TAK-041

The DARS is a dynamic scale that measured desire, motivation, effort and consummatory pleasure across hedonic domains. The DARS is a self-report questionnaire that measured anhedonia across 4 domains: hobbies/past-times, food/drinks, social activities, and sensory experiences. The DARs was rated on a five-point Likert scale from 0 (not at all) to 4 (very much), higher values indicating less anhedonia. All items were summed up to a total score in the range of 0 to 68.

BACS is a reliable and sensitive measure of cognitive function in schizophrenia. The BACS consists of items across six subtests: Verbal Memory, Digit Sequencing, Token Motor, Verbal Fluency, Symbol Coding, and Tower of London. The subtest scale scores were used to compute a composite BACS t-score of 50 (20) is the mean (standard deviation) of a relevant index population. Higher values indicate better performance. Bayesian normal linear model was used for analysis.

Blood-oxygen-level-dependent imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time. The MID task is a reward anticipation paradigm that robustly engages the VS, a key area associated with coding incentive reward. Dysfunctional processing of reward information is associated with motivational impairments in schizophrenia. Motivational impairment is a key aspect of negative symptoms, and has been associated with reduced activity in the VS. Any change in BOLD signal that comes in fMRI is reported.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that occurred or worsened after receiving the first dose of study drug and within 6 weeks after the last dose of study drug. A TEAE may also have been a pre-treatment AE or a concurrent medical condition diagnosed before the date of first dose of study drug that increased in severity after the start of dosing.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment.

Clinical laboratory tests included serum chemistry, hematology and urinalysis. MAV criteria:Alanine aminotransferase(U/L) \>3 x upper limit of normal(ULN);albumin\<2.5g/dL,\<25g/L;alkaline phosphatase (U/L)\>3 x ULN; aspartate aminotransferase (U/L)\>3 x ULN;bicarbonate\<8.0 mmol/L; bilirubin\>2.0mg/dL, \>34.2 μmol/L;blood urea nitrogen\>30 mg/dL,\>10.7mmol/L;calcium\<7.0 mg/dL,\<1.75 mmol/L, \>11.5 mg/dL,\>2.88 mmol/L;chloride\<75 mmol/L,\>126 mmol/L;creatine kinase(U/L) \>5 xULN; creatinine\>2.0 mg/dL,\>177μmol/L;direct bilirubin\>2 x ULN;gamma glutamyl transferase (U/L)\>3 x ULN;glucose\<50 mg/dL,\<2.8 mmol/L,\>350 mg/dL,\>19.4 mmol/L;potassium\<3.0 mmol/L \>6.0 mmol/L; protein(g/L)\<0.8 x LLN \>1.2 x ULN;sodium\<130mmol/L \>150mmol/L;erythrocytes(10\^12erythrocytes/L) \<0.8 x LLN,\>1.2 x ULN;hematocrit(fraction of 1)\<0.8 x LLN,\>1.2xULN;hemoglobin(g/L)\<0.8 x LLN\>1.2 x ULN;leukocytes(10\^9 leukocytes/L)\<0.5 x LLN \>1.5 x ULN;platelets(10\^9 platelets/L)\<75-\>600. Categories with at least one participant are reported.

Vital signs included oral body temperature measurement, supine and standing blood pressure, respiration rate, and pulse. Pulse and blood pressure was measured after 5 minutes supine and again at 1 and 3 minutes after standing. The markedly abnormal value (MAV) criteria for vital signs included systolic blood pressure \< 85 mmHg, \> 180 mmHg; diastolic blood pressure \< 50 mmHg, \> 110 mmHg; pulse \< 50 beats/min, \> 120 beats/min; temperature \< 35.6 C \> 37.7 C. Categories with data in at least one arm group are reported.

The markedly abnormal value (MAV) criteria for 12-lead ECG parameters included ECG Mean Heart Rate \< 50 beats/min, \> 120 beats/min; PR Interval, Aggregate \<= 80 msec, \>= 200 msec; QRS Duration, Aggregate \<= 80 msec, \>= 180 msec; QTcB Interval, Aggregate \<= 300 msec, \>= 500 msec OR (\>= 30 msec change from baseline and \>= 450 msec); QTcF Interval, Aggregate \<= 300 msec, \>= 500 msec OR (\>= 30 msec change from baseline and \>= 450 msec). Categories with data in at least one arm group are reported.

The markedly abnormal value (MAV) criteria for continuous 12-lead Holter ECG parameters included ECG Mean Heart Rate \< 50 beats/min, \> 120 beats/min; PR Interval, Aggregate \<= 80 msec, \>= 200 msec; QRS Duration, Aggregate \<= 80 msec, \>= 180 msec; QTcB Interval, Aggregate \<= 300 msec, \>= 500 msec OR (\>= 30 msec change from baseline and \>= 450 msec); QTcF Interval, Aggregate \<= 300 msec, \>= 500 msec OR (\>= 30 msec change from baseline and \>= 450 msec). Categories with data in at least one arm group are reported.