Safety and Efficacy Study of AC-3933 in Adults With Mild to Moderate Alzheimer's Disease

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00359944
• Collaborator: (none)
• Enrollment: 171
• Locations: 34
• Arms: 3
• Duration (Months): 31
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate efficacy and safety of different doses of AC-3933 in patients with mild to moderate Alzheimer's Disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: AC-3933; Drug: AC-3933; Other: Sugar Pill	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 171 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Dose-Ranging Study Assessing the Efficacy and Safety of AC-3933 Tablets Twice Daily in Adults With Mild to Moderate Alzheimer's Disease
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AC-3933 AC-3933, 5mg twice daily	Drug: AC-3933; 5mg twice daily
Experimental: AC-3933, 20 mg twice daily AC-3933, 20 mg twice daily	Drug: AC-3933; AC-3933, 20 mg twice daily
Placebo Comparator: Placebo Sugar Pill twice daily	Other: Sugar Pill; Sugar Pill twice daily; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Total Score of Alzheimer's Disease Assessment Scale - Cognition Subscale (ADAS-COG)From Best Total Score (0) to Worst Total Score (70) [Baseline to 16 weeks]

   Change from baseline to week 16 of the double blind treatment in the Alzheimer's Disease Assessment Scale - Cognition Subscale (ADAS-COG) total score The Alzheimer's Disease Assessment Scale if used for assessing the severity of dysfuncion and for research in patients with AD, particularly in clinical drug trials. It consists of 11 items testing orientatin, memory, word usage and recognition, receptive speech, spatial abilities, ideational praxis, ability to follow instructions, spontanious speech abilities, and comprehension. The higher the overall score (maximum 70), the more severe the dysfunction/impairment.

Secondary Outcome Measures

1. Clinicians Interview Based Impression of Change (CIBIC)-Plus [Baseline to 16 weeks]

   Clinicians Interview Based Impression of Change (CIBIC)-Plus-Plus scores at week 16 of the double blind treatment. CIBIC-Plus is ranged between 1 and 7 (1=very much improved, 4=no change, and 7=very much worsened). We were expecting smaller value of CIBIC-Plus at the study end.

2. Disability Assessment for Dementia (DAD) [Baseline to 16 Weeks]

   Change from baseline to week 16 of the double blind treatment in the Disability Assessment for Dementia (DAD) scores. The DAD is administered as a clinician-assisted interview with the caregiver and was developed to assess functional abilities in ADLs in community-dwelling dementia patients. The scale consists of 40 questions assessing basic and instumental ADLs. A total score is obtained by adding the rating for each question and converting this total score out of 100. The items rated N/A are not considered for the total score. Higher scores represent less disability in activities of daily living (ADL) while lower scores indicate more dysfunction.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Mild to moderate Alzheimer's Disease

• Male or female 55 years or older

• Living with caregiver

• Read, understand and speak English

Exclusion Criteria:

• Need to drive during the study

• Treatment with acetylcholinesterase inhibitors or NMDA antagonist, such as Aricept or Namenda, within 2 weeks of check-up and during the study

