Trial Outcomes & Findings for PET Study of Repeated ASN51 in Healthy Volunteers (NCT NCT05725005)
NCT ID: NCT05725005
Last Updated: 2025-05-08
Results Overview
Protein O-GlcNAcylation in PBMCs at different time-point is reported.
COMPLETED
PHASE1
12 participants
Pre-dose on Days 1, 2, 11, and 14; 8 hours post-dose on Day 1, 11 and 14; 12 hours post-dose on Day 1 and 14, 24 hours post-dose on Day 15; 72 hours post-dose on Day 17; 144 hours post-dose on Day 20
2025-05-08
Participant Flow
Participants took part in the study at an investigative site in the United Kingdom from 26 January 2023 to 08 June 2023.
Participant milestones
| Measure |
Group 1: ASN51 Low Dose
Participants received low dose of ASN51, orally, once daily (QD), for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
PET Population
|
4
|
4
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PET Study of Repeated ASN51 in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.2 years
STANDARD_DEVIATION 7.68 • n=5 Participants
|
37.3 years
STANDARD_DEVIATION 6.12 • n=7 Participants
|
38.8 years
STANDARD_DEVIATION 6.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose on Days 1, 2, 11, and 14; 8 hours post-dose on Day 1, 11 and 14; 12 hours post-dose on Day 1 and 14, 24 hours post-dose on Day 15; 72 hours post-dose on Day 17; 144 hours post-dose on Day 20Population: Pharmacodynamics (PD) analysis population included all participants in the safety population for who a PBMC measure is available. Number analyzed is the number of participants evaluated in respective arm at a specified timepoint.
Protein O-GlcNAcylation in PBMCs at different time-point is reported.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
Pre-dose on Day 1
|
100.0 percentage of protein O-GlcNAcylation
Standard Deviation 0.00
|
100.0 percentage of protein O-GlcNAcylation
Standard Deviation 0.00
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
8 hours post-dose on Day 1
|
219.33 percentage of protein O-GlcNAcylation
Standard Deviation 74.728
|
232.79 percentage of protein O-GlcNAcylation
Standard Deviation 94.193
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
12 hours post-dose on Day 1
|
291.02 percentage of protein O-GlcNAcylation
Standard Deviation 117.673
|
190.48 percentage of protein O-GlcNAcylation
Standard Deviation 56.442
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
Pre-dose on Day 2
|
183.83 percentage of protein O-GlcNAcylation
Standard Deviation 84.144
|
188.02 percentage of protein O-GlcNAcylation
Standard Deviation 96.636
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
Pre-dose on Day 11
|
205.70 percentage of protein O-GlcNAcylation
Standard Deviation 19.045
|
188.30 percentage of protein O-GlcNAcylation
Standard Deviation 126.761
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
8 hours post-dose on Day 11
|
302.19 percentage of protein O-GlcNAcylation
Standard Deviation 49.840
|
346.01 percentage of protein O-GlcNAcylation
Standard Deviation 233.011
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
Pre-dose on day 14
|
196.42 percentage of protein O-GlcNAcylation
Standard Deviation 99.330
|
197.54 percentage of protein O-GlcNAcylation
Standard Deviation 98.510
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
8 hours post-dose on Day 14
|
297.01 percentage of protein O-GlcNAcylation
Standard Deviation 119.672
|
282.51 percentage of protein O-GlcNAcylation
Standard Deviation 151.609
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
12 hours post-dose on Day 14
|
303.24 percentage of protein O-GlcNAcylation
Standard Deviation 147.572
|
305.26 percentage of protein O-GlcNAcylation
Standard Deviation 167.261
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
24 hours post-dose on Day 15
|
166.19 percentage of protein O-GlcNAcylation
Standard Deviation 62.638
|
160.38 percentage of protein O-GlcNAcylation
Standard Deviation 58.879
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
72 hours post-dose on Day 17
|
169.66 percentage of protein O-GlcNAcylation
Standard Deviation 45.654
|
192.67 percentage of protein O-GlcNAcylation
Standard Deviation 128.801
|
|
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
144 hours post-dose on Day 20
|
168.68 percentage of protein O-GlcNAcylation
Standard Deviation 40.767
|
187.14 percentage of protein O-GlcNAcylation
Standard Deviation 126.539
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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 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 |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
11.47 milliliters/cubic centimeter(mL/cm^3)
|
15.91 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, Day 1
|
1.97 milliliters/cubic centimeter(mL/cm^3)
|
1.60 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, Day 4
|
2.68 milliliters/cubic centimeter(mL/cm^3)
|
3.67 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
|
14.81 milliliters/cubic centimeter(mL/cm^3)
|
13.53 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, Day 1
|
2.02 milliliters/cubic centimeter(mL/cm^3)
|
2.46 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, Day 4
|
—
|
2.91 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, Day 9
|
16.81 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
|
NA milliliters/cubic centimeter(mL/cm^3)
Data was not reported as the PET scan findings failed to converge a meaningful VT.
