Trial Outcomes & Findings for Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil (NCT NCT02822573)
NCT ID: NCT02822573
Last Updated: 2023-09-13
Results Overview
Hopkins Verbal Learning Test-Revised (HVLT-R): The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to patients on three successive learning trials. Free recall scores are recorded for each learning trial. After a 20-minute interval during which patients complete other non-interfering tasks and questionnaires they are asked to recall the target words. Range is 0-36 with higher values representing better verbal learning and memory.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
276 participants
Primary outcome timeframe
Baseline, Weeks 12, 24, 36
Results posted on
2023-09-13
Participant Flow
All eligible patients that consented to participate were enrolled and randomized.
Participant milestones
| Measure |
Donepezil
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Overall Study
STARTED
|
140
|
136
|
|
Overall Study
COMPLETED
|
110
|
117
|
|
Overall Study
NOT COMPLETED
|
30
|
19
|
Reasons for withdrawal
| Measure |
Donepezil
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
3
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
5
|
|
Overall Study
Protocol Violation
|
6
|
4
|
|
Overall Study
Too sick or ill
|
2
|
1
|
|
Overall Study
Disease Progression
|
1
|
1
|
|
Overall Study
No reason given
|
6
|
4
|
Baseline Characteristics
Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil
Baseline characteristics by cohort
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Total
n=276 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Age · Less than 50 years old
|
35 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
70 Participants
n=206 Participants
|
|
Age, Customized
Age · 50-59 years
|
52 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
102 Participants
n=206 Participants
|
|
Age, Customized
Age · 60-69 years
|
36 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
69 Participants
n=206 Participants
|
|
Age, Customized
Age · 70 years or older
|
17 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
140 Participants
n=99 Participants
|
136 Participants
n=107 Participants
|
276 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
128 Participants
n=99 Participants
|
131 Participants
n=107 Participants
|
259 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
128 Participants
n=99 Participants
|
131 Participants
n=107 Participants
|
259 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
140 participants
n=99 Participants
|
136 participants
n=107 Participants
|
276 participants
n=206 Participants
|
|
Body Mass Index (BMI)
|
30.9 kg/m2
STANDARD_DEVIATION 6.5 • n=99 Participants
|
31.1 kg/m2
STANDARD_DEVIATION 6.9 • n=107 Participants
|
31.0 kg/m2
STANDARD_DEVIATION 6.7 • n=206 Participants
|
|
Chemotherapy Received
Anthracycline, cytoxan, and taxane with or without capecitabine
|
63 Participants
n=99 Participants
|
63 Participants
n=107 Participants
|
126 Participants
n=206 Participants
|
|
Chemotherapy Received
Taxane and cytoxan only
|
30 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
61 Participants
n=206 Participants
|
|
Chemotherapy Received
Carboplatin and taxane only
|
25 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
51 Participants
n=206 Participants
|
|
Chemotherapy Received
Other combinations
|
22 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Menopausal Status
Perimenopausal or Postmenopausal
|
129 Participants
n=99 Participants
|
125 Participants
n=107 Participants
|
254 Participants
n=206 Participants
|
|
Menopausal Status
Premenopausal
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Currently taking hormonal therapy
Yes
|
95 Participants
n=99 Participants
|
97 Participants
n=107 Participants
|
192 Participants
n=206 Participants
|
|
Currently taking hormonal therapy
No
|
45 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
84 Participants
n=206 Participants
|
|
Time since completed chemotherapy (months)
|
28.8 months
STANDARD_DEVIATION 14.0 • n=99 Participants
|
30.5 months
STANDARD_DEVIATION 14.4 • n=107 Participants
|
29.6 months
STANDARD_DEVIATION 14.2 • n=206 Participants
|
|
Shipley Institute of Living Scale-2 Vocabulary
|
30.4 score on a scale 0-40
STANDARD_DEVIATION 4.2 • n=99 Participants
|
31.0 score on a scale 0-40
STANDARD_DEVIATION 4.2 • n=107 Participants
|
30.7 score on a scale 0-40
STANDARD_DEVIATION 4.2 • n=206 Participants
|
|
Highest level of Education Completed
High School Graduate/GED or less
|
28 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Highest level of Education Completed
Some college/vocational training
|
55 Participants
