Trial Outcomes & Findings for Safety and Efficacy of Donepezil in Mild to Moderate Alzheimer's Disease (NCT NCT02787746)

Last Updated: 2024-08-23

Results Overview

Physical examinations such as vital signs and weight, clinical laboratory tests, and electrocardiograms (ECGs) during the 20 weeks.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

241 participants

Primary outcome timeframe

20 weeks

Results posted on

2024-08-23

Participant Flow

Participant milestones

Participant milestones
Measure	Donepezil Each enrolled patient received donepezil 10 mg/day (Aricept, two 5 mg-pills, Eisai China Inc, SuZhou, China) every night before sleeping for 20 weeks. If a patient could not tolerate 10 mg/day, the dosage for the patient could be reduced to 5 mg/day for 4 weeks and then increased back to 10 mg/day. If this patient still could not tolerate the 10 mg/day dosage and returned back to 5 mg/day or discontinued the donepezil treatment, he/she should be deemed to have quit the study.
Overall Study STARTED	241
Overall Study COMPLETED	93
Overall Study NOT COMPLETED	148

Reasons for withdrawal

Reasons for withdrawal
Measure	Donepezil Each enrolled patient received donepezil 10 mg/day (Aricept, two 5 mg-pills, Eisai China Inc, SuZhou, China) every night before sleeping for 20 weeks. If a patient could not tolerate 10 mg/day, the dosage for the patient could be reduced to 5 mg/day for 4 weeks and then increased back to 10 mg/day. If this patient still could not tolerate the 10 mg/day dosage and returned back to 5 mg/day or discontinued the donepezil treatment, he/she should be deemed to have quit the study.
Overall Study Adverse Event	42
Overall Study Withdrawal by Subject	65
Overall Study Failure to up-titrate to 10mg/day: 12 patients; Other reasons: 30 patients	41

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donepezil n=241 Participants Daily single dose of donepezil 10mg
Age, Customized <65 Years old	44 Participants n=241 Participants
Age, Customized 65-74 Years old	84 Participants n=241 Participants
Age, Customized 75-84 Years old	110 Participants n=241 Participants
Age, Customized ≥85 Years old	3 Participants n=241 Participants
Sex: Female, Male Female	134 Participants n=241 Participants
Sex: Female, Male Male	107 Participants n=241 Participants
Weight ≤55 kg	97 Participants n=241 Participants
Weight 56-65 kg	74 Participants n=241 Participants
Weight 66-75 kg	47 Participants n=241 Participants
Weight >75 kg	23 Participants n=241 Participants
Heart rate	72.35 beat/min STANDARD_DEVIATION 9.49 • n=241 Participants
Corrected QT interval (QTc)	419.16 msec STANDARD_DEVIATION 29.9 • n=241 Participants
Aspartate aminotransferase (AST)	23.16 U/L STANDARD_DEVIATION 14.09 • n=241 Participants
Past Medical history Cardiovascular diseases	39 Participants n=241 Participants
Past Medical history Neurologic disease	58 Participants n=241 Participants
Past Medical history Mental disease	10 Participants n=241 Participants
Past Medical history Liver disease	13 Participants n=241 Participants
Past Medical history Gastrointestinal diseases	17 Participants n=241 Participants
Past Medical history Other disease	46 Participants n=241 Participants
Past Medical history No disease	58 Participants n=241 Participants
Concomitant drugs Cardiovascular drugs	22 Participants n=241 Participants
Concomitant drugs Central nervous system drugs	106 Participants n=241 Participants
Concomitant drugs Antipsychiatric drugs	18 Participants n=241 Participants
Concomitant drugs Hepatology drugs	1 Participants n=241 Participants
Concomitant drugs Gastrointestinal diseases drugs	5 Participants n=241 Participants
Concomitant drugs Other drugs	3 Participants n=241 Participants
Concomitant drugs Did not use	86 Participants n=241 Participants
MMSE	18.69 score STANDARD_DEVIATION 4.35 • n=241 Participants
ADCS-ADL(Alzheimer's disease cooperative study - activities of daily living)	53.29 Score unit STANDARD_DEVIATION 11.55 • n=241 Participants
HAMD	3.09 Score unit STANDARD_DEVIATION 2.56 • n=241 Participants
Previous duration of donepezil 5mg/d therapy	70.97 day STANDARD_DEVIATION 123.95 • n=241 Participants

PRIMARY outcome

Timeframe: 20 weeks

Physical examinations such as vital signs and weight, clinical laboratory tests, and electrocardiograms (ECGs) during the 20 weeks.

