PAHPhase 2NCT02276872
Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years
A Phase 2 study testing oral treprostinil in people with PAH, run by United Therapeutics at 9 sites in United States.
Trial summary
This was a multi-center, open-label, safety, tolerability and pharmacokinetic study of oral treprostinil in pediatric subjects with stable PAH aged 7 to 17 years who were (1) transitioning from parenteral Remodulin therapy; (2) transitioning from inhaled prostacyclin therapy; or (3) not currently receiving… Read more about this study
- Who is it for?
- Ages 7 to 17 years
- Conditions the study is for
- PAH
- What is being tested?
- oral treprostinil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 9 sitesUnited States
- Study dates
- 18 Dec 2014to 20 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Legal guardian informed consent and subject assent, if appropriate, to participate in the study was voluntarily given.
- The subject was between 7 and 17 years of age, inclusive, on the date informed consent was signed.
- Cohort 3: The subject weighed a minimum of 22 kg at Screening.
- The subject had a current diagnosis of PAH (WHO Group I) associated with:
- IPAH or HPAH
- Persistent PAH for at least 1 year following surgical repair of a congenital systemic-to-pulmonary cardiac shunt, congenital heart disease, or other congenital heart lesions with no clinically significant residual defects and condition was stabilized hemodynamically
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- PAH in subjects with unrepaired restricted atrial septal defect, ventricular septal defect, or patent ductus arteriosus; subject had a resting post-ductal oxygen saturation (off oxygen) of greater than 88%.
- The subject had a current diagnosis of PAH confirmed by RHC prior to the Screening Visit with the following parameters:
- PAPm of ≥25 mmHg
- Pulmonary vascular resistance index (PVRi) of >3 Wood Units*m2
- Left ventricular end-diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg.
- Cohort 1: The subject had received IV/SC Remodulin for at least 90 days without dose change for at least 30 days prior to Baseline. The IV/SC Remodulin dose was between 25 to 75 ng/kg/min, inclusive, for the first 5 subjects in the cohort. Following safety review, the dose range was expanded to 25 to 125 ng/kg/min, inclusive, for the remaining subjects. Subjects must have received stable doses of all other PAH medications for at least 14 days prior to the baseline assessments; exception for diuretics and anticoagulants.
- Cohort 2: The subject must have received inhaled prostacyclin for at least 90 days and had been at the current stable dose without changes for at least 30 days prior to Baseline. Subjects must have received stable doses of all other PAH medications for at least 14 days prior to the baseline assessments; exception for diuretics and anticoagulants.
- All Cohorts: All subjects were optimally treated (as determined by the Investigator) with background PAH therapies (eg, phosphodiesterase type 5 inhibitor [PDE5-I], endothelin receptor antagonist [ERA], soluble guanylate cyclase [sGC]) for at least 90 days and had been on a stable dose without changes (except documented weight based adjustments) for at least 30 days prior to the first dose of oral treprostinil. Subjects must have received stable doses of all other PAH medications for at least 14 days prior to the first dose of oral treprostinil; exception for diuretics and anticoagulants.
- The subject was willing and able to swallow intact tablets whole without chewing, breaking, or splitting.
- The subject was willing and able to comply with the dietary requirements associated with the oral treprostinil dosing regimen.
- The subject was on stable doses of other medical therapy for 14 days prior to the Baseline Visit with no dose adjustments, additions, or discontinuations. Dose changes of diuretics were allowed if within the usual dose adjustments prescribed for the subject. Anticoagulants could have been adjusted, but not discontinued or added, within 14 days of Baseline. Temporary discontinuation of anticoagulants when related to study-related procedures was allowed.
- Females of childbearing potential include any female who had experienced menarche. Females of childbearing potential must have practiced true abstinence from intercourse, had an intrauterine device, or used 2 different forms of highly effective contraception for the duration of the study and for at least 30 days after discontinuing oral treprostinil. Medically acceptable forms of effective contraception included approved hormonal contraceptives (such as birth control pills) or barrier methods (such as a condom or diaphragm) used with a spermicide. For females of childbearing potential, a negative urine pregnancy test was required at Baseline prior to oral treprostinil administration. Males participating in the study must have used a condom during intercourse for the duration of the study and for at least 48 hours after discontinuing oral treprostinil.