n=99 Participants
|
57 Participants
n=107 Participants
|
112 Participants
n=206 Participants
|
|
Highest level of Education Completed
College degree
|
30 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
|
Highest level of Education Completed
Post graduate work or degree
|
16 Participants
n=99 Participants
|
21 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Highest level of Education Completed
Prefer not to answer or unknown
|
11 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Hopkins Verbal Learning Test- Revised (HVLT-R): Total
|
23.3 score on a scale 0-36
STANDARD_DEVIATION 4.2 • n=99 Participants
|
23.1 score on a scale 0-36
STANDARD_DEVIATION 4.7 • n=107 Participants
|
23.3 score on a scale 0-36
STANDARD_DEVIATION 4.4 • n=206 Participants
|
|
Hopkins Verbal Learning Test- Revised (HVLT-R): Delayed Recall
|
8.3 score on a scale 0-12
STANDARD_DEVIATION 2.0 • n=99 Participants
|
8.2 score on a scale 0-12
STANDARD_DEVIATION 2.1 • n=107 Participants
|
8.3 score on a scale 0-12
STANDARD_DEVIATION 2.1 • n=206 Participants
|
|
Hopkins Verbal Learning Test- Revised (HVLT-R): Recognition
|
10.9 score on a scale 0-12
STANDARD_DEVIATION 1.2 • n=99 Participants
|
10.9 score on a scale 0-12
STANDARD_DEVIATION 1.4 • n=107 Participants
|
10.9 score on a scale 0-12
STANDARD_DEVIATION 1.3 • n=206 Participants
|
|
Hopkins Verbal Learning Test- Revised (HVLT-R): Discrimination
|
10.3 score on a scale -12 to 12
STANDARD_DEVIATION 1.5 • n=99 Participants
|
10.3 score on a scale -12 to 12
STANDARD_DEVIATION 1.8 • n=107 Participants
|
10.3 score on a scale -12 to 12
STANDARD_DEVIATION 1.6 • n=206 Participants
|
|
Trail Making Test (TMT) - A
|
37.1 seconds
STANDARD_DEVIATION 27.1 • n=99 Participants
|
25.8 seconds
STANDARD_DEVIATION 23.4 • n=107 Participants
|
36.5 seconds
STANDARD_DEVIATION 25.3 • n=206 Participants
|
|
Trail Making Test (TMT) - B
|
91.2 seconds
STANDARD_DEVIATION 50.4 • n=99 Participants
|
82.3 seconds
STANDARD_DEVIATION 45.7 • n=107 Participants
|
86.9 seconds
STANDARD_DEVIATION 48.3 • n=206 Participants
|
|
Controlled Oral Word Association (COWA)
|
34.7 score on scale 0 to no specified maximum
STANDARD_DEVIATION 10.1 • n=99 Participants
|
34.8 score on scale 0 to no specified maximum
STANDARD_DEVIATION 10.3 • n=107 Participants
|
34.7 score on scale 0 to no specified maximum
STANDARD_DEVIATION 10.2 • n=206 Participants
|
|
Digit Span Test Backward
|
6.4 score on a scale 0-16
STANDARD_DEVIATION 2.2 • n=99 Participants
|
6.8 score on a scale 0-16
STANDARD_DEVIATION 2.2 • n=107 Participants
|
6.5 score on a scale 0-16
STANDARD_DEVIATION 2.2 • n=206 Participants
|
|
Digit Symbol Coding
|
64.2 scores on a scale 0-100
STANDARD_DEVIATION 17.3 • n=99 Participants
|
61.6 scores on a scale 0-100
STANDARD_DEVIATION 16.5 • n=107 Participants
|
62.9 scores on a scale 0-100
STANDARD_DEVIATION 17.0 • n=206 Participants
|
|
The Functional Assessment of Cancer Therapy (FACT)-Cognition: Perceived Cognitive Impairment
|
29.2 scores on a scale 0-80
STANDARD_DEVIATION 14.8 • n=99 Participants
|
33.4 scores on a scale 0-80
STANDARD_DEVIATION 15.9 • n=107 Participants
|
31.3 scores on a scale 0-80
STANDARD_DEVIATION 15.5 • n=206 Participants
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - Short Form 7a
|
55.5 T-score
STANDARD_DEVIATION 7.8 • n=99 Participants
|
55.4 T-score
STANDARD_DEVIATION 8.0 • n=107 Participants
|
55.5 T-score
STANDARD_DEVIATION 7.9 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat analysis. Considered and utilized all data available at each timepoint.
Hopkins Verbal Learning Test-Revised (HVLT-R): The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to patients on three successive learning trials. Free recall scores are recorded for each learning trial. After a 20-minute interval during which patients complete other non-interfering tasks and questionnaires they are asked to recall the target words. Range is 0-36 with higher values representing better verbal learning and memory.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Hopkins Verbal Learning Test-Revised (HVLT-R) - Total
12 Weeks
|
24.4 score on a scale of 0-36
Interval 23.6 to 25.1
|
24.5 score on a scale of 0-36
Interval 23.7 to 25.3
|
|
Hopkins Verbal Learning Test-Revised (HVLT-R) - Total
24 Weeks
|
26.0 score on a scale of 0-36
Interval 25.2 to 26.8
|
26.5 score on a scale of 0-36
Interval 25.8 to 27.2
|
|
Hopkins Verbal Learning Test-Revised (HVLT-R) - Total
36 Weeks
|
25.1 score on a scale of 0-36
Interval 24.3 to 25.9
|
25.9 score on a scale of 0-36
Interval 25.1 to 26.7
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat analysis. All available data from all participants utilized in models.
