteria during the 12 weeks of the study: 1. Death (all causes excluding accident) 2. Transplantation or atrial septostomy 3. Clinical deterioration as defined by: 1. Hospitalization as a result of PAH, or 2. greater than or equal to 20% decrease in 6MWD from Baseline (or too ill to walk) and a decrease in WHO functional class And 3. Initiation of new PAH specific therapy (i.e., ERA, PDE5-I, prostacyclin)
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Clinical Worsening Assessment
|
8 participants
|
15 participants
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Subjects with a WHO functional classification assessment at Week 12.
Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. These patients are comfortable at rest, but ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest. Discomfort is increased by any physical activity.
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
World Health Organization Functional Classification for PAH
WHO Class I
|
1 participants
|
2 participants
|
|
World Health Organization Functional Classification for PAH
WHO Class II
|
29 participants
|
59 participants
|
|
World Health Organization Functional Classification for PAH
WHO Class III
|
38 participants
|
75 participants
|
|
World Health Organization Functional Classification for PAH
WHO Class IV
|
9 participants
|
15 participants
|
SECONDARY outcome
Timeframe: Baseline and Week 12The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-minute walk test. The Borg dyspnea score was assessed immediately following the 6-minute walk test. Scores ranged from 0 (for no shortness of breath) to 10 (for greatest shortness of breath ever experienced).
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Borg Dyspnea Score
Borg dyspnea score at Baseline
|
3 units on a scale
Interval 2.0 to 6.0
|
3 units on a scale
Interval 2.0 to 4.0
|
|
Borg Dyspnea Score
Borg dyspnea score at Week 12
|
3 units on a scale
Interval 2.0 to 5.0
|
3 units on a scale
Interval 1.0 to 5.0
|
|
Borg Dyspnea Score
Change in Borg dyspnea score from Baseline to Wk12
|
0 units on a scale
Interval -1.0 to 1.0
|
0 units on a scale
Interval -1.0 to 1.0
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Two subjects (one in the placebo arm and one in the oral treprostinil arm) from the primary analysis population (n=228) did not have a Baseline dyspnea-fatigue index score and were not included in this analysis.
The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.
Outcome measures
| Measure |
Placebo
n=76 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=150 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Dyspnea-Fatigue Index
Change in dyspnea-fatigue index from BL to Wk 12
|
-0.3 units on a scale
Standard Deviation 2.5
|
-0.3 units on a scale
Standard Deviation 2.4
|
|
Dyspnea-Fatigue Index
Dyspnea-fatigue index at Baseline
|
5.8 units on a scale
Standard Deviation 2.4
|
6.2 units on a scale
Standard Deviation 2.1
|
|
Dyspnea-Fatigue Index
Dyspnea-fatigue index at Week 12
|
5.5 units on a scale
Standard Deviation 2.9
|
5.9 units on a scale
Standard Deviation 2.8
|
SECONDARY outcome
Timeframe: Baseline and Week 12Defined symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain, and orthopnea were assessed at Baseline prior to starting study drug and during the Treatment Phase at Week 12. Severity grade values (i.e., 0, 1, 2, or 3 in increasing severity) were assigned for each symptom.
