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

The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared.

Time frame: Baseline (Week 0) and Weeks 0, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

Heart rate was measured in participants at the indicated time points.

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

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

Systolic and diastolic blood pressure was measured in participants at the indicated time points.

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

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

The weight of participants was recorded at the indicated time points.

Time frame: Baseline (Week 0) and Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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+).

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: From baseline (Week 0) until 2 weeks after the end of treatment (Week 54)

Population: Safety Population: all participants who received at least one dose of study medication

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.

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/Early Withdrawal (EW)

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: Weeks 0, 6, 28, and 52/EW

Population: Safety Population. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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).

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

Population: FAS Population. OC and LOCF datasets were used for analysis. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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).

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: FAS Population. OC and LOCF datasets were used for analysis. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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).

Time frame: Baseline (Week 0) and Weeks 6, 16, 28, 40, and 52/EW

Population: FAS Population. OC and LOCF datasets were used for analysis. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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).

Time frame: Weeks 0, 2, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/EW

Population: Full Analysis Set (FAS): participants who received \>=1 dose of study medication and underwent \>=1 efficacy assessment. Observed Cases (OC; observed data with no imputation) and Last Observation Carried Forward (LOCF; data imputed \[replaced\] by most recent observed value \[compared to planned date of missing observation\]) were used for analysis.

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).

Time frame: Weeks 6, 16, 28, 40, and 52/EW

Population: FAS Population. OC and LOCF datasets were used for analysis. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).

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.

Time frame: from Week 6 to Week 52/EW

Population: Safety Population. Participants (par.) who took at least one dose of drugs that inhibit lamotrigine glucuronidation (i.e., valproate) from the date of the first dose of study medication to the date of the last dose. A total of 8 par. were analyzed; 1 par. had both 100 and 200 mg data, 4 par. had 100 mg data only, and 3 par. had 200 mg data only.

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.

Time frame: from Week 6 to Week 52/EW

Population: Safety Population. Participants who took at least one dose of drugs that induce lamotrigine glucuronidation (e.g., carbamazepine) from the date of the first dose of study medication to the date of the last dose.

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.

Time frame: from Week 6 to Week 52/EW

Population: Safety Population. Participants without concomitant use of inhibitor and inducer from the date of the first dose of study medication to the date of the last dose. Multiple blood samplings were conducted for some participants. A total of 82 participants were analyzed; 4 participants did not have 200 mg dose data but had data for lower doses.

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).

Time frame: Weeks 6, 16, 28, 40, and 52/EW

Population: FAS Population. OC and LOCF datasets were used for analysis. The number of participants with an assessment varied depending on the number of assessments completed at each visit (indicated time points).