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 not accepting patients for this trial.

Lead Sponsor:

United Therapeutics

Stanford Investigator(s):

Intervention(s):

  • Drug: oral treprostinil

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   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
   was signed.

   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
   anticoagulants.

   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
   anticoagulants.

   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.

Exclusion Criteria:

   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
   infections.

   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
   physician.

   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
   study assessments.

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

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Henry Chen
650-723-8922
Recruiting