Clinical trial NCT04938856: Bioequivalence of Lamnet (Lamotrigine)100mg Tablet With the Reference Product Lamictal 100mg (Lamotrigine) Tablet Under Fasting Conditions
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioequivalence
Keywords: Bioequivalence Study
Healthy Volunteers
Pakistani Population
Safety
Lead sponsor: University of Karachi
Sponsor class: OTHER
Collaborators: name: The Searle Company LTD., Pakistan.
First posted: 2021-06-24
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: open label, randomized, single-dose, 2 way cross-over study
Primary purpose: OTHER

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax
timeFrame: 0-120 hours post dose
measure: AUC
timeFrame: 0 to 120 hours post dose
measure: Tmax
timeFrame: 0-120 hours post dose
Secondary outcomes:
measure: Blood Pressure monitoring
timeFrame: 0-120 hours post dose
measure: Body temperature measurement
timeFrame: 0-120 hours post dose
measure: Heart rate measurement
timeFrame: 0-120 hours post dose
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Center for Bioequivalence Studies and clinical research
state: Sindh
Study officials:
affiliation: Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi
name: Prof. Dr. Muhammad R Shah, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi
name: Dr. Naghma Hashmi (Co-PI), PhD
role: PRINCIPAL_INVESTIGATOR
References: