Study to Evaluate the 2-Way Interaction Between Multiple Doses of Epanova™ and a Single Dose of Rosuvastatin (Crestor®)

Phase 1

Completed

• Conditions: Hypertriglyceridemia
• Interventions: Drug: Epanova™ QD (2 x 1 g capsules); Drug: Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose; Drug: Multiple (20) oral doses of 2 g Vascepa® every 12 hours; Drug: rosuvastatin 40 mg tablet

• Registration Number: NCT02859129
• Lead Sponsor: AstraZeneca

Brief Summary

This study is intended to evaluate the potential 2-way reciprocal interaction between multiple doses of Epanova™ and a single dose of rosuvastatin

Detailed Description

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 Timeline

• Study Start: 2013-09
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Study First Submitted: 2016-07-18
• Status Verified: 2016-08
• Study First Submitted QC: 2016-08-03
• Study First Posted: 2016-08-08
• Last Update Submitted: 2016-08-16
• Last Update Posted: 2016-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

• Male or female (non-childbearing potential)
• Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening
• Non-smoker
• Medically healthy with no clinically significant laboratory profiles, vital signs or ECGs

Exclusion Criteria

• mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study
• History or presence of myopathy and/or hypothyroidism.
• History or presence of transaminase elevations
• History or presence of hypersensitivity or idiosyncratic reaction to rosuvastatin, to other HMG-CoA reductase inhibitors, to Epanova™, to Vascepa®, or to related compounds
• Known sensitivity or allergy to soybeans, fish, and/or shellfish.
• Has consumed fish within 7 days prior to check-in.
• Female subjects who are pregnant or lactating.
• Positive urine drug and alcohol results at screening or check-in.
• Positive urine cotinine at screening and check-in
• Use of any drugs known to be inducers of CYP enzymes and/or P-gp
• Donation of blood or significant blood loss within 56 days prior to the first dose of study medication.
• Plasma donation within 7 days prior to the first dose of study medication.
• Participation in another clinical trial within 28 days prior to the first dose of study medication.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epanova®	Epanova™ QD (2 x 1 g capsules)	Multiple oral doses of 2 g (2 x 1 g capsules) Epanova® QD for 10 consecutive days (Days 4 to 13)
Epanova® + Crestor®	Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose	Epanova® multiple oral doses of 4 g (4 x 1 g capsules) QD for 13 consecutive days (Days 14 to 26) with coadministration of single 40 mg (1 x 40 mg tablet) oral dose of rosuvastatin (Crestor®) with the 11th dose of 4 g Epanova® on Day 24
Vascepa®	Multiple (20) oral doses of 2 g Vascepa® every 12 hours	Vascepa® multiple oral doses of 2 g (2 x 1 g capsules) every 12 hours for 20 consecutive days (Days 1 to 20).
Rosuvastatin	rosuvastatin 40 mg tablet	Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).

Primary Outcome Measures

Name	Time	Method
ln-transformed AUC0-tau of baseline-adjusted total EPA, total DHA, and total EPA+DHA	Days 1 and 24	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.
ln-transformed Cmax,ss of baseline-adjusted total EPA, total DHA, and total EPA+DHA	Days 1 and 24	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.

Secondary Outcome Measures

Name	Time	Method
ln-transformed Cmax,ss of unadjusted total EPA, total DHA, and total EPA+DHA	Days 1 and 24	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.
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	Days 1 and 24	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.
ln-transformed AUC0-tau of unadjusted total EPA, total DHA, and total EPA+DHA	Days 1 and 24	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.

Trial Locations

Locations (1)

Celerion; 🇺🇸 Neptune, New Jersey, United States