Clinical trial NCT02859129: Study to Evaluate the 2-Way Interaction Between Multiple Doses of Epanova™ and a Single Dose of Rosuvastatin (Crestor®)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertriglyceridemia
Keywords: Epanova
omega-3 carboxylic acids
Vascepa
Eicosapentaenoic acid ethyl ester
Crestor
rosuvastatin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-08-08
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ln-transformed Cmax,ss of baseline-adjusted total EPA, total DHA, and total EPA+DHA
timeFrame: Days 1 and 24
measure: ln-transformed AUC0-tau of baseline-adjusted total EPA, total DHA, and total EPA+DHA
timeFrame: Days 1 and 24
Secondary outcomes:
measure: ln-transformed Cmax,ss of unadjusted total EPA, total DHA, and total EPA+DHA
timeFrame: Days 1 and 24
measure: 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
timeFrame: Days 1 and 24
measure: ln-transformed AUC0-tau of unadjusted total EPA, total DHA, and total EPA+DHA
timeFrame: Days 1 and 24
Other outcomes:
measure: 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®
timeFrame: Days 1 and 24
measure: AEs, vital signs, ECG, laboratory tests
timeFrame: through study completion (14 days)
measure: 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®
timeFrame: Days 1 and 24
measure: 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®
timeFrame: Days 1 and 24
Locations:
city: Neptune
country: United States
facility: Celerion
state: New Jersey
Study officials:
affiliation: Omthera Pharmaceuticals/AstraZeneca
name: Michael D Davidson, MD
role: STUDY_DIRECTOR
affiliation: Celerion
name: Sandra M Connolly, MD
role: PRINCIPAL_INVESTIGATOR
References: