AUC, Cmax, Pharmacokinetics, Relative Bioavailability
Conditions
Keywords
Omega-3-carboxylic acids,, Phase I,, Healthy Subjects,, Pharmacokinetics,, Relative bioavailability
Brief 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.
Detailed description
To assess the relative bioavailability of the different omega-3-carboxylic acids prototype capsule formulations in relation to Epanova® capsules 1000 mg under fed and fasted conditions.
Interventions
DRUGD1400147
Treatment A
DRUGD14000136
Treatment B
DRUGD14000137
Treatment C
DRUGEpanova®
Treatment D
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Pre-dose: -12, -1 and 0 hours and Post dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC for EPA on baseline subtracted plasma concentrations. |
| AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC for DHA on baseline subtracted plasma concentrations. |
| AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC for Total (combined) EPA + DHA on baseline subtracted plasma concentrations. |
| 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. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (0-72) for EPA on baseline subtracted plasma concentrations. |
| AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (0-72) for DHA on baseline subtracted plasma concentrations. |
| AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (0-72) for Total (combined) EPA + DHA on baseline subtracted plasma concentrations. |
| Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of Cmax for EPA on baseline subtracted plasma concentrations. |
| Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of Cmax for DHA on baseline subtracted plasma concentrations. |
| Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of Cmax for Total (combined) EPA + DHA on baseline subtracted plasma concentrations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of t½λz for EPA on baseline subtracted plasma concentrations. |
| t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of t½λz for DHA on baseline subtracted plasma concentrations. |
| t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of t½λz for Total (combined) EPA + DHA on baseline subtracted plasma concentrations. |
| Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of tmax for EPA on baseline subtracted plasma concentrations. |
| Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of tmax for DHA on baseline subtracted plasma concentrations. |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | From screening (within 28 days of first dosing) up to 14 days after last dosing | To evaluate the safety by assessing the number of subjects with clinically significant pulse after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of tmax for Total (combined) EPA + DHA on baseline subtracted plasma concentrations. |
| Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | From screening (within 28 days of first dosing) up to 14 days after last dosing | To assess the safety summary of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of λz for DHA on baseline subtracted plasma concentrations. |
| λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of λz for Total (combined) EPA + DHA on baseline subtracted plasma concentrations. |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | From screening (within 28 days of first dosing) up to 14 days after last dosing | To evaluate the safety by assessing the number of subjects with clinically significant 12-lead ECGs after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | From screening (within 28 days of first dosing) up to 14 days after last dosing | To evaluate the safety by assessing the number of subjects with clinically significant hematology parameters after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | From screening (within 28 days of first dosing) up to 14 days after last dosing | To evaluate the safety by assessing the number of subjects with clinically significant clinical chemistry laboratory results after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | From screening (within 28 days of first dosing) up to 14 days after last dosing | To evaluate the safety by assessing the number of subjects with clinically significant urinalysis results after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of λz for EPA on baseline subtracted plasma concentrations. |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | From screening (within 28 days of first dosing) up to 14 days after last dosing. | To assess the safety by analyzing the number of subjects with at least one adverse event after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
| 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. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (last) for EPA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentration. |
| AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (last) for DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentration. |
| AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (last) for Total (combined) EPA + DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentration. |
| Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of C0 for EPA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentrations. |
| C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of C0 for DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentrations. |
| C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours | To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of C0 for Total (combined) EPA + DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentrations. |
| Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | From screening (within 28 days of first dosing) up to 14 days after last dosing | To evaluate the safety by assessing the number of subjects with clinically significant blood pressure after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at Baltimore, USA. All enrolled participants were included in the study. A total of 137 participants were enrolled (signed ICF) and underwent screening visits, out of which 55 were screen failures and 82 were independently enrolled in the study.
Pre-assignment details
All the randomized participants were divided into 2 parts. Part 1- 4 sequence for 4 periods, 4 treatments: (ADBC, BACD, CBDA, DCAB) A- D1400147, B- D14000136, C- D14000137 & D- Epanova. Part 2- 6 sequence for 3 treatments, 3 periods: (ABC, BCA, CAB, ACB, BAC, CBA) A-D1400147, B- D14000136 or D14000137 & C- Epanova.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Subjects received a single dose of 4 treatments for 4 periods to assess the relative bioavailability and to characterize and compare the PK profiles of the three different prototype capsule formulations (Treatment A, B, C) in relation to Epanova capsules (Treatment D), under fasted conditions.
