Asthma and Rhinitis, Respiratory Disorders
Conditions
Brief summary
This study is conducted to determine whether the test product (GW483100 10 mg containing montelukast sodium equivalent to 10 mg of montelukast) is bioequivalent to the reference montelukast sodium 10 mg tablets (innovator product) in healthy adult volunteers under fasting conditions. This is an open-label, balanced, randomized, single dose, two-way crossover study, enrolling 32 healthy human subjects to ensure at least 28 subjects complete the study. Each subject enrolled will participate in two treatment periods separated by a washout period of at least 7 days and no more than 14 days between dosing occasions. Total duration in the study for each subject will be approximately 7 weeks from screening to the subject's last visit.
Interventions
DRUGTest Montelukast
Test Montelukast (GW483100) is available as round, biconvex, pink 10 mg film-coated tablet (containing montelukast sodium equivalent to 10 mg of montelukast) and is administered as a single dose with 240 mL of water.
Reference Montelukast (innovator product) is available as pale beige, rounded square shaped,10 mg film-coated tablet (containing montelukast sodium equivalent to 10 mg of montelukast) and is administered as a single dose with 240 mL of water. Singular is the innovator product used for this study, which is a trade name owned by Merck Sharp and Dohme Corporation.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy, non smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 19 - 24.9 kg/square meter (m\^2) (inclusive) * Healthy male or female subjects: MALES: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 24 hours after the last dose of study medication. a.) Vasectomy with documentation of azoospermia. b.) Male condom plus partner use of one of the contraceptive following options: contraceptive subdermal implant; intrauterine device or intrauterine system; oral contraceptive, either combined or progestogen alone; injectable progestogen; contraceptive vaginal ring; and percutaneous contraceptive patches. FEMALES: Eligible to participate, if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies: a.) Non-reproductive potential defined as: Pre-menopausal females with one of the following: documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, Documented Bilateral Oophorectomy Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. b.) Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 24 hours after the last dose of study medication and completion of the follow-up visit. * Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration versus time from time zero to infinity (AUC(0 ∞)) for montelukast in relevant treatments | Samples will be collected at Pre-dose, 0.50, 1.00, 1.50, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dose in each treatment period | Blood samples will be withdrawn on Day 1 and Day 2, and concentrations of montelukast will be determined in plasma samples. Plasma montelukast concentration-time will be analyzed by non-compartmental method and the PK parameters will be derived. |
| AUC from time zero to last time point with measurable concentration (AUC(0-t)) for montelukast in relevant treatments | Samples will be collected at Pre-dose, 0.50, 1.00, 1.50, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dose in each treatment period | Blood samples will be withdrawn on Day 1 and Day 2, and concentrations of montelukast will be determined in plasma samples. Plasma montelukast concentration-time will be analyzed by non-compartmental method and the PK parameters will be derived. |
| Maximum observed concentration (Cmax) for montelukast in relevant treatments | Samples will be collected at Pre-dose, 0.50, 1.00, 1.50, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dose in each treatment period | Blood samples will be withdrawn on Day 1 and Day 2, and concentrations of montelukast will be determined in plasma samples. Plasma montelukast concentration-time will be analyzed by non-compartmental method and the PK parameters will be derived. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure (BP) as a measure of safety and tolerability | 3 days in each treatment period (assessed up to 3 weeks) | Systolic and diastolic BP will be measured in supine position after 5 minutes rest. |
| Pulse rate measurements as a measure of safety and tolerability | 3 days in each treatment period (assessed up to 3 weeks) | Pulse rate measurements will be measured in supine position after 5 minutes rest. |
| Number of participants with adverse events (AEs) | Up to 7 weeks | AEs will be collected from the start of study treatment until the subject's last visit. |
| Time of occurrence of Cmax (tmax) for montelukast in relevant treatments | Samples will be collected at Pre-dose, 0.50, 1.00, 1.50, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dose in each treatment period. | Blood samples will be withdrawn on Day 1 and Day 2, and concentrations of montelukast will be determined in plasma samples. Plasma montelukast concentration-time will be analyzed by non-compartmental method and the PK parameters will be derived. |
| Composite of clinical chemistry parameters as a measure of safety | 1 day in Treatment Period 1 and 2 days in Treatment Period 2 (assessed up to 3 weeks) | — |
| Composite of urinalysis parameters as a measure of safety | 1 day in Treatment Period 1 and 2 days in Treatment Period 2 (assessed up to 3 weeks) | — |
| Composite of hematology parameters as a measure of safety | 1 day in Treatment Period 1 and 2 days in Treatment Period 2 (assessed up to 3 weeks) | — |
| Percentage of AUC(0-∞) obtained by extrapolation (%AUCex) for montelukast in relevant treatments | Samples will be collected at Pre-dose, 0.50, 1.00, 1.50, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dose in each treatment period. | Blood samples will be withdrawn on Day 1 and Day 2, and concentrations of montelukast will be determined in plasma samples. Plasma montelukast concentration-time will be analyzed by non-compartmental method and the PK parameters will be derived. |
| Terminal phase half-life (t½) for montelukast in relevant treatments | Samples will be collected at Pre-dose, 0.50, 1.00, 1.50, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post-dose in each treatment period. | Blood samples will be withdrawn on Day 1 and Day 2, and concentrations of montelukast will be determined in plasma samples. Plasma montelukast concentration-time will be analyzed by non-compartmental method and the PK parameters will be derived. |
Countries
India
Outcome results
None listed