Trial · NCT00325403

FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)

NCT00325403, Phase 3, Completed, United Therapeutics; results first posted 2013-03-18

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH). Trials, record NCT00325403. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00325403

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)
NCT number: NCT00325403
Status: Completed
Phases: Phase 3
Enrollment: 349 participants, actual
Lead sponsor: United Therapeutics
Conditions: Pulmonary Hypertension
Interventions: Oral treprostinil (UT-15C) Sustained Release Tablets, Placebo
First posted: 2006-05-12
Last updated: 2024-01-03
Results first posted: 2013-03-18

Source ClinicalTrials.gov

Registered outcomes9

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Six Minute Walk Distance (6MWD)	Baseline and Week 12	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.
Secondary	Six Minute Walk Distance (6MWD)	Baseline and Week 11	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.
Secondary	Six Minute Walk Distance (6MWD)	Baseline and Week 8	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.
Secondary	Six Minute Walk Distance (6MWD)	Baseline and Week 4	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.
Secondary	Clinical Worsening Assessment	Baseline and Week 12	Definition 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)
Secondary	World Health Organization Functional Classification for PAH	Baseline and 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.
Secondary	Borg Dyspnea Score	Baseline and Week 12	The 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).
Secondary	Dyspnea-Fatigue Index	Baseline and Week 12	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.
Secondary	Symptoms of PAH	Baseline and Week 12	Defined 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.

Source ClinicalTrials.gov

Outcomes16

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Six Minute Walk Distance (6MWD)	Baseline and Week 12	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).	meters	MEDIAN
SECONDARY	Six Minute Walk Distance (6MWD)	Baseline and Week 11	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).	meters	MEDIAN
SECONDARY	Six Minute Walk Distance (6MWD)	Baseline and Week 8	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).	meters	MEDIAN
SECONDARY	Six Minute Walk Distance (6MWD)	Baseline and Week 4	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).	meters	MEDIAN
SECONDARY	Clinical Worsening Assessment	Baseline and Week 12		participants	NUMBER
SECONDARY	World Health Organization Functional Classification for PAH	Baseline and Week 12	Subjects with a WHO functional classification assessment at Week 12.	participants	NUMBER
SECONDARY	Borg Dyspnea Score	Baseline and Week 12		units on a scale	MEDIAN
SECONDARY	Dyspnea-Fatigue Index	Baseline and Week 12	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.	units on a scale	MEAN
SECONDARY	Symptoms of PAH	Baseline and Week 12		units on a scale	MEAN
POST_HOC	Six Minute Walk Distance by Baseline WHO Functional Classification III or IV	Baseline and Week 12		meters	MEDIAN

1 to 10 of 16Source ClinicalTrials.gov

See all 16 outcomes

Results by group102

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Six Minute Walk Distance (6MWD)	Placebo	6MWD at Baseline	339	Inter-Quartile Range 282 to 381	meters
Six Minute Walk Distance (6MWD)	UT-15C (Oral Treprostinil)	6MWD at Baseline	350	Inter-Quartile Range 283 to 386	meters
Six Minute Walk Distance (6MWD)	Placebo	6MWD at Week 12	343	Inter-Quartile Range 246 to 403	meters
Six Minute Walk Distance (6MWD)	UT-15C (Oral Treprostinil)	6MWD at Week 12	370	Inter-Quartile Range 300 to 418	meters
Six Minute Walk Distance (6MWD)	Placebo	Change in 6MWD from Baseline to Week 12	-5	Inter-Quartile Range -41 to 49	meters
Six Minute Walk Distance (6MWD)	UT-15C (Oral Treprostinil)	Change in 6MWD from Baseline to Week 12	25	Inter-Quartile Range -16 to 63	meters
Six Minute Walk Distance (6MWD)	Placebo	6MWD at Baseline	339	Inter-Quartile Range 282 to 381	meters
Six Minute Walk Distance (6MWD)	UT-15C (Oral Treprostinil)	6MWD at Baseline	350	Inter-Quartile Range 283 to 386	meters
Six Minute Walk Distance (6MWD)	Placebo	6MWD at Week 11	335	Inter-Quartile Range 254 to 400	meters
Six Minute Walk Distance (6MWD)	UT-15C (Oral Treprostinil)	6MWD at Week 11	350	Inter-Quartile Range 290 to 400	meters

1 to 10 of 102Source ClinicalTrials.gov

See all 102 results by group

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Placebo	116
Overall Study	STARTED	UT-15C (Oral Treprostinil)	233
Overall Study	COMPLETED	Placebo	98
Overall Study	COMPLETED	UT-15C (Oral Treprostinil)	182
Overall Study	NOT COMPLETED	Placebo	18
Overall Study	NOT COMPLETED	UT-15C (Oral Treprostinil)	51

Source ClinicalTrials.gov

Adverse events134

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	headache	Nervous system disorders	Placebo	15	77	17
other	headache	Nervous system disorders	UT-15C (Oral Treprostinil)	95	151	131
other	diarrhea	Gastrointestinal disorders	Placebo	12	77	12
other	diarrhea	Gastrointestinal disorders	UT-15C (Oral Treprostinil)	46	151	54
other	nausea	Gastrointestinal disorders	Placebo	14	77	14
other	nausea	Gastrointestinal disorders	UT-15C (Oral Treprostinil)	45	151	50
other	vomiting	Gastrointestinal disorders	Placebo	12	77	12
other	vomiting	Gastrointestinal disorders	UT-15C (Oral Treprostinil)	26	151	31
other	flushing	Vascular disorders	Placebo	5	77	5
other	flushing	Vascular disorders	UT-15C (Oral Treprostinil)	23	151	25

1 to 10 of 134Source ClinicalTrials.gov

See all 134 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Placebo	6	77
Total, all-cause mortality	UT-15C (Oral Treprostinil)	9	151
Total, other adverse events	Placebo	68	77
Total, other adverse events	UT-15C (Oral Treprostinil)	138	151
Total, serious adverse events	Placebo	15	77
Total, serious adverse events	UT-15C (Oral Treprostinil)	27	151

Source ClinicalTrials.gov

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
23307827	DERIVED

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons3

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
UT-15C (Oral Treprostinil) vs Placebo: Clinical Worsening Assessment	Trial comparisons
UT-15C (Oral Treprostinil) vs Placebo: deaths from any cause	Trial comparisons
UT-15C (Oral Treprostinil) vs Placebo: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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Read this trial from software.

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