A- D1400147, B- D14000136, C- D14000137 & D- Epanova. | 40 |
| Part 2 Subjects received a single dose of 3 treatments for 3 periods to assess the relative bioavailability and to characterize and compare the PK profiles of the two different prototype capsule formulations (Treatment A, B) in relation to Epanova capsules (Treatment C), under fed conditions.
A-D1400147, B- D14000136 or D14000137 & C- Epanova. | 42 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Eligibility criteria not fulfilled | 3 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Part 1 | Part 2 | Total |
|---|---|---|---|
| Age, Continuous | 38.7 Years STANDARD_DEVIATION 9.97 | 37.1 Years STANDARD_DEVIATION 9.97 | 37.9 Years STANDARD_DEVIATION 9.97 |
| Sex/Gender, Customized Female | 0 Participants | 5 Participants | 5 Participants |
| Sex/Gender, Customized Male | 40 Participants | 37 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 38 | 7 / 39 | 4 / 37 | 5 / 37 | 3 / 39 | 3 / 41 | 3 / 41 |
| serious Total, serious adverse events | 0 / 38 | 0 / 39 | 0 / 37 | 0 / 37 | 0 / 39 | 0 / 41 | 0 / 41 |
Outcome results
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.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (0-72) for EPA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | 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 (μg*h/mL) | Geometric Coefficient of Variation 37.5 |
| Treatment B_Part 1 | 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. | 1080 (μg*h/mL) | Geometric Coefficient of Variation 74.4 |
| Treatment C_Part 1 | 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. | 564 (μg*h/mL) | Geometric Coefficient of Variation 93.8 |
| Treatment D_Part 1 | 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. | 1080 (μg*h/mL) | Geometric Coefficient of Variation 88.4 |
| Treatment A_Part 2 | 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. | 2570 (μg*h/mL) | Geometric Coefficient of Variation 27.8 |
| Treatment B_Part 2 | 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. | 2310 (μg*h/mL) | Geometric Coefficient of Variation 27.5 |
| Treatment C_Part 2 | 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. | 2620 (μg*h/mL) | Geometric Coefficient of Variation 28.4 |
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.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC for EPA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | 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 µg*h/mL | Geometric Coefficient of Variation 47.9 |
| Treatment B_Part 1 | 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. | 1400 µg*h/mL | Geometric Coefficient of Variation 88.6 |
| Treatment C_Part 1 | 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. | 744 µg*h/mL | Geometric Coefficient of Variation 81.5 |
| Treatment D_Part 1 | 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. | 1720 µg*h/mL | Geometric Coefficient of Variation 54.5 |
| Treatment A_Part 2 | 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. | 3460 µg*h/mL | Geometric Coefficient of Variation 34 |
| Treatment B_Part 2 | 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. | 3010 µg*h/mL | Geometric Coefficient of Variation 34.7 |
| Treatment C_Part 2 | 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. | 3450 µg*h/mL | Geometric Coefficient of Variation 33.7 |
Primary
AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (0-72) for DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 577 (μg*h/mL) | Geometric Coefficient of Variation 65.7 |
| Treatment B_Part 1 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 405 (μg*h/mL) | Geometric Coefficient of Variation 78.5 |
| Treatment C_Part 1 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 309 (μg*h/mL) | Geometric Coefficient of Variation 92 |
| Treatment D_Part 1 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 339 (μg*h/mL) | Geometric Coefficient of Variation 135 |
| Treatment A_Part 2 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 610 (μg*h/mL) | Geometric Coefficient of Variation 57 |
| Treatment B_Part 2 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 483 (μg*h/mL) | Geometric Coefficient of Variation 53.4 |
| Treatment C_Part 2 | AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 531 (μg*h/mL) | Geometric Coefficient of Variation 55.6 |
Primary
AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (0-72) for Total (combined) EPA + DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7200 (nmol*hr/mL) | Geometric Coefficient of Variation 44 |
| Treatment B_Part 1 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 4560 (nmol*hr/mL) | Geometric Coefficient of Variation 80.5 |
| Treatment C_Part 1 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 2710 (nmol*hr/mL) | Geometric Coefficient of Variation 92.3 |
| Treatment D_Part 1 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 4470 (nmol*hr/mL) | Geometric Coefficient of Variation 96.9 |
| Treatment A_Part 2 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 10200 (nmol*hr/mL) | Geometric Coefficient of Variation 31.3 |
| Treatment B_Part 2 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 9030 (nmol*hr/mL) | Geometric Coefficient of Variation 28.2 |
| Treatment C_Part 2 | AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 10100 (nmol*hr/mL) | Geometric Coefficient of Variation 32.1 |
Primary
AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC for DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 783 (μg*h/mL) | Geometric Coefficient of Variation 72.6 |
| Treatment B_Part 1 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 502 (μg*h/mL) | Geometric Coefficient of Variation 78.4 |
