Regional VT of [18F]-IMA601 in Putamen at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan.

Participant wise data was reported for this outcome measure.

Regional VT of [18F]-IMA601 in Accumbens at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

Regional VT of [18F]-IMA601 in Amygdala at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

Regional VT of [18F]-IMA601 in cerebral white matter at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

Vital signs including blood pressure, pulse rate, tympanic temperature, and respiratory rate were assessed. Number of participants with clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.

ECG parameters including Ventricular rate, QRS complex of the ECG reflects the rapid depolarization of the right and left ventricles (QRS) interval, portion of the ECG between consecutive R waves, representing the ventricular rate (PR) interval, and QTc interval with Fridericia's correction method (QTcF) was measured. Number of participants with clinically significant abnormal ECG findings were reported. Clinical significance was determined by the investigator.

Complete physical examination including general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities were performed. Number of participants with clinically significant abnormal physical examinations were reported. Clinical significance was determined by the investigator.

Complete neurological examinations including motor system, romberg test, coordination, and direct pupillary reflexes were performed. Number of participants with clinically significant abnormal neurological examinations findings were reported. Clinical significance was determined by the investigator.

Laboratory tests including hematology, clinical chemistry, coagulation, serology, follicle stimulating hormone (FSH) test (only for females), and urinalysis were performed. Number of participants with clinically significant changes in laboratory parameters were reported. Clinical significance was determined by the investigator.

The C-SSRS is a valid and reliable suicidal scale that includes a seven-item subscale that asks participants to self-report on actual attempts, interrupted attempts, aborted attempts, and preparatory acts or behaviors. The suicidal ideation section is rated on a scale from 1 to 5, with higher score indicating a greater severity of suicidal ideation or risk of suicidal behavior. Participants who respond "yes" to any question related to suicidal ideation are reported in this outcome measure.

Cmax was obtained directly from the concentration-time data.

Calculated as Cmax /Dose administered.

The tmax was obtained directly from the concentration-time data.

AUCinf was calculated using the trapezoidal method for the interval 0 to tlast (time tlast is the time at which the last non-zero level was recorded), plus the area under the exponential curve from tlast to infinity.

Calculated as AUCinf /Dose administered. Here, the unit of measure is represented as hours*nanograms per milliliters per milligram (h*ng/mL/mg).

AUClast was calculated using the trapezoidal method.

AUCtau was calculated using the trapezoidal method.

The t1/2 was calculated from the terminal slope of the log concentration-time curve as follows: t1/2 = loge 2 / lambda(λ)z.

Terminal rate constant was estimated by linear regression of logarithmically transformed concentration versus time data.

Calculated using the formula as follows: CLss/F = Dose/ AUCtau.

Calculated using the formula as follows: VZ/F = Dose/λz *AUCtau.

Trough plasma concentration i.e., measured concentration at the end of a dosing interval at steady state (taken directly before next administration, and at 1 dosing interval after the final dose) was obtained directly from the concentration-time data.

Accumulation ratio was calculated from area under the plasma concentration-time curve during a dosing interval at steady state, and after single dose of ASN51.

Rac(Cmax) was calculated from Cmax at steady state and Cmax after single dose.

The analysis of the PD response of PBMCs during repeated ASN51 dosing was conducted using ANOVA. Assessments were conducted at pre-dose and 8 hours post-dose on Day 11 (fed state) and Day 14 (fasted state). The ratio of fed to fasted has been reported.

Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. Participant wise data was reported for this outcome measure.

Row titles include participant number, PET scan session, post-dose time, and plasma concentration.

Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. Participant wise data was reported for this outcome measure.

Row titles include participant number, PET scan session, post-dose time, and plasma concentration.

Change in VT from baseline to post-dose scans were interpreted as an effect of O-GlcNAcase occupancy by ASN51. Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. The following model was fitted to the occupancy data set: Occ=100*Cp/Cp+EC50. Where Occ was the target occupancy (%), Cp was measured plasma concentration of ASN51 (ng/ml) and EC50 was the plasma concentration of ASN51 that corresponds to 50% occupancy. Summarized data was reported for all participants.

Total of all reporting groups

Regional VT of [18F]-IMA601 in frontal lobe at each brain scan was measured with a PET scan. Participants received an intravenous (IV) dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in anterior cingulate at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in Caudate at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in Putamen at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan.

Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in Accumbens at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in Amygdala at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in cerebral white matter at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with that treatment. A TEAE is defined as an AE that emerges during treatment (having been absent before treatment) or that worsens after treatment. Serious TEAE is defined as any adverse event that is fatal, is life-threatening, requires or prolongs in-patient treatment, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect.

Safety population included all participants who received at least one dose of the study drug.

Vital signs including blood pressure, pulse rate, tympanic temperature, and respiratory rate were assessed. Number of participants with clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.

Safety population included participants who received at least one dose of study drug.

ECG parameters including Ventricular rate, QRS complex of the ECG reflects the rapid depolarization of the right and left ventricles (QRS) interval, portion of the ECG between consecutive R waves, representing the ventricular rate (PR) interval, and QTc interval with Fridericia's correction method (QTcF) was measured. Number of participants with clinically significant abnormal ECG findings were reported. Clinical significance was determined by the investigator.

Safety population included participants who received at least one dose of study drug.

Complete physical examination including general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities were performed. Number of participants with clinically significant abnormal physical examinations were reported. Clinical significance was determined by the investigator.

Safety population included participants who received at least one dose of study drug.

Complete neurological examinations including motor system, romberg test, coordination, and direct pupillary reflexes were performed. Number of participants with clinically significant abnormal neurological examinations findings were reported. Clinical significance was determined by the investigator.

Safety population included participants who received at least one dose of study drug.

Laboratory tests including hematology, clinical chemistry, coagulation, serology, follicle stimulating hormone (FSH) test (only for females), and urinalysis were performed. Number of participants with clinically significant changes in laboratory parameters were reported. Clinical significance was determined by the investigator.

Safety population included participants who received at least one dose of study drug.

The C-SSRS is a valid and reliable suicidal scale that includes a seven-item subscale that asks participants to self-report on actual attempts, interrupted attempts, aborted attempts, and preparatory acts or behaviors. The suicidal ideation section is rated on a scale from 1 to 5, with higher score indicating a greater severity of suicidal ideation or risk of suicidal behavior. Participants who respond "yes" to any question related to suicidal ideation are reported in this outcome measure.

Safety population included participants who received at least one dose of study drug.

PK analysis population included the participants who provided evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration. Number analyzed is the number of participants with data available for analysis at a specified time point.

Cmax was obtained directly from the concentration-time data.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Calculated as Cmax /Dose administered.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

The tmax was obtained directly from the concentration-time data.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

AUCinf was calculated using the trapezoidal method for the interval 0 to tlast (time tlast is the time at which the last non-zero level was recorded), plus the area under the exponential curve from tlast to infinity.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Calculated as AUCinf /Dose administered. Here, the unit of measure is represented as hours*nanograms per milliliters per milligram (h*ng/mL/mg).

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

AUClast was calculated using the trapezoidal method.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

AUCtau was calculated using the trapezoidal method.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

The t1/2 was calculated from the terminal slope of the log concentration-time curve as follows: t1/2 = loge 2 / lambda(λ)z.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Terminal rate constant was estimated by linear regression of logarithmically transformed concentration versus time data.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Calculated using the formula as follows: CLss/F = Dose/ AUCtau.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Calculated using the formula as follows: VZ/F = Dose/λz *AUCtau.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Trough plasma concentration i.e., measured concentration at the end of a dosing interval at steady state (taken directly before next administration, and at 1 dosing interval after the final dose) was obtained directly from the concentration-time data.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Accumulation ratio was calculated from area under the plasma concentration-time curve during a dosing interval at steady state, and after single dose of ASN51.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

Rac(Cmax) was calculated from Cmax at steady state and Cmax after single dose.

PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.

The analysis of the PD response of PBMCs during repeated ASN51 dosing was conducted using ANOVA. Assessments were conducted at pre-dose and 8 hours post-dose on Day 11 (fed state) and Day 14 (fasted state). The ratio of fed to fasted has been reported.

PD analysis population included all participants in the safety population for who a PBMC measure is available.

Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. Participant wise data was reported for this outcome measure.

Row titles include participant number, PET scan session, post-dose time, and plasma concentration.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. No summary analysis was done due to low number of participants, therefore participant wise data are reported.

Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. Participant wise data was reported for this outcome measure.

Row titles include participant number, PET scan session, post-dose time, and plasma concentration.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan. No summary analysis was done due to low number of participants, therefore participant wise data are reported.

Data for trough volume of distribution of [18F]-IMA601 was not collected and analyzed because steady state was not achieved due to non-periodic administration before the imaging sessions.

Change in VT from baseline to post-dose scans were interpreted as an effect of O-GlcNAcase occupancy by ASN51. Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. The following model was fitted to the occupancy data set: Occ=100*Cp/Cp+EC50. Where Occ was the target occupancy (%), Cp was measured plasma concentration of ASN51 (ng/ml) and EC50 was the plasma concentration of ASN51 that corresponds to 50% occupancy. Summarized data was reported for all participants.

PET population included all participants in the safety population who had a baseline PET scan, at least 1 post-baseline PET scan, and a PK result immediately preceding a PET scan.

Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.