Trial Outcomes & Findings for Efficacy and Safety Trial of Flexible Doses of Oral Ziprasidone in Children and Adolescents With Bipolar I Disorder (NCT NCT02075047)

NCT ID: NCT02075047

Last Updated: 2021-06-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

171 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2021-06-16

Participant Flow

The study was conducted in the United States and Ukraine. Study started on 23 May 2014 and completed on 18 May 2020. Total 171 participants were randomized to treatment, of which 86 received study medication.

Participant milestones

Participant milestones
Measure	Ziprasidone Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Treatment Phase (4 Weeks) STARTED	86	85
Treatment Phase (4 Weeks) COMPLETED	63	75
Treatment Phase (4 Weeks) NOT COMPLETED	23	10
Follow up Phase (5 Weeks) STARTED	86	85
Follow up Phase (5 Weeks) COMPLETED	60	72
Follow up Phase (5 Weeks) NOT COMPLETED	26	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Ziprasidone Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Treatment Phase (4 Weeks) Adverse Event	14	4
Treatment Phase (4 Weeks) Lack of Efficacy	2	2
Treatment Phase (4 Weeks) Lost to Follow-up	0	1
Treatment Phase (4 Weeks) Medication Error Without Associated Adverse Event	1	0
Treatment Phase (4 Weeks) Screen Failure	1	0
Treatment Phase (4 Weeks) Other	1	1
Treatment Phase (4 Weeks) Withdrawal By Parent/Guardian	4	2
Follow up Phase (5 Weeks) Adverse Event	14	4
Follow up Phase (5 Weeks) Lack of Efficacy	2	2
Follow up Phase (5 Weeks) Lost to Follow-up	0	1
Follow up Phase (5 Weeks) Medication Error Without Associated Adverse Event	1	0
Follow up Phase (5 Weeks) Screen Failure	1	0
Follow up Phase (5 Weeks) Other	1	2
Follow up Phase (5 Weeks) Withdrawal By Parent/Guardian	7	4

Baseline Characteristics

Efficacy and Safety Trial of Flexible Doses of Oral Ziprasidone in Children and Adolescents With Bipolar I Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Total n=171 Participants Total of all reporting groups
Age, Customized 10 - >14 Years	46 Participants n=5 Participants	44 Participants n=7 Participants	90 Participants n=5 Participants
Age, Customized 14-17 Years	40 Participants n=5 Participants	41 Participants n=7 Participants	81 Participants n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	47 Participants n=7 Participants	95 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	38 Participants n=7 Participants	76 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants n=5 Participants	71 Participants n=7 Participants	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	59 Participants n=5 Participants	55 Participants n=7 Participants	114 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Intent-to-treat (ITT) included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 4	-16.51 units on a scale Standard Error 1.15	-12.29 units on a scale Standard Error 1.10

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3, 4

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

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

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Weeks 1, 2, 3, and 4 Change at Week 1	-0.91 units on a scale Standard Error 0.10	-0.47 units on a scale Standard Error 0.10
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Weeks 1, 2, 3, and 4 Change at Week 2	-1.13 units on a scale Standard Error 0.12	-0.91 units on a scale Standard Error 0.12
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Weeks 1, 2, 3, and 4 Change at Week 3	-1.53 units on a scale Standard Error 0.13	-1.14 units on a scale Standard Error 0.13
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Weeks 1, 2, 3, and 4 Change at Week 4	-1.59 units on a scale Standard Error 0.14	-1.32 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Weeks 1, 2, and 3 Change at Week 1	-11.43 units on a scale Standard Error 0.94	-5.58 units on a scale Standard Error 0.93
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Weeks 1, 2, and 3 Change at Week 2	-13.70 units on a scale Standard Error 1.02	-9.53 units on a scale Standard Error 1.01
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Weeks 1, 2, and 3 Change at Week 3	-16.79 units on a scale Standard Error 1.04	-11.17 units on a scale Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3, 4

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

CGI-I: 7-point clinician rated scale which rates the participant's improvement or worsening from baseline, ranging from 1 (very much improved) to 7 (very much worse), higher scores indicate less improvement.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Clinical Global Impression of Improvement (CGI-I) Scores at Weeks 1, 2, 3, and 4 Change at Week 1	2.89 units on a scale Standard Error 0.11	3.41 units on a scale Standard Error 0.11
Clinical Global Impression of Improvement (CGI-I) Scores at Weeks 1, 2, 3, and 4 Change at Week 2	2.75 units on a scale Standard Error 0.12	2.89 units on a scale Standard Error 0.12
Clinical Global Impression of Improvement (CGI-I) Scores at Weeks 1, 2, 3, and 4 Change at Week 3	2.42 units on a scale Standard Error 0.12	2.68 units on a scale Standard Error 0.12
Clinical Global Impression of Improvement (CGI-I) Scores at Weeks 1, 2, 3, and 4 Change at Week 4	2.30 units on a scale Standard Error 0.13	2.64 units on a scale Standard Error 0.13

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks)

Population: The safety analysis set included all participants who were randomized and took at least 1 dose of study medication (ziprasidone or placebo).

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	67 Participants	50 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	3 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (2 Weeks prior to Day 1), Baseline (Day 1), Week 1, 2, 3, 4, Early Termination Visit (anytime from Day 1 to Week 4), Follow up Visit (anytime from Day 1 up to 5 weeks after last dose of study drug = anytime from Day 1 to Week 9)

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit. Here 'number analyzed' signifies number of participants evaluable for each specified row.

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). Rows according to C-CASA categories at specified time points are reported in this outcome measure, only when there was non-zero data/values for at least 1 reporting arm.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Screening: Actual Attempt	5 Participants	3 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Screening: Interrupted Attempt	0 Participants	1 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Screening: Non-Suicidal Self-Injurious Behavior	10 Participants	5 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Screening: Preparatory Acts	0 Participants	1 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Screening: Non-specific Active Suicidal Thoughts	16 Participants	13 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline: Wish To Be Dead	1 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline: Active Suicidal Thoughts With No Plan, Intent	4 Participants	7 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline: Active Suicidal Thoughts With Plan, Intent	4 Participants	3 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4: Non-Suicidal Self-Injurious Behavior	1 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4: Wish To Be Dead	2 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4: Non-specific Active Suicidal Thoughts	1 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Early Termination: Wish To Be Dead	1 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Early Termination: Active Suicidal Thoughts With No Plan, Intent	1 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Follow up: Actual Attempt	1 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Follow up: Wish To Be Dead	2 Participants	0 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Screening: Wish To Be Dead	25 Participants	25 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline: Active Suicidal Thoughts With No Plan, Some Intent	2 Participants	3 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Week 1: Wish To Be Dead	0 Participants	1 Participants
Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Early Termination: Non-specific Active Suicidal Thoughts	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (2 Weeks prior to Day 1) up to 1 Week after administration of the final dose of study medication (maximum for 7 Weeks)

Population: The safety analysis set included all participants who were randomized and took at least 1 dose of study medication (ziprasidone or placebo).

Concomitant medications or treatments were those prescription and over-the-counter drugs and supplements or non drug treatment/procedures other than the study medication.

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Number of Participants Who Took at Least 1 Concomitant Medication and Concomitant Non-Drug Treatments/Procedures Concomitant Medication	55 Participants	47 Participants
Number of Participants Who Took at Least 1 Concomitant Medication and Concomitant Non-Drug Treatments/Procedures Concomitant Non-Drug Treatments/Procedures	6 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (2 Weeks prior to Day 1) up to 1 Week after administration of the final dose of study medication (maximum for 7 Weeks)

Population: The safety analysis set included all participants who were randomized and took at least 1 dose of study medication (ziprasidone or placebo). Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure.

Criteria: Hematology-hemoglobin(Hg),hematocrit,erythrocytes(ery)\<0.8\*LLN,ery mean corpuscular volume \<0.9\*LLN\>1.1\*ULN,platelets\<0.5\*LLN\>1.75\*ULN,leukocytes(leu)\<0.6\*LLN\>1.5\*ULN,lymphocytes(lym),lym/leu,neutrophils(neu),neu/leu\<0.8\*LLN\>1.2\*ULN,basophils (bas),bas/leu, eosinophils(eos), eos/leu, monocytes(mon),mon/leu\>1.2\*ULN; Clinical chemistry bilirubin: total, direct, indirect\>1.5\*ULN, aspartate aminotransferase,alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase,alkaline phosphatase\>3.0\*ULN,protein,albumin\<0.8\*LLN\>1.2\*ULN,blood urea nitrogen,creatinine\>1.3\*ULN, urate\>1.2\*ULN,HDL\<0.8\*LLN;LDL\>1.2\*ULN cholesterol(CH),sodium\<0.95\*LLN\>1.05\*ULN,potassium, chloride,calcium,magnesium,bicarbonate\<0.9\*LLLN\>1.1\*ULN,phosphate,free thyroxine,thyroid stimulating hormone\<0.8\*LLN\>1.2\*ULN,prolactin\>1.1\*ULN,glucose\<0.6\*LLN\>1.5\*ULN,HgA1C,CH, triglycerides\>1.3\*ULN,creatine kinase\>2.0\*ULN; Urinalysis-specific gravity\<1.003\>1.030,pH\<4.5 \>8,urine glucose, protein, Hg, ketones:\>=1.

Outcome measures

Outcome measures
Measure	Ziprasidone n=84 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Number of Participants With Laboratory Abnormalities	50 Participants	62 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (2 Weeks prior to Day 1) up to Week 4

Population: The safety analysis set included all participants who were randomized and took at least 1 dose of study medication (ziprasidone or placebo).

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.

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Number of Participants With Physical Examination Abnormalities	4 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3, 4, Early Termination Visit (anytime from Day 1 to Week 4), Follow up Visit (anytime from Day 1 up to 5 weeks after last dose of study drug = anytime from Day 1 to Week 9)

Population: The safety analysis set included all participants who were randomized and took at least 1 dose of study medication (ziprasidone or placebo). Here 'number analyzed' signifies number of participants evaluable for each specified row.

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

Outcome measures

OTHER_PRE_SPECIFIED outcome

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

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting, Baseline	79.1 beats per minute Standard Deviation 12.58	75.8 beats per minute Standard Deviation 9.80
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting, Change at Week 1	-0.9 beats per minute Standard Deviation 11.24	-2.0 beats per minute Standard Deviation 9.40
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting, Change at Week 2	-2.4 beats per minute Standard Deviation 11.75	1.5 beats per minute Standard Deviation 8.82
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting, Change at Week 3	-0.5 beats per minute Standard Deviation 12.79	2.3 beats per minute Standard Deviation 10.61
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting, Change at Week 4	-2.3 beats per minute Standard Deviation 11.49	-0.2 beats per minute Standard Deviation 10.30
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Early Termination: Sitting	3.5 beats per minute Standard Deviation 14.02	1.6 beats per minute Standard Deviation 7.02
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Follow up: Sitting	2.0 beats per minute Standard Deviation 11.32	3.1 beats per minute Standard Deviation 11.73
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing, Baseline	84.6 beats per minute Standard Deviation 12.23	83.3 beats per minute Standard Deviation 10.95
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing, Change at Week 1	2.1 beats per minute Standard Deviation 10.77	-2.2 beats per minute Standard Deviation 10.18
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing, Change at Week 2	-0.4 beats per minute Standard Deviation 12.25	1.9 beats per minute Standard Deviation 10.19
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing, Change at Week 3	1.4 beats per minute Standard Deviation 13.54	2.6 beats per minute Standard Deviation 11.70
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing, Change at Week 4	-0.7 beats per minute Standard Deviation 11.77	-0.6 beats per minute Standard Deviation 12.83
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Early Termination: Standing	7.9 beats per minute Standard Deviation 13.98	-6.2 beats per minute Standard Deviation 21.12
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Follow up: Standing	5.4 beats per minute Standard Deviation 10.15	4.5 beats per minute Standard Deviation 11.67

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4, Early Termination Visit (anytime from Day 1 to Week 4)

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

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Height, Change at Week 4	0.4 centimeter Standard Deviation 0.60	0.7 centimeter Standard Deviation 1.77
Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Height, Change at Early Termination	0.2 centimeter Standard Deviation 0.54	0.5 centimeter Standard Deviation 0.73
Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Waist Circumference, Baseline	76.9 centimeter Standard Deviation 12.22	74.9 centimeter Standard Deviation 10.56
Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Waist Circumference, Change at Week 4	-0.1 centimeter Standard Deviation 2.79	0.3 centimeter Standard Deviation 3.26
Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Waist Circumference, Change at Early Termination	0.4 centimeter Standard Deviation 3.77	1.0 centimeter Standard Deviation 1.74
Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Height, Baseline	157.9 centimeter Standard Deviation 10.63	159.7 centimeter Standard Deviation 11.41

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4, Early Termination Visit (anytime from Day 1 to Week 4)

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

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Body Weight at Week 4 and Early Termination Visit Baseline	57.5 kilogram Standard Deviation 14.52	58.0 kilogram Standard Deviation 14.54
Change From Baseline in Body Weight at Week 4 and Early Termination Visit Change at Week 4	0.3 kilogram Standard Deviation 1.97	0.8 kilogram Standard Deviation 2.04
Change From Baseline in Body Weight at Week 4 and Early Termination Visit Change at Early Termination	-0.3 kilogram Standard Deviation 1.75	1.0 kilogram Standard Deviation 1.46

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4, Early Termination Visit (anytime from Day 1 to Week 4)

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

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Body Mass Index (BMI) at Week 4 and Early Termination Visit Baseline	22.8 kilogram per meter square Standard Deviation 4.15	22.5 kilogram per meter square Standard Deviation 3.76
Change From Baseline in Body Mass Index (BMI) at Week 4 and Early Termination Visit Change at Week 4	0.1 kilogram per meter square Standard Deviation 0.79	0.2 kilogram per meter square Standard Deviation 0.92
Change From Baseline in Body Mass Index (BMI) at Week 4 and Early Termination Visit Change at Early Termination	-0.3 kilogram per meter square Standard Deviation 0.95	0.3 kilogram per meter square Standard Deviation 0.51

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 4, Early Termination Visit (anytime from Day 1 to Week 4)

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.

Outcome measures

Outcome measures
Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Body Mass Index (BMI) Z-score at Week 4 and Early Termination Visit Baseline	0.8 z-score Standard Deviation 0.87	0.7 z-score Standard Deviation 0.82
Change From Baseline in Body Mass Index (BMI) Z-score at Week 4 and Early Termination Visit Change at Week 4	0.0 z-score Standard Deviation 0.18	-0.0 z-score Standard Deviation 0.24
Change From Baseline in Body Mass Index (BMI) Z-score at Week 4 and Early Termination Visit Change at Early Termination	-0.0 z-score Standard Deviation 0.15	-0.0 z-score Standard Deviation 0.22

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (2 Weeks prior to Day 1) up to 1 Week after administration of the final dose of study medication (maximum for 7 Weeks)

Population: The safety analysis set included all participants who were randomized and took at least 1 dose of study medication (ziprasidone or placebo). Here ' Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure.

Pre-defined categories for ECG were: heart rate intervals - QT interval corrected using the Fridericia's formula (QTCF) value greater than or equal to (\>=450) millisecond (msec), \>=460 msec, \>=480 msec, \>=500 msec, \>=30 msec increase, \>=60 msec increase, \>=75 msec increase, QT interval corrected using the Bazett's correction (QTCB) value \>=450 msec, \>=460 msec, \>=480 msec, \>=500 msec, \>=30 msec increase, \>=60 msec increase, \>=75 msec increase, PR value \>=25 percentage increase, QRS value \>=25 percentage increase, QT value \>=25 percentage increase, Respiratory rate (RR) value \>=25 percentage increase, and Heart rate (HR) value \>=25 percentage increase. Rows according to ECG pre-defined categories are reported in this outcome measure, only when there was non-zero data/values for at least 1 reporting arm.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcF at >=450 msec	3 Participants	1 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcF at >=460 msec	1 Participants	0 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcF at >=30 msec increase	9 Participants	4 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcB at >=450 msec	14 Participants	7 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcB at >=460 msec	8 Participants	3 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcB at >=480 msec	1 Participants	0 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QRS at >=25% increase	3 Participants	1 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings RR at >=25% increase	12 Participants	14 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings HR at >=25% increase	18 Participants	9 Participants
Number of Participants With Pre-defined Categories of Electrocardiogram (ECG) Findings QTcB at >=30 msec increase	16 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3, 4, Early Termination Visit (anytime from Day 1 to Week 4)

CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (maximum impairment). Higher scores indicated greater impairment. Total score calculated as sum of the 17 items ranged from 17 (no impairment) to 119 (maximum impairment); higher score indicated greater impairment.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Weeks 1, 2, 3, and 4 and Early Termination Visit Baseline	29.0 units on a scale Standard Deviation 6.62	28.3 units on a scale Standard Deviation 5.74
Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Weeks 1, 2, 3, and 4 and Early Termination Visit Change at Week 1	-2.5 units on a scale Standard Deviation 5.78	-0.8 units on a scale Standard Deviation 4.85
Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Weeks 1, 2, 3, and 4 and Early Termination Visit Change at Week 2	-2.9 units on a scale Standard Deviation 6.31	-2.4 units on a scale Standard Deviation 5.37
Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Weeks 1, 2, 3, and 4 and Early Termination Visit Change at Week 3	-3.7 units on a scale Standard Deviation 6.39	-3.3 units on a scale Standard Deviation 6.15
Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Weeks 1, 2, 3, and 4 and Early Termination Visit Change at Week 4	-3.6 units on a scale Standard Deviation 6.53	-3.8 units on a scale Standard Deviation 5.99
Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Weeks 1, 2, 3, and 4 and Early Termination Visit Change at Early Termination	2.3 units on a scale Standard Deviation 10.46	-1.2 units on a scale Standard Deviation 4.60

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3, 4

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

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 SARS score is sum of all individual item scores, and ranged from 0 (normal) to 40 (most extreme symptoms and effects); higher score indicates more affected.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Weeks 1, 2, 3, and 4 Change at Week 3	0.11 units on a scale Standard Error 0.05	-0.00 units on a scale Standard Error 0.05
Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Weeks 1, 2, 3, and 4 Change at Week 1	0.09 units on a scale Standard Error 0.04	-0.01 units on a scale Standard Error 0.04
Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Weeks 1, 2, 3, and 4 Change at Week 2	0.11 units on a scale Standard Error 0.05	-0.00 units on a scale Standard Error 0.05
Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Weeks 1, 2, 3, and 4 Change at Week 4	0.09 units on a scale Standard Error 0.04	-0.00 units on a scale Standard Error 0.04

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3, 4

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

BAS: clinician rated scale to assess akathisia by determining the degree of subjective restlessness and distress associated with restlessness. First 3 items (objective, subjective, and distress related to restlessness) were rated on a 4-point scale with range 0 (no symptoms) to 3 (maximum severity of symptoms). Item 4, global clinical assessment of akathisia subscale, was rated on a 6-point scale, and ranged from 0 (no symptoms) to 5 (maximum severity of symptoms); higher score indicates increased severity.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Barnes Akathisia Rating Scale (BAS): Global Clinical Assessment of Akathisia Subscale Score at Weeks 1, 2, 3, and 4 Change at Week 1	-0.01 units on a scale Standard Error 0.01	0.02 units on a scale Standard Error 0.01
Change From Baseline in Barnes Akathisia Rating Scale (BAS): Global Clinical Assessment of Akathisia Subscale Score at Weeks 1, 2, 3, and 4 Change at Week 3	0.01 units on a scale Standard Error 0.02	0.01 units on a scale Standard Error 0.01
Change From Baseline in Barnes Akathisia Rating Scale (BAS): Global Clinical Assessment of Akathisia Subscale Score at Weeks 1, 2, 3, and 4 Change at Week 2	0.04 units on a scale Standard Error 0.03	0.04 units on a scale Standard Error 0.03
Change From Baseline in Barnes Akathisia Rating Scale (BAS): Global Clinical Assessment of Akathisia Subscale Score at Weeks 1, 2, 3, and 4 Change at Week 4	0.01 units on a scale Standard Error 0.01	-0.01 units on a scale Standard Error 0.01

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1, 2, 3, 4

Population: ITT included all randomized participants who had baseline measurements, took at least 1 dose of study medication (ziprasidone or placebo) and had at least 1 post-baseline visit.

