Hypertriglyceridemia
Conditions
Keywords
Epanova, omega-3 carboxylic acids, Vascepa, Eicosapentaenoic acid ethyl ester, Crestor, rosuvastatin
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.
Interventions
DRUGrosuvastatin 40 mg tablet
Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).
DRUGEpanova™ 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)
DRUGMultiple 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
DRUGMultiple (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).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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® | Days 1 and 24 | 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. |
| AEs, vital signs, ECG, laboratory tests | through study completion (14 days) | 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). |
| 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® | Days 1 and 24 | 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. |
| 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® | Days 1 and 24 | 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. |
Countries
United States
Outcome results
None listed