- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02322671
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
An Open-label, Randomised, Single Dose, Three-Way Crossover, Six Sequence, Pilot Study to Determine the Relative Bioavailability of Montelukast Sodium 5mg From Two Candidate Chewable Tablet Formulations of GW483100 Relative to One 5mg Chewable Tablet of Reference Montelukast Sodium in Healthy Adult Subjects Under Fasting Conditions
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Hyderabad, India, 500 013
- GSK Investigational Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Exclusion Criteria:
- Alanine aminotransferase (ALT) and bilirubin >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Corrected QT (QTC) > 450 milliseconds (msec)
- NOTES: The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machineread or manually over-read.
- The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
- For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
- No concomitant medications should be taken by the subject while participating in the study. Refer to Study Protocol for further detail.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 6 months prior to screening.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- Subjects with phenylketonuria
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, subjects with presence of hepatitis B core
- A positive pre-study drug/alcohol screen.
- A positive test for Human Immunodeficiency Virus (HIV) antibody.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Gastrointestinal disease or with gastrointestinal surgical history which can affect the absorption of the investigational drug.
- Any symptoms with a systolic Blood pressure (BP) <95 millimeters of mercury (mmHg)
- Pregnant females as determined by positive serum hCG test at screening or prior to dosing
- Lactating females
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sequence ABC
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
|
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.
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.
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.
|
Experimental: Sequence ACB
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
|
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.
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.
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.
|
Experimental: Sequence BAC
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
|
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.
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.
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.
|
Experimental: Sequence BCA
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
|
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.
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.
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.
|
Experimental: Sequence CAB
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
|
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.
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.
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.
|
Experimental: Sequence CBA
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
|
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite of plasma pharmacokinetic [PK] parameters of montelukast sodium
Time Frame: 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]).
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite of plasma PK parameters of montelukast sodium
Time Frame: 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)
|
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)
Time Frame: 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.
|
Up to 8 weeks
|
Blood pressure assessments
Time Frame: 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.
|
Up to 5 weeks
|
Pulse rate assessments
Time Frame: 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.
|
Up to5 weeks
|
Clinical laboratory assessments
Time Frame: Day -1 and end of treatment period 3 (approximately Week 5)
|
Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis
|
Day -1 and end of treatment period 3 (approximately Week 5)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiration Disorders
- Respiratory Tract Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Asthmatic Agents
- Respiratory System Agents
- Leukotriene Antagonists
- Hormone Antagonists
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 Enzyme Inducers
- Montelukast
Other Study ID Numbers
- 200107
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Study Data/Documents
-
Clinical Study Report
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Informed Consent Form
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Study Protocol
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Statistical Analysis Plan
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Annotated Case Report Form
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Dataset Specification
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Individual Participant Data Set
Information identifier: 200107Information comments: For additional information about this study please refer to the GSK Clinical Study Register
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Respiratory Disorders
-
LmecaRecruitingOther Specified Respiratory DisordersKorea, Republic of
-
Centro Universitário Augusto MottaUniversidade Federal do Rio de JaneiroCompletedRespiratory Failure | Respiratory DisordersBrazil
-
Children's Hospital Medical Center, CincinnatiRecruitingRespiratory DisordersUnited States
-
Children's Hospital Medical Center, CincinnatiRecruitingRespiratory DisordersUnited States
-
GlaxoSmithKlineCompleted
-
GlaxoSmithKlineCompletedRespiratory Disorders
-
GlaxoSmithKlineCompletedRespiratory Disorders
-
Mustafa Kemal UniversityThe Scientific and Technological Research Council of TurkeyCompletedMood Disorders | Physical Inactivity | Respiratory Function ImpairedTurkey
-
Hollister IncorporatedTerminatedRespiratory Failure | Ventilatory Depression | Respiratory DepressionUnited States
-
RespireRxDuke UniversityUnknownOpiate Induced Respiratory DepressionUnited States
Clinical Trials on Reference Montelukast
-
GlaxoSmithKlineCompletedRespiratory Disorders | Asthma and RhinitisIndia
-
The Affiliated Hospital of Qingdao UniversityEnrolling by invitationPharmacokinetics | SafetyChina
-
Academisch Medisch Centrum - Universiteit van Amsterdam...DexCom, Inc.CompletedDiabetes Mellitus, Type 1Netherlands
-
JHP Pharmaceuticals LLCSyneos HealthUnknown
-
Indiana UniversityCompleted
-
Nutricia ResearchRecruitingGlycemic ResponseCanada
-
UCSF Benioff Children's Hospital OaklandAlmond Board of CaliforniaCompletedDyslipidemia | Obesity, AbdominalUnited States
-
Sonova AGCompleted
-
Chinese University of Hong KongUniversity of Sydney; Chongqing Medical University; Hong Kong University of Science... and other collaboratorsNot yet recruitingAtherosclerosis, CoronaryHong Kong
-
Asir John SamuelMaharishi Markandeshwar International School, MullanaCompletedCoordination Disorder, DevelopmentalIndia