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CompletedNCT01934582Updated Jan 3, 2024Results posted

A Pharmacokinetic Substudy of the TDE-PH-304 Protocol

A Phase 3 interventional study of UT-15C SR and treprostinil diethanolamine in Pulmonary Arterial Hypertension, sponsored by United Therapeutics. Completed at 1 site in United States. Open to participants aged 12 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-01-03.

Sponsored by United Therapeutics · Phase 3, Interventional, and Other

Phase
Phase 3
Study type
Interventional
Enrollment
13
Allocation
Not applicable
Ages
12 Years to 75 Years
Sex
All
01

Study summary

A sub-study to the TDE-PH-304 protocol to assess the pharmacokinetics of patients transitioning from a twice daily dosing regimen of oral treprostinil to a three times daily dosing regimen.

Read the detailed description

As noted above in "Brief Summary".

02

Conditions studied

  • Pulmonary Arterial Hypertension
03

In context

Pulmonary Arterial Hypertension

761 studies on the registry are indexed under Pulmonary Arterial Hypertension; 142 are open to participants now.

This study's enrollment of 13 is below the median of 38 across 509 interventional studies indexed under Pulmonary Arterial Hypertension.

Browse Pulmonary Arterial Hypertension studies →

Lead sponsor

United Therapeutics is the lead sponsor of 81 studies on the registry; 6 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 14 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Only subjects who are eligible for and have entered into Protocol TDE-PH-304 may participate in this substudy.

Exclusion criteria

Exclusion Criteria:

  1. The subject must voluntarily give informed consent to participate in the substudy.
  2. No dose changes to study drug are made within 5 days of the pharmacokinetic (PK)substudy visits.
  3. No additions or deletions to concurrent medications are made within 7 days of the pharmacokinetic substudy visit. Note: changes to diuretics and/or anticoagulants are permitted.
  4. The preceding evening dose of study drug should have been taken 9 to 13 hours prior to the BID dose and 6-10 hours prior to the TID morning dose of study drug to ensure a trough level of study drug for PK sampling.
  5. Subject dosing of study drug on the day of PK sampling must be observed in the clinic by study personnel.
  6. Subject has not experienced a significant loss of blood (> 450 mL) within the last 6 weeks of the pharmacokinetic substudy visit.
  7. The subject must not be receiving any CYP 2C8 inducers or inhibitors
05

Study design

Phase
Phase 3
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
13 participants (actual)

Study arms

  • Experimental
    Open label extension

    Drug: UT-15C SR · Drug: treprostinil diethanolamine

Interventions

  • DrugUT-15C SR
  • Drugtreprostinil diethanolamine

    Open label study drug.

    Also known as: UT-15C Sustained Release (SR)

06

What researchers measure

Primary outcomes

  1. To Assess the Pharmacokinetics (Mean AM Dose) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).

    The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

    Time frame: Up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and up to 35 days after transitioning to TID dosing regiment (PK Visit 2)

  2. To Assess the Pharmacokinetics (Cmax, Cmin) in Subjects During BID Dosing (up to 14 Days Prior to Transitioning to TID Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing Regiment (PK Visit 2)

    The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

    Time frame: Up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and up to 35 days after transitioning to TID dosing regiment (PK Visit 2)

  3. To Assess the Pharmacokinetics (AUClast) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).

    The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

    Time frame: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose at up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and at up to 35 days after transitioning to TID dosing regiment (PK Visit 2)

Secondary outcomes

  1. To Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose.

    The 6-minute walk test (6MWT) was conducted at PK Visits 1 and 2, and was performed between hours 3 to 6 post-morning dose to correlate with the predicted peak plasma concentration of oral treprostinil.

    Time frame: The 6MWT was conducted during BID dosing PK collection (up to 14 days prior to transitioning to TID dosing regimen [PK Visit 1]) and during TID dosing PK collection (up to 35 days after transitioning to TID dosing regimen [PK Visit 2]).

  2. To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.

    AE diaries including 8 therapy-specific terms were collected during both BID and TID dosing to allow for comparison of events from both regimens. The therapy-specific events included: diarrhea, extremity pain, flushing, headache, hypotension, jaw pain, nausea, and vomiting.

    Time frame: The AEs were recorded for up to 50 days.

07

Results

Posted Oct 27, 2016

Participant flow

Participant flow — Overall Study
MilestoneOpen-label Extension PK Population
Started13
Completed13
Not completed0

Outcome measures

PrimaryTo Assess the Pharmacokinetics (Mean AM Dose) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).