Outcome measures
| Measure |
Placebo
n=77 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Symptoms of PAH
Change in fatigue symptoms
|
0.1 units on a scale
Standard Deviation 1.0
|
0.0 units on a scale
Standard Deviation 1.0
|
|
Symptoms of PAH
Change in dyspnea symptoms
|
-0.1 units on a scale
Standard Deviation 0.9
|
-0.2 units on a scale
Standard Deviation 0.9
|
|
Symptoms of PAH
Change in edema symptoms
|
0.3 units on a scale
Standard Deviation 1.0
|
0.2 units on a scale
Standard Deviation 1.1
|
|
Symptoms of PAH
Change in dizziness symptoms
|
0.0 units on a scale
Standard Deviation 1.0
|
0.3 units on a scale
Standard Deviation 1.0
|
|
Symptoms of PAH
Change in syncope symptoms
|
0.3 units on a scale
Standard Deviation 1.0
|
0.3 units on a scale
Standard Deviation 0.9
|
|
Symptoms of PAH
Change in chest pain symptoms
|
0.1 units on a scale
Standard Deviation 0.9
|
0.2 units on a scale
Standard Deviation 1.0
|
|
Symptoms of PAH
Change in orthopnea symptoms
|
0.2 units on a scale
Standard Deviation 0.9
|
0.2 units on a scale
Standard Deviation 1.0
|
POST_HOC outcome
Timeframe: Baseline and Week 12Exploratory efficacy analyses were to determine the effect of Baseline WHO functional class on treatment effect for change in 6MWD. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=52 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=98 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance by Baseline WHO Functional Classification III or IV
6MWD at Baseline
|
333.5 meters
Interval 269.0 to 382.5
|
330 meters
Interval 265.0 to 378.0
|
|
Six Minute Walk Distance by Baseline WHO Functional Classification III or IV
6MWD at Week 12
|
316.5 meters
Interval 231.5 to 385.0
|
354 meters
Interval 265.0 to 400.0
|
|
Six Minute Walk Distance by Baseline WHO Functional Classification III or IV
Change in 6MWD from Baseline to Week 12
|
-8.5 meters
Interval -50.5 to 40.0
|
20.5 meters
Interval -20.0 to 63.0
|
POST_HOC outcome
Timeframe: Baseline and Week 12Exploratory efficacy analyses were to determine the effect of Baseline WHO functional class on treatment effect for change in 6MWD. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=25 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=53 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance by Baseline WHO Functional Classification: I or II
6MWD at Baseline
|
370 meters
Interval 297.0 to 378.0
|
366 meters
Interval 315.0 to 390.0
|
|
Six Minute Walk Distance by Baseline WHO Functional Classification: I or II
6MWD at Week 12
|
379 meters
Interval 274.0 to 429.0
|
391 meters
Interval 348.0 to 431.0
|
|
Six Minute Walk Distance by Baseline WHO Functional Classification: I or II
Change in 6MWD from Baseline to Week 12
|
18 meters
Interval -30.0 to 55.0
|
27 meters
Interval -5.0 to 67.0
|
POST_HOC outcome
Timeframe: Baseline and Week 12Exploratory efficacy analyses were to determine the effect of PAH etiology (idiopathic/heritable, associated with collagen vascular disease, and other etiologies) on treatment effect for change in 6MWD. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=56 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=114 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD) by PAH Etiology: Idiopathic or Heritable PAH
6MWD at Baseline
|
332.5 meters
Interval 260.0 to 379.0
|
346 meters
Interval 281.0 to 390.0
|
|
Six Minute Walk Distance (6MWD) by PAH Etiology: Idiopathic or Heritable PAH
6MWD at Week 12
|
310.5 meters
Interval 242.5 to 380.0
|
380 meters
Interval 304.0 to 420.0
|
|
Six Minute Walk Distance (6MWD) by PAH Etiology: Idiopathic or Heritable PAH
Change in 6MWD from BL to Wk 12
|
-7.5 meters
Interval -50.5 to 42.0
|
25 meters
Interval -13.0 to 67.0
|
POST_HOC outcome
Timeframe: Baseline and Week 12Population: This analysis was performed using data from all subjects enrolled in the study, regardless of tablet strength availability at randomization.
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 12, correlates with the historical 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). This outcome measure was assessed using data collected from all subjects enrolled in the study, regardless of tablet strength availability at randomization. The six minute walk test was to be conducted 3 to 6 house after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Wk 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference i
Outcome measures
| Measure |
Placebo
n=116 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=233 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Week 12
|
329.5 meters
Interval 231.5 to 397.5
|
370 meters
Interval 304.0 to 420.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Baseline
|
338.5 meters
Interval 265.5 to 383.5
|
347 meters
Interval 288.0 to 387.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
Change in 6MWD from Baseline to Week 12
|
0 meters
Interval -46.0 to 40.0
|
25 meters
Interval -12.0 to 63.0
|
POST_HOC outcome
Timeframe: Baseline and Week 11Population: This analysis was performed using data from all subjects enrolled in the study, regardless of tablet strength availability at randomization.
