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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Transitioning from Parental) | Experimental | Transitioned from IV or SC Remodulin to oral treprostinil |
|
| Cohort 2 (Transitioning from Inhaled) | Experimental | Transitioned from inhaled prostacyclin to 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oral treprostinil | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dunbar Ivy, MD | Denver Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lucile Packard Children's Hospital | Palo Alto | California | 94304 | United States | ||
| University of California San Francisco |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31215336 | Background | 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. | |
| 32398473 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 (Transitioning From Parental) | Transitioned from IV or SC Remodulin to oral treprostinil |
| FG001 | Cohort 2 (Transitioning From Inhaled) | Transitioned from inhaled prostacyclin to oral treprostinil |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 1, 2016 | Nov 6, 2018 |
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| 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. | 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. | 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). | 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. | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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) |
| San Francisco |
| California |
| 94143 |
| United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Monroe Carell Jr Children's Hospital at Vanderbilt | Nashville | Tennessee | 37232 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Hopper 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. |
| FG002 | Cohort 3 (Add-on to Current PAH Therapy) | Treated with oral treprostinil as a de novo add-on to current PAH therapy |
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 (Transitioning From Parental) | Transitioned from IV or SC Remodulin to oral treprostinil |
| BG001 | Cohort 2 (Transitioning From Inhaled) | Transitioned from inhaled prostacyclin to oral treprostinil |
| BG002 | Cohort 3 (Add-on to Current PAH Therapy) | Treated with oral treprostinil as a de novo add-on to current PAH therapy |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety Population | Posted | Number | participants | Up to 24 weeks |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Testing at Week 24 | Posted | Mean | Standard Deviation | mL/kg/min | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Testing at Week 24 | Posted | Mean | Standard Deviation | VE/VCO2 Slope | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Testing at Week 24 | Posted | Mean | Standard Deviation | Watts | Baseline and Week 24 |
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| Secondary | 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). | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Count of Participants | Participants | No | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Count of Participants | Participants | No | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Count of Participants | Participants | No | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Mean | Standard Deviation | meters | Baseline and Week 24 |
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| Secondary | 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). | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects that Completed Study Week 24 | Posted | Mean | Standard Deviation | pg/mL | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Deviation | percentage of LVEF | Baseline and Week 24 |
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| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | mL/beat/m2 | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | L/min/m2 | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | mL/m^2 | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | percentage of RVEF | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | mL/m2 | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | g/m2 | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Population - Number of Subjects with both Baseline and Week 24 Measurements | Posted | Mean | Standard Error | mL/beat//m2 | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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). | PK Population. To provide a larger sample size for 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK Population. To provide a larger sample size for 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK Population. To provide a larger sample size for 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK Population. To provide a larger sample size for 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK Population. To provide a larger sample size for 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK Population. To provide a larger sample size for 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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) |
|
Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 (Transitioning From Parental) | Transitioned from IV or SC Remodulin to oral treprostinil | 0 | 10 | 5 | 10 | 10 | 10 |
| EG001 | Cohort 2 (Transitioning From Inhaled) | Transitioned from inhaled prostacyclin to oral treprostinil | 0 | 10 | 0 | 10 | 10 | 10 |
| EG002 | Cohort 3 (Add-on to Current PAH Therapy) | Treated with oral treprostinil as a de novo add-on to current PAH therapy | 0 | 12 | 4 | 12 | 12 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Stoma site infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arrhythmia | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Cyanosis | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Right atrial enlargement | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Right ventricular hypertrophy | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Excessive eye blinking | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Perioribital oedema | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Anorectal discomfort | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dyschezia | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Faeces soft | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Facial pain | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Hand-foot-and-mouth disease | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Impetigo | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Stoma site infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Heat exhaustion | Injury, poisoning and procedural complications | MedDRA 20.0 | Non-systematic Assessment |
| |
| N-terminal prohormone brain natriuretic peptide increased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Blood iron decreased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Periodic limb movement disorder | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Enuresis | Psychiatric disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Intentional self injury | Psychiatric disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Stress | Psychiatric disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Erection increased | Reproductive system and breast disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Snoring | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Pallor | Vascular disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Non-systematic Assessment |
|
Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the Study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Derek Solum, PhD | United Therapeutics | 919-425-8122 | dsolum@unither.com |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 15, 2017 | Sep 28, 2018 | SAP_000.pdf |
| ID | Term |
|---|---|
| C427248 | treprostinil |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
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| OG002 | Cohort 3 (Add-on to Current PAH Therapy) | Treated with oral treprostinil as a de novo add-on to current PAH therapy |
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Combined PK data for Cohorts 1, 2, and 3 combined after oral treprostinil administration
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