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

Hypertriglyceridemia Clinical Trial

— ECLIPSEIII  

Official title:

An Open-Label, 2-Cohort Study to Evaluate the 2-Way Interaction Between Multiple Doses of Epanova™ and a Single Dose of Rosuvastatin (Crestor®), to Assess the Dose Proportionality of Epanova™, and to Compare the Systemic Exposure of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) Following Multiple Doses of Epanova™ and Vascepa® in Healthy Normal Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02859129
• Other study ID #: OM-EPA-009
• Status: Completed
• Phase: Phase 1
• First received: July 18, 2016
• Last updated: August 16, 2016
• Start date: September 2013
• Est. completion date: November 2013

Study information

• Verified date: August 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertriglyceridemia

Intervention

Drug:
• rosuvastatin 40 mg tablet
Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).
• 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)
• Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose
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
• Multiple (20) oral doses of 2 g Vascepa® every 12 hours
Multiple oral doses of 2 g (2 x 1 g capsules) Vascepa® every 12 hours for 20 consecutive days (Days 1 to 20).

Locations

Country	Name	City	State
United States	Celerion	Neptune	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ln-transformed AUC0-24 exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa®	The systemic exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa® will be assessed by analyzing the ln-transformed AUC0-24. In addition to an ANOVA, an analysis of covariance (ANCOVA) including the baseline value as a covariate will be performed.	Days 1 and 24	No
Other	AEs, vital signs, ECG, laboratory tests	all AEs, physical examinations, vital signs (heart rate, blood pressure, respiratory rate, and temperature), 12-lead ECGs, and laboratory safety tests (hematology, serum chemistry, coagulation, and urinalysis).	through study completion (14 days)	Yes
Other	ln-transformed Cavg of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa®	The systemic exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa® will be assessed by analyzing the ln-transformed Cavg. In addition to an ANOVA, an analysis of covariance (ANCOVA) including the baseline value as a covariate will be performed.	Days 1 and 24	No
Other	ln-transformed Cmax,ss of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa®	The systemic exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa® will be assessed by analyzing the ln-transformed Cmax,ss. In addition to an ANOVA, an analysis of covariance (ANCOVA) including the baseline value as a covariate will be performed.	Days 1 and 24	No
Primary	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.	Days 1 and 24	No
Primary	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.	Days 1 and 24	No
Secondary	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.	Days 1 and 24	No
Secondary	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.	Days 1 and 24	No
Secondary	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.	Days 1 and 24	No

External Links

•   CSR Synopsis