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 11, a time expected to correlate with trough treprostinil concentration. This outcome measure was assessed using data from all subjects enrolled in the study, regardless of tablet strength availability at the time of randomization. The six minute walk test was to be conducted 8 to 13 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 11. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=116 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=233 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Baseline
|
338.5 meters
Interval 265.5 to 383.5
|
347 meters
Interval 288.0 to 387.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Week 11
|
326.5 meters
Interval 206.0 to 398.0
|
351 meters
Interval 303.0 to 403.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
Change in 6MWD from Baseline to Week 11
|
-2 meters
Interval -58.5 to 36.0
|
6 meters
Interval -18.0 to 48.0
|
POST_HOC outcome
Timeframe: Baseline and Week 8Population: This analysis was performed using data from all subjects enrolled in the study, regardless of tablet strength availability at randomization.
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 8, correlates with the historical 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). This outcome measure was assessed using data from all subjects enrolled in the study, regardless of tablet strength availability at randomization. The six minute walk test was to be conducted 3 to 6 house after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 8. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=116 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=233 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Baseline
|
338.5 meters
Interval 265.5 to 383.5
|
347 meters
Interval 288.0 to 387.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Week 8
|
339.5 meters
Interval 227.0 to 392.0
|
360 meters
Interval 300.0 to 411.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
Change in 6MWD from Baseline to Week 8
|
1.0 meters
Interval -38.5 to 34.5
|
17.0 meters
Interval -13.0 to 54.0
|
POST_HOC outcome
Timeframe: Baseline and Week 4Population: This analysis was performed using data from all subjects enrolled in the study, regardless of tablet strength availability at randomization.
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 4, correlates with the historical 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). This outcome measure was assessed using data from all subjects enrolled in the study, regardless of tablet strength availability at randomization. The six minute walk test was to be conducted 3 to 6 house after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 4. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
Outcome measures
| Measure |
Placebo
n=116 Participants
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=233 Participants
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Baseline
|
338.5 meters
Interval 265.5 to 383.5
|
347 meters
Interval 288.0 to 387.0
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
6MWD at Week 4
|
339.5 meters
Interval 251.0 to 387.0
|
358 meters
Interval 288.0 to 403.2
|
|
Six Minute Walk Distance (6MWD) for the Entire Study Population
Change in 6MWD from Baseline to Week 4
|
-4 meters
Interval -31.5 to 20.0
|
7 meters
Interval -13.0 to 42.0
|
Adverse Events
Placebo
Serious events: 15 serious events
Other events: 68 other events
Deaths: 6 deaths
UT-15C (Oral Treprostinil)
Serious events: 27 serious events
Other events: 138 other events
Deaths: 9 deaths
Serious adverse events
| Measure |
Placebo
n=77 participants at risk
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 participants at risk
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Cardiac disorders
right ventricular failure
|
3.9%
3/77 • Number of events 3 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
6.6%
10/151 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
pulmonary hypertension
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
2.0%
3/151 • Number of events 3 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
death
|
2.6%
2/77 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
1.3%
2/151 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
3.9%
3/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
chest pain
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
1.3%
2/151 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
1.3%
2/151 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
hemoptysis
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Nervous system disorders
anterograde amnesia
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
cardiac failure
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
cardiac failure congestive
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
cardio-respiratory arrest
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
circulatory collapse
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Vascular disorders
collagen-vascular disease
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
cor pulmonale acute
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
diarrhea infectious
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
paroxysmal noturnal dypsnea
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
gastritis
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
gastroenteritis
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Nervous system disorders
headache
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
lower respiratory tract infection
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
nausea
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
palpitations
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
presyncope
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
pulmonary edema
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Renal and urinary disorders
acute renal failure
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Infections and infestations
septic shock
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Skin and subcutaneous tissue disorders
skin ulcer
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
sudden death
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
syncope
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Immune system disorders
systemic lupus erythematosus
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Renal and urinary disorders
urinary tract infection
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
sudden cardiac death
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Renal and urinary disorders
renal impairment
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
respiratory tract infection
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.00%
0/151 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
Other adverse events
| Measure |
Placebo
n=77 participants at risk
These subjects were randomly allocated to receive placebo twice daily and were included in the primary analysis population.
