Extension Study Evaluating The Safety And Tolerability Of Flexible Doses Of Oral Ziprasidone In Children And Adolescents With Bipolar I Disorder

Hemoglobin (Hg), hematocrit, erythrocytes: <0.8*lower limits of normal (LLN); platelets: <0.5*LLN>1.75*upper limits of normal (ULN); leukocytes (leu), glucose-fasting:<0.6*LLN>1.5*ULN; lymphocytes (lym), lym/leu, neutrophils (neu), neu/leu, protein, albumin, phosphate, free thyroxine, thyroid stimulating hormone: <0.8*LLN>1.2*ULN; basophils (bas), bas/leu, eosinophils (eos), eos/leu, monocytes(mon), mon/leu: >1.2*ULN; bilirubin (total, direct, indirect):>1.5*ULN; aspartate aminotransferase(AT), alanine AT, lactate dehydrogenase, alkaline phosphatase:>3.0*ULN; blood urea nitrogen, creatinine, cholesterol (total, LDL, HDL), triglycerides, Hg A1C: >1.3*ULN; sodium: <0.95*LLN>1.05*ULN; potassium, chloride, calcium, magnesium, bicarbonate: <0.9*LLLN>1.1*ULN; prolactin: >1.1*ULN; creatine kinase: >2.0*ULN; urobilinogen: >=1; Urine-specific gravity: <1.003>1.030, pH: <4.5 >8, glucose, protein, bilirubin, nitrite, leukocyte esterase, ketones: >=1.

Parameters assessed for physical examination included: oral/tympanic temperature, general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts (if medically indicated), abdomen, external genitalia (if medically indicated), extremities, back/spinal system, lymph nodes or worsening of medical history conditions. Abnormality in physical examination was at the investigator's discretion.

Change from baseline in sitting and standing systolic and diastolic blood pressure in millimeter of mercury (mmHg) was reported.

Change from baseline pulse rate in beats per minute was reported in sitting and standing positions.

Change from baseline in height and waist circumference in centimeter (cm) was reported.

Change from baseline in body weight in kilogram (kg) was reported.

Change from baseline in BMI in kilogram per meter square (kg/m^2) was reported.

BMI z-score was reported using the Children's Hospital of Philadelphia z-score calculator. Z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.

Change from baseline in heart rate in beats per minute was reported.

Change from baseline in PR interval, QT interval corrected using the Bazett's correction (QTcB), QT interval corrected using the Fridericia's formula (QTcF), QT interval, RR interval, QRS duration in millisecond (msec) was reported.

SARS: 10-item clinician rated instrument to assess parkinsonian symptoms and related extrapyramidal side effects. All 10 items were anchored on a 5-point scale: range 0 (absence of condition, normal) to 4 (the most extreme form of condition). Total score is sum of individual item scores, ranged from 0 (normal) to 40 (most extreme symptoms and effects); higher score indicates more affected. Rows with only non-zero data/values for change in SARS total score at specified time points, for at least 1 reporting arm, are reported below.

BAS: clinician rated scale to assess akathisia by determining the degree of subjective restlessness and distress associated with restlessness. Global clinical assessment of akathisia subscale score of BAS, was rated on a 6-point scale range 0 (no symptoms) to 5 (maximum severity of symptoms); higher score indicates increased severity.

AIMS: clinician rated 12-item scale to document occurrences of dyskinesia in participants, specifically tardive dyskinesia. Items 1 to 10, scored as 0 (none) to 4 (severe); higher score indicates greater severity. Items 11 to 12 are questions with No or Yes response. Only the sum of the first 7 items were calculated to evaluate AIMS movement cluster subscale score, giving it a possible score range of 0 (none) to 28 (maximum severity), higher scores indicate greater severity. Rows with only non-zero data/values for change in AIMS-movement cluster subscale score at specified time points, for at least 1 reporting arm, are reported below.

C-SSRS: a measure used to identify and assess participants at risk for suicide. It is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. C-SSRS items were mapped to the following C-CASA categories: completed suicide, attempted suicide (actual attempt; aborted attempt; interrupted attempt), non-suicidal self-injurious behavior, preparatory acts, suicidal ideation (wish to be dead; non-specific active suicidal thoughts; active suicidal ideation with any methods [not plan], without intent to act; active suicidal ideation with some intent to act, without specific plan; active suicidal ideation with specific plan and intent; self-injurious behavior, no suicidal intent). C-CASA categories with at least 1 participant, for specified time points, for at least 1 reporting arm are reported below.

CDRS-R: clinician-rated interview-based scale to assess 17 distinct symptom areas to derive an index of depression severity. Each symptom area was rated on a 7-point scale; range from 1 (no impairment) to 17 (maximum impairment). Total CDRS-R score was calculated as sum of responses for each 7 symptom areas. Total CDRS-R score ranged from 17 (no impairment) to 119 (maximum impairment); higher score indicated greater impairment.

YMRS: an 11-item scale that measured the severity of manic episodes. Four items (irritability, speech, thought content, and disruptive/ aggressive behavior) were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score was sum of score of all 11 items and ranged from 0 (no symptoms) to 60 (extreme severity of symptoms), higher score indicated higher severity of mania.

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state. CGI-S score ranged from 1 (not ill at all) to 7 (among the most extremely ill), higher scores indicated more severity of illness.

CGAS: a clinician-rated global assessment item for children, based on symptoms and social functioning in home, school, and community settings. Scores ranged from 1 (extremely impaired) to 100 (doing very well), where higher levels indicate better health.