Control Of BioEquivalence With Xenical (COBEX): A Phase I, Randomised, Active-control Study to Evaluate EMP22 Pharmacodynamics and EMP16 Pharmacokinetics Versus Xenical® in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The percent of faecal fat
研究概览
简要总结
This Phase I, active-controlled, randomised trial will be conducted in 2 parts. Part I aims to confirm the PD equivalence of EMP22 and Xenical® based on percent fecal fat excretion at steady state. EMP22 (also referred to as MR orlistat) has the same MR properties as EMP16 but lacks the acarbose component. Part II will explore the PK properties of EMP16 alone and vs. Xenical®. Part I will be conducted in a single-blind, cross-over fashion while Part II will have an open-label, fixed-sequence design. Healthy volunteers will be recruited to the trial.
详细描述
Approximately 35 participants are planned to be screened to achieve 20 randomised participants and at least 16 evaluable participants in Part I.
All participants who complete Part I will continue in Part II.
Each participant is expected to participate in the trial for approximately 9 to 13 weeks (depending on the length of each wash-out period), including a 28-day screening period.
Part I: Participants will self-administer EMP22 for 9 days and Xenical® for 9 days (TID dosing) at home. EMP22 and Xenical® should be taken halfway through each of the 3 main meals during the day (breakfast, lunch, dinner) with approximately 50 to 200 mL water.
EMP22 and Xenical® have different strengths of orlistat, 60 mg and 120 mg, respectively. In order to maintain the blind for the participants, the IMP will be administered as follows:
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
- Single (Participant)
盲法说明
Part I: EMP22 and Xenical® have different strengths of orlistat, 60 mg and 120 mg, respectively. In order to maintain the blind, the IMP will be administered as follows:
- EMP22 60 mg orlistat, 2 capsules TID.
- Xenical® 120 mg orlistat 1 capsule + placebo 1 capsule TID. EMP22, Xenical® and placebo will be identical in appearance.
Part II will be open-label, i.e., the Investigator, trial staff and trial participants will know which treatment, EMP16 or Xenical®, that is given at each visit.
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to give written informed consent for participation in the trial.
- •Healthy male or female aged 20 to 55 years inclusive.
- •Participants with a BMI between 20 and 27 kg/m² or participants with a BMI >27 kg/m2 and normal body fat composition (10 to 25% for men and 20 to 30% for women measured using a bioimpedance scale) at screening.
- •Weight stable (<5% self-reported change during the previous 3 months preceding screening).
- •Participants with a self-perceived normality in defecation habits, normally with a stool frequency of at least once daily.
- •Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, electrocardiogram (ECG) and laboratory values at the time of the screening visit, as judged by the Investigator.
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant's ability to participate in the trial including but not limited to:
- •GI problems/diseases, e.g. inflammatory bowel diseases and irritable bowel syndrome (IBS).
- •Cholestasis.
- •Previous GI surgery that might influence GI function significantly, such as previous bariatric surgery, and previous gallbladder surgery as judged by the investigator.
- •Vitamin B12 deficiency or other signs of achlorhydria.
- •Chronical malabsorption syndrome.
- •History of severe allergic, cardiac or hepatic disease.
- •Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- •Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
- •Any planned major surgery within the duration of the trial.
- •Participants who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
- •Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
- •Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the screening visit, as judged by the Investigator.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class as orlistat or acarbose.
- •Regular use of any prescribed or non-prescribed medications (including, but not limited to, antacids, analgesics, herbal remedies, vitamins and minerals) within 2 weeks prior to the first administration of IMP except as outlined in Section 9.6.2.
- •Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical trial that included drug treatment within 3 months of the first administration of IMP in this trial. Subjects consented and screened but not dosed in previous studies are not excluded.
- •Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times/week is allowed before the screening visit.
- •Positive screening result for drugs of abuse or alcohol at the screening visit.
- •History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- •Presence or history of drug abuse, as judged by the Investigator.
- •History of, or current use of anabolic steroids, as judged by the Investigator.
- •Excessive caffeine consumption defined by a daily intake of > 5 cups (1 cup = approximately 240 mL) of caffeine containing beverages, as judged by the Investigator.
- •Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening.
- •The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
研究组 & 干预措施
Xenical - EMP22 part 1 crossover blinded
After a 5-day diet run-in period, orlistat in its conventional form (Xenical®, 120 mg orlistat) will be taken 3 times daily (ter in die [TID]) together with the 3 main daily meals for a 9-day treatment period. After a 4-to-14-day wash-out period; EMP22 (120 mg modified release orlistat) will be taken TID together with the 3 main daily meals for a 9-day treatment period.
干预措施: Xenical® vs EMP 22 (Drug)
EMP22 - Xenical part 1 crossover blinded
After a 5-day diet run-in period, EMP22 (120 mg modified release orlistat) will be taken 3 times daily (ter in die [TID]) together with the 3 main daily meals for a 9-day treatment period. After a 4-to-14-day wash-out period; orlistat in its conventional form (Xenical®, 120 mg orlistat) will be taken TID together with the 3 main daily meals for a 9-day treatment period.
干预措施: EMP 22 vs Xenical® (Drug)
EMP16 - Xenical part 2 sequential open label
Single dose of EMP16 (120 mg orlistat/40 mg acarbose) will be taken together with breakfast during one PK study day. After a 4-to-14-day wash-out period, Xenical® (120 mg orlistat) will be taken together with breakfast during one PK study day.
干预措施: EMP 16 vs Xenical® (Drug)
结局指标
主要结局
The percent of faecal fat
时间窗: Day -2 , Day -1 , and between the morning of Day 9 and Day 10.
The percent of faecal fat excretion expressed as a ratio of the amount of fat excretion over a 24-hour period at steady-state relative to the amount of daily ingested fat.
次要结局
- Cmax - to explore the PK properties of EMP16(12 hour for each day of treatment)
- AUC0-t - to compare the bioavailability of orlistat in EMP16 and Xenical®(12 hour for each day of treatment)
- Tmax - to compare the bioavailability of orlistat in EMP16 and Xenical®(12 hour for each day of treatment)
- Tmax - to explore the PK properties of EMP16(12 hour for each day of treatment)
- AUC0-t - to explore the PK properties of EMP16(12 hour for each day of treatment)
- Cmax - to compare the bioavailability of orlistat in EMP16 and Xenical®(12 hour for each day of treatment)