Trial Outcomes & Findings for Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of ASN51 (NCT NCT06390098)

NCT ID: NCT06390098

Last Updated: 2025-05-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 3 participants
• Primary outcome timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose
• Results posted on: 2025-05-08

Participant Flow

Participants took part in the study at an investigative site in United Kingdom from 09 August 2021 to 12 October 2021.

Participant milestones

Measure	ASN51 All participants received low, medium, and high doses of ASN51 (as assigned according to the protocol), orally on Day 1 of imaging sessions 2 and 3 before the positron emission tomography (PET) scan during the study.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of ASN51

Baseline characteristics by cohort

Measure	ASN51 n=3 Participants All participants received low, medium, and high doses of ASN51 (as assigned according to the protocol), orally on Day 1 of imaging sessions 2 and 3 before the positron emission tomography (PET) scan during the study.
Age, Continuous	49.3 years STANDARD_DEVIATION 4.93 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a pharmacokinetic (PK) result immediately preceding PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 1, PET Scan 1, Baseline	14.09 milliliters/cubic centimeter (mL/cm^3)	—	—	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.82 milliliters/cubic centimeter (mL/cm^3)
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose, Day 1	—	4.76 milliliters/cubic centimeter (mL/cm^3)	—	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 2, PET Scan 1, Baseline	16.08 milliliters/cubic centimeter (mL/cm^3)	—	—	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	3.90 milliliters/cubic centimeter (mL/cm^3)	—	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose, Day 1	—	4.55 milliliters/cubic centimeter (mL/cm^3)	—	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 3, PET Scan 1, Baseline	16.38 milliliters/cubic centimeter (mL/cm^3)	—	—	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	3.86 milliliters/cubic centimeter (mL/cm^3)	—
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	5.78 milliliters/cubic centimeter (mL/cm^3)	—	—

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding 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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 1, PET Scan 1, Baseline	16.35 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.85 mL/cm^3
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose	—	5.41 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 2, PET Scan 1, Baseline	19.34 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	4.28 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose, Day 1	—	5.13 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 3, PET Scan 1, Baseline	19.89 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	4.21 mL/cm^3	—
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	6.70 mL/cm^3	—	—

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

Regional VT of [18F]-IMA601 in the 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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 1, PET Scan 1, Baseline	10.20 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.23 mL/cm^3
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose, Day 1	—	3.21 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 2, PET Scan 1, Baseline	13.74 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	3.19 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose, Day 1	—	3.89 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 3, PET Scan 1, Baseline	14.70 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	3.31 mL/cm^3	—
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	4.86 mL/cm^3	—	—

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding 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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 1, PET Scan 1, Baseline	15.38 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.98 mL/cm^3
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose, Day 1	—	5.41 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 2, PET Scan 1, Baseline	19.07 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	4.37 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose, Day 1	—	5.22 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 3, PET Scan 1, Baseline	19.32 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	4.39 mL/cm^3	—
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	6.57 mL/cm^3	—	—

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding 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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 1, PET Scan 1, Baseline	15.82 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.69 mL/cm^3
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose, Day 1	—	5.43 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 2, PET Scan 1, Baseline	21.14 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	4.42 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose, Day 1	—	5.36 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 3, PET Scan 1, Baseline	21.80 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	4.28 mL/cm^3	—
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	6.71 mL/cm^3	—	—

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding 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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 1, PET Scan 1, Baseline	16.40 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.90 mL/cm^3
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose, Day 1	—	6.36 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 2, PET Scan 1, Baseline	22.30 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	4.76 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose, Day 1	—	6.00 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 3, PET Scan 1, Baseline	22.18 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	4.49 mL/cm^3	—
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	7.26 mL/cm^3	—	—

PRIMARY outcome

Timeframe: PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose

Population: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding 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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 1, PET Scan 1, Baseline	10.87 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 1, PET Scan 2, 6 hours post-dose, Day 1	—	—	—	1.72 mL/cm^3
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 1, PET Scan 3, 48 hours post-dose, Day 1	—	3.86 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 2, PET Scan 1, Baseline	12.72 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 2, PET Scan 2, 31 hours post-dose, Day 1	—	3.32 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 2, PET Scan 3, 48 hours post-dose	—	3.80 mL/cm^3	—	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 3, PET Scan 1, Baseline	13.49 mL/cm^3	—	—	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 3, PET Scan 2, 31 hours post-dose, Day 1	—	—	3.58 mL/cm^3	—
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan Participant 3, PET Scan 3, 48 hours post-dose, Day 1	—	4.97 mL/cm^3	—	—

SECONDARY outcome

Timeframe: Up to approximately 2.1 months

Population: Safety analysis set included all participants from the all-treated set who had at least one safety assessment post-baseline.

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. 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 an event that results in death, is considered life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent/significant disability/incapacity, results in a congenital anomaly/birth defect; or other medially important serious medical event.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: Safety analysis set included all participants from the all-treated set who had at least one safety assessment post-baseline.

An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Serious TEAE is defined as an event that results in death, is considered life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent/significant disability/incapacity, results in a congenital anomaly/birth defect; or other medially important serious medical event.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Number of Participants With Serious TEAEs up to 4 Weeks After Last Administration	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 2.1 months

Population: Safety analysis set included all participants from the all-treated set who had at least one safety assessment post-baseline.

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

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 2.1 months

Population: Safety analysis set included all participants from the all-treated set who had at least one safety assessment post-baseline.

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

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 2.1 months

Population: Safety analysis set included all participants from the all-treated set who had at least one safety assessment post-baseline.

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) and QTc interval with Bazett's correction method (QTcB) were measured. Number of participants with clinically significant abnormal ECG findings were reported. Clinical significance was determined by the investigator.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 2.1 months

Population: Safety analysis set included all participants from the all-treated set who had at least one safety assessment post-baseline.

Complete physical examination including general appearance; head, eyes, ears, nose, and throat; and cardiovascular, dermatologic, respiratory, gastrointestinal, musculoskeletal, and neurologic systems were performed. Number of participants with clinically significant abnormal physical examinations were reported. Clinical significance was determined by the investigator.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 Participants Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Number of Participants With Clinically Significant Abnormal Physical Examinations	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3 and 72 hours post-dose on Day 4

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

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=1 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 6 hours post-dose	66.2 nanograms/milliliter (ng/mL) Standard Deviation 7.77	121.0 nanograms/milliliter (ng/mL)	199.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 0.5 hour post-dose	37.0 nanograms/milliliter (ng/mL) Standard Deviation 8.78	192.0 nanograms/milliliter (ng/mL)	43.5 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 1 hour post-dose	93.0 nanograms/milliliter (ng/mL) Standard Deviation 6.16	181.0 nanograms/milliliter (ng/mL)	189.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 1.5 hours post-dose	90.0 nanograms/milliliter (ng/mL) Standard Deviation 7.79	159.0 nanograms/milliliter (ng/mL)	293.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 2 hours post-dose	87.1 nanograms/milliliter (ng/mL) Standard Deviation 11.98	144.0 nanograms/milliliter (ng/mL)	283.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 3 hours post-dose	83.6 nanograms/milliliter (ng/mL) Standard Deviation 8.92	142.0 nanograms/milliliter (ng/mL)	245.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 4 hours post-dose	80.5 nanograms/milliliter (ng/mL) Standard Deviation 17.12	134.0 nanograms/milliliter (ng/mL)	253.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 8 hours post-dose	66.9 nanograms/milliliter (ng/mL) Standard Deviation 11.22	115.0 nanograms/milliliter (ng/mL)	201.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 12 hours post-dose	59.9 nanograms/milliliter (ng/mL) Standard Deviation 9.73	103.0 nanograms/milliliter (ng/mL)	153.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 1: 16 hours post-dose	45.0 nanograms/milliliter (ng/mL) Standard Deviation 6.74	96.9 nanograms/milliliter (ng/mL)	153.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 2: 24 hours post-dose	45.5 nanograms/milliliter (ng/mL) Standard Deviation 6.24	81.7 nanograms/milliliter (ng/mL)	133.0 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 2: 36 hours post-dose	34.1 nanograms/milliliter (ng/mL) Standard Deviation 4.71	58.2 nanograms/milliliter (ng/mL)	95.3 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 3: 48 hours post-dose	30.4 nanograms/milliliter (ng/mL) Standard Deviation 3.37	46.3 nanograms/milliliter (ng/mL)	88.2 nanograms/milliliter (ng/mL)	—
Plasma Concentration of ASN51 at Each Post-dose PET Scan Day 4: 72 hours post-dose	20.5 nanograms/milliliter (ng/mL) Standard Deviation 1.28	28.9 nanograms/milliliter (ng/mL)	54.8 nanograms/milliliter (ng/mL)	—

