Clinical trial 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relative Bioavailability
AUC
Cmax
Pharmacokinetics
Keywords: Omega-3-carboxylic acids,
Phase I,
Healthy Subjects,
Pharmacokinetics,
Relative bioavailability
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-02-09
Enrollment: 137
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated written informed consent prior to any study specific procedures.
* Healthy male and female (non-childbearing potential) subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
* Females must have a negative pregnancy test at screening and on admission to the clinical unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:

  * Post-menopausal, defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments, and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
  * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy or tubal ligation.
* Have a body mass index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria:

* History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study.
* History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* Current smokers or those who have smoked or used nicotine products within the previous 3 months.
* Consumption of poppy seeds within 7 days of first administration of IMP.
* Consumption of fish within 7 days prior to admission to the clinical unit.
* Used fish oil, other omega-3 fatty acids (EPA and/or DHA) containing supplements within 1 month of admission to the clinical unit.
* Have a known sensitivity or allergy to soybeans, fish and/or shellfish.

Primary outcomes:
measure: 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.
timeFrame: 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
measure: AUC Assessed for Docosahexaenoic Acids (DHA) After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: 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.
timeFrame: 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
measure: AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: AUC (0-72) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Cmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
Secondary outcomes:
measure: 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.
timeFrame: 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
measure: AUC (Last) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: AUC (Last) Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Baseline Concentration (C0) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: C0 Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: C0 Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: 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.
timeFrame: 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
measure: t½λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: t½λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Time to Reach Maximum Observed Concentration (Tmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Tmax Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Tmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Terminal Elimination Rate Constant (λz ) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: λz Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: λz Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
timeFrame: 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
measure: Safety of Omega-3-carboxylic Acids by Assessing Summary of Adverse Events
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects Who Had at Least One Adverse Event
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing.
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Blood Pressure
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Pulse
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant 12-lead Electrocardiograms (ECGs)
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Hematology Parameters
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Clinical Chemistry Laboratory Results
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
measure: Safety of Omega-3-carboxylic Acids by Assessing Number of Subjects With Clinically Significant Urinalysis
timeFrame: From screening (within 28 days of first dosing) up to 14 days after last dosing
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Research Site
state: Maryland
Study officials:
affiliation: PAREXEL Early Phase Clinical Unit Baltimore, 3001 S. Hanover St., Baltimore, MD 21225, United States of America
name: Ronald Goldwater, Dr.
role: PRINCIPAL_INVESTIGATOR
References: