An Evaluation Of BW430C (Lamotrigine) Versus Placebo In The Prevention Of Mood Episodes In Bipolar I Disorder Patients

Condition(s) targeted: Bipolar Disorder

Intervention: BW430C (lamotrigine) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: GlaxoSmithKline

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

Overall contact:
US GSK Clinical Trials Call Center, Phone: 877-379-3718

This study is planned to objectively assess the efficacy and safety of lamotrigine maintenance therapy after symptoms of mood episode had been stabilised by open-label treatment with lamotrigine alone or in combination with other psychotropic medication in patients with bipolar I disorder.

Official title: Study SCA104779, an Evaluation of BW430C (Lamotrigine) Versus Placebo in the Prevention of Mood Episodes in Bipolar I Disorder Patients

Study design: Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The time from randomization to the time at which the subject is withdrawn from the double blind Phase for any reason (Time to Withdrawal from Study, TWS) - 4 consecutive weeks of treatment

Secondary outcome:

- Time to intervention for any mood episode (TIME) - Time to intervention for manic, hypomanic or mixed episode (TIMan) - Time to intervention for depressive episode (TIDep) - CGI-I - CGI-S - HAM-D - YMRS - 4 consecutive weeks of treatment

Time to intervention for any mood episode (TIME)

Time to intervention for manic, hypomanic or mixed episode (TIMan)

Time to intervention for depressive episode (TIDep)

Change from baseline of Clinical Global Impressions of Severity (CGI-S)

Clinical Global Impressions of Improvement (CGI-I)

Change from baseline of Hamilton Depression Rating Scale (HAM-D)

Change from baseline of Young Mania Rating Scale (YMRS)

Minimum age: 20 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

At Screening Disease to be studied: Has a diagnosis of following disease as defined by DSM-IV-TR criteria.

- Bipolar I Disorder, most recent episode depressed（296. 5x）

- Bipolar I Disorder, most recent episode hypomanic（296. 40）

- Bipolar I Disorder, most recent episode manic（296. 4x） The diagnosis of mood episode

will be made with reference to Mini International Neuropsychiatric Interview: M. I.N. I, Japanese Version.

At Screening

The subject who has a diagnose of bipolar I disorder, most recent episode depressed (296. 5x) must meet the following criteria:

- Is currently experiencing a major depressive episode or has had a major depressive

episode as defined by DSM-IV-TR criteria within 60 days of the screening visit and at least one additional major depressive episode and one manic or hypomanic episode, as defined by DSM-IV-TR criteria, within 3 years of enrolment. A well documented history of a mixed episode that meets DSM-IV-TR criteria may be counted as a previous episode. All subjects must have experienced at least one well-documented manic or mixed episode in the past.

- Has a duration of the most recent/current depressive episode of at least 2 weeks but

not longer than 12 months prior to enrolment.

- The subject without current major depressive episode must have a major depressive

episode within 60 days of screening and has depressive symptoms at screening or is under treatment for depressive symptoms, which can be confirmed by medical record, etc.

- If the subject is currently experiencing a major depressive episode, the subject must

have a minimum total score on the HAM-D (17-item scale) of 18 at the screening. This criterion will not apply to the subject with recent depressive episode.

At Screening

The subject who has a diagnose of bipolar I disorder, most recent episode hypomanic（296. 4x） or bipolar I disorder, most recent episode manic（296. 5x） must meet the following criteria:

- Has experienced a recent manic or hypomanic episode (current or within 60 days of the

Screening Visit) and has had at least one additional manic or hypomanic episode and one depressed episode, as defined by DSM-IV-TR criteria, within three years of enrolment. A well documented history of a mixed episode that meets DSM-IV-TR criteria may be counted as a previous episode. All subjects must have experienced at least one well-documented manic or mixed episode in the past.

- Has a duration of the index manic episode of at least 1 week (unless hospitalised) or

hypomanic episode of at least 4 days. In neither case should the index episode be more than 12 months in duration.

- The subject current experiencing hypomania episode or without current episode must

have a manic episode which can be confirmed by medical record, etc. The subject without current episode must have a episode within 60 days of screening and has manic or hypomanic symptomatology is under treatment for manic or hypomanic symptoms.

- If the subject's index episode is subject initial manic mood event, subject must have

a minimum score of 10 (moderate severity) on the first 11 items of the YMRS at the screening. A threshold YMRS score that indicates significant manic symptoms is not required for patients who previously experienced well-documented DSM-IV-level mania or when the index episode is hypomania or when a subject's index manic or hypomanic episode is documented to have occurred within 60 days of the screening Visit.

At Screening Age: Is at least 20 years of age (at the time of informed consent). At Screening 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 screening visit, 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 screening visit until the end of the follow-up examination.

- Abstinence

- Injectable progestogen

- Implants of levonorgestrel

- 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) At Screening In/Out patient: Either At Screening Informed consent: the subject capable of giving written informed consent. At Week 0 of First Phase (titration) If the subject is currently experiencing a major depressive episode, the subject must have a minimum total score at baseline on the HAM-D (17-item scale) of 18 at the start of First Phase. This criterion will not apply to the subject with recent depressive episode.

At Week 0 of First Phase (titration) If the subject's index episode is subject initial manic mood event, subject must have a minimum total score at baseline of 10 (moderate severity) on the first 11 items of the YMRS at the start of First Phase (titration). A threshold YMRS score that indicates significant manic symptoms is not required for patients who previously experienced well-documented DSM-IV-level mania or when the index episode is hypomania or when a subject's index manic or hypomanic episode is documented to have occurred within 60 days of the screening Visit.

At Week 0 of Second Phase (maintenance therapy) Each subject completing 8 to 16 weeks of open-label lamotrigine treatment in the First Phase must meet all of the following inclusion criteria to be eligible for entry into the Second Phase (maintenance therapy, randomization phase).

At Week 0 of Second Phase (maintenance therapy) Has no tolerability problem with lamotrigine at a minimum dosage of 100 mg/day during the final 2 weeks of the First Phase (titration).

At Week 0 of Second Phase (maintenance therapy) Has improved/stabilised during the First Phase (titration) as indicated by a CGI-S score of ≤3 (mildly ill). Once improved, the subject must also demonstrate sustained improvement by achieving a CGI-S score of ≤3 (mildly ill) for at least 4 consecutive weeks of treatment immediately prior to the Second Phase (maintenance therapy) (randomization).

At Week 0 of Second Phase (maintenance therapy) Has demonstrated adequate compliance with the study treatment in the First Phase (titration) (compliance rate: at least 70%).

At Week 0 of Second Phase (maintenance therapy) In/Out patient: Either

Exclusion Criteria:

At Screening Has a DSM-IV-TR diagnosis of rapid cycling and has had more than six mood episodes including depression, mania, hypomania or mixed, in the 12-month period prior to screening. Note: while 4 or more episodes in the past 12 months constitute rapid cycling up to six episodes in the past 12 months are allowed in this protocol.

At Screening Has a DSM-IV-TR diagnosis of bipolar I disorder, most recent episode mixed (296. 6x).

At Screening Has a DSM-IV-TR diagnosis of Axis II which would suggest non-responsiveness to pharmacotherapy for bipolar disorder.

At Screening Has a DSM-IV-TR diagnosis of or has received treatment for major depressive disorder, panic disorder, obsessive-compulsive disorder, social phobia, bulimia nervosa, schizophrenia or schizoaffective disorder within 12 months of screening.

At Screening Has a history of substance (including alcohol and drugs) dependence within 12 months of screening or abuse within 1 month of screening according to DSM-IV-TR.

At Screening Patients whose mood episode is due to direct physiological effects of a general medical condition (for example, hypothyroidism, hyperthyroidism) At Screening 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.

At Screening Has a history of severe rash or rash due to anti-epileptic drugs. At Screening 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).

At Screening 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).

At Screening Patients with chronic hepatitis typeB and /or typeC which is positive of hepatitis B surface antigen （HBsAg）and/or hepatitis C antibody.

At Screening 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.

At Screening Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study.

At Screening Has a history or current diagnosis of epilepsy. At Screening Has a history of treatment with lamotrigine. At Screening Patients with a history of drug allergy to any ingredient of the test-drug. At Screening Has received an investigational drug within 30 days of screening. At Screening Is morbidly obese (Body Mass Index [BMI] >40) BMI = body weight (kg)/height (m2).

At Screening Patients whom the investigator or sub-investigator considers ineligible for the study.

At Week 0 of First Phase (titration) 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 and continues .to meet the criteria at the screening visit.

At Week 0 of Second Phase (maintenance therapy) Has signs or symptoms of psychosis. At Week 0 of Second Phase (maintenance therapy) 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.

At Week 0 of Second Phase (maintenance therapy) Has had a change in lamotrigine dosage during the final week of the First Phase (titration).

At Week 0 of Second Phase (maintenance therapy) Has a diagnosis of bipolar I disorder, most recent episode of depressed (296. 5x) and has experienced manic, hypomanic or mixed symptoms; Has a diagnosis of bipolar I disorder, most recent episode hypomanic (296. 40) or most recent episode manic (296. 4x) and has experienced depressive symptoms, that require treatment during the First Phase (titration).

US GSK Clinical Trials Call Center, Phone: 877-379-3718

GSK Investigational Site, Tokyo 190-0023, Japan; Recruiting

GSK Investigational Site, Fukuoka 812-8582, Japan; Withdrawn

GSK Investigational Site, Tottori 680-0011, Japan; Not yet recruiting

GSK Investigational Site, Gunma 375-0017, Japan; Recruiting

GSK Investigational Site, Aichi 470-1141, Japan; Recruiting

GSK Investigational Site, Aichi 470-1168, Japan; Withdrawn

GSK Investigational Site, Hokkaido 060-8648, Japan; Recruiting

GSK Investigational Site, Kumamoto 861-8002, Japan; Recruiting

GSK Investigational Site, Chiba 260-8677, Japan; Recruiting

GSK Investigational Site, Chiba 272-8516, Japan; Recruiting

GSK Investigational Site, Gunma 377-0055, Japan; Recruiting

GSK Investigational Site, Mie 510-8575, Japan; Recruiting

GSK Investigational Site, Hokkaido 060-0042, Japan; Recruiting

GSK Investigational Site, Tokyo 183-0042, Japan; Active, not recruiting

GSK Investigational Site, Saitama 332-0012, Japan; Recruiting

GSK Investigational Site, Kyoto 616-8421, Japan; Recruiting

GSK Investigational Site, Mie 515-0044, Japan; Recruiting

GSK Investigational Site, Chiba 289-2511, Japan; Recruiting

GSK Investigational Site, Fukuoka 814-0180, Japan; Recruiting

GSK Investigational Site, Tokyo 187-8551, Japan; Recruiting

GSK Investigational Site, Osaka 569-1041, Japan; Recruiting

GSK Investigational Site, Kyoto 602-8566, Japan; Withdrawn

GSK Investigational Site, Tokyo 113-8602, Japan; Recruiting

GSK Investigational Site, Hiroshima 734-8551, Japan; Recruiting

GSK Investigational Site, Fukuoka 807-8555, Japan; Recruiting

GSK Investigational Site, Hokkaido 002-8029, Japan; Recruiting

GSK Investigational Site, Okayama 700-8558, Japan; Recruiting

GSK Investigational Site, Fukuoka 830-0011, Japan; Recruiting

GSK Investigational Site, Tottori 682-0023, Japan; Recruiting

GSK Investigational Site, Oita 879-7501, Japan; Recruiting

GSK Investigational Site, Oita 874-0011, Japan; Recruiting

GSK Investigational Site, Saga 842-0192, Japan; Recruiting

GSK Investigational Site, Hokkaido 064-0946, Japan; Active, not recruiting

GSK Investigational Site, Tokyo 170-0002, Japan; Recruiting

GSK Investigational Site, Kanagawa 216-8511, Japan; Recruiting

GSK Investigational Site, Kanagawa 238-0042, Japan; Recruiting

GSK Investigational Site, Kanagawa 231-0023, Japan; Not yet recruiting

GSK Investigational Site, Tokyo 180-0005, Japan; Active, not recruiting

GSK Investigational Site, Hiroshima 737-0023, Japan; Not yet recruiting

GSK Investigational Site, Fukuoka 802-0001, Japan; Not yet recruiting

GSK Investigational Site, Fukuoka 802-0006, Japan; Not yet recruiting

GSK Investigational Site, Fukuoka 815-0041, Japan; Not yet recruiting

GSK Investigational Site, Fukuoka 800-0217, Japan; Not yet recruiting

GSK Investigational Site, Ibaraki 311-3117, Japan; Not yet recruiting

GSK Investigational Site, Kanagawa 221-0835, Japan; Recruiting

GSK Investigational Site, Tokyo 100-0006, Japan; Active, not recruiting

GSK Investigational Site, Fukuoka 812-8582, Japan; Active, not recruiting

GSK Investigational Site, Oita 879-5593, Japan; Recruiting

GSK Investigational Site, Kanagawa 220-0004, Japan; Withdrawn

GSK Investigational Site, Tokyo 154-0012, Japan; Active, not recruiting

GSK Investigational Site, Tokyo 166-0003, Japan; Recruiting

GSK Investigational Site, Kanagawa 225-0011, Japan; Recruiting

GSK Investigational Site, Tokyo 151-0053, Japan; Recruiting

GSK Investigational Site, Yamagata 999-2221, Japan; Recruiting

GSK Investigational Site, Osaka 533-0005, Japan; Active, not recruiting

GSK Investigational Site, Fukuoka 810-0004, Japan; Active, not recruiting

GSK Investigational Site, Nara 634-8522, Japan; Recruiting

GSK Investigational Site, Osaka 570-8507, Japan; Recruiting

GSK Investigational Site, Osaka 583-0884, Japan; Active, not recruiting

GSK Investigational Site, Kanagawa 224-8503, Japan; Active, not recruiting

GSK Investigational Site, Tokyo 173-0037, Japan; Active, not recruiting

GSK Investigational Site, Tokyo 154-0004, Japan; Recruiting

GSK Investigational Site, Osaka 590-0018, Japan; Recruiting

GSK Investigational Site, Tokyo 152-0012, Japan; Recruiting

Starting date: November 2007
Ending date: December 2009
Last updated: October 30, 2008