A Single-Dose, Bioequivalence and Food Effect Bioavailability Study in Healthy Volunteers Comparing the Commercial Lumacaftor 200 mg / Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) to the Lumacaftor 200 mg Film-Coated Tablet Formulation, and the Lumacaftor 200 mg Film-Coated Tablet Formulation in the Fasted to Fed State.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Area under the concentration-time curve from time zero to infinity (AUCinf)
研究概览
简要总结
The objective of this study is to assess bioequivalence of lumacaftor from Lumacaftor 200 mg Film-Coated Tablet Formulation (Qanatpharma) versus the reference commercial product, Lumacaftor 200 mg /Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) in the fed state, and food-effect bioavailability of Lumacaftor 200 mg Film-Coated Tablet Formulation (Qanatpharma) in the fasted and fed state in healthy, non-smoking, male and non-pregnant female volunteers, 18 to 55 years of age, inclusive.
详细描述
This single-dose, randomized, open-label, three-way crossover, three-period, three-sequence, three-treatment, single-centre, bioequivalence and food-effect study will compare lumacaftor from Lumacaftor 200 mg Film-Coated Tablet test formulation and the commercial product, Lumacaftor 200 mg/Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) under fed conditions, and food-effect bioavailability study of Lumacaftor 200 mg Film-Coated Tablet test formulation from fasted to fed state.
The products will be studied using a crossover design with 39 healthy, non-smoking male and non-pregnant female volunteers being administered an oral dose of 1 x (2 x lumacaftor 200 mg) under fasted and fed conditions and 1 x (2 x lumacaftor 200 mg/ ivacaftor 125 mg) under fed conditions. There will be at least a 14-day washout period between the study periods to avoid carry-over effects of the preceding treatments.
This study is being conducted to support development of a lumacaftor mono-substance treatment for improving cerebral blood flow.
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
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, non-smoking male and non-pregnant female volunteers, 18 years to 55 years of age, inclusive.
- •Body mass index (BMI) that is between 18.5 and 30.0 kg/m^2, inclusive.
- •Results of clinical laboratory tests are within the normal range or with a deviation that is not considered clinically significant by the principal investigator.
- •Ability to fast for at least 10 hours and consume a high-fat, high-calorie meal, as well as standard meals.
- •Agree not to have a tattoo or body piercing until the end of the study.
- •Agree not to receive the COVID-19 vaccination from 7 days prior to the first study drug dose until 7 days after the last study drug administration in the study.
- •Female subjects of childbearing potential and males who are able to father children must meet the criteria defined in the protocol.
排除标准
- •Known history or presence of any clinically significant diseases or conditions unless determined as not clinically significant by the Investigator.
- •Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the Investigator.
- •Presence of any significant physical or organ abnormality as determined by the Investigator.
- •A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines), alcohol breath test and cotinine. Positive pregnancy test for female subjects.
- •Known history or presence of:
- •Alcohol abuse or dependence within one year prior to first drug administration;
- •Drug abuse or dependence;
- •Hypersensitivity or idiosyncratic reaction to lumacaftor and ivacaftor, its excipients, and/or related substances;
- •Food allergies
- •Presence of any dietary restrictions unless deemed by the Investigator as "Not Clinically Significant".
- •Severe allergic reactions (e.g. anaphylactic reactions, angioedema).
- •Intolerance to and/or difficulty with blood sampling through venipuncture.
- •Abnormal diet patterns (for any reason) during the four weeks preceding the study, including fasting, high protein diets, etc.
- •Individuals who have donated, in the days prior to first study drug administration:
- •50-499 mL of blood in the previous 30 days;
- •500 mL or more in the previous 56 days.
- •Donation of plasma by plasmapheresis within 7 days prior to first study drug administration.
- •Individuals who have participated in another clinical trial or who received an investigational drug within 30 days prior to first study drug administration.
- •Females having used implanted, injected, intravaginal, or intrauterine hormonal contraceptive within 6 months prior to first study drug administration.
- •Females taking oral or transdermal hormonal contraceptives within 30 days prior to first study drug administration.
- •Use of any enzyme-modifying drugs or products in the previous 30 days before first study drug administration.
- •Use of any prescription medication within 14 days prior to first study drug administration (except medically acceptable contraceptive products).
- •Use of any over-the-counter medications within 14 days prior to first study drug administration (except for medically acceptable contraceptive products).
- •Consumption of food or beverages containing grapefruit and/or pomelo within 10 days prior to first study drug administration.
- •Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hours before dosing.
- •Individuals having undergone any major surgery within 6 months prior to the start of the study, unless deemed otherwise by Investigator.
- •Difficulty with swallowing whole film-coated tablet.
- •Women who are pregnant or lactating.
- •Have had a tattoo or body piercing within 30 days prior to first study drug administration.
研究组 & 干预措施
Treatment A (Test-Fed)
Following a 10-hour overnight fasting period, subjects will eat a high-fat, high-calorie breakfast, and 30 minutes later subjects will receive a single dose of 2 Lumacaftor 200 mg Film-Coated Tablets.
干预措施: Lumacaftor 200 mg Film-Coated Tablet Formulation (Drug)
Treatment B (Reference-Fed)
Following a 10-hour overnight fasting period, subjects will eat a high-fat, high-calorie breakfast, and 30 minutes later subjects will receive a single dose of 2 Lumacaftor 200 mg/Ivacaftor 125 mg Combination Film-Coated Tablets (Orkambi®)
干预措施: Lumacaftor 200 mg/Ivacaftor 125 mg Film-Coated Tablet (Drug)
Treatment C (Test-Fasted)
Following a 10-hour overnight fasting period, subjects will receive a single dose of 2 Lumacaftor 200 mg Film-Coated Tablets.
干预措施: Lumacaftor 200 mg Film-Coated Tablet Formulation (Drug)
结局指标
主要结局
Area under the concentration-time curve from time zero to infinity (AUCinf)
时间窗: Up to 72 hours post dose in each treatment period
Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
Time when the maximal plasma concentration is observed (Tmax)
时间窗: Up to 72 hours post dose in each treatment period
Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
Area under the concentration-time curve from time zero to 72 hours (AUC72)
时间窗: Up to 72 hours post dose in each treatment period
Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
The maximal observed plasma concentration (Cmax)
时间窗: Up to 72 hours post dose in each treatment period
Serial blood samples for determination of study drug will be collected pre-dose at 0, and post-dose at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72 hours
次要结局
未报告次要终点