The digit symbol coding (DSC) test measures processing speed, working memory, visuospatial processing, and attention. The DSC test measures processing speed. It requires respondents to transcribe symbols (e.g., \>) associated with a number (0-9) into empty boxes beneath a series of randomly ordered numbers. Total score is number of correctly transcribed symbols in 2 minutes. Scores range from 0 to 100, with higher scores indicating higher cognitive function.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Digit Symbol Coding Results
12 Weeks
|
69.6 score on a scale 0-100
Interval 67.1 to 72.1
|
67.7 score on a scale 0-100
Interval 65.2 to 70.2
|
|
Digit Symbol Coding Results
24 Weeks
|
71.9 score on a scale 0-100
Interval 69.4 to 74.5
|
71.9 score on a scale 0-100
Interval 69.4 to 74.4
|
|
Digit Symbol Coding Results
36 Weeks
|
74.2 score on a scale 0-100
Interval 71.4 to 76.9
|
71.7 score on a scale 0-100
Interval 69.1 to 74.3
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat: all participants and timepoints available were utilized.
This self-report scale assesses fatigue. Scale ranges from 7 to 35 converted to T-scale ranging 29.4 to 83.2 Higher scores representing more fatigue.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
PROMIS 7-item Fatigue Scale Converted to T-scale Results
12 Weeks
|
52.3 T-score
Interval 51.2 to 53.5
|
53.0 T-score
Interval 51.8 to 54.1
|
|
PROMIS 7-item Fatigue Scale Converted to T-scale Results
24 Weeks
|
51.8 T-score
Interval 50.6 to 53.0
|
52.0 T-score
Interval 50.9 to 53.2
|
|
PROMIS 7-item Fatigue Scale Converted to T-scale Results
36 Weeks
|
52.2 T-score
Interval 51.0 to 53.3
|
53.0 T-score
Interval 51.9 to 54.1
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat analyses: all available timepoints and participant data utilized.
The FACT-Cog is a patient-reported outcome (PRO) that includes subscales to measure Perceived Cognitive Impairment (PCI, n = 20 items, score range 0-80). Higher FACT-Cog PCI scores are better and indicate less cognitive impairment.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
FACT-Cognition (Version 3): Perceived Cognitive Impairment
12 Weeks
|
45.6 score on a scale 0-80
Interval 43.0 to 48.1
|
45.6 score on a scale 0-80
Interval 43.1 to 48.1
|
|
FACT-Cognition (Version 3): Perceived Cognitive Impairment
36 Weeks
|
47.6 score on a scale 0-80
Interval 45.0 to 50.3
|
47.5 score on a scale 0-80
Interval 44.9 to 50.0
|
|
FACT-Cognition (Version 3): Perceived Cognitive Impairment
24 Weeks
|
49.4 score on a scale 0-80
Interval 46.7 to 52.1
|
48.8 score on a scale 0-80
Interval 46.1 to 51.4
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat analysis. All available timepoints from all participants utilized.
The Controlled Oral Word Association Test from the Halstead-Reitan Neuropsychological Battery is a verbal fluency test in which participants are asked to say as many words as possible from a given category and in a specified timeframe (typically 60 seconds). Scores are the sum of all acceptable words. Minimum is 0 with no specified maximum; higher values represent better verbal fluency.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Controlled Oral Word Association Test (COWA) Results
12 Weeks
|
6.7 score on a scale 0 to no specified maxim
Interval 6.3 to 7.1
|
6.6 score on a scale 0 to no specified maxim
Interval 6.2 to 7.0
|
|
Controlled Oral Word Association Test (COWA) Results
24 Weeks
|
6.9 score on a scale 0 to no specified maxim
Interval 6.4 to 7.3
|
7.0 score on a scale 0 to no specified maxim
Interval 6.6 to 7.4
|
|
Controlled Oral Word Association Test (COWA) Results
36 Weeks
|
6.8 score on a scale 0 to no specified maxim
Interval 6.3 to 7.2
|
7.3 score on a scale 0 to no specified maxim
Interval 6.8 to 7.7
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat analysis. All available participants and time points utilized.
