Trial Outcomes & Findings for Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease (NCT NCT01082965)

Last Updated: 2013-09-12

Results Overview

Posterior cingulate cortex perfusion was measured by arterial spin labeling (ASL). ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.

Recruitment status

TERMINATED

Study phase

Target enrollment

18 participants

Primary outcome timeframe

Baseline, 4 hours post-dose on Day 1

Results posted on

2013-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Donepezil Donepezil 5 milligram (mg) tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Overall Study STARTED	10	8
Overall Study COMPLETED	9	6
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Donepezil Donepezil 5 milligram (mg) tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Overall Study Protocol Violation	0	1
Overall Study Other	1	1

Baseline Characteristics

Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donepezil n=10 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=8 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.	Total n=18 Participants Total of all reporting groups
Age Continuous	74.7 years STANDARD_DEVIATION 9.6 • n=5 Participants	70.6 years STANDARD_DEVIATION 6.9 • n=7 Participants	72.9 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 4 hours post-dose on Day 1

Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=6 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 Baseline	1.243 ratio Standard Deviation 0.2586	1.564 ratio Standard Deviation 0.2494
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 Change at Hour 4 on Day 1	0.156 ratio Standard Deviation 0.5178	-0.017 ratio Standard Deviation 0.3810

PRIMARY outcome

Timeframe: Baseline, 1 minute post-dose (Hour 0) on Day 8

Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=6 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8	0.263 ratio Standard Deviation 0.4872	0.093 ratio Standard Deviation 0.5624

PRIMARY outcome

Timeframe: Baseline, 4 hours post-dose on Day 8

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=6 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8	-0.008 ratio Standard Deviation 0.2506	-0.004 ratio Standard Deviation 0.3948

SECONDARY outcome

Timeframe: Baseline, 4 hours post-dose on Day 1, 1 minute post-dose (Hour 0), 4 hours post-dose on Day 8

Perfusion in anterior cingulate cortex, medial prefrontal cortex, precuneus, inferior parietal cortex and other regions of interest (whole brain gray, superior, medial and inferior temporal cortex; inferior and superior prefrontal cortex; insula, amygdala, thalamus, basal ganglia, hippocampus, Landau) was measured by ASL technique. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for relative perfusion rate. Relative perfusion rate is defined as the absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point.

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=6 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Precuneus	0.055 ratio Standard Deviation 0.4065	0.059 ratio Standard Deviation 0.3475
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day8:Anterior Cingulate Cortex	0.279 ratio Standard Deviation 0.4424	0.167 ratio Standard Deviation 0.3681
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Whole Brain Gray	1.486 ratio Standard Deviation 0.1215	1.500 ratio Standard Deviation 0.0869
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Superior Temporal Cortex	1.749 ratio Standard Deviation 0.2774	1.773 ratio Standard Deviation 0.1732
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Medial Temporal Cortex	1.753 ratio Standard Deviation 0.3186	1.718 ratio Standard Deviation 0.2778
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Inferior Temporal Cortex	1.260 ratio Standard Deviation 0.4634	1.173 ratio Standard Deviation 0.4024
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Medial Prefrontal Cortex	1.488 ratio Standard Deviation 0.1830	1.709 ratio Standard Deviation 0.1441
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Inferior Prefrontal Cortex	1.381 ratio Standard Deviation 0.2205	1.486 ratio Standard Deviation 0.1673
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Superior Prefrontal Cortex	1.308 ratio Standard Deviation 0.1236	1.443 ratio Standard Deviation 0.2046
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Inferior Parietal Cortex	1.610 ratio Standard Deviation 0.2824	1.714 ratio Standard Deviation 0.1628
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Insula	1.390 ratio Standard Deviation 0.1785	1.533 ratio Standard Deviation 0.2130
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Precuneus	1.357 ratio Standard Deviation 0.1904	1.505 ratio Standard Deviation 0.2781
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Anterior Cingulate Cortex	1.236 ratio Standard Deviation 0.2265	1.442 ratio Standard Deviation 0.1753
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Amygdala	1.067 ratio Standard Deviation 0.3025	1.256 ratio Standard Deviation 0.2966
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Thalamus	1.417 ratio Standard Deviation 0.4886	1.468 ratio Standard Deviation 0.3061
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Basal Ganglia	1.120 ratio Standard Deviation 0.2781	1.241 ratio Standard Deviation 0.2461
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Hippocampus	1.327 ratio Standard Deviation 0.2726	1.389 ratio Standard Deviation 0.1229
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Baseline: Landau	1.916 ratio Standard Deviation 0.3753	2.025 ratio Standard Deviation 0.0940
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Whole Brain Gray	0.018 ratio Standard Deviation 0.2309	0.050 ratio Standard Deviation 0.1010
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1:Superior Temporal Cortex	0.031 ratio Standard Deviation 0.3430	0.023 ratio Standard Deviation 0.3002
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Medial Temporal Cortex	-0.066 ratio Standard Deviation 0.5297	-0.006 ratio Standard Deviation 0.2549
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1:Inferior Temporal Cortex	-0.052 ratio Standard Deviation 0.6289	0.090 ratio Standard Deviation 0.2734
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1:Medial Prefrontal Cortex	0.035 ratio Standard Deviation 0.2704	-0.164 ratio Standard Deviation 0.2054
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour4 on Day1:Inferior Prefrontal Cortex	0.143 ratio Standard Deviation 0.1987	-0.061 ratio Standard Deviation 0.2299
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour4 on Day1:Superior Prefrontal Cortex	0.064 ratio Standard Deviation 0.2702	-0.062 ratio Standard Deviation 0.2361
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1:Inferior Parietal Cortex	-0.054 ratio Standard Deviation 0.2411	-0.016 ratio Standard Deviation 0.1848
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Insula	0.154 ratio Standard Deviation 0.2813	0.096 ratio Standard Deviation 0.3276
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Precuneus	-0.024 ratio Standard Deviation 0.3002	0.053 ratio Standard Deviation 0.2952
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day1:Anterior Cingulate Cortex	0.118 ratio Standard Deviation 0.2168	0.173 ratio Standard Deviation 0.2709
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Amygdala	0.187 ratio Standard Deviation 0.5504	0.175 ratio Standard Deviation 0.3785
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Thalamus	0.244 ratio Standard Deviation 0.5697	-0.038 ratio Standard Deviation 0.2209
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Basal Ganglia	0.292 ratio Standard Deviation 0.4557	0.014 ratio Standard Deviation 0.1761
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Hippocampus	0.128 ratio Standard Deviation 0.2115	0.036 ratio Standard Deviation 0.2915
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 1: Landau	-0.051 ratio Standard Deviation 0.3923	-0.033 ratio Standard Deviation 0.1952
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Whole Brain Gray	0.058 ratio Standard Deviation 0.1024	0.028 ratio Standard Deviation 0.1569
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Medial Temporal Cortex	-0.015 ratio Standard Deviation 0.3095	-0.052 ratio Standard Deviation 0.2575
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8:Inferior Temporal Cortex	0.084 ratio Standard Deviation 0.6856	-0.012 ratio Standard Deviation 0.3842
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8:Medial Prefrontal Cortex	-0.198 ratio Standard Deviation 0.4168	-0.173 ratio Standard Deviation 0.3050
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour0 on Day8:Inferior Prefrontal Cortex	0.043 ratio Standard Deviation 0.3353	0.010 ratio Standard Deviation 0.2188
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour0 on Day8:Superior Prefrontal Cortex	-0.152 ratio Standard Deviation 0.3120	-0.019 ratio Standard Deviation 0.2863
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8:Inferior Parietal Cortex	0.005 ratio Standard Deviation 0.5185	-0.106 ratio Standard Deviation 0.2009
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Insula	0.103 ratio Standard Deviation 0.2679	0.154 ratio Standard Deviation 0.1816
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Amygdala	0.170 ratio Standard Deviation 0.5388	0.083 ratio Standard Deviation 0.4233
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Thalamus	0.195 ratio Standard Deviation 0.6486	-0.063 ratio Standard Deviation 0.4992
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Basal Ganglia	0.243 ratio Standard Deviation 0.3925	0.040 ratio Standard Deviation 0.3106
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Hippocampus	0.170 ratio Standard Deviation 0.2832	0.047 ratio Standard Deviation 0.2551
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8: Landau	-0.030 ratio Standard Deviation 0.5354	-0.105 ratio Standard Deviation 0.2642
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Whole Brain Gray	0.010 ratio Standard Deviation 0.1286	-0.022 ratio Standard Deviation 0.0945
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8:Superior Temporal Cortex	0.126 ratio Standard Deviation 0.3065	-0.037 ratio Standard Deviation 0.1319
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Medial Temporal Cortex	-0.103 ratio Standard Deviation 0.2852	-0.110 ratio Standard Deviation 0.2551
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8:Inferior Temporal Cortex	-0.194 ratio Standard Deviation 0.5644	-0.102 ratio Standard Deviation 0.3114
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8:Medial Prefrontal Cortex	0.111 ratio Standard Deviation 0.3606	-0.038 ratio Standard Deviation 0.2262
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour4 on Day8:Inferior Prefrontal Cortex	-0.031 ratio Standard Deviation 0.2477	-0.001 ratio Standard Deviation 0.2342
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour4 on Day8:Superior Prefrontal Cortex	0.225 ratio Standard Deviation 0.3460	-0.007 ratio Standard Deviation 0.1348
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8:Inferior Parietal Cortex	-0.175 ratio Standard Deviation 0.4557	-0.017 ratio Standard Deviation 0.1560
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Insula	0.148 ratio Standard Deviation 0.1477	0.078 ratio Standard Deviation 0.2317
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Precuneus	-0.110 ratio Standard Deviation 0.3846	0.074 ratio Standard Deviation 0.3035
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day8:Anterior Cingulate Cortex	0.180 ratio Standard Deviation 0.2939	0.062 ratio Standard Deviation 0.1423
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Amygdala	0.097 ratio Standard Deviation 0.4984	0.019 ratio Standard Deviation 0.3100
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Thalamus	-0.124 ratio Standard Deviation 0.5028	-0.077 ratio Standard Deviation 0.5330
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Basal Ganglia	0.084 ratio Standard Deviation 0.3393	-0.066 ratio Standard Deviation 0.2787
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Hippocampus	0.041 ratio Standard Deviation 0.2770	0.017 ratio Standard Deviation 0.1225
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 4 on Day 8: Landau	-0.208 ratio Standard Deviation 0.3152	0.008 ratio Standard Deviation 0.1418
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 Change at Hour 0 on Day 8:Superior Temporal Cortex	0.051 ratio Standard Deviation 0.2678	0.038 ratio Standard Deviation 0.3095

