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NCT Number: NCT02359045

Study in Healthy Subjects to Compare the Concentrations of the Omega-3 Fatty Acids EPA and DHA in Blood When Delivered as Three New Capsules in Relation to the Epanova® Capsule Under Fasting and Fed Conditions

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.

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Key information

Conditions

Relative Bioavailability AUC Cmax Pharmacokinetics

Age range

18 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Research Site

Baltimore, Maryland, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

D1400147

Drug

Treatment A

D14000136

Drug

Treatment B

D14000137

Drug

Treatment C

Epanova®

Drug

Treatment D

Primary outcomes

  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.

    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

    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.

  2. AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  3. AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  4. 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.

    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

    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.

  5. AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  6. AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  7. Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  8. Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  9. Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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 outcomes

  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.

    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

    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.

  2. AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  3. AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  4. Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  5. C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  6. C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  7. 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.

    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

    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.

  8. t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  9. t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  10. Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  11. Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  12. Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  13. Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  14. λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  15. λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.

    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

    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.

  16. Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events

    Time frame: 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

  17. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event

    Time frame: 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

  18. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure

    Time frame: 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

  19. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse

    Time frame: 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

  20. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs)

    Time frame: 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

  21. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters

    Time frame: 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

  22. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results

    Time frame: 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

  23. Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis

    Time frame: 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

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Randomized, Open-label, Single-center, Cross-over Study in Healthy Subjects to Assess the Relative Bioavailability of EPA and DHA Delivered by Three New Capsule Formulation Prototypes in Relation to the Current Epanova® Capsule Under Fasting (Part 1) and Fed (Part 2) Conditions

Important dates

Study start
2015
Primary completion
2015
Study completion
2015
First posted
Feb 9, 2015
Registry last updated
May 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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