A Safety, Tolerability, PD and PK Study in Healthy Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Two-Part Study to Evaluate the Safety, Tolerability, Pharmacodynamics And Pharmacokinetics of TRV734 in Healthy Adult Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Open-label TRV734 125 mg
* Drug: TRV734 blinded
* Drug: Oxycodone IR 10 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Clinically significant conditions, or history of fainting or syncope Medical or psychiatric illness Major surgery within 4 weeks of screening Known difficulty with obtaining intravenous access Any ophthalmologic condition that could interfere with pupillometry History of sensitivity to any of the investigational products, or known intolerance to opioids or a history of medication or other allergy Use of prescription or non prescription medications History of drug abuse within 6 months of screening Use of any illegal drug within 30 days of screening and throughout participation in the study History of smoking or use of nicotine containing products within 3 months of screening and throughout participation in the study Donation of blood or plasma within 4 weeks prior to dosing Participation in a clinical trial and has received a medication within 30 days Weight <50 kg or BMI outside range of 18 - 32 kg/m2 Positive for HIV antibody, hepatitis B virus surface antigen, or hepatitis C virus 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 Part B Only: Active dermatological condition or eczema on non-dominant hand. Peripheral vascular disease If female, of child bearing potential, pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRV734 125 mg<br>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. | Drug: Open-label TRV734 125 mg<br>* 125 mg<br>|
| Active Comparator: Multiple ascending dose study, active and placebo comparators<br>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. | Drug: TRV734 blinded<br>* blinded, multiple ascending dose<br>Drug: Oxycodone IR 10 mg<br> <br> Drug: Placebo<br>* TRV734-matched and oxycodone placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | 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. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on pharmacodynamics of multiple ascending doses (Part B) of TRV734 | Change from baseline in: Pupillometry and Cold Pain Test | 4 days | 
| Effect on pharmacokinetics of multiple ascending (Part B) doses of TRV734 | 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. | 4 days | 
| Effect on pharmacodynamics of 125mg dose or TRV734 (Part A) following various administration paradigms | Change from baseline in: Pupillometry and Cold Pain Test | 7 days | 
| Effect on pharmacokinetics of 125mg dose of TRV734 (Part A) following various administration paradigms. | 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. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Pharmacodynamics (PD), Pharmacokinetics (PK)