Relative Bioavailability Study of Two Montelukast Sodium (GW483100) 5 Milligrams (mg) Chewable Tablets and One Reference Montelukast Sodium 5 mg Chewable Tablet in Healthy Adult Subjects

NCT02322671 | Completed Phase 1

• 1 other identifier: 200107
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Disorders

Keywords

chewable tablet; montelukast sodium; healthy adult subjects; relative bioavailability; GW483100

Outcome Measures

Primary Outcomes (1)

• Composite of plasma pharmacokinetic [PK] parameters of montelukast sodium

  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\[0-t\]).

  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

Secondary Outcomes (5)

• 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

• Number of subjects with Adverse Events (AEs)

  Up to 8 weeks

• Blood pressure assessments

  Up to 5 weeks

• Pulse rate assessments

  Up to5 weeks

• Clinical laboratory assessments

  Day -1 and end of treatment period 3 (approximately Week 5)

Study Arms (6)

Sequence ABC

EXPERIMENTAL

Subjects will be administered a single oral dose of treatment A, B and C in the sequence ABC, where A is Reference Treatment: 5 mg montelukast sodium reference chewable tablets (innovator product); B is Test Formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and 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

Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

Sequence ACB

EXPERIMENTAL

Subjects will be administered a single oral dose of treatment A, B and C in the sequence ACB, where A is Reference Treatment: 5 mg montelukast sodium reference chewable tablets (innovator product); B is Test Formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and 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

Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

Sequence BAC

EXPERIMENTAL

Subjects will be administered a single oral dose of treatment A, B and C in the sequence BAC, where A is Reference Treatment: 5 mg montelukast sodium reference chewable tablets (innovator product); B is Test Formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and 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

Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

Sequence BCA

EXPERIMENTAL

Subjects will be administered a single oral dose of treatment A, B and C in the sequence BCA, where A is Reference Treatment: 5 mg montelukast sodium reference chewable tablets (innovator product); B is Test Formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and 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

Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

Sequence CAB

EXPERIMENTAL

Subjects will be administered a single oral dose of treatment A, B and C in the sequence CAB, where A is Reference Treatment: 5 mg montelukast sodium reference chewable tablets (innovator product); B is Test Formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and 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

Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

Sequence CBA

EXPERIMENTAL

Subjects will be administered a single oral dose of treatment A, B and C in the sequence CBA, where A is Reference Treatment: 5 mg montelukast sodium reference chewable tablets (innovator product); B is Test Formulation 1: 5mg montelukast sodium (GW483100) chewable tablet and 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

Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

Interventions

Reference Montelukast DRUG

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.

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

Test 1 Montelukast DRUG

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.

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

Test 2 Montelukast DRUG

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.

Sequence ABC; Sequence ACB; Sequence BAC; Sequence BCA; Sequence CAB; Sequence CBA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Hyderabad, 500 013, India

Location

Related Links

• Results for study 200107 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Respiration Disorders

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 23, 2014
• Study Start: February 23, 2015
• Primary Completion: April 20, 2015
• Study Completion: April 20, 2015
• Last Updated: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

IN (1)