Bioequivalence and Food Effect Bioavailability Study of Lumacaftor Film-Coated Tablets
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This single-dose, randomized, double-blind, 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 36 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 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. |
Drug: Lumacaftor 200 mg Film-Coated Tablet Formulation
Film-coated tablet administered orally.
|
Active Comparator: 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®) |
Drug: Lumacaftor 200 mg/Ivacaftor 125 mg Film-Coated Tablet
Film-coated tablet administered orally.
|
Experimental: 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. |
Drug: Lumacaftor 200 mg Film-Coated Tablet Formulation
Film-coated tablet administered orally.
|
Outcome Measures
Primary Outcome Measures
- The maximal observed plasma concentration (Cmax) [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) [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 infinity (AUCinf) [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) [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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy, non-smoking male and non-pregnant female volunteers, 18 years to 55 years of age, inclusive.
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Body mass index (BMI) that is between 18.5 and 30.0 kg/m^2, inclusive.
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Results of clinical laboratory tests are within the normal range or with a deviation that is not considered clinically significant by the principal investigator.
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Ability to fast for at least 10 hours and consume a high-fat, high-calorie meal, as well as standard meals.
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Agree not to have a tattoo or body piercing until the end of the study.
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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.
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Female subjects of childbearing potential and males who are able to father children must meet the criteria defined in the protocol.
Exclusion Criteria:
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Known history or presence of any clinically significant diseases or conditions unless determined as not clinically significant by the Investigator.
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Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the Investigator.
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Presence of any significant physical or organ abnormality as determined by the Investigator.
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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.
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Known history or presence of:
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Alcohol abuse or dependence within one year prior to first drug administration;
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Drug abuse or dependence;
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Hypersensitivity or idiosyncratic reaction to lumacaftor and ivacaftor, its excipients, and/or related substances;
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Food allergies
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Presence of any dietary restrictions unless deemed by the Investigator as "Not Clinically Significant".
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Severe allergic reactions (e.g. anaphylactic reactions, angioedema).
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Intolerance to and/or difficulty with blood sampling through venipuncture.
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Abnormal diet patterns (for any reason) during the four weeks preceding the study, including fasting, high protein diets, etc.
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Individuals who have donated, in the days prior to first study drug administration:
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50-499 mL of blood in the previous 30 days;
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500 mL or more in the previous 56 days.
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Donation of plasma by plasmapheresis within 7 days prior to first study drug administration.
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Individuals who have participated in another clinical trial or who received an investigational drug within 30 days prior to first study drug administration.
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Females having used implanted, injected, intravaginal, or intrauterine hormonal contraceptive within 6 months prior to first study drug administration.
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Females taking oral or transdermal hormonal contraceptives within 30 days prior to first study drug administration.
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Use of any enzyme-modifying drugs or products in the previous 30 days before first study drug administration.
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Use of any prescription medication within 14 days prior to first study drug administration (except medically acceptable contraceptive products).
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Use of any over-the-counter medications within 14 days prior to first study drug administration (except for medically acceptable contraceptive products).
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Consumption of food or beverages containing grapefruit and/or pomelo within 10 days prior to first study drug administration.
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Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hours before dosing.
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Individuals having undergone any major surgery within 6 months prior to the start of the study, unless deemed otherwise by Investigator.
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Difficulty with swallowing whole film-coated tablet.
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Women who are pregnant or lactating.
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Have had a tattoo or body piercing within 30 days prior to first study drug administration.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Qanatpharma Canada LTD
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QP586-01