A Clinical Evaluation Of BW430C (Lamotrigine) In Bipolar I Disorder- Long-term Extension Of Study SCA104779 (NCT00550407) -

Official Title: “Study SCA106052, a Clinical Evaluation of BW430C (Lamotrigine) in Bipolar I Disorder- Long-term Extension Study (Extension of Study SCA104779 (NCT00550407)) -”

This study is planned to assess the long-term safety of lamotrigine in Japanese patients with bipolar I disorder who will continue into the 52-week extension upon completion of a double-blind comparative study (Study No.: SCA104779 (NCT00550407)), i.e. the patients who receive the addition of any additional treatment to intervene in a mood episode in the double-blind phase or the patients completing the double-blind phase.

Intervention(s) in this Clinical Trial

• Drug: BW430C (lamotrigine)
  • lamotrigine 50mg/day-400mg/day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Lamotrigine

Primary Measures

• Number of Participants With Any Serious Adverse Event (SAE) and Any Non Serious Adverse Event
  • Time Frame: From baseline (Week 0) until 2 weeks after the end of treatment (Week 54)
    Safety Issue?: No
• Number of Participants With the Indicated Clinical Laboratory Test Values for Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LDH)
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/Early Withdrawal (EW)
    Safety Issue?: Yes
• Number of Participants With Clinical Laboratory Test Values Out of the Normal Range and in the Normal Range for Total Bilirubin and Creatinine at Weeks 0, 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: Yes
• Number of Participants With Clinical Laboratory Test Values Out of the Normal Range and in the Normal Range for Calcium, Cholesterol, Chloride, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at Weeks 0, 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: Yes
• Number of Participants With Clinical Laboratory Test Values Out of the Normal Range and in the Normal Range for Platelet Count and White Blood Cell Count at Weeks 0, 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: Yes
• Number of Participants With Clinical Laboratory Test Values Out of the Normal Range and in the Normal Range for Total Protein, Hemoglobin, and Hematocrit at Weeks 0, 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: Yes
• Number of Participants With Clinical Laboratory Test Values Out of the Normal Range and in the Normal Range for Red Blood Cell Count at Weeks 0, 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: Yes
• Number of Participants in the Indicated Category for Urine Glucose, Urine Protein, and Urine Urobilinogen at Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: Yes
• Mean Systolic Blood Pressure and Diastolic Blood Pressure of Participants at Baseline (Week 0) and Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
    Safety Issue?: Yes
• Mean Heart Rate of Participants at Week 0 (Baseline) and Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
    Safety Issue?: Yes
• Mean Weight of Participants at Baseline (Week 0) and Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
    Safety Issue?: Yes
• Mean Body Mass Index (BMI) of All Participants at Week 0 (Baseline) and Weeks 6, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 0, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
    Safety Issue?: Yes
• Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 0, 6, 28, and 52/EW
  • Time Frame: Weeks 0, 6, 28, and 52/EW
    Safety Issue?: Yes

Secondary Measures

• Clinical Global Impressions of Severity (CGI-S) Total Score at Weeks 0, 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
  • Time Frame: Weeks 0, 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
    Safety Issue?: No
• Change From Baseline in the Clinical Global Impressions of Severity (CGI-S) Total Score at Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW
    Safety Issue?: No
• Hamilton Rating Scale for Depression (HAM-D) Scale Total Score at Weeks 6, 16, 28, 40, and 52/EW
  • Time Frame: Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: No
• Change From Baseline in the Hamilton Rating Scale for Depression (HAM-D) Scale Total Score at Weeks 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: No
• Young Mania Rating Scale (YMRS) Total Score at Weeks 6, 16, 28, 40, and 52/EW
  • Time Frame: Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: No
• Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Weeks 6, 16, 28, 40, and 52/EW
  • Time Frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW
    Safety Issue?: No
• Median Serum Lamotrigine 200 mg Concentration Among Participants With Concomitant Use of Inducer and Without Inhibitor (at the Timing of Blood Sample Collection)
  • Time Frame: from Week 6 to Week 52/EW
    Safety Issue?: No
• Median Serum Lamotrigine 100 mg and 200 mg Concentration Among Participants With Concomitant Use of Inhibitor (at the Timing of Blood Sample Collection)
  • Time Frame: from Week 6 to Week 52/EW
    Safety Issue?: No
• Median Serum Lamotrigine 25, 100, 125, 150, 200, 225, 300, and 400 mg Concentrations Among Participants Without Concomitant Use of Inhibitor and Inducer
  • Time Frame: from Week 6 to Week 52/EW
    Safety Issue?: No

Inclusion Criteria:

• Of subjects participating in the preceding double-blind study, those who are judged by the investigator/sub-investigator to have well tolerated the double-blind treatment and to be eligible for the 52-week extension treatment
• Sex: either sex. Female of child-bearing potential will be eligible for inclusion in this study. However they have to have a negative pregnancy test at the start of this study, agree to further pregnancy testing at the time points determined in study assessments and procedures and practice one of the following methods of contraception from the start of this study until the end of the follow-up examination:
• Abstinence
• Oral contraceptive, either combined or progestogen alone (except during the Dosage
• Adjustment Phase)
• Injectable progestogen
• Implants of levonorgestrel
• Estrogenic vaginal ring (except during the Dosage Adjustment Phase)
• Percutaneous contraceptive patches (except during the Dosage Adjustment Phase)
• Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label
• Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject
• Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (foam / gel / film / cream / suppository)
• In/Out patient: Either
• Informed consent: the subject capable of giving written informed consent

Exclusion Criteria:

• Has a score of 3 or more on item of the HAM-D related to suicide or is at a high suicidal risk in the judgment of the investigator/sub-investigator
• Has a history of severe rash or rash due to anti-epileptic drugs
• Patients with severe hepatic/renal/cardiac/pulmonary disorder or hematopoietic disorder. The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences" (PAB/SD Notification No. 80, dated 29 June 1992)
• Patients have less than 5 years of remission history from clinically significant malignancy (other than e.g. basal cell or squamous cell skin cancer, in-situ carcinoma of cervix or prostate CA in situ)
• Patients with chronic hepatitis typeB and /or typeC which is positive of hepatitis B surface antigen （HBsAg）and/or hepatitis C antibody
• Has an acute or chronic illness likely to impair drug absorption, distribution, metabolism or excretion or has any unstable physical symptoms likely to require hospitalisation during participation in the study
• Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study
• Has a history or current diagnosis of epilepsy
• Has received an investigational drug within 30 days of screening
• Patients with a history of drug allergy to any ingredient of the test-drug
• Patients whom the investigator or sub-investigator considers ineligible for the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: GlaxoSmithKline Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00566020

Study ID Number: SCA106052

ClinicalTrials.gov Identifier: NCT00566020

Health Authority: Japan: Ministry of Health, Labor and Welfare