Clinical trial NCT01357902: Lamotrigine Bioequivalence Study to Compare Dispersible Tables With Compressed Tablets in China
Official title: An Open Label, Randomized, Cross-Over Study to Investigate the Single Dose Bioequivalence of Lamotrigine Dispersible/Chewable Tablets (5mg) Compared to Lamotrigine Compressed/Standard Tablets (25mg) in Chinese Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-05-23
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: It is an open-label, randomised, single dose, two-sequence cross-over study. Twenty-four eligible, healthy, Chinese male subjects will be enrolled after providing written informed consent. Subjects will be randomised into two treatment groups 1 day prior to the first dosing day and will be assigned to regimen sequences (AB or BA) in a balanced fashion in accordance with the randomisation schedule. Regimen A is five lamotrigine 5 mg chewable/dispersible tablets and Regimen B is one lamotrigine 25 mg standard/compressed tablet.

Subjects will receive their allocated regimen on the morning of Day 1 and will undergo study assessments for 7 days (until Day 8). Subjects will receive their alternate randomised treatment after a washout period of 14-21 days from Day 1. Subjects will undergo a further assessment period of 7 days and will attend a follow-up visit during 8-12 days after the second treatment. The total observation period in this study will be 23\~34 days.

Subjects will arrive at the research unit on the evening before each lamotrigine dosing occasion and will remain in the unit until the 24-h post-dose evaluations have been completed (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 h). After this, subjects will return home but must return to the unit for further assessments to be made at 36, 48, 72, 96, 120, 144 and 168 h after dosing Study Endpoints/Assessments A total of 19 serial blood samples (5 mL each) will be collected for the measurement of plasma lamotrigine concentrations at each study assessment. Safety and tolerability assessments (monitoring of adverse events and serious adverse events, routine laboratory determinations, vital sign measurements and 12-lead electrocardiogram) will be conducted throughout the study.


Eligibility criteria: Inclusion Criteria:

1. According to medical history and clinical examination, healthy and non-smoking male subjects
2. Between 18 and 45 years of age, inclusive.
3. Body weight \>=50 kg and BMI 19-24 kg/m2, inclusive.
4. Male subjects with female partners of child-bearing potential must agree to use one of the following contraceptive methods after the first dose of study treatment and until the follow up visit:

   * Condom plus partner use of a highly effective contraceptive such as occlusive cap (diaphragm or cervical/vault cap) plus spermicidal agent (foam/gel/film/cream/suppository), oral contraceptive, injectable progesterone, implant of etonogestrel or levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, or intrauterine device. OR,
   * Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
5. Good compliance with research policies, procedures and restrictions.
6. Can read and understand the informed consent. Informed consent should be obtained prior to admission to the study.
7. No abnormality revealed by the laboratory tests, or any slight abnormality judged by the investigator to have no clinical significance.
8. Aspartate aminotransferase (AST), ALT, alkaline phosphatase and bilirubin=\<1.5 x upper limit of normal (ULN).
9. Normal systolic (90-140 mmHg) and diastolic (\<90 mmHg) blood pressure at screening, and normal pulse (supine).
10. A normal 12-lead ECG at pre-study screening.
11. Single or average QT duration corrected for heart rate by Bazett's formula (QTcB) or by Fridericia's formula (QTcF) \<450 msec; or QTc \<480 msec in subjects with bundle branch block.
12. Liver serum virological and human immunodeficiency virus tests are negative

Exclusion Criteria:

1. Any clinically relevant abnormality identified on the screening history and physical or laboratory examination significant cardiovascular, neurological, psychiatric, haematological or renal abnormalities.
2. 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.
3. Participation in a clinical trial within the 30 days before the start of the study.
4. The subject has received prescribed medication or over-the-counter (OTC) medicine including herbal medicines within 14 days before the first dosing day. The use of lubricant with spermicide or contraceptive barrier devices and other contraceptives is permitted.
5. History of any clinically significant illness within 4 weeks before the study.
6. History of any clinically significant physical or organic abnormalities.
7. Abnormalities of 12-lead ECG which the investigators think increase the risk of participation in the study.
8. History of liver dysfunction such as jaundice, or hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCAb) positive regardless of ALT level or ALT greater than or equal to 2-times ULN. Subjects with Gilbert's syndrome will be excluded from the study.
9. Positive pre-study screening result for hepatitis B antigen, hepatitis C antibodies or HIV-1 or HIV-2 antibody.
10. Subject whose HLA-B\*1502 is positive will be exclude from the study.
11. Abuse of alcohol, defined as an average weekly intake of greater than 21 units or an average daily intake of greater than three units. One unit is equivalent to half a pint (\~ 240 mL) of beer, one (25 mL) measure of spirits or one glass (125 mL) of wine.
12. Positive pre-study drug/alcohol screen.
13. History of obvious active haematological disorder or significant blood loss in the past 3 months.
14. Subject donated blood within a 56-day period or donated plasma within 1 week prior the study.
15. Subject is mentally or legally incapacitated.
16. Any other reason at the Investigators' discretion

Primary outcomes:
measure: AUC(0-infinity)
timeFrame: taken pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h after each dosing
measure: AUC(0-t)
timeFrame: taken pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h after each dosing
measure: Cmax
timeFrame: taken pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h after each dosing
Secondary outcomes:
measure: tmax
timeFrame: taken pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h after each dosing
measure: terminal phase half-life
timeFrame: taken pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h after each dosing
measure: 12-lead electrocardiogram (ECG), vital signs, nursing observations, spontaneous adverse experience reporting and laboratory safety data
timeFrame: at Screening, Day 0, Day1-8, Day15-22 and follow up 7-14 days after second dosing
Other outcomes:
Locations:
city: Shatin, New Territories
country: Hong Kong
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: