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

NCT02359045 | Completed Phase 1 Results

• 1 other identifier: D5884C00003
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 1

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.

Conditions

Relative Bioavailability; AUC; Cmax; Pharmacokinetics

Keywords

Omega-3-carboxylic acids,; Phase I,; Healthy Subjects,; Pharmacokinetics,; Relative bioavailability

Outcome Measures

Primary Outcomes (9)

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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 (23)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Part 1: Treatment A-B-C-D

EXPERIMENTAL

Subjects received a single dose of D1400147 (Treatment A: Omega-3-carboxylic acids 2000 mg uncoated capsules), D14000136 (Treatment B: Omega-3-carboxylic acids 2000 mg coated capsules coat 1), D14000137 (Treatment C: Omega-3-carboxylic acids 2000 mg coated capsules coat 2) and Epanova® (Treatment D: Epanova capsules 1000 mg) under fasted condition.

Drug: D1400147; Drug: D14000136; Drug: D14000137; Drug: Epanova®

Part 2: Treatment A-B/C-D

EXPERIMENTAL

Subjects received a single dose of D1400147 (Treatment A: Omega-3-carboxylic acids 2000 mg uncoated capsules), D14000136 (Treatment B: Omega-3-carboxylic acids 2000 mg coated capsules coat 1) or D14000137 (Treatment C: Omega-3-carboxylic acids 2000 mg coated capsules coat 2) and Epanova® (Treatment D: Epanova capsules 1000 mg) under fed condition.

Drug: D1400147; Drug: D14000136; Drug: D14000137; Drug: Epanova®

Interventions

D1400147 DRUG

Treatment A

Part 1: Treatment A-B-C-D; Part 2: Treatment A-B/C-D

D14000136 DRUG

Treatment B

Part 1: Treatment A-B-C-D; Part 2: Treatment A-B/C-D

D14000137 DRUG

Treatment C

Part 1: Treatment A-B-C-D; Part 2: Treatment A-B/C-D

Epanova® DRUG

Treatment D

Part 1: Treatment A-B-C-D; Part 2: Treatment A-B/C-D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Baltimore, Maryland, United States

Location

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46317761000

Study Officials

• Ronald Goldwater, Dr.

  PAREXEL Early Phase Clinical Unit Baltimore, 3001 S. Hanover St., Baltimore, MD 21225, United States of America

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2015
• First Posted: February 9, 2015
• Study Start: February 12, 2015
• Primary Completion: July 27, 2015
• Study Completion: July 27, 2015
• Last Updated: May 1, 2017
• Results First Posted: May 1, 2017

Record last verified: 2017-03

Locations

US (1)