Bipolar Disorder
Conditions
Keywords
tolerability, repeat dosing, safety, healthy Chinese subjects, Pharmacokinetics, lamotrigine
Brief summary
This Pharmacokinetic (PK) study is going to provide supplemental PK data for supporting bipolar Phase III study for New Drug Application (NDA) filing according to regulatory requirement. The primary objective of this study is to evaluate the PK of lamotrigine following repeat dosing of lamotrigine dispersible tablet in healthy Chinese subjects. This study consisted of Screening Phase (Days-14 to 0), Open-label Phase (Days 1 to 51) and follow-up Phase (10-17 days after last dosing). After signing the informed consent and confirm the eligibility, subjects will start dosing with lamotrigine 25 mg dispersible tablet once daily at Day 1 and remain at this dose level for two weeks (Days 1-14), then will be titrated to 50 mg once daily at Day 15 and last for weeks 3-4 (Days 15-28), and then titrated to 100 mg once daily at Day 29 during weeks 5-6 (Days 29-42). The total duration of the study will be approximately 10 weeks including screening and follow-up phase.
Interventions
DRUGLamotrigine
Lamotrigine dispersible tablets supplied in 3 different strengths 25 mg, 50 mg and 100 mg. These dispersible tablets appear as white or off-white tablets.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Capable of returning to study site for follow-up according to requirement of protocol and willing to comply with the policy, procedure and restriction of the study. Capable of actively communicating with the investigator and completing the study-related documents; Capable of understanding the contents of the informed consent and signing a written informed consent prior to any study related procedures. * Non-smoking Chinese healthy males or females as assessed by medical history and physical examination. Age 18-45 years (inclusive), at the time of signing the informed consent. * Body weight \>=50 kilogram (kg) and Body Mass Index (BMI) 19-24 kilogram per meter square (kg/m\^2) (inclusive) * 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. * Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and total bilirubin \<= 1.5×upper limit of normal (ULN) (acceptable if only total bilirubin\>1.5×ULN but direct bilirubin \<35% of total bilirubin) * No clinically significant abnormality on 12-lead electrocardiogram (ECG). Corrected QT interval (QTc) \<450 millisecond (ms); or QTc \<480 ms in subjects with Bundle Branch Block, based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period. * Normal blood pressure (systolic blood pressure 90-140 millimeter of mercury \[mmHg\], inclusive, diastolic blood pressure \<90 mmHg) and heart rate (60-100 beats per minute \[bpm\], inclusive). * A female subject with negative pregnancy test and not in lactating, and commit to take acceptable contraception measures during the study and in the 1 month post end of study. * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy (for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records); or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 Milli-International Units per Mililiter (MIU/mL) and estradiol \< 40 pico gram per milliliter (pg/mL) (\<147 pico mole per liter \[pmol/L\]) is confirmatory\]. Child-bearing potential with negative pregnancy test as determined by urine pregnancy test at screening or prior to dosing AND. Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit. OR has only same-sex partners, when this is her preferred and usual lifestyle. * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods after the first dose of study treatment and until the follow-up visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK profile will be assessed by AUC (0-tau[24 hours]); Cmax; and accumulation ratios (Rcmax and Ro) following single and repeat dosing of lamotrigine dispersible tablet | Days 1, 14, 15, 28, 29, 42 and 44 to 51 | Blood samples for PK analysis will be collected on Days 1, 14, 28, and 42 before dosing (pre-dose) and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after administration. Other blood samples will be taken at 1 and 3 hours post dose on Day 15, and at 2 and 4 h post dose on Day 29. Additional blood samples will be taken at 48, 72, 96, 120, 168 and 216 hours after the administration of last dose on Day 42. Area under the concentration-time curve for a dose interval (AUC \[0-tau{24 hours}\]); observed maximum concentration (Cmax); and accumulation ratios (Rcmax and Ro) will be determined from the serum concentration-time data. Accumulation ratio will be calculated as follows: Ro = AUC(0-24) of Day14/AUC(0-24) of Day 1; and Rcmax = Cmax of Day14 / Cmax of Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK profile will be assessed by Tmax; T1/2; Cssmax; Css,min; Css,avg; CL/F; and Vz/F and DF following single and repeat dosing of lamotrigine dispersible tablet. | Days 1, 14, 15, 28, 29, 42 and 44 to 51 | Blood samples for PK analysis will be collected on Days 1, 14, 28, and 42 before dosing (pre-dose) and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after administration. Other blood samples will be taken at 1 and 3 hours post dose on Day 15, and at 2 and 4 h post dose on Day 29. Additional blood samples will be taken at 48, 72, 96, 120, 168 and 216 hours after the administration of last dose on Day 42. Time to reach maximum concentration (Tmax), Terminal half-life (T1/2), Maximum concentration at steady state (Css,max), minimum concentration at steady state (Css,min), average steady state concentration (Css,avg), Apparent clearance (CL/F), Appearent volume of distribution (Vz/F), and Degree of fluctuation (DF) will be determined from the serum concentration-time data, as data permit. |
Countries
China
Outcome results
None listed