Epilepsy
Conditions
Brief summary
This is an open-label, randomised, parallel-group study to demonstrate the bioequivalence of lamotrigine 100mg in two different formulations, dispersible/chewable tablet and compressed tablet, in healthy subjects under fasting conditions. Subjects will be randomized in equal numbers to be dosed with either lamotrigine dispersible/chewable (Test) 100mg tablet or lamotrigine compressed (Reference) 100mg tablet. Pharmacokinetic blood sampling will be collected over 216 hours post dose. Safety (tolerability) will be observed up to 216 hours post dose. Safety assessments will include regular monitoring of vital signs, ECG's, adverse events (AEs) and safety laboratory tests. A follow-up visit is scheduled within 10-17 days post-dose.
Detailed description
This is a single dose, open-label, randomized, parallel-group study to demonstrate the bioequivalence of lamotrigine dispersible/chewable tablet and lamotrigine compressed tablet at 100mg in healthy Chinese male subjects in fasting conditions. Approximate 138 Chinese healthy male subjects will be enrolled in accordance with the inclusion and exclusion criteria. Subjects will be 18 to 45 years, healthy and body mass index between 19-24 kg/m2 and sign the informed consent. Having given written informed consent, subjects will be required to undergo a pre-study medical screen within 14 days of the dosing day. Subjects will be admitted on Day 0 (the day before dosing) and will stay in the unit until after the 24-hour post-dose assessments on Day 2. The time that a subject is discharged from the unit may be agreed with unit staff but subjects must return for all designated pharmacokinetic (PK) samples and on scheduled time for observation. The subjects will be randomized in equal numbers to be dosed under fasting conditions with either lamotrigine dispersible/chewable tablet or lamotrigine compressed tablet. The pharmacokinetic assessment will last 10 days. The blood samples will be collected immediately before dosing (pre-dose) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 216 hours post dose for determination of lamotrigine concentration in blood. Safety and tolerability evaluation will be observed up to 216 hours post-dose, including adverse events, vital signs, physical examination, electrocardiogram. All subjects will be required to undergo a follow-up assessment within 10-17 days after receiving the study medication.
Interventions
DRUGLamotrigine Dispersible/Chewable tablet
Single dose of lamotrigine dispersible/chewable 100mg tablet at Day1
DRUGLamotrigine Compressed tablet
Single dose of lamotrigine compressed 100mg tablet at Day1
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Chinese male non-smoker, based on medical history and physical examination, aged between 18 and 45 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, 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 GlaxoSmithKline (GSK) 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 kg and BMI within the range 19 - 24 kg/m2 (inclusive). * Capable of returning to study site for follow-up according to the requirement of protocol and willing to comply with the policy, procedure and restriction of the study. * Capable of reading and understanding the information listed in the consent form. Signing the informed consent prior to any study related procedure. * Aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin \<= 1.5✕Upper limit of normal (ULN) (total bilirubin \>1.5 x ULN alone is acceptable if direct bilirubin \<35% of total bilirubin). * Normal blood pressure (systolic blood pressure 90-140 mmHg, inclusive, diastolic blood pressure \< 90mmHg) and pulse rate (60-100, inclusive). * No clinically significant abnormality on 12-lead ECG. * Corrected QT interval (QTc) \< 450 ms; or corrected QT interval \< 480 ms for subjects with bundle-branch block, based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period. * Male subjects with female partners of child-bearing potential must use one of the contraceptive methods after the first dose of study treatment and until the follow-up visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve [AUC(0-inf)] of lamotrigine if coefficients of variation (CV)% of λz<=30%, or AUC(0-inf)• λz if CV% of λz >30%, or AUC(0-t) if AUC(0-inf) cannot be accurately determined, including bioequivalence evaluation | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216 hours post-dose |
| The observed maximum serum drug concentration (Cmax), including bioequivalence evaluation | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216 hours post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Time to reach Cmax (Tmax) as data permit. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216 hours post-dose |
| Elimination half-time (t1/2) as data permit | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216 hours post-dose |
| Elimination rate constant, linear regression according to linear serum drug concentration-time curve (λz) as data permit. | pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216 hours post-dose |
| Safety and tolerability as measured by adverse events, vital sign, ECG and clinical laboratory measurements. | at screeing, Day0-10, follow-up visit |
Countries
China
Outcome results
None listed