- Subjects with a history of metallic implants, prior neurosurgical clip placement, or other potential contraindications to cMRI were individually evaluated per site standard operating procedures for MRI performance.
- In the opinion of the Principal Investigator, the subject and/or legal guardian was able to communicate effectively with study personnel, and was considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
Who cannot join
- The subject had a diagnosis of large unrestrictive ventricular septal defect or patent ductus arteriosus, Eisenmenger syndrome, congenital diaphragmatic hernia, or a chronic lung disease, such as bronchopulmonary dysplasia or interstitial lung disease.
- The subject had a current disease severity of Panama FC IIIb or IV.
- The subject had previously been exposed to oral treprostinil.
- Cohort 1: The subject had previous intolerance to treprostinil or epoprostenol due to systemic adverse effects that resulted in discontinuation of therapy. This did not include site pain reactions or central venous catheter-related blood stream infections.
- Cohort 1 and 2: The subject was receiving IV/SC Remodulin or Tyvaso® (as the inhaled prostacyclin) for any other disease or condition other than the treatment of PAH in accordance with the IV/SC Remodulin or Tyvaso package inserts (ie, eligible subjects must have had a WHO Group I PAH classification as defined in inclusion criterion #4).
- Cohort 3: The subject had been previously exposed to a prostacyclin within 30 days of Screening, with the exception of vasoreactivity testing.
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- The subject was pregnant or lactating.
- The subject had a current diagnosis of uncontrolled sleep apnea as defined by their physician.
- The subject had severe renal insufficiency as defined by an estimated creatinine clearance <30 mL/min (Schwartz Formula) or the requirement for dialysis at Screening.
- The subject had moderate to severe hepatic dysfunction as defined by elevated liver function tests (aspartate aminotransferase or alanine aminotransferase) ≥3 times the upper limit of normal at Screening, or Child Pugh class B or C hepatic disease.
- The subject had clinically significant anemia as defined by a hemoglobin and/or hematocrit level <75% of the lower limit of normal ranges according to age and gender.
- The subject had Down Syndrome.
- The subject had uncontrolled systemic hypertension as evidenced by a systolic or diastolic blood pressure greater than the 95th percentile for age, height, and gender at Screening or Baseline.
- The subject and/or legal guardian had an unstable psychiatric condition or was mentally incapable of understanding the objectives, nature, or consequences of the study, or had any condition in which the Investigator's opinion would constitute an unacceptable risk to the subject's safety.
- The subject had an active infection or any other cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease or condition that, in the opinion of the Investigator, might have adversely affected the safety of the subject or interfered with the interpretation of study assessments.
- Subject was actively listed for transplantation.
- The subject was receiving an investigational drug, had an investigational device in place, or had participated in an investigational drug or device study within 30 days prior to Baseline. Participation in an observational study did not disqualify a potential subject from study participation.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Monroe Carell Jr Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Lucile Packard Children's Hospital
Palo Alto, California, 94304
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of California San Francisco
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
About this study
Official title: A Multicenter, Open-Label, 24-Week, Uncontrolled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil Extended Release Tablets Following Transition From Remodulin or Inhaled Prostacyclin Therapy or as Add-on to Current PAH Therapy in De Novo Prostacyclin Pediatric Subjects Aged 7 to 17 Years With Pulmonary Arterial Hypertension
This was a multi-center, open-label, safety, tolerability and pharmacokinetic study of oral treprostinil in pediatric subjects with stable PAH aged 7 to 17 years who were (1) transitioning from parenteral Remodulin therapy; (2) transitioning from inhaled prostacyclin therapy; or (3) not currently receiving prostacyclin therapy.
