A Study for Assessing Treatment of Patients Ages 10-17 With Bipolar Depression

CDRS-R Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) mean was adjusted for baseline, country, treatment, visit, and treatment times (*) visit interaction.

Remission is defined as a CDRS-R total score less than or equal to (≤)28, and Young Mania Rating Scale (YMRS) total score ≤ 8 and Clinical Global Impressions-Bipolar Version (CGI-BP) total score ≤3. CDRS-R is a 17-item scale measuring presence/severity of depression in children and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Scores range: 17 to 113. Scores <20 indicate an absence of depression, scores 20 to 30 indicate borderline depression, scores 40 to 60 indicate moderate depression. The YMRS is an 11-item scale measuring severity of manic episodes; 4 items are rated on a scale from 0 (symptoms not present) to 8 (symptom extremely severe) with remaining items rated on a scale from 0 (symptoms not present) to 4 (symptom extremely severe). YMRS score ranges from 0 to 60. CGI-BP measures participant's overall severity of bipolar symptoms. Scores range: 1 (normal, not at all ill ) to 7 (among the most extremely ill participants).

Response is defined as a CDRS-R total score greater than or equal to (≥)50% reduction from baseline and YMRS elevated mood score ≤2. CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Scores range: 17 to 113. In general, <20 indicate an absence of depression, scores 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptoms not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptoms not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.

CDRS-R scores: No/low improvement is < 25 percent (%) of maximum reduction from baseline. Mild improvement: maximum reduction from baseline on CDRS-R score ≥ 25% up to <50% and YMRS elevated mood score ≤ 2. Moderate improvement: maximum reduction from baseline on CDRS-R score ≥50% and <75% and YMRS elevated mood score ≤ 2. Major improvement: maximum reduction from baseline on CDRS-R score ≥75% and YMRS elevated mood score ≤ 2. CDRS-R measures presence/severity of depression in children. Scale is 17 items scored 1-to-5- or 1-to-7. Rating of 1 indicates normal function. Scores range: 17 to 113. Scores < 20 absence of depression, scores 20 to 30 borderline depression, scores 40 to 60 indicate moderate depression. YMRS is an 11-item scale that measures severity of manic episodes. Four items rated 0 (symptoms not present) to 8 (symptom extremely severe). Remaining items rated 0 (symptoms not present) to 4 (symptom extremely severe). Score range: 0 to 60.

The YMRS is an 11-item scale measuring the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total scores ranges: 0 to 60. LS mean was adjusted for baseline, country, treatment, visit, and treatment * visit interaction.

CGI-BP measures severity of illness for bipolar illness. Scores range: 1 (normal, not ill at all) to 7 (among the most extremely ill patients). LS mean was adjusted for baseline, country, treatment, visit, and treatment * visit interaction.

CDRS-R Total score measure the presence and severity of depression in children and consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Total scores range from 17 to 113. In general, scores < 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. LS mean was adjusted for baseline, country, and treatment.

Akathisia was measured using the Barnes Akathisia Rating Scale where the global scores range from 0 (absent) to 5 (severe) and a score ≥ 2 is considered abnormal.

Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Percentage of participants with suicidal ideation, behavior, and acts are provided. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal act: a "yes" answer to actual attempt or completed suicide.

Worsening of mania was defined as YMRS score of ≥20 and a CGI severity of mania score of ≥ 5 at the same visit. The YMRS is an 11-item scale measuring severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe) with remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. CGI measures severity of the participant's overall severity of bipolar symptoms and scores range from 1 (normal) to 7 (among the most extremely ill participants).

Attention Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS-IV-PI): Investigator Administered and Scored measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Scores range: 0 to 54. The LS mean was adjusted for baseline and treatment.

The KINDL consists of 24 Likert-scale items. Total scores were standardized to a 0 (lowest quality of life) to 100 (highest quality of life). LS mean was adjusted for baseline, country, and treatment.

Parkinsonism was measured using the Simpson-Angus Scale with a total scores range from 0 to 40. A score > 3 was considered abnormal. Simpson-Angus Scale consists of 10 items, each rated on a 5-point scale, 0 (complete absence of the condition) to 4 (presence of the condition in extreme form).

Dyskinesia was measured using the Abnormal Involuntary Movement Scale (AIMS) a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 through 10 are rated on a 5-point scale: 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 are yes/no questions regarding the dental condition of a patient. Total score (0-40) is obtained by adding the scores of the first 10 items. An abnormal result is defined as having a score ≥3 for at least 1 of the first 7 items or a score ≥2 for at least two of the first 7 items.

The KINDL consists of 24 Likert-scale items. Kid-KINDL was administered to ages 8-11 and Kiddo-KINDL to ages 12-16. Total scores were standardized to a 0 (lowest quality of life) to 100 (highest quality of life). LS mean was adjusted for baseline, country, and treatment.

Weight LS mean was adjusted for baseline and treatment.

Fasting glucose, fasting cholesterol and fasting triglycerides. LS means were adjusted for baseline and treatment.

ALT/SGPT LS mean was adjusted for baseline and treatment.

Prolactin LS mean was adjusted for baseline and treatment.

QTcF is defined as ECG QT interval corrected for heart rate using the Fridericia correction factor.