• Frequent Smoker

• Frequent Consumer of Caffeine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trials Inc.	LIttle Rock	Alaska	United States	72205
2	PsyPharma Clinical Research Inc.	Phoenix	Arizona	United States	85013
3	ClinicalStudies Center LLC	Little Rock	Arkansas	United States	72205
4	Vertex Clinical Research	Bakersfield	California	United States	93311
5	East Bay Physicians Medical Grou[	Berkeley	California	United States	94705
6	Margolin Brain Institute	Fresno	California	United States	93720
7	Clinical Trials Associates	Mission Viejo	California	United States	92691
8	University of California	Orange	California	United States	92868
9	Pacific Research Network	San Diego	California	United States	92103
10	Memory Disorder Clinic	Deerfield Beach	Florida	United States	33064
11	Berma Research Group	Hialeah	Florida	United States	33016
12	Advanced Research Institute of Miami	Miami	Florida	United States	33135
13	Research Institute of Miami	Miami	Florida	United States	33135
14	Research Center of Florida Inc.	Miami	Florida	United States	33173
15	Medical Research Group of Central Florida	Orange City	Florida	United States	32763
16	Compass Research LLC	Orlando	Florida	United States	32806
17	Department of Psychiatry and Behavioral Medicine	Tampa	Florida	United States	33613
18	Stedman Clinical Trials LLC	Tampa	Florida	United States	33613
19	Four Rivers Clinical Research Inc.	Paducah	Kentucky	United States	42003
20	Northern Michigan Neurology	Traverse City	Michigan	United States	49684
21		Minneapolis	Minnesota	United States	53454
22	Clinical Psychopharmacology Consultants PA	Saint Louis Park	Minnesota	United States	55416
23	Precise Research Centers INc.	Flowood	Mississippi	United States	37232
24	Psych Care Consultants Research	Saint Louis	Missouri	United States	63128
25	Odyssey Researcfh	Fargo	North Dakota	United States	58104
26	Paradigm Research Professionals LLP	Oklahoma City	Oklahoma	United States	73112
27	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
28	Tulsa Clinical Research LLC	Tulsa	Oklahoma	United States	74104
29	The Clinical Trial Center	Jenkintown	Pennsylvania	United States	19046
30	UT Medical Group Inc.	Memphis	Tennessee	United States	38105
31	Neurological Research Center, Inc.	Bennington	Vermont	United States	05201
32	International Clinical Research Associates LLC	Richmond	Virginia	United States	23229
33	The Center for Excellence in Aging and Geriatric Health	Williamsburg	Virginia	United States	23185
34	Internal Medicine Northwest	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Medical Director, MD, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT00359944
• Other Study ID Numbers: AC-3933-271
• First Posted: Aug 3, 2006
• Last Update Posted: Jul 2, 2013
• Last Verified: May 1, 2013

• Keywords provided by Sunovion: Alzheimer; Dementia
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Pre-assignment Detail	17 patients were excluded from analysis because of QA issues at a study site.

Arm/Group Title	AC-3933, 5 mg	AC-3933, 20 mg	Placebo
Arm/Group Description	AC-3933, 5mg twice daily	AC-3933, 20 mg twice daily	Sugar Pill twice daily
Period Title: Overall Study
STARTED	50	47	57
COMPLETED	34	28	38
NOT COMPLETED	16	19	19

Baseline Characteristics

Arm/Group Title	AC-3933	AC-3933, 20 mg	Placebo	Total
Arm/Group Description	AC-3933, 5mg twice daily	AC-3933, 20 mg twice daily	Sugar Pill twice daily	Total of all reporting groups
Overall Participants	43	40	49	132
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	43 100%	40 100%	49 100%	132 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.5 (8.57)	74.8 (9.54)	76.3 (8.73)	75.6 (8.88)
Sex: Female, Male (Count of Participants)
Female	30 69.8%	27 67.5%	38 77.6%	95 72%
Male	13 30.2%	13 32.5%	11 22.4%	37 28%
Region of Enrollment (participants) [Number]
United States	43 100%	40 100%	49 100%	132 100%

Outcome Measures

1. Primary Outcome

Title	Total Score of Alzheimer's Disease Assessment Scale - Cognition Subscale (ADAS-COG)From Best Total Score (0) to Worst Total Score (70)
Description	Change from baseline to week 16 of the double blind treatment in the Alzheimer's Disease Assessment Scale - Cognition Subscale (ADAS-COG) total score The Alzheimer's Disease Assessment Scale if used for assessing the severity of dysfuncion and for research in patients with AD, particularly in clinical drug trials. It consists of 11 items testing orientatin, memory, word usage and recognition, receptive speech, spatial abilities, ideational praxis, ability to follow instructions, spontanious speech abilities, and comprehension. The higher the overall score (maximum 70), the more severe the dysfunction/impairment.
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AC-3933, 5 mg	AC-3933, 20 mg	Placebo
Arm/Group Description	AC-3933, 5mg twice daily	AC-3933, 20 mg twice daily	Sugar Pill twice daily
Measure Participants	43	40	49
Mean (Standard Deviation) [units on a scale]	-1.3 (0.84)	-2.9 (0.88)	-1.5 (0.78)

2. Secondary Outcome

Title	Clinicians Interview Based Impression of Change (CIBIC)-Plus
Description	Clinicians Interview Based Impression of Change (CIBIC)-Plus-Plus scores at week 16 of the double blind treatment. CIBIC-Plus is ranged between 1 and 7 (1=very much improved, 4=no change, and 7=very much worsened). We were expecting smaller value of CIBIC-Plus at the study end.
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AC-3933, 5 mg	AC-3933, 20 mg	Placebo
Arm/Group Description	AC-3933, 5mg twice daily	AC-3933, 20 mg twice daily	Sugar Pill twice daily
Measure Participants	43	40	49
Mean (Standard Deviation) [units on a scale]	4.1 (0.97)	3.9 (1.11)	3.9 (0.91)

