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

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.

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