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