Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy (FREEDOM-EV)
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ClinicalTrials.gov Identifier: NCT01560624 |
Recruitment Status :
Completed
First Posted : March 22, 2012
Results First Posted : February 13, 2020
Last Update Posted : February 13, 2020
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Sponsor:
United Therapeutics
Information provided by (Responsible Party):
United Therapeutics
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Tracking Information | |||||
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First Submitted Date ICMJE | March 9, 2012 | ||||
First Posted Date ICMJE | March 22, 2012 | ||||
Results First Submitted Date ICMJE | November 20, 2019 | ||||
Results First Posted Date ICMJE | February 13, 2020 | ||||
Last Update Posted Date | February 13, 2020 | ||||
Actual Study Start Date ICMJE | June 26, 2012 | ||||
Actual Primary Completion Date | June 24, 2018 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Time to First Clinical Worsening Event [ Time Frame: From randomization to approximately 4 years ] Clinical worsening was assessed continuously from randomization until the subject's last study visit. Clinical worsening events were defined as death (all causes), hospitalizations due to worsening pulmonary arterial hypertension (PAH), initiation of an inhaled or infused prostacyclin (PGI2) for the treatment of worsening PAH, disease progression, or unsatisfactory long-term clinical response. All clinical worsening events reported by the study sites were reviewed by the Sponsor Medical Monitors. Once a clinical worsening event occurred, it was entered in the eCRF and a narrative was submitted for review by the Sponsor's Medical Monitor within 48 hours after the event became known to the Investigator or designee. Subsequently, the narratives for subjects with the reported clinical worsening events were sent to an independent adjudication committee. The independent adjudication committee reviewed and adjudicated all clinical worsening events throughout the study.
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Not Provided | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy | ||||
Official Title ICMJE | A Phase III, International, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Clinical Worsening Study of UT-15C in Subjects With Pulmonary Arterial Hypertension Receiving Background Oral Monotherapy | ||||
Brief Summary | This is an international, multicenter, randomized, double-blind, placebo-controlled, event driven study in subjects with pulmonary arterial hypertension. | ||||
Detailed Description | Study TDE-PH-310 is an international, multicenter, randomized (1:1 oral treprostinil (UT-15C): placebo), double-blind, placebo-controlled study in subjects with pulmonary arterial hypertension (PAH) who are receiving background oral monotherapy for PAH for at least 30 days at randomization. Subjects are randomly allocated to receive oral treprostinil extended-release tablets or placebo by a stratified randomization by type of background therapy (Strata 1: phosphodiesterase type 5 inhibitor [PDE5-I] or soluble guanylate cyclase [sGC] stimulator; Strata 2: endothelin receptor antagonist [ERA]. Subjects are also stratified by baseline 6-minute walk distance (6MWD) less than or equal to 350 m or greater than 350 m. Subjects receive their first dose of study drug (0.125 mg) or matching placebo on the day of randomization. Oral dosing of study drug is continued at 0.125 mg 3 times daily (TID; every 6 to 8 hours) with food. The dose (or matching placebo) is titrated throughout the study up to a maximum dose of 12 mg TID to reach and maintain a tolerated dosing regimen that provided optimal clinical benefit. Once randomized, subjects return for study visits every 4 weeks for the first 12 weeks, then every 12 weeks for the duration of the study. Subjects continue in the study until experiencing clinical worsening, the number of adjudicated events necessary for study closure occurr, or prematurely discontinue participation in the study for any reason other than protocol-specified clinical worsening. At each scheduled visit, subjects undergo efficacy assessments for clinical worsening, exercise capacity (6MWD and Borg dyspnea score), WHO functional class (FC), and plasma N-Terminal pro-brain natriuretic peptide (NT-proBNP). Subjects could participate in an optional hemodynamic sub-study (assessed by RHC). Safety assessments consist of adverse events (AEs), physical examinations, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory parameters. Patients who complete all required assessments are eligible to enter a long-term, open-label, extension study (TDE-PH-311). | ||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 3 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Pulmonary Arterial Hypertension | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | White RJ, Jerjes-Sanchez C, Bohns Meyer GM, Pulido T, Sepulveda P, Wang KY, Grunig E, Hiremath S, Yu Z, Gangcheng Z, Yip WLJ, Zhang S, Khan A, Deng CQ, Grover R, Tapson VF; FREEDOM-EV Investigators. Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial. Am J Respir Crit Care Med. 2020 Mar 15;201(6):707-717. doi: 10.1164/rccm.201908-1640OC. | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
690 | ||||
Original Estimated Enrollment ICMJE |
858 | ||||
Actual Study Completion Date ICMJE | June 24, 2018 | ||||
Actual Primary Completion Date | June 24, 2018 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Subject Inclusion Criteria:
Subject Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Argentina, Australia, Austria, Brazil, Canada, Chile, China, Denmark, France, Germany, Greece, India, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Singapore, Sweden, Taiwan, United Kingdom, United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT01560624 | ||||
Other Study ID Numbers ICMJE | TDE-PH-310 | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | United Therapeutics | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | United Therapeutics | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | United Therapeutics | ||||
Verification Date | February 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |