Trial Outcomes & Findings for MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia (0249-016) (NCT NCT00506077)

Last Updated: 2015-08-03

Results Overview

The mean change from baseline after 4 weeks of treatment in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

Baseline and 4 weeks of treatment

Results posted on

2015-08-03

Participant Flow

First Patient Dosed: 11 February 2008; Last Patient Last Treatment: 08 October 2008. Six ex-U.S. study centers (3 Russia, 3 India).

At visit 1, patients were assessed using the protocol eligibility criteria. Eligible patients continued into an 8 day single-blind placebo washout/run-in period, and then were randomized at visit 3 to 1 of 2 cross-over treatment sequences.

Participant milestones

Participant milestones
Measure	MK0249 Then Placebo These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2.	Placebo Then MK0249 These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2.
Treatment Period 1 STARTED	28	27
Treatment Period 1 COMPLETED	24	24
Treatment Period 1 NOT COMPLETED	4	3
Washout STARTED	24	24
Washout COMPLETED	24	24
Washout NOT COMPLETED	0	0
Treatment Period 2 STARTED	24	24
Treatment Period 2 COMPLETED	23	23
Treatment Period 2 NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	MK0249 Then Placebo These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2.	Placebo Then MK0249 These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2.
Treatment Period 1 Adverse Event	2	1
Treatment Period 1 Lost to Follow-up	0	2
Treatment Period 1 Withdrawal by Subject	2	0
Treatment Period 2 Adverse Event	0	1
Treatment Period 2 Withdrawal by Subject	1	0

Baseline Characteristics

MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia (0249-016)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK0249 Then Placebo n=28 Participants These subjects received MK0249 during Treatment Period 1 and Placebo during Treatment Period 2.	Placebo Then MK0249 n=27 Participants These subjects received Placebo during Treatment Period 1 and MK0249 during Treatment Period 2.	Total n=55 Participants Total of all reporting groups
Age, Continuous	30.7 years STANDARD_DEVIATION 7.5 • n=5 Participants	32.5 years STANDARD_DEVIATION 8.4 • n=7 Participants	31.6 years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 4 weeks of treatment

Population: Full Analysis Set (FAS): The FAS included all randomized patients who took at lease one dose of study medication and had at least one post-randomization efficacy measurement in either of the two treatment periods. The data as observed (DAO) approach was used to handle missing data.

Outcome measures

Outcome measures
Measure	MK0249 n=47 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=46 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.	0.4 Composite T-score Interval -1.2 to 2.1	0.5 Composite T-score Interval -1.1 to 2.2

SECONDARY outcome

Timeframe: Baseline and 4 weeks of treatment

The Attention/Processing Speed Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Penn Continuous Performance Test (PCPT) and BACS battery Symbol Coding. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -91 and 91, respectively. Higher values (positive changes from baseline) indicate better performance.

Outcome measures

Outcome measures
Measure	MK0249 n=45 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=45 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score	0.5 Composite T-score Interval -0.4 to 1.5	0.0 Composite T-score Interval -0.9 to 0.9

SECONDARY outcome

Timeframe: Baseline and 4 weeks of treatment

The Episodic Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Face Memory and BACS battery Verbal Memory. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -202 and 202, respectively. Higher values (positive changes from baseline) indicate better performance.

Outcome measures

Outcome measures
Measure	MK0249 n=47 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=45 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score	0.9 Composite T-score Interval -0.9 to 2.6	0.1 Composite T-score Interval -1.6 to 1.8

SECONDARY outcome

Timeframe: Baseline and 4 weeks of treatment

The Working Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological (CNP) battery N-back test and the BACS battery Digit Sequencing test. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -122 and 122, respectively. Higher values (positive changes from baseline) indicate better performance.

Outcome measures

Outcome measures
Measure	MK0249 n=44 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=43 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score	0.8 Composite T-score Interval -1.0 to 2.6	-0.2 Composite T-score Interval -2.0 to 1.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-randomization Baseline

Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).

Outcome measures

Outcome measures
Measure	MK0249 n=47 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=46 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.	40.5 Composite T-score Standard Error 0.98	40.5 Composite T-score Standard Error 0.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-randomization Baseline

Outcome measures

Outcome measures
Measure	MK0249 n=45 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=45 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Pre-randomization Baseline: Attention/Processing Speed Composite Score	47.8 Composite T-score Standard Error 0.73	47.8 Composite T-score Standard Error 0.73

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-randomization Baseline

Outcome measures

Outcome measures
Measure	MK0249 n=47 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=45 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Pre-randomization Baseline: Episodic Memory Composite Score	43.9 Composite T-score Standard Error 1.16	43.9 Composite T-score Standard Error 1.16

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-randomization Baseline

Outcome measures

Outcome measures
Measure	MK0249 n=44 Participants 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=43 Participants 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Pre-randomization Baseline: Working Memory Composite Score	43.5 Composite T-score Standard Error 0.98	43.5 Composite T-score Standard Error 0.98

Adverse Events

MK0249

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK0249 n=52 participants at risk 10 mg per day of MK-0249 were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.	Placebo n=51 participants at risk 10 mg per day of matching placebo were taken orally for Treatment Period 1 or Treatment Period 2 (depending on the sequence). At any time after 3 days of double-blind treatment if patients who were unable to tolerate 10 mg per day, they were allowed to titrate down to 7 mg per day and remained on 7 mg per day for the remainder of the treatment period.
Gastrointestinal disorders nausea	7.7% 4/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	5.9% 3/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
General disorders irritability	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	5.9% 3/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Infections and infestations nasopharyngitis	1.9% 1/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	3.9% 2/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations alanine aminotransferase increased	1.9% 1/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	4.2% 2/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations aspartate aminotransferase increased	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	4.2% 2/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations blood creatine phosphokinase increased	1.9% 1/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations blood creatinine increased	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations blood urea increased	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations eosinophil count increased	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations lymphocyte count increased	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations neutrophil count decreased	0.00% 0/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations platelet count increased	1.9% 1/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	2.1% 1/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Investigations white blood cell count increased	1.9% 1/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	4.2% 2/48 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Musculoskeletal and connective tissue disorders pain in extremity	1.9% 1/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	3.9% 2/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Nervous system disorders headache	11.5% 6/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	3.9% 2/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Psychiatric disorders anxiety	9.6% 5/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	3.9% 2/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Psychiatric disorders insomnia	13.5% 7/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	7.8% 4/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.
Psychiatric disorders middle insomnia	3.8% 2/52 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.	0.00% 0/51 • Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up. Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) were administered at visit 1 (V1), visit 6 (V6), and visit 10 (V10) to help assess for certain AEs.