Read the detailed description
Study TDE-PH-206 was a multicenter, open-label study designed to investigate the safety, tolerability, and PK of oral treprostinil administered 3 times daily (TID) or 4 times daily (QID), at the discretion of the Investigator, with food in pediatric PAH subjects aged 7 to 17 years of age (1) transitioning from continuous IV/SC Remodulin, (2) transitioning from inhaled prostacyclin, or (3) as add-on to current PAH therapies in de novo prostacyclin subjects. Eligible subjects were assigned to a cohort based upon their background therapy. All subjects received oral treprostinil provided as 0.125, 0.25, 1, or 2.5 mg extended-release tablets. Subjects in Cohort 1 began the transition from IV/SC Remodulin in the hospital with a goal of complete transition to oral treprostinil within 5 days. The initial dose of oral treprostinil for Cohort 1 was calculated from the subject's dose of IV/SC Remodulin and weight. Subjects in Cohorts 2 and 3 were initiated on 0.125 mg TID or QID oral treprostinil with dose escalations possible every 24 hours in increments of 0.125 mg TID or QID at the discretion of the Investigator during the first 4 weeks, and in increments of either 0.125 mg or 0.25 mg every 24 hours thereafter. Cross titration occurred for Cohorts 1 and 2 such that doses of IV/SC Remodulin or inhaled prostacyclin were decreased as subjects were fully transitioned to oral treprostinil.
- Conditions
- PAH
- Being tested
- oral treprostinil
- Keywords
- pediatric, treprostinil, transition, Remodulin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral treprostinilDrug
Also called Orenitram
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (Transitioning from Parental) | Experimental | Transitioned from IV or SC Remodulin to oral treprostinil Receives: Drug: oral treprostinil |
| Cohort 2 (Transitioning from Inhaled) | Experimental | Transitioned from inhaled prostacyclin to oral treprostinil Receives: Drug: oral treprostinil |
| Cohort 3 (Add-on to Current PAH Therapy) | Experimental | Treated with oral treprostinil as a de novo add-on to current PAH therapy Receives: Drug: oral treprostinil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3).
A successful transition was defined as a subject from Cohort 1 or Cohort 2 who was receiving oral treprostinil and no longer receiving IV/SC Remodulin or inhaled prostacyclin, respectively, at Week 4 and clinically maintained on oral treprostinil treatment through Week 24. A successful initiation of oral treprostinil for Cohort 3 was defined as a subject who was clinically maintained on oral treprostinil through Week 24.
Measured: Up to 24 weeks
Secondary outcomes (24)
Cardiopulmonary Exercise Testing - Change From Baseline in Peak Oxygen Uptake (VO2) at Week 24
Cardiopulmonary Exercise Testing (CPET) was performed with progressive cycle ergometry and ventilatory expired gas analysis obtained using a metabolic cart at Baseline and Week 24/Premature Termination. CPET consisted of measuring oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and other variables in addition to a 12-lead ECG, blood pressure (BP) monitoring, and pulse oximetry.
Measured: Baseline and Week 24
Cardiopulmonary Exercise Testing - Change From Baseline in Minute Ventilation (VE)/Carbon Dioxide Output (VCO2) Slope at Week 24
Cardiopulmonary Exercise Testing (CPET) was performed with progressive cycle ergometry and ventilatory expired gas analysis obtained using a metabolic cart at Baseline and Week 24/Premature Termination. CPET consisted of measuring oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and other variables in addition to a 12-lead ECG, blood pressure (BP) monitoring, and pulse oximetry.
Measured: Baseline and Week 24
Cardiopulmonary Exercise Testing - Change From Baseline in Peak Watts at Week 24
Cardiopulmonary Exercise Testing (CPET) was performed with progressive cycle ergometry and ventilatory expired gas analysis obtained using a metabolic cart at Baseline and Week 24/Premature Termination. CPET consisted of measuring oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and other variables in addition to a 12-lead ECG, blood pressure (BP) monitoring, and pulse oximetry.
Measured: Baseline and Week 24
Change in Symptoms of PAH From Baseline to Week 24
PAH symptoms (fatigue, dyspnea, edema, dizziness, syncope, chest pain, orthopnea) were assessed at the Baseline Visit prior to the initiation of oral treprostinil dosing and at Week 24. Scores range from 0 (for the best condition) to 3 (for the worst condition).