| Treatment C_Part 1 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 399 (μg*h/mL) | Geometric Coefficient of Variation 106 |
| Treatment D_Part 1 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 674 (μg*h/mL) | Geometric Coefficient of Variation 38.4 |
| Treatment A_Part 2 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 791 (μg*h/mL) | Geometric Coefficient of Variation 40.4 |
| Treatment B_Part 2 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 501 (μg*h/mL) | Geometric Coefficient of Variation 79.1 |
| Treatment C_Part 2 | AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 325 (μg*h/mL) | Geometric Coefficient of Variation 15.8 |
Primary
AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC for Total (combined) EPA + DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 10400 (nmol*hr/mL) | Geometric Coefficient of Variation 52.3 |
| Treatment B_Part 1 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6870 (nmol*hr/mL) | Geometric Coefficient of Variation 72.7 |
| Treatment C_Part 1 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 4250 (nmol*hr/mL) | Geometric Coefficient of Variation 102 |
| Treatment D_Part 1 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7710 (nmol*hr/mL) | Geometric Coefficient of Variation 92.6 |
| Treatment A_Part 2 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 15300 (nmol*hr/mL) | Geometric Coefficient of Variation 47.6 |
| Treatment B_Part 2 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 12500 (nmol*hr/mL) | Geometric Coefficient of Variation 43.8 |
| Treatment C_Part 2 | AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 15800 (nmol*hr/mL) | Geometric Coefficient of Variation 50.6 |
Primary
Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of Cmax for DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 46.7 (μg/mL) | Geometric Coefficient of Variation 44.9 |
| Treatment B_Part 1 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 31.6 (μg/mL) | Geometric Coefficient of Variation 67.7 |
| Treatment C_Part 1 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 19.0 (μg/mL) | Geometric Coefficient of Variation 67.7 |
| Treatment D_Part 1 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 24.0 (μg/mL) | Geometric Coefficient of Variation 83 |
| Treatment A_Part 2 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 55.4 (μg/mL) | Geometric Coefficient of Variation 46.3 |
| Treatment B_Part 2 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 45.3 (μg/mL) | Geometric Coefficient of Variation 41.8 |
| Treatment C_Part 2 | Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 58.0 (μg/mL) | Geometric Coefficient of Variation 50.7 |
Primary
Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of Cmax for Total (combined) EPA + DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 447 (nmol/mL) | Geometric Coefficient of Variation 46.2 |
| Treatment B_Part 1 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 276 (nmol/mL) | Geometric Coefficient of Variation 84 |
| Treatment C_Part 1 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 139 (nmol/mL) | Geometric Coefficient of Variation 84.4 |
| Treatment D_Part 1 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 241 (nmol/mL) | Geometric Coefficient of Variation 91.4 |
| Treatment A_Part 2 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 626 (nmol/mL) | Geometric Coefficient of Variation 42.1 |
| Treatment B_Part 2 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 522 (nmol/mL) | Geometric Coefficient of Variation 39.9 |
| Treatment C_Part 2 | Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 690 (nmol/mL) | Geometric Coefficient of Variation 42 |
Primary
Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of Cmax for EPA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 93.5 (μg/mL) | Geometric Coefficient of Variation 46.5 |
| Treatment B_Part 1 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 54.5 (μg/mL) | Geometric Coefficient of Variation 94.8 |
| Treatment C_Part 1 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 24.8 (μg/mL) | Geometric Coefficient of Variation 98.1 |
| Treatment D_Part 1 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 50.0 (μg/mL) | Geometric Coefficient of Variation 108 |
| Treatment A_Part 2 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 140 (μg/mL) | Geometric Coefficient of Variation 41.4 |
| Treatment B_Part 2 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 119 (μg/mL) | Geometric Coefficient of Variation 38.2 |
| Treatment C_Part 2 | Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 156 (μg/mL) | Geometric Coefficient of Variation 40.3 |
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.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (last) for EPA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentration.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A_Part 1 | 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. | EPA (Baseline Subtracted) | 1670 (μg*h/mL) | Geometric Coefficient of Variation 37.7 |
| Treatment A_Part 1 | 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. | EPA (Baseline Unadjusted) | 2800 (μg*h/mL) | Geometric Coefficient of Variation 31 |
| Treatment B_Part 1 | 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. | EPA (Baseline Subtracted) | 1080 (μg*h/mL) | Geometric Coefficient of Variation 74.9 |
| Treatment B_Part 1 | 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. | EPA (Baseline Unadjusted) | 2190 (μg*h/mL) | Geometric Coefficient of Variation 41.8 |
