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A Pharmacokinetic Substudy of the TDE-PH-304 Protocol

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT01934582
First received: August 29, 2013
Last updated: September 6, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: UT-15C SR
Drug: treprostinil diethanolamine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • 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). [ 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) ] [ Designated as safety issue: No ]
    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 (Cmax, Cmin) 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 [ 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) ] [ Designated as safety issue: No ]
    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). [ 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) ] [ Designated as safety issue: No ]
    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:
  • To Assess 6-minute Walk Distance for Both Groups (BID and TID) 3 to 6 Hours Post-morning Dose. [ 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]). ] [ Designated as safety issue: No ]
    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. [ Time Frame: The AEs were recorded for up to 50 days. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 13
Study Start Date: August 2013
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open label extension Drug: UT-15C SR Drug: treprostinil diethanolamine
Open label study drug.
Other Name: UT-15C Sustained Release (SR)

Detailed Description:
As noted above in "Brief Summary".
  Eligibility

Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01934582

Locations
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14623
Sponsors and Collaborators
United Therapeutics
Investigators
Principal Investigator: James R White, MD, PhD University of Rochester
  More Information

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01934582     History of Changes
Other Study ID Numbers: TDE-PH-309  TDE-PH-304 
Study First Received: August 29, 2013
Results First Received: July 14, 2016
Last Updated: September 6, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Treprostinil
Antihypertensive Agents

ClinicalTrials.gov processed this record on December 08, 2016