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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 137
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Part 1: Treatment A-B-C-D
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.
干预措施: D1400147 (Drug)
Part 1: Treatment A-B-C-D
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.
干预措施: D14000136 (Drug)
Part 1: Treatment A-B-C-D
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.
干预措施: D14000137 (Drug)
Part 1: Treatment A-B-C-D
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.
干预措施: Epanova® (Drug)
Part 2: Treatment A-B/C-D
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.
干预措施: D1400147 (Drug)
Part 2: Treatment A-B/C-D
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.
干预措施: D14000136 (Drug)
Part 2: Treatment A-B/C-D
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.
干预措施: D14000137 (Drug)
Part 2: Treatment A-B/C-D
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.
干预措施: Epanova® (Drug)
结局指标
主要结局
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.
时间窗: 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 Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
时间窗: 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.
AUC (0-72) Assessed for DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
时间窗: 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.
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.
时间窗: 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.
时间窗: 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.
Cmax Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
时间窗: 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.
AUC Assessed for Total (Combined) EPA + DHA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
时间窗: 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.
Maximum Observed Plasma Concentration (Cmax) Assessed for EPA After Administration of Test Formulation 1, 2 and 3 and Reference Formulation.
时间窗: 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.
时间窗: 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.
次要结局
- 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 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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.)
- 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)
- 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)
- 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)
- 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)