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

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

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.

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