This study is intended to evaluate the potential 2-way reciprocal interaction between multiple doses of Epanova™ and a single dose of rosuvastatin
The PK of rosuvastatin will be monitored following single-dose administration of rosuvastatin with and without multiple-dose administration of 4 g Epanova™ for 13 consecutive days in order to detect a possible interaction between rosuvastatin and Epanova™. The PK of total EPA, total DHA and total EPA+DHA will also be monitored following multiple-dose administration of Epanova™ with and without single-dose administration of 40 mg rosuvastatin. A single dose administration for rosuvastatin has been judged sufficient to yield plasma concentrations that will be detectable with an adequate validated analytical method and characterize adequately the PK of rosuvastatin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
114
Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).
Multiple oral doses of 2 g (2 x 1 g capsules) Epanova™ QD for 10 consecutive days (Days 4 to 13)
Multiple oral doses of 4 g Epanova™ QD for 13 consecutive days with coadministration of single 40 mg oral dose of rosuvastatin (Crestor®) with the 11th dose of Epanova™ on Day 24
Celerion
Neptune City, New Jersey, United States
ln-transformed Cmax,ss of baseline-adjusted total EPA, total DHA, and total EPA+DHA
ln-transformed Cmax,ss of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model.
Time frame: Days 1 and 24
ln-transformed AUC0-tau of baseline-adjusted total EPA, total DHA, and total EPA+DHA
ln-transformed AUC0-tau of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model.
Time frame: Days 1 and 24
ln-transformed Cmax,ss of unadjusted total EPA, total DHA, and total EPA+DHA
ln-transformed Cmax,ss of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model.
Time frame: Days 1 and 24
dose proportionality of baseline-adjusted total EPA, total DHA, and total EPA+DHA systemic exposure will be assessed following multiple doses of Epanova™ 2 g and 4 g
In Cohort 1 only, dose proportionality of baseline-adjusted total EPA, total DHA, and total EPA+DHA systemic exposure will be assessed following multiple doses of Epanova™ 2 g and 4 g using an analysis of variance (ANOVA) on dose normalized data.
Time frame: Days 1 and 24
ln-transformed AUC0-tau of unadjusted total EPA, total DHA, and total EPA+DHA
ln-transformed AUC0-tau of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model.
Time frame: Days 1 and 24
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Multiple oral doses of 2 g (2 x 1 g capsules) Vascepa® every 12 hours for 20 consecutive days (Days 1 to 20).