TMT Part A consists of 25 circles on a piece of paper with the numbers 1 to 25 written randomly in each. For Part A, the person is tasked with drawing a line from one circle to the next in ascending numerical order, from 1 to 25, as quickly as possible. The lines between the circles are referred to as the "trail." Range 1-300 in seconds. Lower values indicate completing task faster with less difficulty. It is a measure of executive functioning with lower values being better. TMT Part B also consists of 25 circles on a piece of paper, But, rather than all of the circles containing numbers, they contain numbers (1 to 12) and letters (A through L). For Part B, the person is tasked with connecting the circles in ascending order, alternating back and forth from numbers to letters. In other words, the "trail" would be connected like this:1-A-2-B-3-C-4-D-5-E-6-F-7-G-8-H-9-I-10-J-11-K-12-L-13. The range 1-300 seconds. Higher values indicate worse executive functioning.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
TMT-A 12 Weeks
|
32.8 time (seconds)
Interval 28.6 to 36.9
|
34.1 time (seconds)
Interval 30.0 to 38.1
|
|
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
TMT-B 12 Weeks
|
76.7 time (seconds)
Interval 70.7 to 82.7
|
78.1 time (seconds)
Interval 72.3 to 83.9
|
|
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
TMT-B 36 Weeks
|
70.1 time (seconds)
Interval 65.2 to 75.0
|
73.6 time (seconds)
Interval 68.9 to 78.2
|
|
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
TMT-A 24 Weeks
|
31.4 time (seconds)
Interval 28.6 to 34.3
|
29.9 time (seconds)
Interval 27.1 to 32.7
|
|
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
TMT-A 36 Weeks
|
28.8 time (seconds)
Interval 26.3 to 31.4
|
30.4 time (seconds)
Interval 28.0 to 32.8
|
|
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
TMT-B 24 Weeks
|
74.8 time (seconds)
Interval 68.6 to 80.9
|
75.1 time (seconds)
Interval 69.2 to 81.1
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36Population: Intent to treat analyses: all timepoints and participant data used.
The Digit Span Task (Backwards-Only Version) measures working memory. On each question the participant repeats the numbers in reverse order of that presented aloud by the examiner (e.g., If the examiner says "5-6", the correct response would be "6-5"; If the examiner says "5-1-7-4-2-3-8", the correct response would be "8-3-2-4-7-1-5"). Score is 0 to 16 with higher scores representing better working memory.
Outcome measures
| Measure |
Donepezil
n=140 Participants
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 Participants
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Digit Span Test-Backwards (DST-B)
12 Weeks
|
6.7 score on a scale 0-16
Interval 6.3 to 7.1
|
6.6 score on a scale 0-16
Interval 6.2 to 7.0
|
|
Digit Span Test-Backwards (DST-B)
24 Weeks
|
6.9 score on a scale 0-16
Interval 6.4 to 7.3
|
7.0 score on a scale 0-16
Interval 6.6 to 7.4
|
|
Digit Span Test-Backwards (DST-B)
36 Weeks
|
6.8 score on a scale 0-16
Interval 6.3 to 7.2
|
7.3 score on a scale 0-16
Interval 6.8 to 7.7
|
Adverse Events
Donepezil
Serious events: 12 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 8 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Donepezil
n=140 participants at risk
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Donepezil 5 mg: Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
Placebo
n=136 participants at risk
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Placebo: Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
|
|---|---|---|
|
Psychiatric disorders
Insomnia
|
3.6%
5/140 • Number of events 5 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
2.2%
3/136 • Number of events 3 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Vascular disorders
Hypertension
|
1.4%
2/140 • Number of events 2 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
2.9%
4/136 • Number of events 4 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Nervous system disorders
Headache
|
1.4%
2/140 • Number of events 2 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
1.5%
2/136 • Number of events 2 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
0.00%
0/140 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.74%
1/136 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Gastrointestinal disorders
Diarrhea
|
0.71%
1/140 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.00%
0/136 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/140 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.74%
1/136 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Investigations
Pain
|
0.71%
1/140 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.00%
0/136 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Nervous system disorders
Syncope
|
0.00%
0/140 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.74%
1/136 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Investigations
Weight Gain
|
0.00%
0/140 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.74%
1/136 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Investigations
Constitutional Symptoms Other
|
0.71%
1/140 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.00%
0/136 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
|
Infections and infestations
Infection
|
0.71%
1/140 • Number of events 1 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
0.00%
0/136 • Adverse events were collected at baseline, 3 weeks, 6 weeks, 12 weeks, 24 weeks, and 36 weeks. And participants could report additional events at any time.
Each adverse event will include the date of onset, date of resolution, severity, and the relationship to the study agent or intervention, and any action taken with respect to the study agent or intervention. Grade 1 and 2 adverse events (AEs), expected grade 3 or grade 4 AEs will not be collected. Unexpected grade 3 AEs that are unrelated or unlikely will also not be collected.
|
Other adverse events
Adverse event data not reported
Additional Information
Lead Biostatistician (Emily Dressler, PhD)
Wake Forest NCORP Research Base
Phone: 336-716-0891
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place