Outcome measures

Outcome measures
Measure	Donepezil n=241 Participants Daily single dose of donepezil 10mg	Week 4 Daily single dose of donepezil 10mg	Change From Baseline at Week 4 Daily single dose of donepezil 10mg	Week 20 Daily single dose of donepezil 10mg	Change From Baseline at Week 20 Daily single dose of donepezil 10mg	APOE ɛ3/e4 Carriers Number of APOE ɛ3/e4 carriers
Number of Patients With Adverse Events (AEs)	93 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: 20 weeks

Number of patients who withdrew due to adverse events

Outcome measures

Outcome measures
Measure	Donepezil n=241 Participants Daily single dose of donepezil 10mg	Week 4 Daily single dose of donepezil 10mg	Change From Baseline at Week 4 Daily single dose of donepezil 10mg	Week 20 Daily single dose of donepezil 10mg	Change From Baseline at Week 20 Daily single dose of donepezil 10mg	APOE ɛ3/e4 Carriers Number of APOE ɛ3/e4 carriers
Number of Patients Who Withdrew From the Trial Due to Adverse Events.	42 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 4, 20 weeks

Population: 241 patients were included in the full analysis set (FAS) and 93 patients who completed the study constituted the per-protocol set (PPS). Therefore, FAS last-observation-carried-forward \[LOCF\] and PPS \[LOCF\] included 241 and 93 patients, respectively. FAS \[actual data\] at baseline, Week 4 and Week 20 included 238, 145 and 94 patients, respectively. PPS \[actual data\] at baseline, Week 4 and Week 20 included 148, 113 and 93 patients, respectively.

Comparison of Mental state examination (MMSE) scores (range 0-30) at 4 weeks and 20 weeks with baseline in mild to moderate AD patients. A higher score indicates better cognitive function.Higher score indicates better cognition function.

Outcome measures

Outcome measures
Measure	Donepezil n=241 Participants Daily single dose of donepezil 10mg	Week 4 n=241 Participants Daily single dose of donepezil 10mg	Change From Baseline at Week 4 n=241 Participants Daily single dose of donepezil 10mg	Week 20 n=241 Participants Daily single dose of donepezil 10mg	Change From Baseline at Week 20 n=241 Participants Daily single dose of donepezil 10mg	APOE ɛ3/e4 Carriers Number of APOE ɛ3/e4 carriers
Changes in Mini-Mental State Examination Scores From Baseline PPS (actual data)	18.45 score on a scale Standard Deviation 4.39	19.33 score on a scale Standard Deviation 5.53	1.01 score on a scale Standard Deviation 2.86	19.57 score on a scale Standard Deviation 5.81	0.94 score on a scale Standard Deviation 3.18	—
Changes in Mini-Mental State Examination Scores From Baseline FAS LOCF	18.69 score on a scale Standard Deviation 4.35	19.12 score on a scale Standard Deviation 5.06	0.44 score on a scale Standard Deviation 2.51	19.07 score on a scale Standard Deviation 5.30	0.39 score on a scale Standard Deviation 2.64	—
Changes in Mini-Mental State Examination Scores From Baseline FAS (actual data)	18.69 score on a scale Standard Deviation 4.35	18.87 score on a scale Standard Deviation 5.76	0.72 score on a scale Standard Deviation 3.19	19.62 score on a scale Standard Deviation 5.8	0.97 score on a scale Standard Deviation 3.18	—
Changes in Mini-Mental State Examination Scores From Baseline PPS LOCF	18.45 score on a scale Standard Deviation 4.39	19.22 score on a scale Standard Deviation 5.18	0.77 score on a scale Standard Deviation 2.53	19.11 score on a scale Standard Deviation 5.54	0.66 score on a scale Standard Deviation 2.74	—

SECONDARY outcome

Timeframe: Baseline, 4, 20 weeks

Population: 241 patients were included in the FAS and 93 patients who completed the study constituted the PPS. Therefore, FAS \[LOCF\] and PPS \[LOCF\] included 241 and 93 patients, respectively. FAS \[actual data\] at baseline, Week 4 and Week 20 all included 42 patients, while PPS \[actual data\] at baseline, Week 4 and Week 20 all included 26 patients

Comparison of Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores (range 0-78) at 4 weeks and 20 weeks with baseline scores in patients with mild to moderate Alzheimer's Disease. A higher score indicates better activities of daily living (ADL).

