Pulmonary Hypertension Associated With HFpEF
Conditions
Keywords
Pulmonary Hypertension, HFpEF, 6-Minute Walk Test, Oral Treprostinil
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.
Interventions
Sustained-release oral tablets for TID administration
Sponsors
United Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
1. The subject was pregnant or lactating. 2. The subject was prematurely discontinued from Study TDE-HF-301 for any reason. 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301 | Baseline through study completion, up to approximately 25 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Treprostinil Sustained-release tablets for TID administration
Oral Treprostinil: Sustained-release oral tablets for TID administration | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Progressive Disease | 2 |
| Overall Study | Study Terminated by Sponsor | 39 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Oral Treprostinil |
|---|---|
| Age, Continuous | 76.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 48 |
| other Total, other adverse events | 47 / 48 |
| serious Total, serious adverse events | 19 / 48 |
Outcome results
Primary
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.
Time frame: Baseline through study completion, up to approximately 25 months
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Treprostinil | Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301 | 47 Participants |