SECONDARY outcome

Timeframe: At 6 hours post-dose on Day 1 (for participant 1) and 31 hours post-dose on Day 1 (for participants 2 and 3), and at 48 hours post-dose on Day 1 (all participants)

Population: PET population included participants who received the study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding PET scan. No summary analysis was done due to low number of participants, therefore participant-wise data are reported. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

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.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=1 Participants Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 Participants Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and PET Scan Participant 1: PET Scan 3, 48 hours at 30.3 ng/mL	68.2 percentage of receptor occupancy	—	—	—
Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and PET Scan Participant 1: PET Scan 2, 6 hours at 199.0 ng/mL	—	—	92.2 percentage of receptor occupancy	—
Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and PET Scan Participant 2: PET Scan 2, 31 hours at 42.2 ng/mL	84.5 percentage of receptor occupancy	—	—	—
Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and PET Scan Participant 2: PET Scan 3, 48 hours at 29.4 ng/mL	79.4 percentage of receptor occupancy	—	—	—
Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and PET Scan Participant 3: PET Scan 2, 31 hours at 65.8 ng/mL	—	89.7 percentage of receptor occupancy	—	—
Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and PET Scan Participant 3: PET Scan 3, 48 hours at 26.7 ng/mL	75.9 percentage of receptor occupancy	—	—	—

SECONDARY outcome

Timeframe: At 6, 31 and at 48 hours post-dose on Day 1

Population: PET population included participants who received the study medication, had a baseline PET scan, at least one post-baseline PET scan, and a PK result immediately preceding PET scan.

Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to post-dose PET scan. The following model was fitted to 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. The relationship between exposure and occupancy was explored by direct fitting of a saturation model to pooled (across participants and scans) VT data, to obtain an estimate of EC50 for occupancy by ASN51.

Outcome measures

Measure	All Participants n=3 Participants Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
Receptor Occupancy as Assessed by Plasma Concentration That Corresponds to 50% Occupancy (EC50)	9.4 ng/mL Interval 6.4 to 12.3	—	—	—

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

ASN51 Low Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

ASN51 Medium Dose

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

ASN51 High Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Participants n=3 participants at risk Participants participated in imaging session 1 (Baseline) of PET scan before dosing during the study.	ASN51 Low Dose n=3 participants at risk Participants received low dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 Medium Dose n=1 participants at risk Participants received medium dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.	ASN51 High Dose n=1 participants at risk Participants received high dose of ASN51, orally on Day 1 of imaging sessions 2 and 3 before the PET scan during the study.
General disorders Catheter site related reaction	66.7% 2/3 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/3 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/1 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/1 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/3 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	100.0% 1/1 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/1 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.
Nervous system disorders Dysgeusia	33.3% 1/3 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/3 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/1 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.	0.00% 0/1 • Up to approximately 2.1 months Safety analysis set included participants from the all-treated set who had at least one safety assessment post-baseline.

Additional Information

Asceneuron Clinical Research

Asceneuron SA

Phone: + 41 21 353 8245

Email: clinicaltrials.gov@asceneuron.com

Results disclosure agreements

• Principal investigator is a sponsor employee Agreement finally allows PI to publish independently.
• Publication restrictions are in place

Restriction type: OTHER