Outcome measures

Outcome measures
Measure	Donepezil n=241 Participants Daily single dose of donepezil 10mg	Week 4 n=241 Participants Daily single dose of donepezil 10mg	Change From Baseline at Week 4 n=241 Participants Daily single dose of donepezil 10mg	Week 20 n=241 Participants Daily single dose of donepezil 10mg	Change From Baseline at Week 20 n=241 Participants Daily single dose of donepezil 10mg	APOE ɛ3/e4 Carriers Number of APOE ɛ3/e4 carriers
Changes in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Scores From Baseline FAS LOCF	53.29 score on a scale Standard Deviation 11.55	53.71 score on a scale Standard Deviation 12.97	0.43 score on a scale Standard Deviation 7.34	53.62 score on a scale Standard Deviation 12.82	0.33 score on a scale Standard Deviation 7.47	—
Changes in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Scores From Baseline FAS (actual data)	34.76 score on a scale Standard Deviation 14.04	33.31 score on a scale Standard Deviation 13.75	-0.66 score on a scale Standard Deviation 6.04	30.86 score on a scale Standard Deviation 11.01	-1.15 score on a scale Standard Deviation 11.04	—
Changes in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Scores From Baseline PPS LOCF	54.31 score on a scale Standard Deviation 10.63	54.35 score on a scale Standard Deviation 12.50	0.04 score on a scale Standard Deviation 6.20	54.19 score on a scale Standard Deviation 12.25	-0.12 score on a scale Standard Deviation 6.44	—
Changes in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Scores From Baseline PPS (actual data)	33.31 score on a scale Standard Deviation 13.58	32.71 score on a scale Standard Deviation 13.5	-0.65 score on a scale Standard Deviation 6.69	30.9 score on a scale Standard Deviation 11.07	-1.13 score on a scale Standard Deviation 11.11	—

SECONDARY outcome

Timeframe: 20 weeks

Population: 115 patients in the safety set had their APOE gene sequenced and have data on their APOE genotype. Among these patients, 1 carries APOE ɛ2/ɛ2, 58 carry APOE ɛ3/ɛ3, 7 carry APOE ɛ4/ɛ4, 11 carry APOE ɛ2/ɛ3, 1 carries APOE ɛ2/ɛ4, and 37 carry APOE ɛ3/e4.

Comparison of incidence of adverse events among patients with different APOE genotypes

Outcome measures

Outcome measures
Measure	Donepezil n=1 Participants Daily single dose of donepezil 10mg	Week 4 n=58 Participants Daily single dose of donepezil 10mg	Change From Baseline at Week 4 n=7 Participants Daily single dose of donepezil 10mg	Week 20 n=11 Participants Daily single dose of donepezil 10mg	Change From Baseline at Week 20 n=1 Participants Daily single dose of donepezil 10mg	APOE ɛ3/e4 Carriers n=37 Participants Number of APOE ɛ3/e4 carriers
Correlation Between Apolipoprotein E.(APOE) Genotype and Incidence of Adverse Events of Donepezil Numbe of patients who experienced adverse events	0 Participants	34 Participants	5 Participants	6 Participants	0 Participants	13 Participants
Correlation Between Apolipoprotein E.(APOE) Genotype and Incidence of Adverse Events of Donepezil Number of patients who did not experience adverse events	1 Participants	24 Participants	2 Participants	5 Participants	1 Participants	24 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: 115 patients in the study had their APOE genotype tested by Sanger sequencing from blood collected from the the patient at Visit 2.

