A Pharmacokinetic Substudy of the TDE-PH-304 Protocol

A Pharmacokinetic Substudy of Subjects Transitioning From Twice Daily to Three Times Daily Dosing of UT-15C SR (Treprostinil Diethanolamine) in the TDE-PH-304 Protocol

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: UT-15C SR; Drug: treprostinil diethanolamine

Detailed Description

As noted above in "Brief Summary".

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 71 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label extension	Drug: UT-15C SR; Drug: treprostinil diethanolamine; Open label study drug.; Other Names: UT-15C Sustained Release (SR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)
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.	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)
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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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]).
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.	The AEs were recorded for up to 50 days.

Collaborators and Investigators

• Sponsor: United Therapeutics
• Investigators: Principal Investigator: James R White, MD, PhD, University of Rochester

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 29, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimated): September 4, 2013

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-309; TDE-PH-304