| Treatment C_Part 1 | 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. | EPA (Baseline Unadjusted) | 1620 (μg*h/mL) | Geometric Coefficient of Variation 42.6 |
| Treatment C_Part 1 | 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. | EPA (Baseline Subtracted) | 518 (μg*h/mL) | Geometric Coefficient of Variation 116 |
| Treatment D_Part 1 | 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. | EPA (Baseline Unadjusted) | 2150 (μg*h/mL) | Geometric Coefficient of Variation 44.9 |
| Treatment D_Part 1 | 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. | EPA (Baseline Subtracted) | 1080 (μg*h/mL) | Geometric Coefficient of Variation 89.1 |
| Treatment A_Part 2 | 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. | EPA (Baseline Unadjusted) | 3730 (μg*h/mL) | Geometric Coefficient of Variation 27.3 |
| Treatment A_Part 2 | 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. | EPA (Baseline Subtracted) | 2570 (μg*h/mL) | Geometric Coefficient of Variation 27.9 |
| Treatment B_Part 2 | 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. | EPA (Baseline Subtracted) | 2310 (μg*h/mL) | Geometric Coefficient of Variation 27.4 |
| Treatment B_Part 2 | 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. | EPA (Baseline Unadjusted) | 3500 (μg*h/mL) | Geometric Coefficient of Variation 24.8 |
| Treatment C_Part 2 | 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. | EPA (Baseline Subtracted) | 2620 (μg*h/mL) | Geometric Coefficient of Variation 28.5 |
| Treatment C_Part 2 | 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. | EPA (Baseline Unadjusted) | 3850 (μg*h/mL) | Geometric Coefficient of Variation 25.2 |
Secondary
AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (last) for DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentration.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 553 (μg*h/mL) | Geometric Coefficient of Variation 72.3 |
| Treatment A_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 4770 (μg*h/mL) | Geometric Coefficient of Variation 22.2 |
| Treatment B_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 391 (μg*h/mL) | Geometric Coefficient of Variation 83.3 |
| Treatment B_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 4700 (μg*h/mL) | Geometric Coefficient of Variation 24.4 |
| Treatment C_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 4510 (μg*h/mL) | Geometric Coefficient of Variation 19.3 |
| Treatment C_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 286 (μg*h/mL) | Geometric Coefficient of Variation 98.5 |
| Treatment D_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 328 (μg*h/mL) | Geometric Coefficient of Variation 142 |
| Treatment D_Part 1 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 4520 (μg*h/mL) | Geometric Coefficient of Variation 20.8 |
| Treatment A_Part 2 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 588 (μg*h/mL) | Geometric Coefficient of Variation 60.2 |
| Treatment A_Part 2 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 5340 (μg*h/mL) | Geometric Coefficient of Variation 28.4 |
| Treatment B_Part 2 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 484 (μg*h/mL) | Geometric Coefficient of Variation 57.7 |
| Treatment B_Part 2 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 5290 (μg*h/mL) | Geometric Coefficient of Variation 26 |
| Treatment C_Part 2 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 5360 (μg*h/mL) | Geometric Coefficient of Variation 27.7 |
| Treatment C_Part 2 | AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 527 (μg*h/mL) | Geometric Coefficient of Variation 58.2 |
Secondary
AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of AUC (last) for Total (combined) EPA + DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentration.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 7180 (nmol*hr/mL) | Geometric Coefficient of Variation 44.5 |
| Treatment A_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 24000 (nmol*hr/mL) | Geometric Coefficient of Variation 23.3 |
| Treatment B_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 4540 (nmol*hr/mL) | Geometric Coefficient of Variation 81.4 |
| Treatment B_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 21800 (nmol*hr/mL) | Geometric Coefficient of Variation 26 |
| Treatment C_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 2570 (nmol*hr/mL) | Geometric Coefficient of Variation 100 |
| Treatment C_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 19400 (nmol*hr/mL) | Geometric Coefficient of Variation 21.3 |
| Treatment D_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 4340 (nmol*hr/mL) | Geometric Coefficient of Variation 112 |
| Treatment D_Part 1 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 21200 (nmol*hr/mL) | Geometric Coefficient of Variation 25 |
| Treatment A_Part 2 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 10200 (nmol*hr/mL) | Geometric Coefficient of Variation 31.4 |
| Treatment A_Part 2 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 28800 (nmol*hr/mL) | Geometric Coefficient of Variation 25.4 |
| Treatment B_Part 2 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 27900 (nmol*hr/mL) | Geometric Coefficient of Variation 22.5 |
| Treatment B_Part 2 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 9040 (nmol*hr/mL) | Geometric Coefficient of Variation 28.2 |
| Treatment C_Part 2 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Subtracted) | 10200 (nmol*hr/mL) | Geometric Coefficient of Variation 32.1 |
| Treatment C_Part 2 | AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA(Baseline Unadjusted) | 29300 (nmol*hr/mL) | Geometric Coefficient of Variation 24 |
Secondary
Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of C0 for EPA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 13.7 (μg/mL) | Geometric Coefficient of Variation 54.2 |
| Treatment A_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 13.3 (μg/mL) | Geometric Coefficient of Variation 40.3 |
| Treatment C_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment C_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 13.2 (μg/mL) | Geometric Coefficient of Variation 42.3 |
| Treatment D_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment D_Part 1 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 12.8 (μg/mL) | Geometric Coefficient of Variation 38.8 |
| Treatment A_Part 2 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 14.8 (μg/mL) | Geometric Coefficient of Variation 48.6 |
| Treatment A_Part 2 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 2 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 2 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 15.6 (μg/mL) | Geometric Coefficient of Variation 38.3 |
| Treatment C_Part 2 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment C_Part 2 | Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | EPA (Baseline Unadjusted) | 15.9 (μg/mL) | Geometric Coefficient of Variation 40.6 |
Secondary
C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of C0 for DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 57.2 (μg/mL) | Geometric Coefficient of Variation 24.8 |
| Treatment A_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 59.0 (μg/mL) | Geometric Coefficient of Variation 26.4 |
| Treatment C_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment C_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 58.0 (μg/mL) | Geometric Coefficient of Variation 20.9 |
| Treatment D_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 57.1 (μg/mL) | Geometric Coefficient of Variation 22.7 |
| Treatment D_Part 1 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment A_Part 2 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 65.8 (μg/mL) | Geometric Coefficient of Variation 29.4 |
| Treatment A_Part 2 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 2 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 2 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 66.6 (μg/mL) | Geometric Coefficient of Variation 26.9 |
| Treatment C_Part 2 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Unadjusted) | 66.7 (μg/mL) | Geometric Coefficient of Variation 29.1 |
| Treatment C_Part 2 | C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | DHA (Baseline Subtracted) | 0 (μg/mL) | Geometric Coefficient of Variation 0 |
Secondary
C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of C0 for Total (combined) EPA + DHA on baseline subtracted plasma concentrations and baseline unadjusted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 223 (nmol/mL) | Geometric Coefficient of Variation 27.8 |
| Treatment A_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 0 |
| Treatment B_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 225 (nmol/mL) | Geometric Coefficient of Variation 26.6 |
| Treatment B_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 0 |
| Treatment C_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 223 (nmol/mL) | Geometric Coefficient of Variation 21.8 |
| Treatment C_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 0 |
| Treatment D_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 0 |
| Treatment D_Part 1 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 218 (nmol/mL) | Geometric Coefficient of Variation 22.4 |
| Treatment A_Part 2 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 0 |
| Treatment A_Part 2 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 65.8 (nmol/mL) | Geometric Coefficient of Variation 29.4 |
| Treatment B_Part 2 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 66.6 (nmol/mL) | Geometric Coefficient of Variation 26.9 |
| Treatment B_Part 2 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 0 |
| Treatment C_Part 2 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Unadjusted) | 66.7 (nmol/mL) | Geometric Coefficient of Variation 29.1 |
| Treatment C_Part 2 | C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | Total (combined) EPA + DHA (Baseline Subtracted) | 0 (nmol/mL) | Geometric Coefficient of Variation 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.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of t½λz for EPA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | 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 (hour) | Geometric Coefficient of Variation 44.3 |
| Treatment B_Part 1 | 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. | 26.0 (hour) | Geometric Coefficient of Variation 49.3 |
| Treatment C_Part 1 | 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. | 23.1 (hour) | Geometric Coefficient of Variation 59.7 |
| Treatment D_Part 1 | 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. | 29.2 (hour) | Geometric Coefficient of Variation 39.4 |
| Treatment A_Part 2 | 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. | 33.8 (hour) | Geometric Coefficient of Variation 42.8 |
| Treatment B_Part 2 | 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. | 31.2 (hour) | Geometric Coefficient of Variation 39.2 |
| Treatment C_Part 2 | 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. | 33.1 (hour) | Geometric Coefficient of Variation 49.5 |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event
To assess the safety by analyzing the number of subjects with at least one adverse event after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing.
