PRC-4016 (Icosabutate) Phase I Drug-drug Interaction Study

A Phase I, Open-Label Study to Assess the Effects of PRC-4016 (Icosabutate) on the Pharmacokinetics of Midazolam, Omeprazole, Flurbiprofen and Simvastatin in Healthy Male/Female Subjects

The aim of the study is to evaluate the effect of PRC-4016 at steady state on the pharmacokinetics (PK) of cytochrome P450 (CYP) 3A substrates (midazolam, simvastatin), a CYP2C9 substrate (omeprazole) and a CYP2C19 substrate (flurbiprofen) in healthy male/female subjects.

Day 1: Subject will receive single oral doses of 2.5 mg midazolam, 20 mg omeprazole and 50 mg flurbiprofen morning Day 2: Subject will receive a single oral dose of 40 mg simvastatin on the morning of Day 2. Day 4: Subjects will commence the multiple-dose regimen for PRC-4016 (600 mg once daily) for 11 days. Day 12: Subjects will be given single oral doses of 2.5 mg midazolam, 20 mg omeprazole and 50 mg flurbiprofen co-administered with 600 mg PRC-4016.

Day 13, subjects will be given a single oral dose of 40 mg simvastatin co-administered with 600 mg PRC-4016.

All subjects will return for a post-study visit 7 to 10 days after their final dose.

Inclusion Criteria:

• males or females
• any ethnic origin
• age 18-60 years
• BMI 8.0 - 35.0 kg/m2
• generally good health
• signed informed consent

Exclusion Criteria:

• males or females not willing to use appropriate contraception
• recent blood donation
• recent blood received
• high consumption of alcohol
• high consumption og tobacco
• subjects who have engaged in heavy exercise last two weeks
• prescribed systemic or topical medication taken recently, or supplements/remedies interfering with study procedures or safety
• other medication known to alter drug absorption or elimination
• abnormal hearth rate or blood pressure
• significant history of drug allergy or hypersensitivity to treatment ingredients
• other significant medical history or physical findings
• pregnant or lactating
• Poor metabolizers for CYP2C9 or CYP2C19
• subjects previously taken part in or withdrawn from study or subjects that according to investigator should not participate