Measured: Baseline and Week 24
Change in Panama Functional Class From Baseline to Week 24
Change from Baseline in subject clinical status was recorded according to the Panama Functional Class.
Measured: Baseline and Week 24
Change in WHO Functional Class From Baseline to Week 24
Change from Baseline in subject clinical status was recorded according to the WHO Functional Class.
Measured: Baseline and Week 24
Change in 6-Minute Walk Distance (6MWD) From Baseline to Week 24
The intent of the 6MWT was to evaluate exercise capacity associated with carrying out activities of daily living. Total distance covered in a total of 6 minutes was measured. Oxygen saturation and heart rate (HR) were measured at rest prior to the 6MWT and monitored continuously during the walk. Recovery monitoring (HR and oxygen saturation) was performed and documented at Minute 0 (immediately upon stopping the 6MWT), Minute 1, Minute 2, and Minute 3 post walk.
Measured: Baseline and Week 24
Change in Borg Dyspnea Score From Baseline to Week 24
The Borg dyspnea score was assessed prior to and following the completion of the 6MWT at Week 24. The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) to 10 (for the worst condition).
Measured: Baseline and Week 24
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24
Four subscales [items]: (Physical [8], Emotional [5], Social [5], School Functioning [5]). Subjects and subjects' parent(s) completed PedsQL at Week 24. Response to each item on the subscales were graded 0-4 (0=never a problem, 1=almost never a problem, 2=sometimes a problem, 3=often a problem, 4=almost always a problem). Response to each item was transformed from the 0-4 scale to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Using transformed values, mean was computed as sum of the items in each subscale over number of items answered in the same subscale. Two summary scores (Psychosocial Health Summary Score and Total Scale Score) were calculated with a range of 0-100 (higher values indicating better outcome). Psychosocial Health Summary Score was mean computed as sum of the items over the number of items answered in the Emotional, Social, and School Functioning Scales. Total Score was calculated as sum of all items over number of items answered on all the scales.
Measured: Baseline and Week 24
Change in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) From Baseline to Week 24
Plasma NT-proBNP concentration is a useful biomarker for PAH as it is associated with changes in right heart morphology and function.
Measured: Baseline and Week 24
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Left Ventricular (LV) Stroke Volume Index at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Right Ventricular (RV) Cardiac Output Index at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Right Ventricular End-diastolic Volume (RVEDV) Index at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Right Ventricular Ejection Fraction (RVEF) at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Right Ventricular End-systolic Volume (RVESV) Index at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Right Ventricular (RV) Mass Index at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Change From Baseline in Right Ventricular (RV) Stroke Volume Index at Week 24
Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.
Measured: Baseline and Week 24
Maximum Observed Drug Concentration in Plasma (Cmax)
Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able. For the purposes of PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).
Measured: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Last Observed Drug Concentration in Plasma (Clast)
Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.
Measured: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Average Drug Concentration in Plasma (Cavg)
Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.
Measured: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Observed Minimum Drug Concentration in Plasma (Cmin)
Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.
Measured: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Area Under the Concentration-Time Curve From Zero to Tau Hours Post-dose (AUCtau)
Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.
Measured: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Area Under the Concentration-Time Curve From Zero to 8 Hours Post-dose (AUC0-8)
Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.
Measured: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study start18 Dec 2014
- Primary completion20 Jul 2017
- Study completion20 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PAHStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dunbar Ivy, MD, Principal investigator, Denver Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276872
- Sponsor's protocol ID
- TDE-PH-206
- Status last verified
- Mar 2025
- First submitted
- 21 Oct 2014
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ivy DD, Feinstein JA, Yung D, Mullen MP, Kirkpatrick EC, Hirsch R, Austin ED, Fineman J, Truong U, Solum D, Deng CQ, Hopper RK. Oral treprostinil in transition or as add-on therapy in pediatric pulmonary arterial hypertension. Pulm Circ. 2019 Jul-Sep;9(3):2045894019856471. doi: 10.1177/2045894019856471.
PubMed 31215336Hopper RK, Ivy DD, Yung D, Mullen MP, Hanna BD, Kirkpatrick E, Hirsch R, Austin ED, Fineman J, Solum D, Deng CQ, Feinstein JA. Pharmacokinetics of Oral Treprostinil in Children With Pulmonary Arterial Hypertension. J Cardiovasc Pharmacol. 2020 Jul;76(1):94-100. doi: 10.1097/FJC.0000000000000842.
PubMed 32398473
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, 24-Week, Uncontrolled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil Extended Release Tablets Following Transition From Remodulin or Inhaled Prostacyclin Therapy or as Add-on to Current PAH Therapy in De Novo Prostacyclin Pediatric Subjects Aged 7 to 17 Years With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT02276872
- Acronym / sponsor ID
- TDE-PH-206
- Conditions
- PAH
- Keywords
- pediatric, treprostinil, transition, Remodulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2014 (actual)
- Primary completion
- 20 Jul 2017 (actual)
- Study completion
- 20 Jul 2017 (actual)
- First posted
- 28 Oct 2014 (estimated)
- Results
- Posted 4 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multi-center, open-label, safety, tolerability and pharmacokinetic study of oral treprostinil in pediatric subjects with stable PAH aged 7 to 17 years who were (1) transitioning from parenteral Remodulin therapy; (2) transitioning from inhaled prostacyclin therapy; or (3) not currently receiving prostacyclin therapy.
Detailed description
Study TDE-PH-206 was a multicenter, open-label study designed to investigate the safety, tolerability, and PK of oral treprostinil administered 3 times daily (TID) or 4 times daily (QID), at the discretion of the Investigator, with food in pediatric PAH subjects aged 7 to 17 years of age (1) transitioning from continuous IV/SC Remodulin, (2) transitioning from inhaled prostacyclin, or (3) as add-on to current PAH therapies in de novo prostacyclin subjects. Eligible subjects were assigned to a cohort based upon their background therapy. All subjects received oral treprostinil provided as 0.125, 0.25, 1, or 2.5 mg extended-release tablets. Subjects in Cohort 1 began the transition from IV/SC Remodulin in the hospital with a goal of complete transition to oral treprostinil within 5 days. The initial dose of oral treprostinil for Cohort 1 was calculated from the subject's dose of IV/SC Remodulin and weight. Subjects in Cohorts 2 and 3 were initiated on 0.125 mg TID or QID oral treprostinil with dose escalations possible every 24 hours in increments of 0.125 mg TID or QID at the discretion of the Investigator during the first 4 weeks, and in increments of either 0.125 mg or 0.25 mg every 24 hours thereafter. Cross titration occurred for Cohorts 1 and 2 such that doses of IV/SC Remodulin or inhaled prostacyclin were decreased as subjects were fully transitioned to oral treprostinil.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (Transitioning from Parental) | Experimental | Drug: oral treprostinilTransitioned from IV or SC Remodulin to oral treprostinil |
| Cohort 2 (Transitioning from Inhaled) | Experimental | Drug: oral treprostinilTransitioned from inhaled prostacyclin to oral treprostinil |
| Cohort 3 (Add-on to Current PAH Therapy) | Experimental | Drug: oral treprostinilTreated with oral treprostinil as a de novo add-on to current PAH therapy |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (20 listed)
- Legal guardian informed consent and subject assent, if appropriate, to participate in the study was voluntarily given.
- The subject was between 7 and 17 years of age, inclusive, on the date informed consent was signed.
- Cohort 3: The subject weighed a minimum of 22 kg at Screening.
- The subject had a current diagnosis of PAH (WHO Group I) associated with:
- The subject had a current diagnosis of PAH confirmed by RHC prior to the Screening Visit with the following parameters:
Key exclusion criteria (17 listed)
- The subject had a diagnosis of large unrestrictive ventricular septal defect or patent ductus arteriosus, Eisenmenger syndrome, congenital diaphragmatic hernia, or a chronic lung disease, such as bronchopulmonary dysplasia or interstitial lung disease.
- The subject had a current disease severity of Panama FC IIIb or IV.
- The subject had previously been exposed to oral treprostinil.
