Open-label Extension of Oral Treprostinil in Subjects With PH Associated With HFpEF

Study Overview
=================
Brief Summary
-----------------
This was an open-label study to evaluate the safety of continued therapy with oral treprostinil in subjects who completed Study TDE-HF-301. This study provided long-term, open-label data regarding the effect of continued long-term oral treprostinil therapy for the treatment of pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). Subject visits occurred at Baseline, Weeks 6, 12, 18, 24, and every 12 weeks thereafter until either oral treprostinil was commercially available to treat PH associated with HFpEF or the study was discontinued by the Sponsor. The Sponsor terminated Studies TDE-HF-301 and TDE-HF-302 on 14 October 2019 due to slow enrollment. Safety data from the final subject in Study TDE-HF-302 were recorded on 02 March 2020. Due to the lower than expected number of subjects enrolled, the planned secondary efficacy-related endpoints were not analyzed.

Detailed Description
-----------------
Study TDE-HF-302 was a multicenter, open-label study in subjects participating and completing all required visits for Study TDE-HF-301. This study assessed the long-term safety of oral treprostinil in subjects with PH associated with HFpEF. Subjects received oral treprostinil as 0.125-, 0.25-, 1-, and 2.5-mg sustained-release tablets. For subjects who were randomly allocated to receive oral treprostinil in Study TDE-HF-301, the initial dose of oral treprostinil was the same as the final dose in Study TDE-HF-301. Subjects randomly allocated to receive placebo in Study TDE-HF-301 were administered the initial dose of oral treprostinil at 0.125 mg 3 times daily (TID). Dose increases could occur in 0.125-mg increments every 72 hours at the discretion of the Investigator up to 6 mg TID, the maximum allowable dose determined by the Data Monitoring Committee during Study TDE-HF-301. Doses of study drug were to be increased in the absence of dose-limiting drug-related adverse events (AEs) to ensure that each subject received the optimal dose throughout the study. Subjects returned for visits at Weeks 6, 12, 18, and 24, and every 12 weeks thereafter. Subjects who terminated the study early were asked to return to the study center for a final evaluation. Safety assessments consisted of AEs, clinical laboratory parameters, and clinical assessment of heart failure signs and symptoms. Due to the lower than expected number of subjects enrolled, the planned secondary efficacy-related endpoints were not analyzed.

Official Title
-----------------
An Open-label Extension Study of Oral Treprostinil in Subjects With Pulmonary Hypertension (PH) Associated With Heart Failure With Preserved Ejection Fraction (HFpEF) - A Long-term Follow-up to Study TDE-HF-301

Conditions
-----------------
Pulmonary Hypertension Associated With HFpEF

Intervention / Treatment
-----------------
* Drug: Oral treprostinil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. The subject participated in Study TDE-HF-301, remained on study drug, was compliant with study procedures and assessments during Study TDE-HF-301, and completed through Week 24 of that study. Exclusion Criteria: The subject was pregnant or lactating. The subject was prematurely discontinued from Study TDE-HF-301 for any reason. The subject developed a concurrent illness or condition during Study TDE-HF-301, which, in the opinion of the Investigator, represented a risk to the subject's overall health if they enrolled in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral treprostinil<br>Sustained-release tablets for TID administration | Drug: Oral treprostinil<br>* Sustained-release oral tablets for TID administration<br>* Other names: Treprostinil diethanolamine, Treprostinil diolamine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301 | The primary objective of this study was to evaluate the long-term safety of oral treprostinil in subjects with PH associated with HFpEF for subjects who completed Study TDE-HF-301. The number of subjects with adverse events during the study is reported as the primary outcome measure, which was the only outcome measurement reported for this Sponsor-terminated study. | Baseline through study completion, up to approximately 25 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pulmonary Hypertension, HFpEF, 6-Minute Walk Test, Oral Treprostinil