Clinical trial NCT02367937: PRC-4016 (Icosabutate) Phase I Drug-drug Interaction Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Phase I drug-drug interaction
Lead sponsor: Pronova BioPharma
Sponsor class: INDUSTRY
First posted: 2015-02-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under curve for effect of PRC-4016 at steady state on the PK of CYP3A substrates (midazolam, simvastatin), a CYP2C9 substrate (omeprazole) and a CYP2C19 substrate (flurbiprofen) in healthy male/female subjects.
timeFrame: 24 h postdose
measure: Peak plasma concentration for effect of PRC-4016 at steady state on the PK of CYP3A substrates (midazolam, simvastatin), a CYP2C9 substrate (omeprazole) and a CYP2C19 substrate (flurbiprofen) in healthy male/female subjects.
timeFrame: 24 hours post-dose
Secondary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability of PRC-4016 co-administered with midazolam, omeprazole, flurbiprofen and simvastatin in healthy male/female subjects.
timeFrame: 24 h postdose
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance Clinical research Unit (CRU) Ltd,Springfield House, Hyde street
Study officials:
affiliation: Covance
name: Joseph Chiesa, MD
role: PRINCIPAL_INVESTIGATOR
References: