Trial Outcomes & Findings for Safety and Efficacy of Ziprasidone in Children and Adolescents With Bipolar I Disorder (Manic or Mixed) (NCT NCT00257166)

Last Updated: 2021-03-03

Results Overview

YMRS: an 11-item scale that measured the severity of manic episodes. Four items 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 ranged from 0 to 60, higher score indicated higher severity of mania.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

238 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2021-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	Ziprasidone Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Overall Study STARTED	150	88
Overall Study Treated	149	88
Overall Study COMPLETED	97	51
Overall Study NOT COMPLETED	53	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Ziprasidone Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Overall Study Adverse Event	18	13
Overall Study Laboratory abnormality	1	0
Overall Study Lost to Follow-up	8	1
Overall Study Withdrawal by Subject	9	2
Overall Study Other	16	21
Overall Study Randomized, but not treated	1	0

Baseline Characteristics

Safety and Efficacy of Ziprasidone in Children and Adolescents With Bipolar I Disorder (Manic or Mixed)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ziprasidone n=149 Participants Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=88 Participants Placebo matched to ziprasidone capsule orally twice daily up to Week 4.	Total n=237 Participants Total of all reporting groups
Age, Customized 10 to 13 years	74 participants n=93 Participants	35 participants n=4 Participants	109 participants n=27 Participants
Age, Customized 14 to 17 years	74 participants n=93 Participants	53 participants n=4 Participants	127 participants n=27 Participants
Age, Customized >=18 years	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Sex: Female, Male Female	65 Participants n=93 Participants	41 Participants n=4 Participants	106 Participants n=27 Participants
Sex: Female, Male Male	84 Participants n=93 Participants	47 Participants n=4 Participants	131 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Intent-to-treat (ITT): all randomized participants who had baseline measurements, took at least (\>=) 1 dose of study medication (ziprasidone or placebo) and had \>=1 post-baseline visit. Here, 'n' signifies those participants who were available for this measure at given time points for each group.

Outcome measures

Outcome measures
Measure	Ziprasidone n=143 Participants Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=86 Participants Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 Baseline (n=143,86)	26.2 units on a scale Standard Deviation 6.6	27.0 units on a scale Standard Deviation 6.6
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 Change at Week 4 (n=97,51)	-13.8 units on a scale Standard Deviation 7.8	-9.9 units on a scale Standard Deviation 7.7

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3

Population: ITT population. 'N' (number of participants analyzed) signifies those participants who were available for this measure. 'n' signifies those participants who were available for this measure at given time points for each group respectively.

Outcome measures

Outcome measures
Measure	Ziprasidone n=131 Participants Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=85 Participants Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 Change at Week 1 (n=131,85)	-9.3 units on a scale Standard Deviation 7.5	-6.3 units on a scale Standard Deviation 7.1
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 Change at Week 2 (n=120,81)	-11.5 units on a scale Standard Deviation 8.7	-8.1 units on a scale Standard Deviation 7.9
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 Change at Week 3 (n=108,65)	-13.0 units on a scale Standard Deviation 8.1	-9.0 units on a scale Standard Deviation 7.3

SECONDARY outcome

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

Population: ITT population. Here, 'n' signifies those participants who were available for this measure at given time points for each group respectively.

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).

Outcome measures

Outcome measures
Measure	Ziprasidone n=143 Participants Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=86 Participants Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 Baseline (n=143,86)	4.5 units on a scale Standard Deviation 0.7	4.5 units on a scale Standard Deviation 0.7
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 Change at Week 1 (n=131,85)	-0.9 units on a scale Standard Deviation 0.8	-0.5 units on a scale Standard Deviation 0.9
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 Change at Week 2 (n=120,82)	-1.1 units on a scale Standard Deviation 1.0	-0.6 units on a scale Standard Deviation 0.9
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 Change at Week 3 (n=108,65)	-1.3 units on a scale Standard Deviation 1.0	-0.7 units on a scale Standard Deviation 1.0
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 Change at Week 4 (n=96,51)	-1.4 units on a scale Standard Deviation 1.1	-0.9 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Week 1, 2, 3, 4

Population: ITT population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were available for this measure at given time points for each group respectively.

CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.

Outcome measures

Outcome measures
Measure	Ziprasidone n=132 Participants Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=85 Participants Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Clinical Global Impression - Improvement (CGI-I) Score Week 1 (n=132,85)	2.8 units on a scale Standard Deviation 0.9	3.4 units on a scale Standard Deviation 0.9
Clinical Global Impression - Improvement (CGI-I) Score Week 2 (n=120,82)	2.5 units on a scale Standard Deviation 1.1	3.2 units on a scale Standard Deviation 1.1
Clinical Global Impression - Improvement (CGI-I) Score Week 3 (n=108,65)	2.4 units on a scale Standard Deviation 1.0	3.1 units on a scale Standard Deviation 1.3
Clinical Global Impression - Improvement (CGI-I) Score Week 4 (n=96,51)	2.3 units on a scale Standard Deviation 1.0	2.8 units on a scale Standard Deviation 1.1

Adverse Events

Ziprasidone

Serious events: 6 serious events

Other events: 128 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ziprasidone n=149 participants at risk Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=88 participants at risk Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Nervous system disorders Dystonia	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Overdose	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Viral infection	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicidal ideation	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 3/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Liver function test abnormal	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Mania	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Aggression	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 2/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Hypersexuality	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Bipolar I disorder	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Bipolar disorder	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Hallucination	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Paranoia	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

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=149 participants at risk Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo n=88 participants at risk Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Eye disorders Vision blurred	6.0% 9/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	5.4% 8/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 3/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	14.1% 21/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 6/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	8.1% 12/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	15.4% 23/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 6/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	5.4% 8/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Overdose	4.0% 6/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 5/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.4% 8/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Akathisia	5.4% 8/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	12.8% 19/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 2/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	22.1% 33/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	21.6% 19/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Sedation	32.9% 49/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 5/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	24.8% 37/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.0% 7/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Tremor	6.0% 9/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	9.4% 14/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 3/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Restlessness	5.4% 8/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 1/88 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.