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 2 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 2 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 1 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 0 Partcipants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 1 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 2 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 1 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 1 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 1 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 1 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 0 Partcipants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 1 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 1 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 1 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 1 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 0 Partcipants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 2 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 2 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 1 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 1 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 1 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 0 Partcipants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 1 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 1 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 1 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 1 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 1 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 0 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 1 Partcipants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 1 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 1 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 0 Partcipants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Neck Pain | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Phlebitis | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Distension | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hepatic Enzyme Increased | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Swelling | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Catheter Site Bruise | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Frequent Bowel Movements | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Somnolence | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Eyelid Edema | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Flatulence | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vessel Puncture Site Hematoma | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Epistaxis | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hordeolum | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dizziness | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dysgeusia | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vision Blurred | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Headache | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain Upper | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Rhinorrhea | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Hematoma | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Sneezing | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dry Mouth | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Abdominal Pain | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Nausea | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Ocular Hyperemia | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Diarrhea | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Dyspepsia | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Vomiting | 1 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Presyncope | 0 Partcipants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event | Acne | 0 Partcipants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs)
To evaluate the safety by assessing the number of subjects with clinically significant 12-lead ECGs after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs) | 0 Participants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure
To evaluate the safety by assessing the number of subjects with clinically significant blood pressure after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure | 0 Participants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results
To evaluate the safety by assessing the number of subjects with clinically significant clinical chemistry laboratory results after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results | 0 Participants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters
To evaluate the safety by assessing the number of subjects with clinically significant hematology parameters after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters | 0 Participants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse
To evaluate the safety by assessing the number of subjects with clinically significant pulse after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse | 0 Participants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis
To evaluate the safety by assessing the number of subjects with clinically significant urinalysis results after administration of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis | 0 Participants |
Secondary
Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events
To assess the safety summary of single doses of the omega-3-carboxylic acids test formulations and Epanova in healthy subjects
Time frame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Population: Subjects were analyzed based on safety analysis set. Safety Analysis Set is defined as All subjects who received at least one dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 8 Participants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment A_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment B_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 7 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 4 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 0 Participants |
| Treatment C_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 5 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment D_Part 1 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 3 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment A_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 0 Participants |
| Treatment B_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 3 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE leading to discontinuationof IP | 1 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE | 3 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment C_Part 2 | Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events | Any AE (including events with outcome = death) | 0 Participants |
Secondary
t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of t½λz for DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 24.1 (hour) | Geometric Coefficient of Variation 88.7 |
| Treatment B_Part 1 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 18.8 (hour) | Geometric Coefficient of Variation 51.7 |
| Treatment C_Part 1 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 13.0 (hour) | Geometric Coefficient of Variation 85.6 |
| Treatment D_Part 1 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 22.5 (hour) | Geometric Coefficient of Variation 77.1 |
| Treatment A_Part 2 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 24.6 (hour) | Geometric Coefficient of Variation 50.3 |
| Treatment B_Part 2 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 18.4 (hour) | Geometric Coefficient of Variation 135 |
| Treatment C_Part 2 | t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 4.56 (hour) | Geometric Coefficient of Variation 737 |
Secondary
t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of t½λz for Total (combined) EPA + DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 30.4 (hour) | Geometric Coefficient of Variation 65.5 |
| Treatment B_Part 1 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 23.8 (hour) | Geometric Coefficient of Variation 70.1 |
| Treatment C_Part 1 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 19.1 (hour) | Geometric Coefficient of Variation 76.1 |
| Treatment D_Part 1 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 23.4 (hour) | Geometric Coefficient of Variation 82.1 |
| Treatment A_Part 2 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 33.9 (hour) | Geometric Coefficient of Variation 62.5 |
| Treatment B_Part 2 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 30.3 (hour) | Geometric Coefficient of Variation 67.3 |
| Treatment C_Part 2 | t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 40.7 (hour) | Geometric Coefficient of Variation 80.7 |
Secondary
Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of λz for EPA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0274 (1/hour) | Geometric Coefficient of Variation 44.3 |
| Treatment B_Part 1 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0267 (1/hour) | Geometric Coefficient of Variation 49.3 |
| Treatment C_Part 1 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0301 (1/hour) | Geometric Coefficient of Variation 59.7 |
| Treatment D_Part 1 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0237 (1/hour) | Geometric Coefficient of Variation 39.4 |
| Treatment A_Part 2 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0205 (1/hour) | Geometric Coefficient of Variation 42.8 |
| Treatment B_Part 2 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0222 (1/hour) | Geometric Coefficient of Variation 39.2 |
| Treatment C_Part 2 | Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0209 (1/hour) | Geometric Coefficient of Variation 49.5 |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of tmax for EPA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A_Part 1 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.02 (hour) |
| Treatment B_Part 1 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.50 (hour) |
| Treatment C_Part 1 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 8.99 (hour) |
| Treatment D_Part 1 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.50 (hour) |
| Treatment A_Part 2 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
| Treatment B_Part 2 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.02 (hour) |
| Treatment C_Part 2 | Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
Secondary
Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of tmax for DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A_Part 1 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
| Treatment B_Part 1 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.5 (hour) |
| Treatment C_Part 1 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.50 (hour) |
| Treatment D_Part 1 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.49 (hour) |
| Treatment A_Part 2 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 5.98 (hour) |
| Treatment B_Part 2 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
| Treatment C_Part 2 | Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 5.49 (hour) |
Secondary
Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of tmax for Total (combined) EPA + DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A_Part 1 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.02 (hour) |
| Treatment B_Part 1 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.50 (hour) |
| Treatment C_Part 1 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.50 (hour) |
| Treatment D_Part 1 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 7.51 (hour) |
| Treatment A_Part 2 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
| Treatment B_Part 2 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
| Treatment C_Part 2 | Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 6.00 (hour) |
Secondary
λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of λz for DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0287 (1/h) | Geometric Coefficient of Variation 88.7 |
| Treatment B_Part 1 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0369 (1/h) | Geometric Coefficient of Variation 51.7 |
| Treatment C_Part 1 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0531 (1/h) | Geometric Coefficient of Variation 85.6 |
| Treatment D_Part 1 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0308 (1/h) | Geometric Coefficient of Variation 77.1 |
| Treatment A_Part 2 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0282 (1/h) | Geometric Coefficient of Variation 50.3 |
| Treatment B_Part 2 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0377 (1/h) | Geometric Coefficient of Variation 135 |
| Treatment C_Part 2 | λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.152 (1/h) | Geometric Coefficient of Variation 737 |
Secondary
λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
To assess the rate and extent of absorption of omega-3-carboxylic acids following single-dose oral administration of test formulation 1, 2 and 3 (Omega-3-carboxylic acids 2000 mg uncoated/coated capsules) and reference formulation (Epanova 1000 mg) under fasted (Part 1) and fed condition (Part 2), by assessment of λz for Total (combined) EPA + DHA on baseline subtracted plasma concentrations.
Time frame: Pre-dose: -12, -1 and 0 hours and Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 7.5, 9, 12, 24, 36, 48 and 72 hours
Population: Subjects were analyzed based on PK analysis set. It consisted of all subjects in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A_Part 1 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0228 (1/h) | Geometric Coefficient of Variation 65.5 |
| Treatment B_Part 1 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0291 (1/h) | Geometric Coefficient of Variation 70.1 |
| Treatment C_Part 1 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0363 (1/h) | Geometric Coefficient of Variation 76.1 |
| Treatment D_Part 1 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0297 (1/h) | Geometric Coefficient of Variation 82.1 |
| Treatment A_Part 2 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0204 (1/h) | Geometric Coefficient of Variation 62.5 |
| Treatment B_Part 2 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0229 (1/h) | Geometric Coefficient of Variation 67.3 |
| Treatment C_Part 2 | λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation. | 0.0170 (1/h) | Geometric Coefficient of Variation 80.7 |