Phase 1
Completed N=82
Study in Healthy Subjects to Compare the Concentrations of the Omega-3 Fatty Acids EPA and DHA in Blood When Delivered as Three New Capsules in Relation to the Epanova® Capsule Under Fasting and Fed Conditions
Relative Bioavailability · AUC · Cmax · Pharmacokinetics
Source: ClinicalTrials.gov NCT02359045 ↗
Enrolled (actual)
82
Serious AEs
0.0%
Results posted
May 2017
Primary outcomePrimary: Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC) Assessed for Eicosapentaenoic Acid (EPA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. — 2010; 1400; 744; 1720 µg*h/mL
Summary
This study is a randomized, open-label, cross-over study in healthy subjects performed at a single study center. The study is divided into two parts, Part 1 and Part 2. The purpose of the study is to compare the pharmacokinetics (PK) of three different prototype capsule formulations (omega-3-carboxylic acids test formulations) with Epanova® capsules 1000 mg under fasted conditions in Part 1 and under fed conditions in Part 2. The results will be used as basis for choice of formulation for further pharmaceutical development.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC) Assessed for Eicosapentaenoic Acid (EPA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
2010; 1400; 744; 1720; 3460; 3010 | — |
| PRIMARY AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
783; 502; 399; 674; 791; 501 | — |
| PRIMARY AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
10400; 6870; 4250; 7710; 15300; 12500 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours After Dosing {AUC(0-72)} Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
1680; 1080; 564; 1080; 2570; 2310 | — |
| PRIMARY AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
577; 405; 309; 339; 610; 483 | — |
| PRIMARY AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
7200; 4560; 2710; 4470; 10200; 9030 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
93.5; 54.5; 24.8; 50.0; 140; 119 | — |
| PRIMARY Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
46.7; 31.6; 19.0; 24.0; 55.4; 45.3 | — |
| PRIMARY Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
447; 276; 139; 241; 626; 522 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte Concentration {AUC (Last)} Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
1670; 1080; 518; 1080; 2570; 2310 | — |
| SECONDARY AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
553; 391; 286; 328; 588; 484 | — |
| SECONDARY AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
7180; 4540; 2570; 4340; 10200; 9040 | — |
| SECONDARY Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
25.3; 26.0; 23.1; 29.2; 33.8; 31.2 | — |
| SECONDARY t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
24.1; 18.8; 13.0; 22.5; 24.6; 18.4 | — |
| SECONDARY t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
30.4; 23.8; 19.1; 23.4; 33.9; 30.3 | — |
| SECONDARY Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
6.02; 7.50; 8.99; 7.50; 6.00; 6.02 | — |
| SECONDARY Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
6.00; 7.5; 7.50; 7.49; 5.98; 6.00 | — |
| SECONDARY Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
6.02; 7.50; 7.50; 7.51; 6.00; 6.00 | — |
| SECONDARY Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
0.0274; 0.0267; 0.0301; 0.0237; 0.0205; 0.0222 | — |
| SECONDARY λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
0.0287; 0.0369; 0.0531; 0.0308; 0.0282; 0.0377 | — |
| SECONDARY λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. |
0.0228; 0.0291; 0.0363; 0.0297; 0.0204; 0.0229 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events |
8; 7; 4; 5; 3; 3 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Provision of signed and dated written informed consent prior to any study specific procedures.
- Healthy male and female (non-childbearing potential) subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the clinical unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- Post-menopausal, defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments, and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy or tubal ligation.
- Have a body mass index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Exclusion Criteria
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Current smokers or those who have smoked or used nicotine products within the previous 3 months.
- Consumption of poppy seeds within 7 days of first administration of IMP.
- Consumption of fish within 7 days prior to admission to the clinical unit.
- Used fish oil, other omega-3 fatty acids (EPA and/or DHA) containing supplements within 1 month of admission to the clinical unit.
- Have a known sensitivity or allergy to soybeans, fish and/or shellfish.
Data sourced from ClinicalTrials.gov (NCT02359045). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.