A 28-Week Open Label Extension Study Evaluating Safety and Tolerability of Donepezil Hydrochloride in Subjects With Mild Cognitive Impairment

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00934375
• Collaborator: (none)
• Enrollment: 145
• Locations: 49
• Arms: 2
• Duration (Months): 19
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a multi-center, open-label study of 28 weeks duration in subjects with Mild Cognitive Impairment who have completed the double-blind study (E2020-A001-412).

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment	Drug: Aricept (donepezil hydrochloride); Drug: placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 145 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 28-Week Open Label Extension Study Evaluating Safety and Tolerability of Donepezil Hydrochloride in Subjects With Mild Cognitive Impairment
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Sep 1, 2007
• Actual Study Completion Date: Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Aricept (donepezil hydrochloride); 5 mg or 10 mg of donepezil hydrochloride (Aricept) taken orally once a day.; Other Names: donepezil hydrochloride
Placebo Comparator: 2	Drug: placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events [Baseline, Week 6, Week 12 and Week 28.]

   Overview of Treatment-Emergent Adverse Events and Safety Population (TEAEs)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 90 Years
• Sexes Eligible for Study: All

Inclusion Criteria:

1. Age Range: Adult subjects (45 to 90 years of age inclusive)

2. Sex distribution: Men and women. Women of child-bearing potential (<1 year post menopausal) must be practicing effective contraception and have negative serum B-HCG at Screening. [Women who are breast-feeding are excluded.]

3. Subjects must have completed the one year, double-blind core trial (E2020-A001-412).

4. A completed Diagnostic Worksheet at the end of the double-blind core trial (E2020-A001-412) indicating no conversion to Alzheimer's Disease or dementia.

5. Health: Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane).

6. The subject must be expected to complete the entire study.

7. Subjects must be sufficiently fluent in English.

8. Subjects must have an informant who has daily contact with the subject (e.g., an average of 10 or more hours per week), can observe for possible adverse events and will accompany the subject to all visits.

9. Clinical laboratory values must be within normal limits, or if abnormal, judged clinically insignificant by the investigator (not likely to cause cognitive impairment or medical instability).

Exclusion Criteria:

1. Subjects who have not completed or have terminated early from the one year, double-blind core trial (E2020-A001-412).

2. Any subject without a completed diagnostic worksheet from Week 51 of the core double-blind trial (E2020-A001-412).

3. Any subject with a completed diagnostic worksheet from Week 51 of the core double-blind trial (E2020-A001-412) indicating conversion to Alzheimer's or other dementia.

4. Subjects with uncontrolled hypertension (sitting systolic >= 160mmHg and/or diastolic

=95mmHg) as assessed by the investigator, regardless of whether or not the subject is taking anti-hypertensive medications.

1. Subjects with a history of malignant neoplasms treated within five years prior to study entry (other than basal or squamous cell carcinoma of the skin); current evidence of malignant neoplasm; or recurrent or matastatic disease.

2. Subjects who have suffered a severe infection or a major surgical procedure within three months prior to baseline.

3. Subjects who may not be able to comply with the protocol.

4. Subjects with known hypersensitivity to piperidine derivatives or acetylcholinesterase(AChE)inhibitors.

5. Subjects with diabetes mellitis not controlled by diet and/or medication with a random serum glucose value of >170mg/dl.

6. Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study.

