A Safety, Tolerability, PD and PK Study in Healthy Adults
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02211625
- Lead Sponsor
- Trevena Inc.
- Brief Summary
The primary objective of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of TRV734 given as a single dose (Part A) and as multiple ascending doses (Part B) in healthy subjects.
- Detailed Description
This will be conducted in two-parts enrolling a total of approximately 72 healthy volunteers.
* Part A will assess the safety, tolerability, PD and PK of a 125mg dose of TRV734 in an open-label, randomized, three-period crossover study in which subjects are fasted, fed a standard meal, or fed a high-fat meal.
* Part B of the trial will assess the safety, tolerability, PD and PK of multiple ascending doses of TRV734 in a double blind, double dummy, randomized, active- and placebo-controlled, adaptive study. Oxycodone immediate release (IR) 10 mg will be used as a benchmark.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
- Healthy as determined by a responsible physician or trained qualified designee
- Males (Part A) or males and females (Part B) between 18 & 64 years of age, inclusive. Females must be of non-childbearing
- Capable of giving written informed consent
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Clinically significant conditions, or history of fainting or syncope
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Medical or psychiatric illness
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Major surgery within 4 weeks of screening
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Known difficulty with obtaining intravenous access
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Any ophthalmologic condition that could interfere with pupillometry
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History of sensitivity to any of the investigational products, or known intolerance to opioids or a history of medication or other allergy
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Use of prescription or non prescription medications
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History of drug abuse within 6 months of screening
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Use of any illegal drug within 30 days of screening and throughout participation in the study
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History of smoking or use of nicotine containing products within 3 months of screening and throughout participation in the study
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Donation of blood or plasma within 4 weeks prior to dosing
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Participation in a clinical trial and has received a medication within 30 days
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Weight <50 kg or BMI outside range of 18 - 32 kg/m2
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Positive for HIV antibody, hepatitis B virus surface antigen, or hepatitis C virus
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If male, unwillingness to abstain from sexual intercourse with a pregnant or lactating woman and, if engaging in sexual intercourse with a female partner of childbearing potential, use a condom and spermicide, in addition to having their female partner use another form of contraception, and abstain from sperm donation
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Part B Only:
- Active dermatological condition or eczema on non-dominant hand.
- Peripheral vascular disease
- If female, of child bearing potential, pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Multiple ascending dose study, active and placebo comparators TRV734 blinded Part B will assess the safety, tolerability, PD and PK of TRV734. Subjects will be randomized in a ratio of 3:1:1 to receive either multiple doses of TRV734, oxycodone IR 10mg or placebo. Multiple ascending dose study, active and placebo comparators Placebo Part B will assess the safety, tolerability, PD and PK of TRV734. Subjects will be randomized in a ratio of 3:1:1 to receive either multiple doses of TRV734, oxycodone IR 10mg or placebo. Multiple ascending dose study, active and placebo comparators Oxycodone IR 10 mg Part B will assess the safety, tolerability, PD and PK of TRV734. Subjects will be randomized in a ratio of 3:1:1 to receive either multiple doses of TRV734, oxycodone IR 10mg or placebo. TRV734 125 mg Open-label TRV734 125 mg Part A, open-label will evaluate the the safety, PK and PD profile of a 125mg dose of TRV734 in which subjects are fasted, fed a standard meal, or fed a high-fat meal. Part A will also inform the dosing paradigm for Part B.
- Primary Outcome Measures
Name Time Method Safety 7 days Clinical safety data from adverse event reporting, clinical observations, 12-lead ECGs, cardiac telemetry monitoring, vital signs (blood pressure, heart rate, respiratory rate and oral temperature), oxygen saturation and safety laboratory tests.
- Secondary Outcome Measures
Name Time Method Effect on pharmacodynamics of multiple ascending doses (Part B) of TRV734 4 days Change from baseline in: Pupillometry and Cold Pain Test
Effect on pharmacodynamics of 125mg dose or TRV734 (Part A) following various administration paradigms 7 days Change from baseline in: Pupillometry and Cold Pain Test
Effect on pharmacokinetics of multiple ascending (Part B) doses of TRV734 4 days From the plasma concentration-time data, the following PK parameters will be determined, as data permit: AUC, Cmax, tmax, t½,eff, Vss/F, C, AR, and CL/F. From the urine concentration data, the following will PK parameters will be determined, as data permit: %UR and CLR.
Effect on pharmacokinetics of 125mg dose of TRV734 (Part A) following various administration paradigms. 7 days From the plasma concentration-time data, the following PK parameters will be determined, as data permit: AUC, Cmax, tmax, t½,eff, Vss/F, C, AR, and CL/F. From the urine concentration data, the following will PK parameters will be determined, as data permit: %UR and CLR.
Trial Locations
- Locations (1)
ICON Development Solutions
🇺🇸San Antonio, Texas, United States