Trial Outcomes & Findings for A Pharmacokinetic Substudy of the TDE-PH-304 Protocol (NCT NCT01934582)
NCT ID: NCT01934582
Last Updated: 2024-01-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
13 participants
Primary outcome timeframe
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)
Results posted on
2024-01-03
Participant Flow
Participant milestones
| Measure |
Open-label Extension PK Population
The PK population included all subjects enrolled in the PK substudy having met the study criteria who received at least 1 treatment of open-label treprostinil diethanolamine.
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|---|---|
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Overall Study
STARTED
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13
|
|
Overall Study
COMPLETED
|
13
|
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pharmacokinetic Substudy of the TDE-PH-304 Protocol
Baseline characteristics by cohort
| Measure |
Open-label Extension PK Population
n=13 Participants
The PK population included all subjects enrolled in the PK substudy having met the study criteria, who had sufficient treprostinil concentration-time data to derive noncompartmental PK parameters for at least 1 treatment of open-label treprostinil diethanolamine.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
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Age, Categorical
Between 18 and 65 years
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7 Participants
n=5 Participants
|
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Age, Categorical
>=65 years
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6 Participants
n=5 Participants
|
|
Age, Continuous
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60.6 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
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Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
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1 Participants
n=5 Participants
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Race (NIH/OMB)
White
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12 Participants
n=5 Participants
|
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
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13 participants
n=5 Participants
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PRIMARY outcome
Timeframe: 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)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.
Outcome measures
| Measure |
PK Visit 1
n=13 Participants
UT-15C SR (treprostinil diethanolamine) BID
|
PK Visit 2
n=13 Participants
UT-15C SR (treprostinil diethanolamine) TID
|
|---|---|---|
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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 mg
Interval 2.0 to 17.5
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6.75 mg
Interval 1.25 to 15.0
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PRIMARY outcome
Timeframe: 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)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.
Outcome measures
| Measure |
PK Visit 1
n=13 Participants
UT-15C SR (treprostinil diethanolamine) BID
|
PK Visit 2
n=13 Participants
UT-15C SR (treprostinil diethanolamine) TID
|
|---|---|---|
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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)
Cmax
|
8.60 ng/mL
Interval 1.7 to 18.2
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8.94 ng/mL
Interval 2.25 to 16.8
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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)
Cmin
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1.19 ng/mL
Interval 0.29 to 2.5
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2.14 ng/mL
Interval 0.263 to 6.12
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PRIMARY outcome
Timeframe: 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)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.
Outcome measures
| Measure |
PK Visit 1
n=13 Participants
UT-15C SR (treprostinil diethanolamine) BID
|
PK Visit 2
n=13 Participants
UT-15C SR (treprostinil diethanolamine) TID
|
|---|---|---|
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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).
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47.8 h*ng/mL
Interval 8.92 to 80.6
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58.0 h*ng/mL
Interval 10.8 to 109.0
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SECONDARY outcome
Timeframe: 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]).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.
Outcome measures
| Measure |
PK Visit 1
n=13 Participants
UT-15C SR (treprostinil diethanolamine) BID
|
PK Visit 2
n=13 Participants
UT-15C SR (treprostinil diethanolamine) TID
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|---|---|---|
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To Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose.
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332.5 Meters
Interval 177.0 to 525.0
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347.9 Meters
Interval 223.0 to 541.0
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SECONDARY outcome
Timeframe: The AEs were recorded for up to 50 days.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.
Outcome measures
| Measure |
PK Visit 1
n=13 Participants
UT-15C SR (treprostinil diethanolamine) BID
|
PK Visit 2
n=13 Participants
UT-15C SR (treprostinil diethanolamine) TID
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|---|---|---|
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Diarrhea
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46 percentage of subjects
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38 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Extremity pain
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54 percentage of subjects
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38 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Flushing
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85 percentage of subjects
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54 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Headache
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69 percentage of subjects
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85 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Hypotension
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23 percentage of subjects
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23 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Jaw Pain
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38 percentage of subjects
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46 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Nausea
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38 percentage of subjects
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77 percentage of subjects
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To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.
Vomiting
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0 percentage of subjects
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0 percentage of subjects
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Adverse Events
PK Visit 1
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
PK Visit 2
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PK Visit 1
n=13 participants at risk
UT-15C SR (treprostinil diethanolamine): open-label study drug
|
PK Visit 2
n=13 participants at risk
UT-15C SR (treprostinil diethanolamine): open-label study drug
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|---|---|---|
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Gastrointestinal disorders
Diarrhea
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46.2%
6/13 • Number of events 22 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
38.5%
5/13 • Number of events 20 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
|
Musculoskeletal and connective tissue disorders
Extremity pain
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53.8%
7/13 • Number of events 41 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
38.5%
5/13 • Number of events 47 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
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Vascular disorders
Flushing
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84.6%
11/13 • Number of events 57 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
53.8%
7/13 • Number of events 58 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
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Nervous system disorders
Headache
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69.2%
9/13 • Number of events 57 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
84.6%
11/13 • Number of events 70 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
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Vascular disorders
Hypotension
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23.1%
3/13 • Number of events 8 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
23.1%
3/13 • Number of events 9 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
|
Musculoskeletal and connective tissue disorders
Jaw pain
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38.5%
5/13 • Number of events 18 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
46.2%
6/13 • Number of events 28 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
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Gastrointestinal disorders
Nausea
|
38.5%
5/13 • Number of events 31 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
76.9%
10/13 • Number of events 80 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
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Gastrointestinal disorders
Vomiting
|
0.00%
0/13 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
|
0.00%
0/13 • Approximately 50 days.
The AEs were recorded by subjects in an AE diary during BID dosing (within 14 days prior to transitioning to TID dosing regimen) and during TID dosing (within 35 days from transition).
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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, except as provided below. 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.
- Publication restrictions are in place
Restriction type: OTHER