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 score, giving a score range of 0 (none) to 28 (maximum severity), higher score indicates greater severity.

Outcome measures

Outcome measures
Measure	Ziprasidone n=85 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=83 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) - Movement Cluster Score at Weeks 1, 2, 3, and 4 Change at Week 1	0.03 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) - Movement Cluster Score at Weeks 1, 2, 3, and 4 Change at Week 2	0.03 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) - Movement Cluster Score at Weeks 1, 2, 3, and 4 Change at Week 3	0.08 units on a scale Standard Error 0.03	0.00 units on a scale Standard Error 0.03
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) - Movement Cluster Score at Weeks 1, 2, 3, and 4 Change at Week 4	0.05 units on a scale Standard Error 0.02	0.00 units on a scale Standard Error 0.02

Adverse Events

Ziprasidone

Serious events: 3 serious events

Other events: 65 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ziprasidone n=86 participants at risk Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 participants at risk Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
General disorders Chest pain	1.2% 1/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Injury, poisoning and procedural complications Sunburn	1.2% 1/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Anxiety	1.2% 1/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Suicidal ideation	1.2% 1/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Suicide attempt	1.2% 1/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ziprasidone n=86 Participants Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 Participants Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Change at Follow up	1.2 millimeter of mercury Standard Deviation 8.41	-2.1 millimeter of mercury Standard Deviation 12.89
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Change at Follow up	2.7 millimeter of mercury Standard Deviation 8.64	1.7 millimeter of mercury Standard Deviation 6.75
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Baseline	70.3 millimeter of mercury Standard Deviation 6.98	72.3 millimeter of mercury Standard Deviation 7.91
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Change at Week 1	1.5 millimeter of mercury Standard Deviation 7.40	-1.6 millimeter of mercury Standard Deviation 8.46
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Change at Follow up	-1.4 millimeter of mercury Standard Deviation 12.44	-2.2 millimeter of mercury Standard Deviation 8.35
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Baseline	110.7 millimeter of mercury Standard Deviation 9.53	112.0 millimeter of mercury Standard Deviation 10.16
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Change at Week 1	0.8 millimeter of mercury Standard Deviation 7.67	-2.5 millimeter of mercury Standard Deviation 10.38
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Change at Week 4	-0.8 millimeter of mercury Standard Deviation 9.50	-2.5 millimeter of mercury Standard Deviation 10.77
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Change at Early Termination	-2.1 millimeter of mercury Standard Deviation 10.14	5.6 millimeter of mercury Standard Deviation 13.58
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Change at Week 4	1.1 millimeter of mercury Standard Deviation 8.18	-0.6 millimeter of mercury Standard Deviation 10.22
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Change at Early Termination	-1.8 millimeter of mercury Standard Deviation 9.65	2.0 millimeter of mercury Standard Deviation 8.46
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Change at Week 1	0.7 millimeter of mercury Standard Deviation 6.90	0.2 millimeter of mercury Standard Deviation 8.71
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Change at Week 2	0.2 millimeter of mercury Standard Deviation 9.65	0.1 millimeter of mercury Standard Deviation 9.26
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Change at Follow up	-4.9 millimeter of mercury Standard Deviation 11.86	-4.4 millimeter of mercury Standard Deviation 10.01
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Baseline	68.8 millimeter of mercury Standard Deviation 7.99	70.3 millimeter of mercury Standard Deviation 7.94
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Change at Week 1	0.7 millimeter of mercury Standard Deviation 7.72	-1.5 millimeter of mercury Standard Deviation 8.49
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Change at Week 2	1.0 millimeter of mercury Standard Deviation 9.76	-0.6 millimeter of mercury Standard Deviation 9.40
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Diastolic Blood Pressure, Change at Week 3	0.2 millimeter of mercury Standard Deviation 9.36	0.1 millimeter of mercury Standard Deviation 8.03
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Change at Week 2	-0.1 millimeter of mercury Standard Deviation 7.83	-1.7 millimeter of mercury Standard Deviation 8.75
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Change at Week 3	-1.1 millimeter of mercury Standard Deviation 7.91	-1.6 millimeter of mercury Standard Deviation 10.27
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Change at Week 4	1.0 millimeter of mercury Standard Deviation 7.76	-0.5 millimeter of mercury Standard Deviation 9.83
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Diastolic Blood Pressure, Change at Early Termination	1.3 millimeter of mercury Standard Deviation 10.22	1.6 millimeter of mercury Standard Deviation 7.60
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Change at Week 2	0.1 millimeter of mercury Standard Deviation 9.13	-1.8 millimeter of mercury Standard Deviation 9.71
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Standing Systolic Blood Pressure, Change at Week 3	-0.1 millimeter of mercury Standard Deviation 9.68	-1.8 millimeter of mercury Standard Deviation 9.71
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Change at Week 3	-0.7 millimeter of mercury Standard Deviation 10.12	-0.6 millimeter of mercury Standard Deviation 8.93
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Change at Week 4	-0.7 millimeter of mercury Standard Deviation 10.60	-2.2 millimeter of mercury Standard Deviation 10.39
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Change at Early Termination	0.7 millimeter of mercury Standard Deviation 7.87	6.4 millimeter of mercury Standard Deviation 5.90
Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Sitting Systolic Blood Pressure, Baseline	110.5 millimeter of mercury Standard Deviation 9.84	110.9 millimeter of mercury Standard Deviation 11.45

