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Pharmacokinetics, Safety and Tolerability of Repeat Dosing Lamotrigine in Healthy Chinese Subjects

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Bipolar Disorder

Intervention: Lamotrigine (Drug)

Phase: Phase 1

Status: Not yet recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Overall contact:
US GSK Clinical Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com


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.

Clinical Details

Official title: An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat Dosing Lamotrigine in Healthy Chinese Subjects

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome: 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.


Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.


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. Exclusion Criteria:

- Unstable disease conditions; any laboratory measurements assessed by the investigator

as clinically relevant (including ECG, hematology, biochemistry and urine analysis, etc.); Current or chronic history of cardiovascular, respiratory, gastrointestinal, endocrine, hematological, psychical or nervous system diseases, use of drug that can change the absorption, metabolism or elimination of study drug, or result in danger or other drugs or diseases that interfere with the interpretation of study data.

- Current or chronic history of liver disease, or known hepatic or biliary

abnormalities (with the exception of Gilbert's syndrome and asymptomatic gallstones).

- Definite or suspected personal history or family history of adverse reactions or

hypersensitivity to the study drug or to drugs with a similar chemical structure. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

- Subject with concurrent or previous neuropsychological disorders, as assessed by

Columbia Suicidality Severity Rating Scale-Baseline Assessment or by the investigator, have suicidal tendency, or have committed suicidal behavior/attempt.

- Having any disease within 4 weeks prior to enrollment.

- Unable to refrain from the use of prescription or non-prescription drugs, including

vitamins, herbal and dietary supplements (including St John's Wort) within 14 days prior to the dosing day, which in the opinion of the Principal Investigator, may interfere with the study procedures or compromise safety.

- Drug or alcohol abuse or dependency within one year prior to enrollment. History of

regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1. 5 ounces (45 mL) of 80 proof distilled spirits.

- The subject has participated in a clinical trial and has received an investigational

product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

- Women of child bearing potential used oral or implanted contraceptives within the 30

days prior to study initiation, or received injections of chronically acting contraceptives in the 1 year prior to study initiation.

- Obvious evidence of active hematological diseases, or significant blood loss in the

last 3 months.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- History of asthma, anaphylaxis or anaphylactic reactions, severe allergic responses.

- Subjects who have received lamotrigine previously (subjects who received placebo in a

previous study will be allowed)

- Blood donation in the 3 months prior to enrollment. Where participation in the study

would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

- Exposure to more than four new chemical entities within 12 months prior to the first

dosing day.

- A positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody

(HCAb) result at screening

- A positive pre-study drug/alcohol screen.

- A positive test for human immunodeficiency virus (HIV) at screening.

- A positive test for syphilis at screening.

- Subject is mentally or legally incapacitated.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Other conditions which, in the Investigator's judgment, render patients unsuitable

for the clinical study.

Locations and Contacts

US GSK Clinical Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

Additional Information

Starting date: August 2015
Last updated: July 30, 2015

Page last updated: August 23, 2015

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