3. Secondary Outcome

Title	Disability Assessment for Dementia (DAD)
Description	Change from baseline to week 16 of the double blind treatment in the Disability Assessment for Dementia (DAD) scores. The DAD is administered as a clinician-assisted interview with the caregiver and was developed to assess functional abilities in ADLs in community-dwelling dementia patients. The scale consists of 40 questions assessing basic and instumental ADLs. A total score is obtained by adding the rating for each question and converting this total score out of 100. The items rated N/A are not considered for the total score. Higher scores represent less disability in activities of daily living (ADL) while lower scores indicate more dysfunction.
Time Frame	Baseline to 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AC-3933, 5 mg	AC-3933, 20 mg	Placebo
Arm/Group Description	AC-3933, 5mg twice daily	AC-3933, 20 mg twice daily	Sugar Pill twice daily
Measure Participants	43	40	49
Mean (Standard Deviation) [units on a scale]	-2.7 (1.89)	4.0 (2.10)	4.2 (1.80)

Adverse Events

Time Frame	February 2006 to September 2008
Adverse Event Reporting Description	The AE summary was based on the safety population, which was defined as all randomized patients who received at least one dose of the study drug (58 placebo, 50 AC-3933 5mg, 46 AC-3933 20mg. Once subject randomized to AC-3933 20mg group received placebo during the course of the study. So this subject was summarized in the placebe group.
Arm/Group Title	AC-3933, 5 mg		AC-3933, 20 mg		Placebo
Arm/Group Description	AC-3933, 5mg twice daily		AC-3933, 20 mg twice daily		Sugar Pill twice daily
All Cause Mortality
	AC-3933, 5 mg		AC-3933, 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AC-3933, 5 mg		AC-3933, 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/50 (10%)		4/46 (8.7%)		5/58 (8.6%)
Cardiac disorders
Cardiac Failure congestive	0/50 (0%)	0	1/46 (2.2%)	1	0/58 (0%)	0
Cardiomyopathy	0/50 (0%)	0	0/46 (0%)	0	1/58 (1.7%)	1
Tachycardia	0/50 (0%)	0	0/46 (0%)	0	1/58 (1.7%)	1
Gastrointestinal disorders
Abdominal Mass	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
General disorders
Fatigue	0/50 (0%)	0	0/46 (0%)	0	1/58 (1.7%)	1
Infections and infestations
Bronchitis acute	0/50 (0%)	0	1/46 (2.2%)	1	0/58 (0%)	0
Injury, poisoning and procedural complications
Eye Injury	0/50 (0%)	0	1/46 (2.2%)	1	0/58 (0%)	0
Fall	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Rib Fracture	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Investigations
Blood Pressure Increased	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer stage IV	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Metastases to liver	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Prostate cancer	1/50 (2%)	1	0/46 (0%)	0	0/58 (0%)	0
Nervous system disorders
Syncope	0/50 (0%)	0	0/46 (0%)	0	2/58 (3.4%)	2
Psychiatric disorders
Abnormal Behavior	0/50 (0%)	0	0/46 (0%)	0	1/58 (1.7%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/50 (0%)	0	1/46 (2.2%)	1	0/58 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/50 (0%)	0	1/46 (2.2%)	1	0/58 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/50 (0%)	0	0/46 (0%)	0	1/58 (1.7%)	1
Other (Not Including Serious) Adverse Events
	AC-3933, 5 mg		AC-3933, 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/50 (22%)		12/46 (26.1%)		17/58 (29.3%)
Gastrointestinal disorders
Nausea	2/50 (4%)	2	6/46 (13%)	6	2/58 (3.4%)	2
Vomiting	1/50 (2%)	1	2/46 (4.3%)	2	3/58 (5.2%)	3
Infections and infestations
Urinary Tract infection	2/50 (4%)	2	2/46 (4.3%)	2	5/58 (8.6%)	5
Investigations
Electroencephalogram abnormal	1/50 (2%)	1	3/46 (6.5%)	3	4/58 (6.9%)	4
Nervous system disorders
Headache	4/50 (8%)	4	4/46 (8.7%)	4	1/58 (1.7%)	1
Dizziness	1/50 (2%)	1	2/46 (4.3%)	2	5/58 (8.6%)	5
Psychiatric disorders
Anxiety	3/50 (6%)	3	1/46 (2.2%)	1	0/58 (0%)	0

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.