Trial Search Results
Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years
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.
Stanford is currently accepting patients for this trial.
- Drug: oral treprostinil
1. Legal guardian informed consent and subject assent, if appropriate, to participate in
the study was voluntarily given.
2. The subject was between 7 and 17 years of age, inclusive, on the date informed consent
3. Cohort 3: The subject weighed a minimum of 22 kg at Screening.
4. The subject had a current diagnosis of PAH (WHO Group I) associated with:
1. IPAH or HPAH
2. 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
3. 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%.
5. The subject had a current diagnosis of PAH confirmed by RHC prior to the Screening
Visit with the following parameters:
1. PAPm of ≥25 mmHg
2. Pulmonary vascular resistance index (PVRi) of >3 Wood Units*m2
3. Left ventricular end-diastolic pressure (LVEDP) or pulmonary capillary wedge
pressure (PCWP) of ≤15 mmHg.
6. 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.
7. 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
8. 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
9. The subject was willing and able to swallow intact tablets whole without chewing,
breaking, or splitting.
10. The subject was willing and able to comply with the dietary requirements associated
with the oral treprostinil dosing regimen.
11. 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.
12. 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.
13. 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.
14. 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.
1. 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.
2. The subject had a current disease severity of Panama FC IIIb or IV.
3. The subject had previously been exposed to oral treprostinil.
4. 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
5. 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).
6. Cohort 3: The subject had been previously exposed to a prostacyclin within 30 days of
Screening, with the exception of vasoreactivity testing.
7. The subject was pregnant or lactating.
8. The subject had a current diagnosis of uncontrolled sleep apnea as defined by their
9. 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.
10. 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.
11. 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.
12. The subject had Down Syndrome.
13. 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.
14. 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.
15. 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
16. Subject was actively listed for transplantation.
17. 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.
Ages Eligible for Study
7 Years - 17 Years
Genders Eligible for Study