BIIB118

The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) mood (average of 2 items \[total range 0 to 100, where higher scores indicated elevated mood\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1.

The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) mood (average of 2 items \[total range 0 to 100, where higher scores indicated elevated mood\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1.

The Bond and Lader Visual Analogue Scales (VAS) monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) mood (average of 2 items \[total range 0 to 100, where higher scores indicated elevated mood\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1.

The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts toward imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), 4: any suicidal behavior or ideation, suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). The new onset and worsening of post-baseline suicidality for C-SSRS was reported.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; The event has a causal relationship with the treatment or usage.

The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, MCV, MCH, MCHC, platelets, white blood cell count, absolute lymphocytes, absolute total neutrophils, absolute basophils, absolute eosinophils and absolute monocytes), coagulation (PPT, prothrombin, PT international, ratio and fibrinogen, liver function(total bilirubin, direct bilirubin, aspartate, AST, Alanine, ALT, gamma GT, alkaline phosphatase, total protein and albumin), renal function (blood urea nitrogen, creatinine, HDL cholesterol, LDL cholesterol, triglycerides), Electrolytes (sodium, potassium, chloride, calcium, phosphate, venous bicarbonate), clinical chemistry (glucose, creatinine kinase), urinalysis dipstick (urine PH, urine glucose, urine ketones, urine protein, urine blood, urine urobilinogen, urine nitrite, urine leukocyte, esterase), urinalysis microscopy (urine RBC, urine WBC, urine casts, urine bacteria), miscellaneous (absolute lymphocyte marker CD4, CD8, CD19)

Number of participants with vital signs data of absolute values meeting categorical criteria was reported as following: (1) Supine systolic BP \< 90 mmHg; (2) Supine Diastolic BP \< 50 mmHg; (3) Supine Pulse Rate \< 40 BPM ; (4) Supine Pulse Rate \> 120 BPM.

Number of participants with vital signs data of increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine systolic BP \>= 30 mmHg; Criterion B: maximum increase from baseline in supine diastolic BP \>= 20 mmHg. Baseline was defined as the last available recording prior to dosing.

Number of participants with vital signs data of increase from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine systolic BP \>= 30 mmHg; Criterion B: maximum decrease from baseline in supine diastolic BP \>= 20 mmHg. Baseline was defined as the last available recording prior to dosing.

Number of participants with ECG data of absolute values meeting categorical criteria was reported as following: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>= 300 msec; Criterion B: maximum QRS complex (time from Q wave to the end of S wave, corresponding to ventricle depolarization)\>= 140 msec; Criterion C: Maximum QT interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole)\>= 500 msec; Criterion D: maximum QTC interval (QT interval corrected for heart rate) 450-\<480 msec; Criterion E: maximum QTC interval 480-\<500 msec; Criterion F: maximum QTC interval \>=500 msec; Criterion G: maximum QTCF interval (QT interval corrected for heart rate using Fridericia's formula) 450 -\< 480 msec; Criterion H: maximum QTCF interval 480 -\< 500 msec; Criterion I: maximum QTCF interval \>=500 msec.

Number of participants with ECG Data of increase from baseline meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>=25/50%; Criterion B: maximum QRS complex increase from baseline PctChg \>=50%; Criterion C: maximum QTC interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate) increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTC interval increase from baseline change \>=60 msec; Criterion E: maximum QTCF (Fridericia's correction) interval increase from baseline 30\<=change\<60; Criterion F: maximum QTCF interval increase from baseline change \>=60 msec. Baseline was defined as the average of the triplicate measurements prior to dosing on Day 1.

Physical examination included examination of ears, eyes, gastrointestinal, head, heart, lungs, lymph nodes, mouth, musculoskeletal, nose, skin. The number of participants with new-intensified physical examination findings were reported.

The number of participants with new-intensified neurological examination findings were reported.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (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.

Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(\<)0.8\*lower limit of normal(LLN), MCV,MCH,MCHC,MPV:\<0.9\*LLN or \>1.1\*upper limit of normal(ULN), platelet:\<0.5\*LLN or \>1.75\*ULN, white blood cell(WBC):\<0.6\*LLNor\>1.5\*ULN, lymphocyte,neutrophil,total neutrophil:\<0.8\*LLN or \>1.2\*ULN,basophil,eosinophil,monocyte:\>1.2\*ULN; PTT, PT:\>1.1\*ULN,Fibrinogen\<0.75\*ULNor\>1.25ULN; total, direct, indirect bilirubin \>1.5\*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,alkaline phosphatase:\> 3.0\*ULN,total protein,albumin:\<0.8\*LLN or \>1.2\*ULN;blood urea nitrogen,creatinine:\>1.3\*ULN,uric acid\>1.2\*ULN;sodium:\<0.95\*LLN or\>1.05\*ULN,potassium,chloride, calcium,magnesium,bicarbonate:\<0.9\*LLN or \>1.1\*ULN, phosphate\<0.8\*LLN or \>1.2\*ULN; glucose \<0.6\*LLN or \>1.5\*ULN,creatine kinase\>2.0\*ULN;urine(specific gravity\<1.003or\>1.030,pH \<4.5or\>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals\>=1,RBC,WBC \>=20\*ULN,bacteria\>20);CSF (WBC\>=6,RBC\>0,Albumin\>35).

Criteria for clinically significant change from baseline in vital signs: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm. Maximum increase or decrease from baseline in supine SBP greater than or equal to (\>=)30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.

ECG parameters included maximum pulse rate (PR) interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for abnormal ECG: Maximum PR interval \>=300 milliseconds (msec) or \>=25 percent increase when baseline is \>200 msec and \>=50 percent increase when baseline is less than or equal to (=\<) 200 msec; QRS interval \>=140 msec or \>=50 percent increase from baseline (IFB); and QTcF 30\<=change\<60 or change\>=60 msec increase. The number of participants with abnormal ECG findings are reported.

The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.

The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.

The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.

ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.

ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.