Respiratory Disorders
Conditions
Keywords
chewable tablet, montelukast sodium, healthy adult subjects, relative bioavailability, GW483100
Brief summary
This study is designed to estimate the bioavailability of montelukast from the 5 milligrams (mg) montelukast sodium (GW483100) test formulations relative to 5 mg montelukast sodium reference chewable tablets (innovator product). It is an open-label, randomized, single dose, three-way cross over, six sequence study in 18 healthy human subjects. Each subject will participate in all three treatment periods. Subjects will be randomized to one of six sequences and administered one of the three treatments A, B or C in each treatment period, where Treatment A is 5mg chewable tablet of reference 5 mg montelukast sodium reference chewable tablets (innovator product), Treatment B is test formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and Treatment C is test formulation 2: 5mg montelukast sodium (GW483100) chewable tablet. The treatment periods will be separated by a washout period of 7 to 14 days. Total duration in the study for each subject will be approximately 8 weeks from screening to the follow-up visit.
Interventions
It is available as pink, round, bi-convex-shaped chewable tablet of reference 5 mg montelukast sodium (innovator product). that has to be placed on the tongue and chewed immediately.
DRUGTest 1 Montelukast
It will be provided as pink, round, bi-convex-shaped chewable tablet of test formulation 1: 5mg montelukast sodium (GW483100) that has to be placed on the tongue and chewed immediately.
DRUGTest 2 Montelukast
It will be provided as pink, round, bi-convex-shaped chewable tablet of test formulation 2: 5mg montelukast sodium (GW483100) that has to be placed on the tongue and chewed immediately.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy 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 kilograms per square meter (kg/m\^2) (inclusive). * Male subject * Female subject: is 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: 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)\]. 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. * Reproductive potential and agrees to follow one of the options listed below in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until \[at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer\] after the last dose of study medication and completion of the follow-up visit. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis. * Contraceptive subdermal implant that meets the standard operating procedure (SOP)effectiveness criteria including a \<1% rate of failure per year, as stated in the product label * Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label * Oral Contraceptive, either combined or progestogen alone * Injectable progestogen * Contraceptive vaginal ring * Percutaneous contraceptive patches * Male partner sterilisation with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject * Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository) only for the following 3 situations when there is a very low risk for developmental toxicity: Vaccines; Monoclonal antibodies when there is no target biology concern; Compounds that have a complete reproductive toxicology package and have not shown any signal for developmental toxicity. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * 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 \[at least five half-lives of study medication or for a cycle of spermatogenesis following five terminal half-lives\] after the last dose of study medication. * Vasectomy with documentation of azoospermia. * Male condom plus partner use of one of the contraceptive options below: * Contraceptive subdermal implant that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label * Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label * Oral Contraceptive, either combined or progestogen alone. Injectable progestogen * Contraceptive vaginal ring * Percutaneous contraceptive patches These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of plasma pharmacokinetic [PK] parameters of montelukast sodium | Pre-dose, 0.50, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post dose during each treatment period | Plasma PK parameters includes Maximum observed concentration (Cmax), Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite\[inf\] time (AUC\[0-inf\]) and Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC\[0-t\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of plasma PK parameters of montelukast sodium | Pre-dose, 0.50, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 16.00 and 24.00 hours post dose during each treatment period | Plasma PK parameters includes time of occurrence of Cmax (tmax), Percentage of AUC(0-inf) obtained by extrapolation (%AUCex) and Terminal phase half-life (t½) |
| Number of subjects with Adverse Events (AEs) | Up to 8 weeks | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. |
| Blood pressure assessments | Up to 5 weeks | In each treatment period, systolic and diastolic blood pressure will be measured in supine position after 5 minutes(min) rest at pre-dose (-2.00 to 0.00 hours.), 1, 2, 4, 8, 12 and 24 hours within ±30min. |
| Pulse rate assessments | Up to5 weeks | In each treatment period, pulse rate will be measured in supine position after 5 min rest at pre-dose (-2.00 to 0.00 hours.), 1, 2, 4, 8, 12 and 24 hours within ±30min. |
| Clinical laboratory assessments | Day -1 and end of treatment period 3 (approximately Week 5) | Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis |
Countries
India
Outcome results
None listed