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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rosuvastatin | Experimental | Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1). |
|
| Epanova® | Experimental | Multiple oral doses of 2 g (2 x 1 g capsules) Epanova® QD for 10 consecutive days (Days 4 to 13) |
|
| Epanova® + Crestor® | Experimental | 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® | Active Comparator | Vascepa® multiple oral doses of 2 g (2 x 1 g capsules) every 12 hours for 20 consecutive days (Days 1 to 20). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rosuvastatin 40 mg tablet | Drug | Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael D Davidson, MD | Omthera Pharmaceuticals/AstraZeneca | Study Director |
| Sandra M Connolly, MD | Celerion | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Neptune City | New Jersey | 07753 | United States |
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| Label | URL |
|---|---|
| CSR Synopsis | View source |
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| Epanova™ QD (2 x 1 g capsules) | Drug | 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 | Drug | 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 | Drug | Multiple oral doses of 2 g (2 x 1 g capsules) Vascepa® every 12 hours for 20 consecutive days (Days 1 to 20). |
|
|
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 |
| 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 |
| Days 1 and 24 |
| 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) |
| 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 |
| 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 |
| ID | Term |
|---|---|
| D015228 | Hypertriglyceridemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| D013607 | Tablets |
| C035276 | eicosapentaenoic acid ethyl ester |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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