|
17.34 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, Day 1
|
2.20 milliliters/cubic centimeter(mL/cm^3)
|
1.56 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, Day 4
|
2.77 milliliters/cubic centimeter(mL/cm^3)
|
2.62 milliliters/cubic centimeter(mL/cm^3)
|
|
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
13.62 milliliters/cubic centimeter(mL/cm^3)
|
14.90 milliliters/cubic centimeter(mL/cm^3)
|
|
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
2.07 milliliters/cubic centimeter(mL/cm^3)
|
2.11 milliliters/cubic centimeter(mL/cm^3)
|
|
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.84 milliliters/cubic centimeter(mL/cm^3)
|
—
|
|
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
7.72 milliliters/cubic centimeter(mL/cm^3)
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
13.57 mL/cm^3
|
18.51 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 1, PET Scan 2, Day 1
|
1.97 mL/cm^3
|
1.60 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 1, PET Scan 3, Day 4
|
2.85 mL/cm^3
|
3.98 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 2, PET Scan 1, Baseline
|
17.45 mL/cm^3
|
16.08 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 2, PET Scan 2, Day 1
|
2.13 mL/cm^3
|
2.56 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 2, PET Scan 3, Day 4
|
—
|
3.17 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 2, PET Scan 3, Day 9
|
19.79 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 3, PET Scan 1, Baseline
|
18.34 mL/cm^3
|
20.14 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 3, PET Scan 2, Day 1
|
2.26 mL/cm^3
|
1.60 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 3, PET Scan 3, Day 4
|
2.94 mL/cm^3
|
2.82 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
15.87 mL/cm^3
|
17.02 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
1.94 mL/cm^3
|
2.04 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.69 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
8.53 mL/cm^3
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
8.25 mL/cm^3
|
13.28 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 1, PET Scan 2, Day 1
|
1.21 mL/cm^3
|
1.23 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 1, PET Scan 3, Day 4
|
1.76 mL/cm^3
|
2.97 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 2, PET Scan 1, Baseline
|
12.89 mL/cm^3
|
11.43 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 2, PET Scan 2, Day 1
|
1.74 mL/cm^3
|
2.32 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 2, PET Scan 3, Day 4
|
—
|
2.75 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 2, PET Scan 3, Day 9
|
14.98 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 3, PET Scan 1, Baseline
|
13.77 mL/cm^3
|
13.95 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 3, PET Scan 2, Day 1
|
1.77 mL/cm^3
|
1.17 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 3, PET Scan 3, Day 4
|
2.27 mL/cm^3
|
1.94 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
11.50 mL/cm^3
|
13.44 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
1.66 mL/cm^3
|
1.91 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.04 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
6.99 mL/cm^3
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
12.74 mL/cm^3
|
17.00 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 1, PET Scan 2, Day 1
|
2.03 mL/cm^3
|
1.63 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 1, PET Scan 3, Day 4
|
2.86 mL/cm^3
|
3.89 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 2, PET Scan 1, Baseline
|
17.46 mL/cm^3
|
15.89 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 2, PET Scan 2, Day 1
|
2.32 mL/cm^3
|
2.76 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 2, PET Scan 3, Day 4
|
—
|
3.35 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 2, PET Scan 3, Day 9
|
20.27 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 3, PET Scan 1, Baseline
|
16.76 mL/cm^3
|
20.70 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 3, PET Scan 2, Day 1
|
2.31 mL/cm^3
|
1.78 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 3, PET Scan 3, Day 4
|
2.87 mL/cm^3
|
2.96 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
14.88 mL/cm^3
|
17.00 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
2.02 mL/cm^3
|
2.07 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.74 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
8.50 mL/cm^3
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 1, PET Scan 3, Day 4
|
2.51 mL/cm^3
|
3.91 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 2, PET Scan 1, Baseline
|
18.94 mL/cm^3
|
16.58 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
13.16 mL/cm^3
|
19.29 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 1, PET Scan 2, Day 1
|
1.73 mL/cm^3
|
1.51 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 2, PET Scan 2, Day 1
|
2.22 mL/cm^3
|
2.66 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 2, PET Scan 3, Day 4
|
—
|
3.29 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 2, PET Scan 3, Day 9
|
22.18 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 3, PET Scan 1, Baseline
|
18.57 mL/cm^3
|
20.52 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 3, PET Scan 2, Day 1
|
2.14 mL/cm^3
|
1.49 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 3, PET Scan 3, Day 4
|
2.80 mL/cm^3
|
2.67 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
16.18 mL/cm^3
|
18.65 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
1.87 mL/cm^3
|
2.64 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.62 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
9.09 mL/cm^3
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
15.00 mL/cm^3
|
18.91 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 1, PET Scan 2, Day 1
|
2.13 mL/cm^3
|
1.54 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 1, PET Scan 3, Day 4
|
3.13 mL/cm^3
|
4.42 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 2, PET Scan 1, Baseline
|
19.84 mL/cm^3
|
17.77 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 2, PET Scan 2, Day 1
|
2.30 mL/cm^3
|
2.50 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 2, PET Scan 3, Day 4
|
—
|
3.40 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 2, PET Scan 3, Day 9
|
22.25 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 3, PET Scan 1, Baseline
|
19.37 mL/cm^3
|
22.00 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 3, PET Scan 2, Day 1
|
2.32 mL/cm^3
|
1.76 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 3, PET Scan 3, Day 4
|
3.11 mL/cm^3
|
3.12 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
16.77 mL/cm^3
|
17.57 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
1.89 mL/cm^3
|
2.10 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.94 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
9.38 mL/cm^3
|
PRIMARY outcome
Timeframe: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dosePopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=4 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 1, PET Scan 1, Baseline
|
8.39 mL/cm^3
|
10.72 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 1, PET Scan 2, Day 1
|
1.67 mL/cm^3
|
1.32 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 1, PET Scan 3, Day 4
|
2.30 mL/cm^3
|
2.96 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 2, PET Scan 1, Baseline
|
11.39 mL/cm^3
|
10.15 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 2, PET Scan 2, Day 1
|
1.89 mL/cm^3
|
2.43 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 2, PET Scan 3, Day 4
|
—
|
2.96 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 2, PET Scan 3, Day 9
|
13.25 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 3, PET Scan 1, Baseline
|
12.39 mL/cm^3
|
12.86 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 3, PET Scan 2, Day 1
|
2.03 mL/cm^3
|
1.51 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 3, PET Scan 3, Day 4
|
2.46 mL/cm^3
|
2.45 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 4, PET Scan 1, Baseline
|
9.95 mL/cm^3
|
11.45 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 4, PET Scan 2, Day 1
|
1.81 mL/cm^3
|
1.78 mL/cm^3
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 4, PET Scan 3, Day 4
|
2.34 mL/cm^3
|
—
|
|
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Participant 4, PET Scan 3, Day 10
|
—
|
6.34 mL/cm^3
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: Safety population included all participants who received at least one dose of the study drug.
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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with TEAEs
|
4 Participants
|
3 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants with Serious TEAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: Safety population included participants who received at least one dose of 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Vital Signs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal 12-lead Safety Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Physical Examinations
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Neurological Examinations Findings
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes in Laboratory Parameters
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 monthsPopulation: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Number of Participants With Suicidal Ideation According to Columbia - Suicide Severity Rating Scale (C-SSRS) Ideation
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours; Day 11: 8 hours; Day 14: 0.25, 0.5, 1, 2, 4, 6, 12 hours; Day 15, Day 16, Day 17, Day 18, Day 20, and Day 23Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 0.25 hour post-dose
|
4.833 nanograms/milliliter (ng/mL)
Standard Deviation 11.839
|
20.18 nanograms/milliliter (ng/mL)
Standard Deviation 31.680
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 0.5 hour post-dose
|
132.9 nanograms/milliliter (ng/mL)
Standard Deviation 65.354
|
232.7 nanograms/milliliter (ng/mL)
Standard Deviation 228.23
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 1 hour post-dose
|
173.8 nanograms/milliliter (ng/mL)
Standard Deviation 28.174
|
355.3 nanograms/milliliter (ng/mL)
Standard Deviation 66.704
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 1.5 hours post-dose
|
155.2 nanograms/milliliter (ng/mL)
Standard Deviation 11.089
|
311.3 nanograms/milliliter (ng/mL)
Standard Deviation 40.934
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 2 hours post-dose
|
152.5 nanograms/milliliter (ng/mL)
Standard Deviation 13.867
|
310.3 nanograms/milliliter (ng/mL)
Standard Deviation 45.559
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 3 hours post-dose
|
155.2 nanograms/milliliter (ng/mL)
Standard Deviation 11.476
|
277.3 nanograms/milliliter (ng/mL)
Standard Deviation 40.143
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 4 hours post-dose
|
140.3 nanograms/milliliter (ng/mL)
Standard Deviation 21.630
|
281.8 nanograms/milliliter (ng/mL)
Standard Deviation 34.032
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 6 hours post-dose
|
125.7 nanograms/milliliter (ng/mL)
Standard Deviation 11.183
|
254.7 nanograms/milliliter (ng/mL)
Standard Deviation 38.568
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 8 hours post-dose
|
123.8 nanograms/milliliter (ng/mL)
Standard Deviation 7.2503
|
244.0 nanograms/milliliter (ng/mL)
Standard Deviation 28.071
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 12 hours post-dose
|
97.30 nanograms/milliliter (ng/mL)
Standard Deviation 8.8050
|
199.2 nanograms/milliliter (ng/mL)
Standard Deviation 31.212
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 1: 16 hours post-dose
|
82.98 nanograms/milliliter (ng/mL)
Standard Deviation 4.2687
|
154.3 nanograms/milliliter (ng/mL)
Standard Deviation 23.036
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 11: 8 hours post-dose
|
326.0 nanograms/milliliter (ng/mL)
Standard Deviation 43.253
|
567.3 nanograms/milliliter (ng/mL)
Standard Deviation 228.33
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 0.25 hour post-dose
|
264.2 nanograms/milliliter (ng/mL)
Standard Deviation 55.333
|
416.2 nanograms/milliliter (ng/mL)
Standard Deviation 175.02
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 0.5 hour post-dose
|
417.8 nanograms/milliliter (ng/mL)
Standard Deviation 130.39
|
541.7 nanograms/milliliter (ng/mL)