SECONDARY outcome

Timeframe: Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

CPAL: a cognitive test which assessed visual episodic learning. Participant was to learn and remember picture locations on the screen and was to tap the target on the central location to begin. As each picture was revealed, the participant was to remember where the picture was located and tap that location. After 4 pictures were placed correctly, second round started. In second round pictures remain in the same locations, but their order of presentation in the center of the screen was different to that of the first round (randomized). The same process was repeated for round 3 and round 4. The outcome was the number of errors made in correctly placing each of the 4 patterns in their location 4 times.

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=8 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 Baseline (n=9, 8)	46.222 errors Standard Deviation 28.7436	37.625 errors Standard Deviation 17.8641
Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 Change at Hour 5 on Day 1 (n=9, 8)	4.333 errors Standard Deviation 24.0936	-2.625 errors Standard Deviation 28.9084
Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 Change at Hour 1 on Day 8 (n=9, 6)	-5.444 errors Standard Deviation 31.9653	-15.833 errors Standard Deviation 15.8293
Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 Change at Hour 5 on Day 8 (n=9, 6)	2.000 errors Standard Deviation 16.3325	-8.000 errors Standard Deviation 17.4126

SECONDARY outcome

Timeframe: Baseline, 5 hours post-dose on Day 8

RAVLT, in immediate recall (IR) list of 15 words (list A) was read aloud to participant 5 times followed by a test of spontaneous retrieval (A1 to A5). After fifth attempt a list of interference, comprising 15 words (list B) was read to participant followed by its retrieval (B1). After attempt B1 examiner asked individual to recall words from list A, without reading it again (A6). Score range: 0-105, higher scores=less impairment. Delayed recall (DR):after a 20-minute interval examiner asked individual to remember words from list A without reading this list; in recognition performance a list comprising 15 words from list A, 15 words from list B, 20 distracting words (similar to words in list A, B) was read to individual. Upon each word read aloud, individual asked to indicate if it belonged to list A, or not. Score range: 0-30, higher scores=less impairment.

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=8 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 Baseline: Total IR (n=9, 8)	25.667 units on a scale Standard Deviation 7.3144	27.000 units on a scale Standard Deviation 9.3960
Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 Baseline: Total DR (n=9, 8)	2.444 units on a scale Standard Deviation 2.3511	2.375 units on a scale Standard Deviation 2.1998
Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 Change at Hour 5 on Day 8:Total IR (n=9, 6)	3.333 units on a scale Standard Deviation 4.1833	5.667 units on a scale Standard Deviation 4.3665
Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 Change at Hour 5 on Day 8: Total DR (n=9, 6)	0.444 units on a scale Standard Deviation 1.9437	0.333 units on a scale Standard Deviation 3.0111

SECONDARY outcome

Timeframe: Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

Computerized test battery used to assess detection and identification task. CogState detection task: a measure of simple reaction time, provided valid assessment of psychomotor function. Participants were required to press a "YES" response key as soon as they detected an event (a card turning face up presented in center of the computer screen). The software measured the response time to detect each event. CogState identification task: measure of choice reaction time, provided a valid assessment of visual attention. Participants were required to decide "YES" or "NO" as to whether the event met a predefined and unchanging criterion (is the color of the card red?) while the event (a card turning face up) occurred in the center of the computer screen. The software measured the speed and accuracy of each response.

Outcome measures

Outcome measures
Measure	Donepezil n=9 Participants Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=8 Participants Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Baseline: Detection Task (n=9, 8)	2.572 log10 milliseconds Standard Deviation 0.1192	2.542 log10 milliseconds Standard Deviation 0.0953
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Baseline: Identification Task (n=9, 8)	2.708 log10 milliseconds Standard Deviation 0.0635	2.727 log10 milliseconds Standard Deviation 0.0540
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Change at Hour 5 on Day 1: Detection Task (n=9, 8)	0.002 log10 milliseconds Standard Deviation 0.0931	0.024 log10 milliseconds Standard Deviation 0.0706
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Change at Hour5 on Day1:Identification Task(n=9,8)	0.020 log10 milliseconds Standard Deviation 0.0355	0.012 log10 milliseconds Standard Deviation 0.0371
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Change at Hour 0 on Day 8: Detection Task (n=9, 6)	0.004 log10 milliseconds Standard Deviation 0.1184	-0.032 log10 milliseconds Standard Deviation 0.0512
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Change at Hour5 on Day8:Identification Task(n=9,6)	0.034 log10 milliseconds Standard Deviation 0.0782	0.004 log10 milliseconds Standard Deviation 0.0625
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Change at Hour0 on Day8:Identification Task(n=9,6)	0.005 log10 milliseconds Standard Deviation 0.0630	0.004 log10 milliseconds Standard Deviation 0.0493
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 Change at Hour 5 on Day 8: Detection Task (n=9, 6)	-0.005 log10 milliseconds Standard Deviation 0.1001	0.004 log10 milliseconds Standard Deviation 0.0508

Adverse Events

Donepezil

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Donepezil n=10 participants at risk Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8.	Placebo n=8 participants at risk Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8.
Gastrointestinal disorders Abdominal discomfort	10.0% 1/10	0.00% 0/8
Gastrointestinal disorders Diarrhoea	10.0% 1/10	12.5% 1/8
General disorders Asthenia	10.0% 1/10	0.00% 0/8
General disorders Fatigue	0.00% 0/10	12.5% 1/8
Injury, poisoning and procedural complications Excoriation	0.00% 0/10	12.5% 1/8
Nervous system disorders Sensory disturbance	0.00% 0/10	12.5% 1/8

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER