Trial Outcomes & Findings for Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors (NCT NCT00369785)

Last Updated: 2021-10-20

Results Overview

Memory is quantified using the Hopkins Verbal Learning Test (HVLT) - immediate recall. Participants are asked to recall 12 words. Each recalled word is given one point. They are given three trials. The total score is the sum of the recalled words. The range for HVLT-Immediate recall is 0 to 36. Higher scores represent better memory.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

198 participants

Primary outcome timeframe

24 weeks

Results posted on

2021-10-20

Participant Flow

Patients were accrued between 2/2008 and 12/2011 at NCI CCOP sites across the nation.

Participant milestones

Participant milestones
Measure	Arm I - Donepezil Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Overall Study STARTED	99	99
Overall Study COMPLETED	72	74
Overall Study NOT COMPLETED	27	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I - Donepezil Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Overall Study Physician Decision	3	2
Overall Study Death	1	2
Overall Study Withdrawal by Subject	7	6
Overall Study Toxicity	6	4
Overall Study Never started	0	2
Overall Study Progression	4	4
Overall Study Multiple reasons	6	5

Baseline Characteristics

Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I - Donepezil n=99 Participants Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control n=99 Participants Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day	Total n=198 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	72 Participants n=93 Participants	83 Participants n=4 Participants	155 Participants n=27 Participants
Age, Categorical >=65 years	27 Participants n=93 Participants	16 Participants n=4 Participants	43 Participants n=27 Participants
Age, Continuous	56.1 years n=93 Participants	54.9 years n=4 Participants	55.1 years n=27 Participants
Sex: Female, Male Female	56 Participants n=93 Participants	50 Participants n=4 Participants	106 Participants n=27 Participants
Sex: Female, Male Male	43 Participants n=93 Participants	49 Participants n=4 Participants	92 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=93 Participants	97 Participants n=4 Participants	193 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	7 Participants n=93 Participants	9 Participants n=4 Participants	16 Participants n=27 Participants
Race (NIH/OMB) White	91 Participants n=93 Participants	90 Participants n=4 Participants	181 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	99 participants n=93 Participants	99 participants n=4 Participants	198 participants n=27 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Participants with 24 week HVLT data.

Outcome measures

Outcome measures
Measure	Arm I - Donepezil n=72 Participants Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control n=73 Participants Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Memory as Quantified by HVLT-immediate Recall	22.5 units on a scale Standard Error 0.45	22.2 units on a scale Standard Error 0.45

PRIMARY outcome

Timeframe: 24 weeks

Population: Number of participants with 24 week memory data

In the Hopkins Verbal Learning Test - discrimination, participants are given lists of 12 correct words and 12 incorrect words. HVLT-discrimination is the number of correctly recognized words minus the number incorrectly recognized. The range for this outcome measure is -12 to 12. Higher scores represent better memory.

Outcome measures

Outcome measures
Measure	Arm I - Donepezil n=72 Participants Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control n=73 Participants Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Memory as Quantified by the HVLT-discrimination	10.1 units on a scale Standard Error 0.24	9.2 units on a scale Standard Error 0.24

Adverse Events

Arm I - Donepezil

Serious events: 12 serious events

Other events: 88 other events

Deaths: 0 deaths

Arm II - Control

Serious events: 10 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm I - Donepezil n=96 participants at risk Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control n=92 participants at risk Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Psychiatric disorders Anorexia	21.9% 21/96 • Number of events 33 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	14.1% 13/92 • Number of events 17 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Psychiatric disorders Cognitive Disturbance	27.1% 26/96 • Number of events 64 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	30.4% 28/92 • Number of events 73 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Constipation	3.1% 3/96 • Number of events 6 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	5.4% 5/92 • Number of events 11 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Diarrhea	25.0% 24/96 • Number of events 29 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	7.6% 7/92 • Number of events 13 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Ear and labyrinth disorders Dizziness	5.2% 5/96 • Number of events 5 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	7.6% 7/92 • Number of events 13 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Metabolism and nutrition disorders Fatigue	57.3% 55/96 • Number of events 105 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	66.3% 61/92 • Number of events 122 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Headache	43.8% 42/96 • Number of events 70 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	43.5% 40/92 • Number of events 73 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
General disorders Insomnia	44.8% 43/96 • Number of events 81 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	39.1% 36/92 • Number of events 70 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Memory Impairment	35.4% 34/96 • Number of events 83 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	37.0% 34/92 • Number of events 91 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Musculoskeletal and connective tissue disorders Muscle Weakness	2.1% 2/96 • Number of events 5 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	5.4% 5/92 • Number of events 11 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Musculoskeletal and connective tissue disorders Muscle Cramps	33.3% 32/96 • Number of events 58 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	28.3% 26/92 • Number of events 48 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Nausea	13.5% 13/96 • Number of events 19 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	18.5% 17/92 • Number of events 21 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Vomiting	8.3% 8/96 • Number of events 10 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	4.3% 4/92 • Number of events 4 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.

Additional Information

Dr. Doug Case

Wake Forest NCORP Research Base

Phone: (336) 716-1048

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I - Donepezil n=96 participants at risk Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day donepezil hydrochloride: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily	Arm II - Control n=92 participants at risk Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Placebo: Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Ear and labyrinth disorders Auditory/Ear - Other	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 3 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Psychiatric disorders Cognitive Disturbance	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Confusion	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
General disorders Death NOS	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	2.2% 2/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
General disorders Dental: peridontal disease	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Dental: teeth	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Diarrhea	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
General disorders Fatigue	3.1% 3/96 • Number of events 5 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	0.00% 0/92 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Headache	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Ear and labyrinth disorders Hearing	1.0% 1/96 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 3 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Infections and infestations Infection	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Psychiatric disorders Insomnia	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Psychiatric disorders Mood Alteration: Depression	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	0.00% 0/92 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Musculoskeletal and connective tissue disorders Muscle weakness	2.1% 2/96 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	0.00% 0/92 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Musculoskeletal and connective tissue disorders Muscle Cramps	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Nausea	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	2.2% 2/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Neuropathy: cranial: CN II Vision	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 3 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Neuropathy: cranial: CN VII Motor-face; Sensory-taste	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 3 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Neuropathy: sensory	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Pain - Other	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	0.00% 0/92 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Pain: Back	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	0.00% 0/92 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Seizure	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	0.00% 0/92 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Nervous system disorders Somnolence/depressed level of consciousness	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
General disorders Syncope (fainting)	1.0% 1/96 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	1.1% 1/92 • Number of events 1 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.
Gastrointestinal disorders Vomiting	0.00% 0/96 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.	2.2% 2/92 • Number of events 2 • 24 weeks Analysis includes everyone with post-treatment AE/toxicity data.