Lamotrigine Bioequivalence Study to Compare Dispersible Tables With Compressed Tablets in China

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01357902
First received: May 12, 2011
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Epilepsy
Drug: lamotrigine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • AUC(0-infinity) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • AUC(0-t) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Cmax [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • tmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • terminal phase half-life [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 12-lead electrocardiogram (ECG), vital signs, nursing observations, spontaneous adverse experience reporting and laboratory safety data [ Time Frame: at Screening, Day 0, Day1-8, Day15-22 and follow up 7-14 days after second dosing ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: April 2011
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lamictal Drug: lamotrigine

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01357902

Locations
Hong Kong
GSK Investigational Site
Shatin, New Territories, Hong Kong
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01357902     History of Changes
Other Study ID Numbers: 115261
Study First Received: May 12, 2011
Last Updated: June 9, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Hong Kong: Department of Health

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Anticonvulsants
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 28, 2014