A Study to Assess the Safety and Efficacy of ASP4345 as Add-on Treatment for Cognitive Impairment in Subjects With Schizophrenia on Stable Doses of Antipsychotic Medication

The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB neurocognitive composite score is a standardized mean of the six domain scores (excluding social cognition). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher score indicates less impairment.

Time frame: Baseline and week 12/end of treatment (EoT)

Population: The full analysis set (FAS) consisted of all participants who were randomized and received at least 1 dose of study drug and had at least 1 postbaseline MCCB measurement. FAS population with available data at baseline and week12/EoT.

Treatment emergent adverse event (TEAE) is defined as an AE observed after starting administration of the study drug and 28 days after the last dose of study drug. A study drug-related TEAE is defined as any TEAE with at least possible relationship to study treatment as assessed by the investigator or with missing assessment of the causal relationship. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, metabolic parameters etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant.

Time frame: Baseline up to end of study (EoS) (week 14)

Population: The safety analysis set (SAF) consisted of all participants who took at least 1 dose of study drug.

AIMS is a 14-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 to 14 are yes/no questions regarding the global judgement and dental status of the participant. The total score is the sum of the scores for the 14 items and the possible total score ranges from 0 to 44. A higher total score is indicative of more severe dyskinetic movements.

Time frame: Baseline, week 6 and week 12

Population: SAF population with available data at each time point.

BARS is used to rate observable, restless movements of drug induced akathisia and subjective awareness of restlessness and any distress associated with the akathisia. BARS consists of the following 4 items: objective assessment of akathisia symptoms, subjective assessment of the participants's awareness of inner restlessness, distress restlessness, and global clinical assessment of akathisia. First three items are rated on a 4-point scale ranging from 0 (no abnormal movements or absence of inner restlessness or no distress) to 3 (severe akathisia or awareness of intense compulsion to move most of the time or severe distress). The last item, the global clinical assessment of akathisia, is rated on a 6-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia). Total BARS score ranges from 0 to 14 with a higher score representing worse results.

Time frame: Baseline, week 6 and week 12

Population: SAF population with available data at each time point.

The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses are provided to items 1 to 5 for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods \[not plan\] without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and items 6 to 10 for suicide behavior (6. Preparatory acts or behavior, 7. Aborted attempt, 8. Interrupted attempt, 9. Actual attempt, 10. Completed suicide).

Time frame: Baseline up to EoS (week 14)

Population: SAF population

SAS scale consists of 10 items including 7 items that address bradykinesia-rigidity and additional single items for tremor, glabellar tap, and salivation. Each item represents a specific physical condition and is rated on a 5-point category rating scale ranging from 0 (complete absence of the condition) to 4 (the condition is present to an extreme degree).The total score is obtained by adding the scores for the 10 individual items making the maximum possible score is 40. Higher scores are indicative of more severe Parkinsonian-type symptoms.

Time frame: Baseline, week 6 and week 12

Population: SAF population with available data at each time point.

The UPSA-2-ER assesses the functional abilities of the participant with schizophrenia in 6 domains: household management, communication, financial skills, transportation, comprehension/planning and medication management. The UPSA-2-ER total score has a range from 0 to 105. A higher score indicates less impairment.

Time frame: Baseline and week 12/EoT

Population: FAS population with available data at baseline and at week 12/EoT.

Ctrough concentration for ASP4345 was reported.

Time frame: Predose: day 7, day 14, day 21, day 42 and day 84/EoT

Population: The pharmacokinetic analysis set (PKAS) consisted of all participants who took at least 1 dose of study drug and who had at least 1 plasma concentration. PKAS population with available data at each time point.