Bioequivalence and Food Effect Bioavailability Study of Lumacaftor Film-Coated Tablets

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.