A Bioequivalence Study of Two Formulations Lamotrigine 100 mg Tablets and Lamictal 100 mg Tablets in Healthy Adult Volunteers Under Fasting Conditions

NCT03898011 | Completed Phase 1

• 1 other identifier: LMTR-270418 v.1.1 01/29/2019
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-labeled, randomized, crossover, two-period, single-center, comparative study, where each participant will be randomly assigned to the reference (Lamictal, 100 mg tablets) or the test (Lamotrigine, 100 mg tablets) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent

Conditions

Healthy Adults

Keywords

Bioequivalence; Lamotrigine

Outcome Measures

Primary Outcomes (2)

• Cmax of lamotrigine for the test and the reference products

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

  Time points: 0,00 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

• AUC0-t of lamotrigine 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 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

Secondary Outcomes (6)

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

  Time points: 0,00 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

• Tmax of lamotrigine for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

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

  Time points: 0,00 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

• Kel of lamotrigine for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

• AUCresid% of lamotrigine for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.5, 1.00, 1.5, 1.75, 2.00, 2.25, 2.5, 2.75.3.00, 3.5, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00, 120.00 hours after dosing

Study Arms (2)

Sequence Test-Reference (TR)

OTHER

14 participants (total number of enrolled volunteers - 28) assigned to sequence TR will receive a single 100 mg dose of the test product Lamotrigine (1 x 100 mg tablet) marked as T in period 1 and a single 100 mg dose of the reference product Lamictal (1 x 100 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: Lamotrigine; Drug: Lamictal

Sequence Reference-Test (RT)

OTHER

14 participants (total number of enrolled volunteers - 28) assigned to sequence RT will receive a single 100 mg dose of the reference product Lamictal (1 x 100 mg tablet) marked as R in period 1 and a single 100 mg dose of the test product Lamotrigine (1 x 100 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: Lamotrigine; Drug: Lamictal

Interventions

Lamotrigine DRUG

Lamotrigine, 100 mg Tablets, manufactured by Pharmtechnology LLC, Belarus

Also known as: the test product

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

Lamictal DRUG

Lamictal®, 100 mg Tablets, marketed by GlaxoSmithKline Trading CJSC, Russia

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 be practicing 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
• 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 its' completion
• 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 lamotrigine or to any of the excipients of the test and the reference product
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption
• 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 child bearingpotential having unprotected intercourse with an unsterilized sexual partner within 30 days prior to start of the study
• Consumption of xanthine-containing foods and drinks (tea, coffee, coca-cola, chocolate), alcohol, products containing poppy 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

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

Lamotrigine

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: May 4, 2019
• Study Completion: May 4, 2019
• Last Updated: June 6, 2019

Record last verified: 2019-03

Locations

RU (1)