Standard Deviation 224.05
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 1 hour post-dose
|
427.8 nanograms/milliliter (ng/mL)
Standard Deviation 54.455
|
682.5 nanograms/milliliter (ng/mL)
Standard Deviation 280.47
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 2 hours post-dose
|
398.8 nanograms/milliliter (ng/mL)
Standard Deviation 46.525
|
695.3 nanograms/milliliter (ng/mL)
Standard Deviation 285.19
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 4 hours post-dose
|
362.2 nanograms/milliliter (ng/mL)
Standard Deviation 46.357
|
640.2 nanograms/milliliter (ng/mL)
Standard Deviation 258.28
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 6 hours post-dose
|
339.2 nanograms/milliliter (ng/mL)
Standard Deviation 28.117
|
599.0 nanograms/milliliter (ng/mL)
Standard Deviation 255.59
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 14: 12 hours post-dose
|
268.0 nanograms/milliliter (ng/mL)
Standard Deviation 28.390
|
499.2 nanograms/milliliter (ng/mL)
Standard Deviation 214.34
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 15
|
242.3 nanograms/milliliter (ng/mL)
Standard Deviation 33.279
|
455.8 nanograms/milliliter (ng/mL)
Standard Deviation 180.41
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 16
|
150.2 nanograms/milliliter (ng/mL)
Standard Deviation 26.347
|
295.4 nanograms/milliliter (ng/mL)
Standard Deviation 134.63
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 17
|
97.23 nanograms/milliliter (ng/mL)
Standard Deviation 17.151
|
105.8 nanograms/milliliter (ng/mL)
Standard Deviation 40.751
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 18
|
63.52 nanograms/milliliter (ng/mL)
Standard Deviation 22.281
|
141.0 nanograms/milliliter (ng/mL)
Standard Deviation 69.510
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 20
|
29.38 nanograms/milliliter (ng/mL)
Standard Deviation 15.536
|
78.52 nanograms/milliliter (ng/mL)
Standard Deviation 45.813
|
|
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Day 23
|
11.01 nanograms/milliliter (ng/mL)
Standard Deviation 11.685
|
35.24 nanograms/milliliter (ng/mL)
Standard Deviation 33.575
|
SECONDARY outcome
Timeframe: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose, and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: PK analysis population included participants who had evaluable data for the comparisons of interest. These participants had at least one quantifiable plasma concentration.
Cmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of ASN51
Day 1
|
183 ng/mL
Geometric Coefficient of Variation 14.8
|
386 ng/mL
Geometric Coefficient of Variation 30.4
|
|
Maximum Observed Plasma Concentration (Cmax) of ASN51
Day 14
|
462 ng/mL
Geometric Coefficient of Variation 20.0
|
624 ng/mL
Geometric Coefficient of Variation 71.8
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Dose-normalised Cmax (Cmax/Dose) of ASN51
Day 1
|
18.3 ng/mL/milligram (mg)
Geometric Coefficient of Variation 14.8
|
19.3 ng/mL/milligram (mg)
Geometric Coefficient of Variation 30.4
|
|
Dose-normalised Cmax (Cmax/Dose) of ASN51
Day 14
|
46.2 ng/mL/milligram (mg)
Geometric Coefficient of Variation 20.0
|
31.2 ng/mL/milligram (mg)
Geometric Coefficient of Variation 71.8
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ASN51
Day 1
|
1.00 hours
Interval 0.5 to 1.5
|
1.00 hours
Interval 0.5 to 2.05
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ASN51
Day 14
|
0.767 hours
Interval 0.5 to 2.0
|
2.00 hours
Interval 1.0 to 2.0
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of ASN51
|
20428 hours*nanograms/milliliters (h*ng/mL)
Geometric Coefficient of Variation 24.3
|
40365 hours*nanograms/milliliters (h*ng/mL)
Geometric Coefficient of Variation 56.3
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1, Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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).
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Dose-normalised AUC Infinity (AUCinf /D) of ASN51
|
2043 h*ng/mL/mg
Geometric Coefficient of Variation 24.3
|
2018 h*ng/mL/mg
Geometric Coefficient of Variation 56.3
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASN51
|
19655 h*ng/mL
Geometric Coefficient of Variation 21.3
|
36574 h*ng/mL
Geometric Coefficient of Variation 60.6
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1, Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of ASN51
Day 1
|
2527 h*ng/mL
Geometric Coefficient of Variation 8.2
|
4888 h*ng/mL
Geometric Coefficient of Variation 15.1
|
|
Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of ASN51
Day 14
|
7067 h*ng/mL
Geometric Coefficient of Variation 11.6
|
11237 h*ng/mL
Geometric Coefficient of Variation 73.4
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Terminal Half-life (t1/2) of ASN51
|
45.1 hours
Standard Deviation 13.9
|
66.0 hours
Standard Deviation 25.8
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Terminal Rate Constant (λz) of ASN51
|
0.0163 1 per hour (1/h)
Standard Deviation 0.00392
|
0.0119 1 per hour (1/h)
Standard Deviation 0.00444
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Apparent Total Clearance From Plasma After Oral Administration (CLss/F) of ASN51 at Steady State
|
1.42 Liters/hour (L/h)
Standard Deviation 0.174
|
2.25 Liters/hour (L/h)
Standard Deviation 2.12
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Apparent Volume of Distribution After Oral Administration (VZ/F) of ASN51
|
92.1 Liters
Standard Deviation 28.9
|
254 Liters
Standard Deviation 340
|
SECONDARY outcome
Timeframe: Pre-dose on Days 2, 4, 7, 11 and 14; and 8 hours post-dose on Day 11; 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14, and on Day 15Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Trough Plasma Concentration (Ctrough) of ASN51
Day 2
|
82.4 ng/mL
Interval 71.3 to 95.2
|
149 ng/mL
Interval 112.0 to 180.0
|
|
Trough Plasma Concentration (Ctrough) of ASN51
Day 4
|
173 ng/mL
Interval 148.0 to 201.0
|
316 ng/mL
Interval 247.0 to 404.0
|
|
Trough Plasma Concentration (Ctrough) of ASN51
Day 7
|
227 ng/mL
Interval 195.0 to 263.0
|
444 ng/mL
Interval 365.0 to 539.0
|
|
Trough Plasma Concentration (Ctrough) of ASN51
Day 11
|
238 ng/mL
Interval 202.0 to 279.0
|
431 ng/mL
Interval 284.0 to 654.0
|
|
Trough Plasma Concentration (Ctrough) of ASN51
Day 14
|
236 ng/mL
Interval 199.0 to 280.0
|
377 ng/mL
Interval 179.0 to 795.0
|
|
Trough Plasma Concentration (Ctrough) of ASN51
Day 15
|
240 ng/mL
Interval 206.0 to 281.0
|
405 ng/mL
Interval 210.0 to 778.0
|
SECONDARY outcome
Timeframe: Pre-dose up to Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Accumulation Ratio for AUC (Rac[AUC]) of ASN51
|
2.81 Ratio
Interval 2.52 to 3.09
|
2.52 Ratio
Interval 1.6 to 3.44
|
SECONDARY outcome
Timeframe: Pre-dose up to Day 14Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Accumulation Ratio for Cmax (Rac[Cmax]) of ASN51
|
2.55 Ratio
Interval 2.22 to 2.88
|
1.74 Ratio
Interval 1.12 to 2.37
|
SECONDARY outcome
Timeframe: Predose and 8 hours post-dose on Days 11 and 14Population: PD analysis population included all participants in the safety population for who a PBMC measure is available.
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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=6 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 Participants
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Effect of Food on PBMC Protein O-GlcNAcylation Levels During Repeated Dosing of ASN51
Predose
|
0.87 Ratios
Interval 0.56 to 1.35
|
1.05 Ratios
Interval 0.56 to 1.97
|
|
Effect of Food on PBMC Protein O-GlcNAcylation Levels During Repeated Dosing of ASN51
8 hours post-dose
|
0.94 Ratios
Interval 0.69 to 1.28
|
0.86 Ratios
Interval 0.55 to 1.34
|
SECONDARY outcome
Timeframe: At 5.1, 75.9 hours post-dose on Day 1 (Participant 1); 6.0, 196.9 hours post-dose on Day 1 (Participant 2); 5.2, 79.3 hours post-dose on Day 1 (Participant 3) and 5.5 and 77.0 hours post-dose on Day 1 (Participant 4)Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 4: PET Scan 3, 77.0 hours at 91.4 ng/mL
|
91.9 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 1: PET Scan 2, 5.1 hours at 118.0 ng/mL
|
92.0 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 1: PET Scan 3, 75.9 hours at 101.0 ng/mL
|
84.6 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 2: PET Scan 2, 6.0 hours at 118.0 ng/mL
|
94.3 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 2: PET Scan 3, 196.9 hours at 4.8 ng/mL
|
-16.0 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 3: PET Scan 2, 5.2 hours at 121.0 ng/mL
|
95.6 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 3: PET Scan 3, 79.3 hours at 127.0 ng/mL
|
91.3 percentage of receptor occupancy
|
—
|
|
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Participant 4: PET Scan 2, 5.5 hours at 171.0 ng/mL
|
97.8 percentage of receptor occupancy
|
—
|
SECONDARY outcome
Timeframe: At 5.5, 75.6 hours post-dose on Day 1 (Participant 5); 5.3, 75.4 hours post-dose on Day 1 (Participant 6); 4.9, 75.9 hours post-dose on Day 1 (Participant 7) and 5.0 and 220.5 hours post-dose on Day 1 (Participant 8)Population: 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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=4 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 5: PET Scan 2, 5.5 hours at 232.0 ng/mL
|
98.5 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 5: PET Scan 3, 75.6 hours at 67.3 ng/mL
|
83.4 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 6: PET Scan 2, 5.3 hours at 309.0 ng/mL
|
98.1 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 6: PET Scan 3, 75.4 hours at 152.0 ng/mL
|
93.3 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 7: PET Scan 2, 4.9 hours at 267.0 ng/mL
|
98.1 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 7: PET Scan 3, 75.9 hours at 132.0 ng/mL
|
91.4 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 8: PET Scan 2, 5.0 hours at 304.0 ng/mL
|
97.5 percentage of receptor occupancy
|
—
|
|
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Participant 8: PET Scan 3, 220.5 hours at 21.7ng/mL
|
53.9 percentage of receptor occupancy
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 10Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 220.5 hours post-dose on Day 1Population: 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.
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.
Outcome measures
| Measure |
Group 1: ASN51 Low Dose
n=8 Participants
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
Receptor Occupancy as Assessed by Plasma Concentration That Corresponds to 50% Occupancy (EC50)
|
17.6 ng/mL
Interval 9.2 to 25.9
|
—
|
Adverse Events
Group 1: ASN51 Low Dose
Group 2: ASN51 High Dose
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1: ASN51 Low Dose
n=6 participants at risk
Participants received low dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
Group 2: ASN51 High Dose
n=6 participants at risk
Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.
|
|---|---|---|
|
General disorders
Catheter site pain
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
General disorders
Catheter site related reaction
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
33.3%
2/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Lethargy
|
0.00%
0/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
0.00%
0/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
0.00%
0/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
Infections and infestations
Hordeolum
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
0.00%
0/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
16.7%
1/6 • Baseline up to end of the study (approximately 4.5 months)
Safety population included all participants who received at least one dose of the study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place