Measure	Ziprasidone n=86 participants at risk Participants were randomized to receive ziprasidone capsules orally once daily for 4 weeks. Dose was titrated over the first 7-14 days of treatment, and the stable dose was maintained for remaining treatment period. Participants with body weight less than 45 kilogram (kg) received 60 to 80 milligram per day (mg/day) and participants with body weight greater than or equal to (\>=) 45 kg received 120 to 160 mg/day, as per investigator discretion. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).	Placebo n=85 participants at risk Participants were randomized to receive placebo capsules matched to ziprasidone once daily for 4 weeks. Participants after completion or discontinuation of treatment were followed-up to 35 days (5 weeks) after last dose in this study or were eligible to enroll in open label extension study A1281201 (NCT03768726).
Gastrointestinal disorders Abdominal pain upper	3.5% 3/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	1.2% 1/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Gastrointestinal disorders Diarrhoea	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	1.2% 1/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Gastrointestinal disorders Nausea	14.0% 12/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	5.9% 5/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Gastrointestinal disorders Salivary hypersecretion	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Gastrointestinal disorders Vomiting	10.5% 9/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	3.5% 3/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
General disorders Fatigue	22.1% 19/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	2.4% 2/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Infections and infestations Upper respiratory tract infection	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	3.5% 3/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Metabolism and nutrition disorders Decreased appetite	11.6% 10/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Metabolism and nutrition disorders Increased appetite	3.5% 3/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	1.2% 1/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Musculoskeletal and connective tissue disorders Joint stiffness	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Musculoskeletal and connective tissue disorders Myalgia	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Akathisia	5.8% 5/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Dizziness	7.0% 6/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	2.4% 2/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Headache	10.5% 9/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	9.4% 8/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Hypersomnia	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Sedation	9.3% 8/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	3.5% 3/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Somnolence	31.4% 27/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	8.2% 7/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Speech disorder	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Nervous system disorders Tremor	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Agitation	0.00% 0/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	4.7% 4/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Anxiety	3.5% 3/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Initial insomnia	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Insomnia	3.5% 3/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	1.2% 1/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Psychiatric disorders Irritability	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	0.00% 0/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.
Skin and subcutaneous tissue disorders Rash	2.3% 2/86 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.	1.2% 1/85 • Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE.