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AzTrials

Respiratory DisordersPhase 1NCT02322671

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

A Phase 1 study testing Reference Montelukast, Test 1 Montelukast and Test 2 Montelukast in people with Respiratory Disorders, run by GlaxoSmithKline at 1 site in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Respiratory Disorders
What is being tested?
Reference Montelukast, Test 1 Montelukast and Test 2 Montelukast
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteIndia
Study dates
23 Feb 2015to 20 Apr 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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).
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  • 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

Trial locations and contacts

1 site in 1 country.

India1 site

  • GSK Investigational Site

    Hyderabad, 500 013

Other trials in India

About this study

Official title: 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

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.

Being tested
Reference Montelukast, Test 1 Montelukast, Test 2 Montelukast
Keywords
chewable tablet, montelukast sodium, healthy adult subjects, relative bioavailability, GW483100
Medical subject headings
Respiration Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Reference MontelukastDrug

    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.

  • Test 1 MontelukastDrug

    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.

  • Test 2 MontelukastDrug

    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.

Study groups in NCT02322671
Study groupRoleWhat they receive
Sequence ABCExperimentalSubjects 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
Receives: Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast
Sequence ACBExperimentalSubjects 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
Receives: Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast
Sequence BACExperimentalSubjects 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
Receives: Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast
Sequence BCAExperimentalSubjects 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
Receives: Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast
Sequence CABExperimentalSubjects 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
Receives: Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast
Sequence CBAExperimentalSubjects 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
Receives: Drug: Reference Montelukast; Drug: Test 1 Montelukast; Drug: Test 2 Montelukast

What is being measured

The primary outcome is the main question the study is designed to answer.

  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]).

    Measured: 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)

  1. Composite of plasma PK parameters of montelukast sodium

    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)

    Measured: 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

  2. Number of subjects with Adverse Events (AEs)

    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.

    Measured: Up to 8 weeks

  3. Blood pressure assessments

    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.

    Measured: Up to 5 weeks

  4. Pulse rate assessments

    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.

    Measured: Up to5 weeks

  5. Clinical laboratory assessments

    Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2014 (estimated)
  2. Study start23 Feb 2015
  3. Primary completion20 Apr 2015
  4. Study completion20 Apr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02322671
Sponsor's protocol ID
200107
Status last verified
May 2017
First submitted
18 Dec 2014
Last updated
15 May 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Reference Montelukast, Test 1 Montelukast and Test 2 Montelukast in people with Respiratory Disorders, run by GlaxoSmithKline at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02322671.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.

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