The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

Time frame:
Up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and up to 35 days after transitioning to TID dosing regiment (PK Visit 2)
Reported as:
Mean · mg
To Assess the Pharmacokinetics (Mean AM Dose) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).
mgPK Visit 1PK Visit 2
To Assess the Pharmacokinetics (Mean AM Dose) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).8.12 (2.00 to 17.5)6.75 (1.25 to 15.0)
PrimaryTo Assess the Pharmacokinetics (Cmax, Cmin) in Subjects During BID Dosing (up to 14 Days Prior to Transitioning to TID Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing Regiment (PK Visit 2)

The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

Time frame:
Up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and up to 35 days after transitioning to TID dosing regiment (PK Visit 2)
Reported as:
Mean · ng/mL
To Assess the Pharmacokinetics (Cmax, Cmin) in Subjects During BID Dosing (up to 14 Days Prior to Transitioning to TID Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing Regiment (PK Visit 2)
ng/mLPK Visit 1PK Visit 2
Cmax8.60 (1.70 to 18.2)8.94 (2.25 to 16.8)
Cmin1.19 (0.290 to 2.50)2.14 (0.263 to 6.12)
PrimaryTo Assess the Pharmacokinetics (AUClast) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).

The PK sampling occurred over a 12-hour period in subjects during BID dosing (PK Visit 1) and during TID dosing (PK Visit 2). Prior to each PK sampling day, subjects must have been receiving a stable dose for at least 5 days.

Time frame:
0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose at up to 14 days prior to transitioning to TID dosing regimen (PK Visit 1) and at up to 35 days after transitioning to TID dosing regiment (PK Visit 2)
Reported as:
Mean · h*ng/mL
To Assess the Pharmacokinetics (AUClast) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).
h*ng/mLPK Visit 1PK Visit 2
To Assess the Pharmacokinetics (AUClast) in Subjects During Twice Daily (BID) Dosing (up to 14 Days Prior to Transitioning to Three Times Daily [TID] Dosing Regimen at PK Visit 1) and up to 35 Days After Transitioning to TID Dosing (at PK Visit 2).47.8 (8.92 to 80.6)58.0 (10.8 to 109)
SecondaryTo Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose.

The 6-minute walk test (6MWT) was conducted at PK Visits 1 and 2, and was performed between hours 3 to 6 post-morning dose to correlate with the predicted peak plasma concentration of oral treprostinil.

Time frame:
The 6MWT was conducted during BID dosing PK collection (up to 14 days prior to transitioning to TID dosing regimen [PK Visit 1]) and during TID dosing PK collection (up to 35 days after transitioning to TID dosing regimen [PK Visit 2]).
Reported as:
Mean · Meters
To Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose.
MetersPK Visit 1PK Visit 2
To Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose.332.5 (177 to 525)347.9 (223 to 541)
SecondaryTo Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.

AE diaries including 8 therapy-specific terms were collected during both BID and TID dosing to allow for comparison of events from both regimens. The therapy-specific events included: diarrhea, extremity pain, flushing, headache, hypotension, jaw pain, nausea, and vomiting.

Time frame:
The AEs were recorded for up to 50 days.
Reported as:
Number · percentage of subjects
To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
percentage of subjectsPK Visit 1PK Visit 2
Diarrhea4638
Extremity pain5438
Flushing8554
Headache6985
Hypotension2323
Jaw Pain3846
Nausea3877
Vomiting00

Adverse events

Collected over Approximately 50 days.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PK Visit 1—0/13 (0%)13/13 (100%)
PK Visit 2—0/13 (0%)13/13 (100%)
Most frequent other events
Most frequent other events
EventPK Visit 1PK Visit 2
FlushingVascular disorders11/137/13
HeadacheNervous system disorders9/1311/13
NauseaGastrointestinal disorders5/1310/13
Extremity painMusculoskeletal and connective tissue disorders7/135/13
DiarrheaGastrointestinal disorders6/135/13
Jaw painMusculoskeletal and connective tissue disorders5/136/13
HypotensionVascular disorders3/133/13
VomitingGastrointestinal disorders0/130/13

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Open-label Extension PK Population
<=18 years0
Between 18 and 65 years7
>=65 years6
Age, Continuous
Age, Continuous(years)Open-label Extension PK Population
Mean60.6 (38 to 71)
Sex: Female, Male
Sex: Female, Male(Participants)Open-label Extension PK Population
Female11
Male2
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Open-label Extension PK Population
Hispanic or Latino0
Not Hispanic or Latino13
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Open-label Extension PK Population
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White12
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Open-label Extension PK Population
United States13
08

Study locations

1 site
  • University of Rochester Medical Center
    Rochester, New York 14623, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01934582
Lead sponsor
United Therapeutics
Responsible party
Sponsor
First posted
Sep 4, 2013
Start date
Aug 2013
Primary completion
Nov 2013
Completion
Nov 2013
Results posted
Oct 27, 2016
Last update
Jan 3, 2024

Study contacts

James R White, MD, PhD
principal investigator · University of Rochester

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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