7. Subjects who do not have a reliable informant (e.g., the informant has contact with the subject less than 10 hours per week).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurology Neurodiagnostic Lab, LLC	Alabaster	Alabama	United States	35007
2	Pivotal Research Centers	Peoria	Arizona	United States	85381
3	Sun Health Research Institute	Sun City	Arizona	United States	85351
4	Northwest Neurospecialists, PLLC	Tucson	Arizona	United States	85741-3537
5	The Neurology Center	Encinitas	California	United States	92024
6	Margolin Brain Institute	Fresno	California	United States	93720
7	Colaborative Neuroscience Network (CNS Network)	Garden Grove	California	United States	92845
8	Nerve Pro Research	Irvine	California	United States	92618
9	Optimum Health Services	La Mesa	California	United States	91942
10	Pacific Research Network	San Diego	California	United States	92103
11	Neurological Research Institute	Santa Monica	California	United States	90404
12	CA Neuroscience Research	Sherman Oaks	California	United States	91403
13	Pacific Research Network	Vista	California	United States	92081
14	Yale University Alzheimers Disease Research Unit School of Medicine Department of Psychiatry	New Haven	Connecticut	United States	06510
15	North Broward Medical Center Memory Disorder Center	Deerfield Beach	Florida	United States	33064
16	Neurologic Consultants	Ft. Lauderdale	Florida	United States	33308
17	Berma Research Group	Hialeah	Florida	United States	33016
18	Sunrise Clinical Research	Hollywood	Florida	United States	33021
19	Wien Center for Memory Disorders, Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
20	Berma Research Group	Plantation	Florida	United States	33317
21	The Roskamp Institute	Sarasota	Florida	United States	34243
22	Comprehensive Neuroscience, Inc.	St. Petersburg	Florida	United States	33702
23	Stedman Clinical Trials, LLC	Tampa	Florida	United States	33613
24	USF Memory Disorder's Clinic	Tampa	Florida	United States	33613
25	USF Suncoast Gerontalogy Center	Tampa	Florida	United States	33617
26	Center for Clinical Trials. L.C.	Venice	Florida	United States	34285
27	Palm Beach Neurology	West Palm Beach	Florida	United States	33407
28	Lexington Clinic	Lexington	Kentucky	United States	40504
29	Borgess Research Institute	Kalamazoo	Michigan	United States	49048
30	St. Louis University - Clinical Trials Unit	St. Louis	Missouri	United States	63104
31	Comprehensive Neuroscience, Inc	Kenilworth	New Jersey	United States	07033
32	Neurological Associates of Albany, PC Neurology	Albany	New York	United States	12208
33	Neurobehavioral Research Inc.	Lawrence	New York	United States	11559
34	New York University School of Medicine Aging and Dementia Research Center	New York	New York	United States	10016
35	Columbia University	New York	New York	United States	10032
36	Monroe Community Hospital Program in Neurobehavioral Therapeutics	Rochester	New York	United States	14620
37	Behavioral Medical Research of Staten Island	Staten Island	New York	United States	10305
38	The Ohio State University	Columbus	Ohio	United States	43210
39	Neurology Center of Ohio	Toledo	Ohio	United States	43623
40	Pahl Pharmaceutical Research, LLC	Oklahoma City	Oklahoma	United States	73118
41	Summit Research Network(Oregon) Inc.	Portland	Oregon	United States	97210
42	Clinical Trial Specialists	Bala Cynwyd	Pennsylvania	United States	19004
43	Westmoreland Neurology Associates	Greensburg	Pennsylvania	United States	15601
44	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
45	Medical University of South Carolina-Alzheimer's Research	Charleston	South Carolina	United States	29406
46	The University of Texas Mental Sciences Instittute	Houston	Texas	United States	77030
47	START Center	San Antonio	Texas	United States	78229-3900
48	Grayline Clinical Drug Trials	Wichita Falls	Texas	United States	76309
49	Southwestern Vermont Medical Center - The Memory Clinc	Bennington	Vermont	United States	05201

Sponsors and Collaborators

• Eisai Inc.

Investigators

• Study Director: Anita Murthy, Eisai Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00934375
• Other Study ID Numbers: E2020-A001-414
• First Posted: Jul 8, 2009
• Last Update Posted: Jan 14, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by , ,: Mild Cognitive Impairment
• Additional relevant MeSH terms: Cognitive Dysfunction; Donepezil

Study Results

Participant Flow

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	5 mg or 10 mg of donepezil hydrochloride (Aricept) taken orally once a day.
Period Title: Overall Study
STARTED	68	77
COMPLETED	55	55
NOT COMPLETED	13	22

Baseline Characteristics

Arm/Group Title	Donepezil	Placebo	Total
Arm/Group Description	5 mg or 10 mg of donepezil hydrochloride (Aricept) taken orally once a day.	Total of all reporting groups
Overall Participants	68	77	145
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.7 (8.46)	73.4 (8.73)	72.6 (8.62)
Sex: Female, Male (Count of Participants)
Female	30 44.1%	36 46.8%	66 45.5%
Male	38 55.9%	41 53.2%	79 54.5%
Region of Enrollment (participants) [Number]
United States	68 100%	77 100%	145 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events
Description	Overview of Treatment-Emergent Adverse Events and Safety Population (TEAEs)
Time Frame	Baseline, Week 6, Week 12 and Week 28.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	5 mg or 10 mg of donepezil hydrochloride (Aricept) taken orally once a day.
Measure Participants	68	77
Any Serious TEAE	3 4.4%	2 2.6%
Any Severe TEAE	2 2.9%	3 3.9%
Any possibly/probably drug-related TEAE	16 23.5%	32 41.6%
Any TEAE causing discontinuation of study drug.	7 10.3%	17 22.1%

Adverse Events

Arm/Group Title	Donepezil		Placebo
Arm/Group Description	5 mg or 10 mg of donepezil hydrochloride (Aricept) taken orally once a day.
All Cause Mortality
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/68 (4.4%)		2/77 (2.6%)
Injury, poisoning and procedural complications
Pelvic Fracture	1/68 (1.5%)		0/77 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/68 (0%)		1/77 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/68 (2.9%)		0/77 (0%)
Prostate Cancer	0/68 (0%)		1/77 (1.3%)
Other (Not Including Serious) Adverse Events
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/68 (16.2%)		20/77 (26%)
Gastrointestinal disorders
Diarrhea	4/68 (5.9%)		12/77 (15.6%)
Nausea	1/68 (1.5%)		7/77 (9.1%)
Musculoskeletal and connective tissue disorders
Muscle Spasms	6/68 (8.8%)		7/77 (9.1%)
Psychiatric disorders
Abnormal dreams	1/68 (1.5%)		5/77 (6.5%)
Insomnia	3/68 (4.4%)		5/77 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.