Bioequivalence of Lamnet (Lamotrigine)100mg Tablet With the Reference Product Lamictal 100mg (Lamotrigine) Tablet Under Fasting Conditions (BE)

A Single Center, Open Label, Randomized, Single-dose, 2 Way Cross-over Study to Explore the Bioequivalence of Lamnet (Lamotrigine)100mg Tablet With the Reference Product Lamictal 100mg (Lamotrigine) Tablet Under Fasting Conditions in Healthy Male Pakistani Subjects

Single oral administrations of study drug (Lamnet and Lamictal) in two periods separated by a washout period of 14 days. The washout period will be calculated from day of dosing (Day 2) to at least 14 days post dose in each period.

Study Overview

• Status: Completed
• Conditions: Bioequivalence
• Intervention / Treatment: Drug: Lamotrigine tablet

Detailed Description

The study drugs will be administered with 240 mL ambient Temperature water after at least 10 hours fasting in each periods.

Pharmacokinetic parameters include Lamotrigine plasma concentrations at the given sampling times. In each period 18 blood samples for plasma Lamotrigine concentrations will be taken on Day 2, Day 3, Day 4, Day 5, Day 6 and Day 7 (at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5 ,4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose.) The primary parameters to be analyzed are the maximum plasma concentration (Cmax), area under the plasma concentration-time curve from zero to the time of the last measurable time point t (AUClast or also termed as AUC0-t) and area under the plasma concentration-time curve from zero to infinity (AUCtotal or, also termed as AUC0-inf) and (AUC0-t)/ (AUC0-inf).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 75270
      • Center for Bioequivalence Studies and clinical research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers aged 18 to 55 years inclusive.
• Subjects with a body mass index from 18.5 to 30 kg/m2 (both inclusive).
• Subjects who are healthy as determined by routine physical examination, including vital sign monitoring (i.e., blood pressure, heart rate and temperature), ECG monitoring and laboratory analysis (ie, hematology, blood biochemistry, and urinalysis)and viral serology as determined by the investigator.
• Tested negative for COVID-19 (through COVID-19 antibody testing).
• Subjects should have negative urine test for drugs of abuse (morphine, cannabinoids will be tested) and alcohol breath analysis at screening and prior to each check-in.
• Subjects will be able to, understand and sign the Informed Consent Form for Medical Screening during their screening visit and Participation Informed Consent Form on study check-In day.
• Subject agreed not to use special diet including fasting, high protein diet within the next 4 weeks.
• Subject agreed not to consume Alcohol, cigarette, gutka, caffeine or related xanthines containing foods or beverages (e.g. tea, coffee, cola drinks, chocolates, cocoa) etc and poppy seeds (khash khash) within 48 hours prior to drug administration.
• Subject agreed not to intake prescription drugs within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medicine.
• Subject agreed not to intake non-prescription drugs (OTC) within 14 days prior to first dose of study medicine.
• Subject agreed to discontinue vitamins ,dietary and herbal supplements within 14 days prior to the first dose of study medication.
• Subject agreed not to consume grapefruit and/or its products within 14 days prior to the start of study.

Exclusion Criteria:

• Inability to take oral medication.
• Tested positive for COVID-19 (through COVID-19 antibody testing).
• History of smoking (≤3cigarette/day), alcoholism, and positive test for drug of abuse, heavy pan or gutka user as judged by teeth / mouth inspection.
• Subjects with clinically relevant evidence of cardiovascular, gastrointestinal/hepatic, renal, psychiatric, respiratory, urogenital, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, drug hypersensitivity, allergy, endocrine, major surgery or other relevant diseases as revealed by medical history, physical examination, and laboratory assessments which may interfere with the absorption, distribution, metabolism or elimination of drugs or constitute a risk factor when taking study medication.
• Subject is allergic to Lamotrigine and any of the product of lamotrigine .
• Subject has received any investigational drug within four weeks.
• Participated in any clinical trials within 30 days.
• Subjects with salt imbalance in the blood (especially low levels of potassium or magnesium in the blood).
• Donation or loss of more than 450 mL of blood within 3 months prior to the screening.
• History of any significant illness in the last four weeks which might confound in the result of the study or post additional risk in administrating lamotrigine to the subject.
• Concomitant treatment with Valproate, Carbamazepine, phenytoin, phenobarbital, primidone,, rifampin, Estrogen-containing oral contraceptives, Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir.
• Subjects who test positive for syphilis (VDRL) or who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBs Ag) or are carriers of antibodies to hepatitis C virus (anti-HCV) or to the human immunodeficiency virus (HIV-1 or HIV-2).
• Individuals having undergone any major surgery within 3 months prior to the start of the study, unless deemed eligible, otherwise by the Principal Investigator or whomever he/she may designate.
• Subjects with any condition, which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or elimination of drugs.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of asthma, anaphylaxis or anaphylactic reactions, severe allergic responses.
• Current or past history of nervous-psychiatric disorder, in the opinion of investigator that the subject is at risk of suicide or with history of suicide behavior/attempt.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Oral administration of Lamnet (100mg) Tablet after at least 10 hours fast together with 240 mL of ambient temperature water at their scheduled dosing time-point.	Drug: Lamotrigine tablet; Lamotrigine 100 mg immediate release Tablet; Other Names: Test Group (Lamnet 100 mg), Reference Group (Lamictal 100 mg)
Active Comparator: Reference Group; Oral administration of Lamictal (100mg) Tablet after at least 10 hours fast together with 240 mL of ambient temperature water at their scheduled dosing time-point.	Drug: Lamotrigine tablet; Lamotrigine 100 mg immediate release Tablet; Other Names: Test Group (Lamnet 100 mg), Reference Group (Lamictal 100 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximum plasma concentration of Lamotrigine	0-120 hours post dose
AUC	Area Under the Plasma Drug Concentration versus Time curve	0 to 120 hours post dose
Tmax	Time required for maximum plasma drug concentration	0-120 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure monitoring	monitoring if blood pressure after dose administration	0-120 hours post dose
Body temperature measurement	Measurement of body temprature after dose administration	0-120 hours post dose
Heart rate measurement	Measurement of heart rate after dose administration	0-120 hours post dose

Collaborators and Investigators

• Sponsor: University of Karachi
• Collaborators: The Searle Company LTD., Pakistan.
• Investigators: Principal Investigator: Prof. Dr. Muhammad R Shah, PhD, Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi; Principal Investigator: Dr. Naghma Hashmi (Co-PI), PhD, Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Actual): September 24, 2020
• Study Completion (Actual): October 25, 2020

Study Registration Dates

• First Submitted: June 12, 2021
• First Submitted That Met QC Criteria: June 19, 2021
• First Posted (Actual): June 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Safety; Healthy Volunteers; Bioequivalence Study; Pakistani Population
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine
• Other Study ID Numbers: CB-026-LAM-2018/Protocol/2.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The study related information can be obtained via proper request to the PI unless the confidentiality of the participants are not compromised.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No