|
UT-15C (Oral Treprostinil)
n=151 participants at risk
These subjects were randomly allocated to receive oral treprostinil twice daily and were included in the primary analysis population.
|
|---|---|---|
|
Nervous system disorders
headache
|
19.5%
15/77 • Number of events 17 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
62.9%
95/151 • Number of events 131 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
diarrhea
|
15.6%
12/77 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
30.5%
46/151 • Number of events 54 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
nausea
|
18.2%
14/77 • Number of events 14 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
29.8%
45/151 • Number of events 50 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
vomiting
|
15.6%
12/77 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
17.2%
26/151 • Number of events 31 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Vascular disorders
flushing
|
6.5%
5/77 • Number of events 5 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
15.2%
23/151 • Number of events 25 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.8%
6/77 • Number of events 6 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
13.9%
21/151 • Number of events 25 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
pain in jaw
|
3.9%
3/77 • Number of events 3 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
11.3%
17/151 • Number of events 18 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
fatigue
|
7.8%
6/77 • Number of events 6 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
9.3%
14/151 • Number of events 15 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
abdominal pain
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
8.6%
13/151 • Number of events 13 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Vascular disorders
peripheral edema
|
6.5%
5/77 • Number of events 5 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
8.6%
13/151 • Number of events 15 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Endocrine disorders
hypokalemia
|
2.6%
2/77 • Number of events 3 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
8.6%
13/151 • Number of events 16 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
decreased appetite
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
7.9%
12/151 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Nervous system disorders
insomnia
|
2.6%
2/77 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
7.3%
11/151 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Cardiac disorders
right ventricular failure
|
3.9%
3/77 • Number of events 3 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
6.6%
10/151 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
nasopharyngitis
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
6.0%
9/151 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
abdominal discomfort
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
6.0%
9/151 • Number of events 9 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
upper abdominal pain
|
2.6%
2/77 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
5.3%
8/151 • Number of events 12 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
back pain
|
2.6%
2/77 • Number of events 2 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 8 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 7 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Gastrointestinal disorders
gastritis
|
1.3%
1/77 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 7 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
pain
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 7 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Skin and subcutaneous tissue disorders
rash
|
0.00%
0/77 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 7 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
asthenia
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.0%
6/151 • Number of events 9 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Musculoskeletal and connective tissue disorders
muscle spasms
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
3.3%
5/151 • Number of events 8 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary hypertension
|
6.5%
5/77 • Number of events 5 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
2.0%
3/151 • Number of events 3 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
oropharyngeal pain
|
5.2%
4/77 • Number of events 4 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
0.66%
1/151 • Number of events 1 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
General disorders
dizziness
|
14.3%
11/77 • Number of events 11 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
11.3%
17/151 • Number of events 19 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Infections and infestations
pyrexia
|
10.4%
8/77 • Number of events 8 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 7 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Infections and infestations
upper respiratory tract infection
|
6.5%
5/77 • Number of events 5 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
5.3%
8/151 • Number of events 8 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
11.7%
9/77 • Number of events 9 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
9.3%
14/151 • Number of events 15 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
10.4%
8/77 • Number of events 8 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
4.6%
7/151 • Number of events 8 • Adverse events were recorded throughout the 12 week study which was conducted between October 2006 and April 2011.
Adverse events are reported for the modified intention to treat (mITT) group, which includes subjects with access to 0.25 mg tablets at randomization (n=228).
|
Additional Information
Kevin Laliberte; Senior Director, Product Development
United Therapeutics Corporation
Phone: 919-425-8176
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER