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

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00566020

Purpose

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.

Condition	Intervention	Phase
Bipolar Disorder	Drug: BW430C (lamotrigine)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Study SCA106052, a Clinical Evaluation of BW430C (Lamotrigine) in Bipolar I Disorder- Long-term Extension Study (Extension of Study SCA104779 (NCT00550407)) -

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder Potassium Urine and Urination

Drug Information available for: Lamotrigine

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome 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) ] [ Designated as safety issue: No ]
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of medicinal product, which does not necessarily have a causal relationship with the treatment. An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes its prolongation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A complete list of all SAEs and AEs experienced in the study can be found in the SAE/AE section.
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) ] [ Designated as safety issue: Yes ]
Participants in the study were evaluated for the following clinical laboratory parameters at the indicated time points: ALP, ALT, AST, GGT, and LDH. Participants were categorized as "High" for laboratory values above normal (reference) and as "Low" for laboratory values below normal ranges used by the central laboratory. Normal ranges: ALP, 104-338 International Units per liter (IU/L); ALT, 5-45 IU/L; AST, 10-40 IU/L; GGT, Male: 0-79 IU/L, Female: 0-48 IU/L; LDH 120-245 IU/L.
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 ] [ Designated as safety issue: Yes ]
Participants in the study were evaluated for the following clinical laboratory parameters at the indicated time points: total bilirubin and creatinine. Participants were categorized as "High" for laboratory values above normal (reference) and as "Low" for laboratory values below normal ranges used by the central laboratory. Normal ranges: total bilirubin, 3.42-17.1 micromoles per liter (UMOL/L); creatinine, Male: 57.46-96.356 UMOL/L, Female: 40.664-72.488 UMOL/L.
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 ] [ Designated as safety issue: Yes ]
Participants were evaluated for the following clinical laboratory parameters for blood chemistry at the indicated time points: electrolytes (calcium, chloride, potassium, sodium), cholesterol, triglycerides, and urea/BUN. Participants were categorized as "High" for laboratory values above normal (reference) and as "Low" for laboratory values below normal ranges used by the central laboratory. Normal ranges (micromoles per liter [MMOL/L]): calcium, 2.0459-2.495; chloride, 98-108; potassium, 3.5-5; sodium, 135-145; cholesterol, 3.879-5.66334; triglycerides, 0.565-1.6837; urea/BUN, 2.856-7.14.
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 ] [ Designated as safety issue: Yes ]
Participants in the study were evaluated for the following clinical laboratory parameters of hematology at the indicated time points: platelet count and white blood cell count. Participants were categorized as "High" for laboratory values above normal (reference) and as "Low" for laboratory values below normal ranges used by the central laboratory. Normal ranges: platelet count, 140-379 GI (gibi; 10^9) per liter (GI/L); white blood cell count, 3.5-9.7 GI/L.
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 ] [ Designated as safety issue: Yes ]
Participants in the study were evaluated for total protein, hemoglobin, and hematocrit at the indicated time points. Participants were categorized as "High" for laboratory values above normal (reference) and as "Low" for laboratory values below normal ranges used by the central laboratory. Normal ranges: total protein, 65-82 grams per liter (G/L); hemoglobin, Male: 136-183 G/L, Female: 112-152 G/L; hematocrit (proportion of 1), Male: 0.404-0.519, Female: 0.343-0.452.
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 ] [ Designated as safety issue: Yes ]
Red blood cell count was measured in participants at the indicated time points. Participants were categorized as "High" for laboratory values above normal (reference) and as "Low" for laboratory values below normal ranges used by the central laboratory. Normal ranges: red blood cell count, Male: 4.38-5.77 TI (tebi; 10^12)/L, Female: 3.76-5.16 TI/L.
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 ] [ Designated as safety issue: Yes ]
Urine glucose, urine protein, and urine urobilinogen were measured in participants at the indicated time points. In this dipstick (qualitative) test, the level of glucose, protein, and urobilinogen in urine samples was recorded as negative (NEG [-]), trace (TRA [+/-]), 1+, 2+, 3+, 4+, and 5+ (the plus sign increases with a higher level of glucose, protein, or urobilinogen in the urine: 1+=slightly positive, 2+=positive, 3+=high positive, 4+=very high positive, 5+=more positive than 4+).
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 ] [ Designated as safety issue: Yes ]
Systolic and diastolic blood pressure was measured in participants at the indicated time points.
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 ] [ Designated as safety issue: Yes ]
Heart rate was measured in participants at the indicated time points.
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 ] [ Designated as safety issue: Yes ]
The weight of participants was recorded at the indicated time points.
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 ] [ Designated as safety issue: Yes ]
The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared.
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 ] [ Designated as safety issue: Yes ]
ECGs were recorded in participants at the indicated time points. ECG findings, as determined by the physicians, were reported as normal, abnormal but not clinically significant (NCS), abnormal but clinically significant (CS), and no result. Specific definitions of ECG categorizations were not provided; physicians were expected to apply reasonable standards of clinical judgment.

Secondary Outcome 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 ] [ Designated as safety issue: No ]
The CGI-S is a standardized assessment tool that uses a 7-point scale to assess a participant's severity of illness. The total score ranges from 0 to 7: 0=not assessed, 1=normal, 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severly ill, 7=extremely ill. Higher scores reflect a higher severity of current illness states. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).
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 ] [ Designated as safety issue: No ]
The CGI-S is a standardized assessment tool that uses a 7-point scale to assess a participant's severity of illness. The total score ranges from 0 to 7: 0=not assessed, 1=normal, 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severly ill, 7=extremely ill. Higher scores reflect a higher severity of current illness states. Change from baseline was calculated as the values at Weeks 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (or EW) minus the baseline value (Week 0).
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 ] [ Designated as safety issue: No ]
The HAMD-17 is a 17-item questionnaire that detects change and measures illness severity. Individual items were rated on a scale of 0-4 and 0-2, with the total HAMD-17 score ranging from 0 (not ill) to 52 (severely ill).
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 ] [ Designated as safety issue: No ]
The HAMD-17 is a 17-item questionnaire that detects change and measures illness severity. Individual items were rated on a scale of 0-4 and 0-2, with the total HAMD-17 score ranging from 0 (not ill) to 52 (severely ill). Change from baseline was calculated as the values at Week 6, 16, 28, 40, and 52 (or EW) minus the baseline value (Week 0).
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 ] [ Designated as safety issue: No ]
The YMRS is an 11-item, multiple-choice diagnostic questionnaire used to measure the severity of disease in participants. Individual items (1=elevated mood, 2=increased motor activity, 3=sexual interest, 4=sleep, 5=irritability, 6=speech, 7=language thought disorder, 8=content, 9=disruptive aggressive behaviour, 10=appearance, 11=insight) were rated on a scale of 0-4 and 0-8. For all items, 0 is the "best" rating and 4 or 8 is the "worst" rating. YMRS total score was computed as the sum of the scores for the 11 items on the scale. The possible total scores range from 0 (best) to 60 (worst).
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 ] [ Designated as safety issue: No ]
The YMRS is an 11-item, multiple-choice diagnostic questionnaire used to measure the severity of disease in participants. Individual items (1=elevated mood, 2=increased motor activity, 3=sexual interest, 4=sleep, 5=irritability, 6=speech, 7=language thought disorder, 8=content, 9=disruptive aggressive behaviour, 10=appearance, 11=insight) were rated on a scale of 0-4 and 0-8. YMRS total score (range of 0-60) was computed as sum of the scores for the 11 items on the scale. Change from baseline was calculated as the values at Week 6, 16, 28, 40, and 52 (or EW) minus the baseline value (Week 0).
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 ] [ Designated as safety issue: No ]
Pharmacokinetic (PK) samples were collected at Weeks 6, 16, 28, 40, 52/EW, and the plasma lamotrigine concentrations were measured. Participants were required to visit the study site without taking the investigational product on the morning of the PK blood sampling. Inhibitors are defined as drugs that inhibit lamotrigine glucuronidation (i.e., valproate). Inducers are defined as drugs that induce lamotrigine glucuronidation (e.g., carbamazepine). The median value presented is the median of all samples collected at Weeks 6, 16, 28, 40, and 52/EW.
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 ] [ Designated as safety issue: No ]
PK samples were collected at Weeks 6, 16, 28, 40, 52/EW, and the plasma lamotrigine concentrations were measured. Participants were required to visit the study site without taking the investigational product on the morning of the PK blood sampling. Inhibitors are defined as drugs that inhibit lamotrigine glucuronidation (i.e., valproate). The median value presented is the median of all samples collected at Weeks 6, 16, 28, 40, and 52/EW.
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 ] [ Designated as safety issue: No ]
PK samples were collected at Weeks 6, 16, 28, 40, 52/EW, and the plasma lamotrigine concentrations were measured. Participants were required to visit the study site without taking the investigational product on the morning of the PK blood sampling. Inhibitors are defined as drugs that inhibit lamotrigine glucuronidation (i.e., valproate). Inducers are defined as drugs that induce lamotrigine glucuronidation (e.g., carbamazepine). The median value presented is the median of all samples collected at Weeks 6, 16, 28, 40, and 52/EW.

Enrollment:	92
Study Start Date:	May 2008
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lamotrigine	Drug: BW430C (lamotrigine) lamotrigine 50mg/day-400mg/day

Eligibility

Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00566020

Locations

Japan
GSK Investigational Site
Aichi, Japan, 470-1141
GSK Investigational Site
Chiba, Japan, 260-8677
GSK Investigational Site
Chiba, Japan, 289-2511
GSK Investigational Site
Chiba, Japan, 272-8516
GSK Investigational Site
Fukuoka, Japan, 800-0217
GSK Investigational Site
Fukuoka, Japan, 812-8582
GSK Investigational Site
Fukuoka, Japan, 810-0004
GSK Investigational Site
Fukuoka, Japan, 815-0041
GSK Investigational Site
Fukuoka, Japan, 807-8555
GSK Investigational Site
Gunma, Japan, 377-0055
GSK Investigational Site
Gunma, Japan, 375-0017
GSK Investigational Site
Hiroshima, Japan, 734-8551
GSK Investigational Site
Hiroshima, Japan, 737-0023
GSK Investigational Site
Hokkaido, Japan, 060-0042
GSK Investigational Site
Hokkaido, Japan, 060-8648
GSK Investigational Site
Hokkaido, Japan, 002-8029
GSK Investigational Site
Ibaraki, Japan, 311-3193
GSK Investigational Site
Kanagawa, Japan, 221-0835
GSK Investigational Site
Kanagawa, Japan, 231-0023
GSK Investigational Site
Kanagawa, Japan, 216-8511
GSK Investigational Site
Kanagawa, Japan, 224-8503
GSK Investigational Site
Kanagawa, Japan, 225-0011
GSK Investigational Site
Kanagawa, Japan, 238-0042
GSK Investigational Site
Kumamoto, Japan, 861-8002
GSK Investigational Site
Kyoto, Japan, 616-8421
GSK Investigational Site
Mie, Japan, 510-8575
GSK Investigational Site
Nara, Japan, 634-8522
GSK Investigational Site
Oita, Japan, 879-7501
GSK Investigational Site
Oita, Japan, 874-0011
GSK Investigational Site
Oita, Japan, 879-5593
GSK Investigational Site
Okayama, Japan, 700-8558
GSK Investigational Site
Osaka, Japan, 569-1041
GSK Investigational Site
Saitama, Japan, 332-0012
GSK Investigational Site
Tokyo, Japan, 113-8603
GSK Investigational Site
Tokyo, Japan, 180-0005
GSK Investigational Site
Tokyo, Japan, 151-0053
GSK Investigational Site
Tokyo, Japan, 187-8551
GSK Investigational Site
Tokyo, Japan, 152-0012
GSK Investigational Site
Tokyo, Japan, 166-0003
GSK Investigational Site
Tokyo, Japan, 154-0004
GSK Investigational Site
Tokyo, Japan, 170-0002
GSK Investigational Site
Tottori, Japan, 682-0023
GSK Investigational Site
Yamagata, Japan, 999-2221

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:	NCT00566020 History of Changes
Other Study ID Numbers:	SCA106052
Study First Received:	November 28, 2007
Results First Received:	June 30, 2011
Last Updated:	August 4, 2011
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:

Open-label extension
Tolerability
Lamotrigine
Safety
Bipolar I disorder

Additional relevant MeSH terms:

Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
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 February 12, 2012