A Bioavailability Study Comparing Treprostinil Diethanolamine Oral Tablets and Oral Solution in Healthy Volunteers

A Comparative Bioavailability Study of UT-15C SR (Treprostinil Diethanolamine, Sustained Release) Oral Tablets and UT-15C (Treprostinil Diethanolamine) Administered as an Oral Solution in Healthy Volunteers

This single center, open label, randomized, two-period, two-sequence cross-over study is designed to evaluate the relative bioavailability of a treprostinil diethanolamine 1 mg tablet in reference to treprostinil diethanolamine 1 mg oral solution (administered as four 0.25 mg doses every 2 hours for a 1 mg total dose) in twenty-four healthy volunteers. Other secondary outcomes of interest include assessment of pharmacokinetic parameters of treprostinil diethanolamine 1 mg tablets and a treprostinil diethanolamine 1 mg oral solution administered as four doses (0.25 mg every 2 hours for a 1 mg total dose) and evaluation of the safety and tolerability of each treatment regimen.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: treprostinil diethanolamine

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Ppd Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is healthy between the ages of 18-55 years of age
• Female subjects must weigh between 55 and 100 kg, with a BMI between 19.0-29.9. kg/m2; inclusive at screening. Male subjects must weigh between 55 and 120 kg, with a BMI between 19.0-32.0 kg/m2; inclusive at screening.
• Subject has a medical history, physical examination, vital signs, ECG and clinical laboratory results within normal limits or considered not clinically significant by the Investigator at Screening.
• Female subjects with childbearing potential will practice abstinence or effective birth control methods from the time of providing written informed consent to the end of the study. Effective birth control is defined as an intrauterine device (IUD), barrier methods preferably in combination with a spermicidal foam or suppository, or the use of oral, transdermal or intra-vaginal hormonal contraceptives.
• Subject agrees to abstain from taking any prescription medication (except contraceptives) for 14 days prior to starting study procedures and to abstain from taking any non-prescription medications (except multivitamins) or herbal supplements for 7 days prior to beginning study procedures until discharge from the study (unless prescribed by the Investigator to treat an AE).
• Subject agrees to abstain from consuming alcohol from 3 days prior beginning study procedures until discharge from the study.
• Subject agrees to abstain from consuming grapefruit or xanthine-containing food or beverages for 3 days prior beginning study procedures until discharge from the study.
• Subject agrees to refrain from strenuous exercise from beginning study procedures until discharge from the study.
• Subject is able to communicate effectively with study personnel and be considered reliable, willing and cooperative in terms of compliance with the protocol requirements.

Exclusion Criteria:

• Subject has any clinically relevant abnormality identified during the screening physical examination, 12-lead ECG, or laboratory examinations.
• Subject has a history of anaphylaxis, a previous documented hypersensitivity reaction, or a clinically significant idiosyncratic reaction to any drug.
• Subject has a clinically significant history of neurological, cardiovascular, respiratory, endocrine, hematological, hepatic, renal, gastrointestinal, genitourinary, pulmonary, and/or musculoskeletal disease; glaucoma; a psychiatric disorder, or any other chronic disease, whether controlled by medication or not.
• The subject has a history of postural hypotension, unexplained syncope, a blood pressure that is less than 85 mmHg systolic or 50 mmHg diastolic, or a pulse rate that is greater than 90 bpm after sitting at rest for 5 minutes at Screening or Baseline.
• Subject has a predisposing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Subject has tested positive at the screening visit for HIV infection, HBsAg, or the HCV antibody.
• Subject is pregnant or lactating.
• Subject currently uses tobacco products or has a history of tobacco use within six months prior to Period 1.
• Subject has a history of alcohol abuse or a history of or current impairment of organ function reasonably related to alcohol abuse.
• Subject has a history of or current evidence of abuse of licit or illicit drugs or a positive urine screen for drugs of abuse.
• Subject has a history of abnormal bleeding tendencies.
• Subject has donated blood or plasma or has lost a significant volume of blood (greater than 450 mL) within four weeks prior to Period 1.
• Subject has participated in any investigational drug study within 30 days prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1 mg tablet; 1mg solution	Drug: treprostinil diethanolamine; Subjects will be administered a 1 mg dose of treprostinil diethanolamine as a single tablet, and treprostinil diethanolamine oral solution 0.25 mg dose every 2 hours for four doses (1 mg total).
EXPERIMENTAL: 1mg solution; 1mg tablet	Drug: treprostinil diethanolamine; Subjects will be administered a 1 mg dose of treprostinil diethanolamine as a single tablet, and treprostinil diethanolamine oral solution 0.25 mg dose every 2 hours for four doses (1 mg total).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma treprostinil concentrations	Pharmacokinetic blood sampling will occur twice for each subject. Pharmacokinetic parameters will be derived from treprostinil concentration-time data	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
vital sign measurements, clinical laboratory parameters, electrocardiograms (ECGs) and adverse events (AEs)	1 month

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (ESTIMATE): July 29, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): October 13, 2010
• Last Update Submitted That Met QC Criteria: October 8, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-123