A Pharmacokinetic Substudy of the TDE-PH-304 Protocol

Phase 3

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: UT-15C SR; Drug: treprostinil diethanolamine

• Registration Number: NCT01934582
• Lead Sponsor: United Therapeutics

Brief 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.

Detailed Description

As noted above in "Brief Summary".

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2013-08-29
• Study First Submitted QC: 2013-08-29
• Study First Posted: 2013-09-04
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Results First Submitted: 2016-07-14
• Status Verified: 2016-09
• Results First Submitted QC: 2016-09-06
• Results First Posted: 2016-10-27
• Last Update Submitted: 2023-12-12
• Last Update Posted: 2024-01-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label extension	treprostinil diethanolamine	-
Open label extension	UT-15C SR	-

Primary Outcome Measures

Name	Time	Method
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)	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.
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).	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.
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).	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.

Secondary Outcome Measures

Name	Time	Method
To Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose.	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.
To Compare the Adverse Event (AE) Profile of BID Versus TID Dosing.	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.

Trial Locations

Locations (1)

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States