Bioequivalence Study of Montelukast, 5 mg Chewable Tablets (Pharmtechnology LLC, Belarus), and Singulair®, 5 mg Chewable Tablets (Merck Sharp & Dohme B.V., the Netherlands), in Healthy Volunteers Under Fasting Conditions

NCT03898193 | Completed Phase 1

• 1 other identifier: FRM-07-MONT v.2.1 01/29/2019
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, single-center, single-dose, crossover, in two periods and in two sequences comparative study, where each participant is randomly assigned to the reference or the test formulation in each period of the study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent.

Conditions

Healthy Adults

Keywords

Bioequivalence; Montelukast; Singulair

Outcome Measures

Primary Outcomes (2)

• Cmax of montelukast for the test and the reference products

  Maximum concentration in plasma among observed concentrations at pre-specified time points

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

• AUC0-t of montelukast for the test and the reference products

  Area under the plasma concentration versus time curve from time 0 to the last measured concentration

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

Secondary Outcomes (6)

• AUC0-∞ of montelukast for the test and the reference products

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

• Tmax of montelukast for the test and the reference products

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

• T1/2 of montelukast for the test and the reference products

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

• Kel of montelukast for the test and the reference products

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

• AUCresid of montelukast for the test and the reference products

  Time points: 0.00 (withing 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75, 3.00, 3.25, 3.5, 4.00, 4.5, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00 hours after dosing

Study Arms (2)

Sequence Test-Reference (TR)

OTHER

17 participants (total number of enrolled volunteers - 34) assigned to sequence TR will receive a single 5 mg dose of the test product Montelukast (1 x 5 mg tablet) marked as T in period 1 and a single 5 mg dose of the reference product Singulair (1 x 5 mg tablet) marked as R in period 2. These treatments will be administered orally with 200 ml of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Montelukast; Drug: Singulair

Sequence Reference-Test (RT)

OTHER

17 participants (total number of enrolled volunteers - 34) assigned to sequence RT will receive a single 5 mg dose of the reference product Singulair (1 x 5 mg tablet) marked as R in period 1 and a single 5 mg dose of the test product Montelukast (1 x 5 mg tablet) marked as T in period 2. These treatments will be administered orally with 200 ml of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Montelukast; Drug: Singulair

Interventions

Montelukast DRUG

Montelukast, 5 mg Chewable Tablets, manufactured by Pharmtechnology LLC, Republic of Belarus

Also known as: The test product

Sequence Reference-Test (RT); Sequence Test-Reference (TR)

Singulair DRUG

Singulair, 5 mg Chewable Tablets, marketed by Merck Sharp \& Dohme B.V., the Netherlands

Also known as: The reference product

Sequence Reference-Test (RT); Sequence Test-Reference (TR)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy caucasian men or women aged between 18 to 45 years
• Subjects having no clinically significant medical history and no clinically significant abnormalities in general physical examination, laboratory assessments and imaging studies
• Body mass index 18.5-30 kg/m² with body mass \>45 kg and ≤100 kg
• Non-breastfeeding women
• Non-pregnant women (negative pregnancy test)
• If subject is a female and is of childbearing potential, she should practice an acceptable non-hormonal method of birth control for the duration of the study (the entire time from the moment of signing the informed consent form and within 14 days after the completion of the study), such as a combination of male condom and diaphragm with spermicide, the use of which has begun at least 30 days before the start of participation in the study
• If subject is a male and has a female partner of childbearing potential, he should be practicing an acceptable method of birth control for the duration of the study (the entire time from the moment of signing the informed consent form and within 14 days after the completion of the study), such as a double barrier method of birth control or sexual continence during the whole study and within 14 days after completion of the study
• Subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations

You may not qualify if:

• Subjects with a known history of allergic disorders
• Hypersensitivity to montelukast or to any of the excipients of the test and the reference product
• Subjects with a known history of drug intolerance
• Dehydration due to diarrhea, vomiting, or another cause in the last 24 hours before the beginning of the first period of the study
• Subjects with history of psychiatric disorders
• History of convulsions, epilepsy and any other neurological disorders
• Adherence to any low sodium diet for 2 weeks before starting research, or adherence to a special diet (for example, vegetarian, vegan, with restriction of the use of salt) or lifestyle (work at night, extreme physical exertion)
• Use of gestagen-containing injectable hormonal contraceptives, implants, intrauterine hormonal therapeutic systems within 6 months prior to start of the study
• Female subjects of childbearing potential having unprotected intercourse with an unsterilized male partner within 30 days prior to start of the study
• Consumption of xanthine-containing foods and drinks (tea, coffee, coca-cola, chocolate) within 72 hours prior to start of the first period of the study
• Consumption of citrus fruits (including grapefruit and grapefruit juice) and cranberries (including cranberry juice and other cranberry drinks) within 14 days prior to start of the study
• Acute and chronic cardiovascular, respiratory, gastrointestinal diseases, neuroendocrine disorders, renal and/or hepatic impairment, blood system disorders
• Other conditions which, according to the researcher's judgment, may affect absorption, distribution, biotransformation and elimination of any formulation or increase risks of deterioration of volunteer's condition
• Surgical interventions on the gastrointestinal tract with the exception of appendectomy
• Acute infectious diseases less than 4 weeks prior to the start of the study

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• ClinPharmInvest, LLC: collaborator

Study Sites (1)

State Autonomous Healthcare Facility of the Yaroslavl Region "Clinical Hospital No. 2"

Yaroslavl, Yaroslavl Oblast, 150010, Russia

Location

MeSH Terms

Interventions

montelukast

Study Officials

• Alexander Khokhlov

  ClinPharmInvest, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The participants and the investigator will not be blinded towards the identity of the study products. However, bioanalytical laboratory will be blinded towards identity of the study products administered.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 1, 2019
• Study Start: March 23, 2019
• Primary Completion: April 8, 2019
• Study Completion: April 8, 2019
• Last Updated: June 6, 2019

Record last verified: 2019-03

Locations

RU (1)