- Cohort 1: The subject had previous intolerance to treprostinil or epoprostenol due to systemic adverse effects that resulted in discontinuation of therapy. This did not include site pain reactions or central venous catheter-related blood stream infections.
- Cohort 1 and 2: The subject was receiving IV/SC Remodulin or Tyvaso® (as the inhaled prostacyclin) for any other disease or condition other than the treatment of PAH in accordance with the IV/SC Remodulin or Tyvaso package inserts (ie, eligible subjects must have had a WHO Group I PAH classification as defined in inclusion criterion #4).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oral treprostinilAlso: Orenitram | Drug | Cohort 1 (Transitioning from Parental), Cohort 2 (Transitioning from Inhaled), Cohort 3 (Add-on to Current PAH Therapy) |
Primary outcome
Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3).
Time frame: Up to 24 weeks
A successful transition was defined as a subject from Cohort 1 or Cohort 2 who was receiving oral treprostinil and no longer receiving IV/SC Remodulin or inhaled prostacyclin, respectively, at Week 4 and clinically maintained on oral treprostinil treatment through Week 24. A successful initiation of oral treprostinil for Cohort 3 was defined as a subject who was clinically maintained on oral treprostinil through Week 24.
24 secondary outcomes
Cardiopulmonary Exercise Testing - Change From Baseline in Peak Oxygen Uptake (VO2) at Week 24
Time frame: Baseline and Week 24
Cardiopulmonary Exercise Testing - Change From Baseline in Minute Ventilation (VE)/Carbon Dioxide Output (VCO2) Slope at Week 24
Time frame: Baseline and Week 24
Cardiopulmonary Exercise Testing - Change From Baseline in Peak Watts at Week 24
Time frame: Baseline and Week 24
Change in Symptoms of PAH From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Panama Functional Class From Baseline to Week 24
Time frame: Baseline and Week 24
Change in WHO Functional Class From Baseline to Week 24
Time frame: Baseline and Week 24
Change in 6-Minute Walk Distance (6MWD) From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Borg Dyspnea Score From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24
Time frame: Baseline and Week 24
Change in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) From Baseline to Week 24
Time frame: Baseline and Week 24
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Left Ventricular (LV) Stroke Volume Index at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular (RV) Cardiac Output Index at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular End-diastolic Volume (RVEDV) Index at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular Ejection Fraction (RVEF) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular End-systolic Volume (RVESV) Index at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular (RV) Mass Index at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Right Ventricular (RV) Stroke Volume Index at Week 24
Time frame: Baseline and Week 24
Maximum Observed Drug Concentration in Plasma (Cmax)
Time frame: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Last Observed Drug Concentration in Plasma (Clast)
Time frame: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Average Drug Concentration in Plasma (Cavg)
Time frame: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Observed Minimum Drug Concentration in Plasma (Cmin)
Time frame: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Area Under the Concentration-Time Curve From Zero to Tau Hours Post-dose (AUCtau)
Time frame: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Area Under the Concentration-Time Curve From Zero to 8 Hours Post-dose (AUC0-8)
Time frame: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31215336Ivy DD, Feinstein JA, Yung D, Mullen MP, Kirkpatrick EC, Hirsch R, Austin ED, Fineman J, Truong U, Solum D, Deng CQ, Hopper RK. Oral treprostinil in transition or as add-on therapy in pediatric pulmonary arterial hypertension. Pulm Circ. 2019 Jul-Sep;9(3):2045894019856471. doi: 10.1177/2045894019856471.
- Background: PubMed 32398473Hopper RK, Ivy DD, Yung D, Mullen MP, Hanna BD, Kirkpatrick E, Hirsch R, Austin ED, Fineman J, Solum D, Deng CQ, Feinstein JA. Pharmacokinetics of Oral Treprostinil in Children With Pulmonary Arterial Hypertension. J Cardiovasc Pharmacol. 2020 Jul;76(1):94-100. doi: 10.1097/FJC.0000000000000842.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dunbar Ivy, MD principal investigator
Denver Children's Hospital
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing oral treprostinil in people with PAH, run by United Therapeutics at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3). (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02276872, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.