A patient's APOE genotype (ɛ2/ɛ2, ɛ3/ɛ3, ɛ4/ɛ4, ɛ2/ɛ3, ɛ2/ɛ4 and ɛ3/e4) was tested by tested by Sanger sequencing from blood collected from the the patient at Visit 2. APOE genotype is not mandatory

Outcome measures

Outcome measures
Measure	Donepezil n=115 Participants Daily single dose of donepezil 10mg	Week 4 Daily single dose of donepezil 10mg	Change From Baseline at Week 4 Daily single dose of donepezil 10mg	Week 20 Daily single dose of donepezil 10mg	Change From Baseline at Week 20 Daily single dose of donepezil 10mg	APOE ɛ3/e4 Carriers Number of APOE ɛ3/e4 carriers
APOE Genotype APOE ɛ2/ɛ2	1 Participants	—	—	—	—	—
APOE Genotype APOE ɛ3/ɛ3	58 Participants	—	—	—	—	—
APOE Genotype APOE ɛ4/ɛ4	7 Participants	—	—	—	—	—
APOE Genotype APOE ɛ2/ɛ3	11 Participants	—	—	—	—	—
APOE Genotype APOE ɛ2/ɛ4	1 Participants	—	—	—	—	—
APOE Genotype APOE ɛ3/e4	37 Participants	—	—	—	—	—

Adverse Events

Donepezil

Serious events: 3 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Donepezil n=241 participants at risk Daily single dose of donepezil 10mg
Gastrointestinal disorders Emesis	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Renal and urinary disorders Acute kidney injury	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders acute myocardial infarction	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.

Other adverse events

Other adverse events
Measure	Donepezil n=241 participants at risk Daily single dose of donepezil 10mg
Blood and lymphatic system disorders anemia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Hyperhomocysteinemia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Angina pectoris	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Bradycardia	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Myocardial ischemia	0.41% 1/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Sinus bradycardia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Cardiac discomfort	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Ear and labyrinth disorders tinnitus	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders hypogastralgia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Constipation	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Diarrhea	5.4% 13/241 • Number of events 13 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Gastritis	0.83% 2/241 • Number of events 3 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Nausea	3.3% 8/241 • Number of events 8 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders hygrostomia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Vomiting	2.5% 6/241 • Number of events 6 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
General disorders fever	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Hepatobiliary disorders abnormal liver function	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations urocystitis	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations shingles	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations upper respiratory infection	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations urinary tract infection	2.1% 5/241 • Number of events 5 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations bacterial infection	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations pulmonary infection	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Injury, poisoning and procedural complications Wrist fracture	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Injury, poisoning and procedural complications contusion	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Injury, poisoning and procedural complications thoracic injury	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Elevated alanine aminotransferase	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased aspartate aminotransferase	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased blood albumin	0.41% 1/241 • Number of events 4 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Elevated blood bilirubin	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Reduced blood chloride	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased blood creatine phosphokinase	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased blood creatinine	1.2% 3/241 • Number of events 3 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased blood glucose	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased blood lactate dehydrogenase	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased blood lactate dehydrogenase	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased blood sodium	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased blood urea	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Abnormal ECG	1.7% 4/241 • Number of events 4 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Abnormal EEG	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Reduced heart rate	1.2% 3/241 • Number of events 4 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased red blood cell count	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Urinary erythrocyte positive	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased white blood cell count	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Urine leukocyte positive	1.2% 3/241 • Number of events 3 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Increased platelet count	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased blood alkaline phosphatase	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Investigations Decreased blood creatine phosphokinase	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders diabetes	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders hyperuricemia	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Loss of appetite	1.2% 3/241 • Number of events 3 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Hyperlipidemia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Type 2 diabetes	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Muscle spasm	2.1% 5/241 • Number of events 5 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Skeletal muscle pain	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Physical discomfort	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders dizziness	1.7% 4/241 • Number of events 5 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Memory impairment	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Drowsiness	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Trigeminal neuralgia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders Depression	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders Hallucination	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders insomnia	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders sleep disorder	2.1% 5/241 • Number of events 6 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders Amnesia	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Renal and urinary disorders renal failure	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders hidrosis	0.83% 2/241 • Number of events 3 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Night sweats	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders rash	0.83% 2/241 • Number of events 2 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders skin disease	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.
Vascular disorders Flushing	0.41% 1/241 • Number of events 1 • 20 weeks Systematic assessment due to regular investigator assessment at study visits.

Additional Information

Jianping Jia

Department of Neurology, Xuan Wu Hospital of Capital Medical University; Freindship Hospital of Capital Medical University

Phone: +86 10 83188730

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place