Evaluation of the Efficacy of Varenicline on Cognition, Safety, Tolerability and Pharmacokinetics in Subjects With Mild-to-Moderate Alzheimer's Disease
This study has been completed.
Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00744978
First received: August 29, 2008
Last updated: October 12, 2011
Last verified: October 2011
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Purpose
- Assess the efficacy of varenicline, relative to placebo, on a performance based measure of cognition in patients with mild to moderate Alzheimer's disease
- Evaluate the effects of varenicline on clinically relevant measures including attention and executive function, behavior, and clinician rated global change.
- Evaluate the safety and tolerability of varenicline, relative to placebo, in patients with mild to moderate Alzheimer's disease
- Evaluate the pharmacokinetics of varenicline in patients with mild to moderate Alzheimer's disease.
| Condition | Intervention | Phase |
|---|---|---|
|
Alzheimer's Disease |
Drug: Varenicline Drug: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | A Phase 2 Multicenter, Double-Blind, Placebo-Controlled, Crossover Trial of Varenicline Tartrate (CP-526,555) in Patients With Mild to Moderate Alzheimer's Disease |
Resource links provided by NLM:
Genetics Home Reference related topics:
Alzheimer disease
MedlinePlus related topics:
Alzheimer's Disease
U.S. FDA Resources
Further study details as provided by Pfizer:
Primary Outcome Measures:
- Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]12-item scale to assess severity of cognitive impairment in AD. Items include word recall, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition, spoken language ability, comprehension of spoken language, word finding difficulty in spontaneous speech, remembering test instructions, and concentration/distractibility. Total score range from 0-75 with 75 indicating worse cognition.
Secondary Outcome Measures:
- Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]12-item scale to assess severity of cognitive impairment in AD. Items include word recall, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition, spoken language ability, comprehension of spoken language, word finding difficulty in spontaneous speech, remembering test instructions, and concentration/distractibility. Total score range from 0-75 with 75 indicating worse cognition.
- Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]11-item scale designed to assess the severity of cognitive impairments in AD subjects. Items include word recall, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition, spoken language ability, comprehension of spoken language, word finding difficulty in spontaneous speech, and remembering test instructions. Total score range from 0-70 with 70 indicating worse cognition.
- Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]11-item scale designed to assess the severity of cognitive impairments in AD subjects. Items include word recall, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition, spoken language ability, comprehension of spoken language, word finding difficulty in spontaneous speech, and remembering test instructions. Total score range from 0-70 with 70 indicating worse cognition.
- Mean Clinical Global Impression - Improvement (CGI-I) Score at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
- Neuropsychiatric Inventory (NPI) Total Score at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Caregiver interview-based rating scale assessing 12 behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, appetite/eating, and sleep. Each symptom score derived by frequency of symptoms * severity of symptoms (range 0-12). Total score = sum of symptom scores; range: 0-144 with higher score indicating greater behavioral disturbances.
- Neuropsychiatric Inventory (NPI) Total Score at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]Caregiver interview-based rating scale assessing 12 behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, appetite/eating, and sleep. Each symptom score derived by frequency of symptoms * severity of symptoms (range 0-12). Total score = sum of symptom scores; range: 0-144 with higher score indicating greater behavioral disturbances.
- Computerized Test Battery for Cognition (CogState) Tasks: Detection at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]Assessment of the cognitive domain psychomotor function through yes or no responses within 5 minutes to 30 trials; score range: 0 to 3.69. Performance variable: speed of performance; average of the log10 t transformed reaction time for correct responses. Reaction times longer than 5 seconds (log10 [5000]) were excluded as reflecting responses that were abnormally slow.
- Computerized Test Battery for Cognition (CogState) Tasks: Detection at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Assessment of the cognitive domain psychomotor function through yes or no responses within 5 minutes to 30 trials; score range: 0 to 3.69. Performance variable: speed of performance; average of the log10 t transformed reaction time for correct responses. Reaction times longer than 5 seconds (log10 [5000]) were excluded as reflecting responses that were abnormally slow.
- Computerized Test Battery for Cognition (CogState) Tasks: Detection at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]Assessment of the cognitive domain psychomotor function through yes or no responses within 5 minutes to 30 trials; score range: 0 to 3.69. Performance variable: speed of performance; average of the log10 t transformed reaction time for correct responses. Reaction times longer than 5 seconds (log10 [5000]) were excluded as reflecting responses that were abnormally slow.
- Computerized Test Battery for Cognition (CogState) Tasks: Continuous Paired Associate Learning (CPAL) at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]Assessment of the cognitive domain visual episodic memory (associate learning) through responses within 7 minutes to 4 targets x 4 rounds (mild AD) or 3 targets x 4 rounds (moderate AD); score range: 35 to 100. Performance variable: number of errors made in correctly placing each of the 4 patterns in their location four times.
- Computerized Test Battery for Cognition (CogState) Tasks: Continuous Paired Associate Learning (CPAL) at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Assessment of the cognitive domain visual episodic memory (associate learning) through responses within 7 minutes to 4 targets x 4 rounds (mild AD) or 3 targets x 4 rounds (moderate AD); score range: 35 to 100. Performance variable: number of errors made in correctly placing each of the 4 patterns in their location four times.
- Computerized Test Battery for Cognition (CogState) Tasks: Continuous Paired Associate Learning (CPAL) at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]Assessment of the cognitive domain visual episodic memory (associate learning) through responses within 7 minutes to 4 targets x 4 rounds (mild AD) or 3 targets x 4 rounds (moderate AD); score range: 35 to 100. Performance variable: number of errors made in correctly placing each of the 4 patterns in their location four times.
- Computerized Test Battery for Cognition (CogState) Tasks: One Back Working Memory at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]Assessment of the cognitive domain working memory through yes or no responses to 30 trials within 5 minutes; score range: 0 to 1.57. Performance variable: accuracy of performance; arcsine transformation of proportion correct responses.
- Computerized Test Battery for Cognition (CogState) Tasks: One Back Working Memory at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Assessment of the cognitive domain working memory through yes or no responses to 30 trials within 5 minutes; score range: 0 to 1.57. Performance variable: accuracy of performance; arcsine transformation of proportion correct responses.
- Computerized Test Battery for Cognition (CogState) Tasks: One Back Working Memory at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]Assessment of the cognitive domain working memory through yes or no responses to 30 trials within 5 minutes; score range: 0 to 1.57. Performance variable: accuracy of performance; arcsine transformation of proportion correct responses.
- Computerized Test Battery for Cognition (CogState) Tasks: Visual Learning at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]Assessment of the cognitive domain episodic memory through yes or no responses within 5 minutes to 4 targets repeated among 6 distractors on 4 rounds (mild Alzheimer's disease [AD], or 3 targets repeated among 4 distractors on 4 rounds (moderate AD) ; score range: 0 to 1.57. Performance variable: accuracy of performance; arcsine transformation of proportion correct responses.
- Computerized Test Battery for Cognition (CogState) Tasks: Visual Learning at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Assessment of the cognitive domain episodic memory through yes or no responses within 5 minutes to 4 targets repeated among 6 distractors on 4 rounds (mild Alzheimer's disease [AD], or 3 targets repeated among 4 distractors on 4 rounds (moderate AD) ; score range: 0 to 1.57. Performance variable: accuracy of performance; arcsine transformation of proportion correct responses.
- Computerized Test Battery for Cognition (CogState) Tasks: Visual Learning at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]Assessment of the cognitive domain episodic memory through yes or no responses within 5 minutes to 4 targets repeated among 6 distractors on 4 rounds (mild Alzheimer's disease [AD], or 3 targets repeated among 4 distractors on 4 rounds (moderate AD) ; score range: 0 to 1.57. Performance variable: accuracy of performance; arcsine transformation of proportion correct responses.
- Computerized Test Battery for Cognition (CogState) Tasks: Identification at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]Assessment of the cognitive domain visual attention through a yes or no response to 30 trials within 5 minutes; score range: 0 to 3.69. Performance variable: speed of performance; average log10 transformed reaction time for correct responses. Reaction times longer than 5 seconds ( log10 [5000]) were excluded as reflecting responses that were abnormally slow.
- Computerized Test Battery for Cognition (CogState) Tasks: Identification at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Assessment of the cognitive domain visual attention through a yes or no response to 30 trials within 5 minutes; score range: 0 to 3.69. Performance variable: speed of performance; average log10 transformed reaction time for correct responses. Reaction times longer than 5 seconds ( log10 [5000]) were excluded as reflecting responses that were abnormally slow.
- Computerized Test Battery for Cognition (CogState) Tasks: Identification at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]Assessment of the cognitive domain visual attention through a yes or no response to 30 trials within 5 minutes; score range: 0 to 3.69. Performance variable: speed of performance; average log10 transformed reaction time for correct responses. Reaction times longer than 5 seconds ( log10 [5000]) were excluded as reflecting responses that were abnormally slow.
| Enrollment: | 66 |
| Study Start Date: | July 2009 |
| Study Completion Date: | November 2010 |
| Primary Completion Date: | November 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Varenicline |
Drug: Varenicline
0.5 mg once daily for 1 week followed by 0.5 mg twice daily for 1 week followed by 1 mg twice daily for 4 weeks
Other Name: Chantix, Champix
|
| Placebo Comparator: Placebo |
Drug: Placebo
Placebo once daily for 1 week followed by placebo twice daily for 5 weeks.
|
Eligibility| Ages Eligible for Study: | 55 Years to 85 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Males or females, age 55-85
- Diagnosis of probable Alzheimer's disease, consistent with criteria from both: 1) National Institute of Neurological and Communicable Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and 2) Diagnostic and Statistical Manual of Mental Disorders (DSM IV)
- Mini-mental status exam score of 14-26 inclusive
- Rosen-Modified Hachinski Ischemia Score of < or = 4
Exclusion Criteria:
- Diagnosis or history of other dementia or neurodegenerative disorders
- Diagnosis or history of clinically significant cerebrovascular or cardiovascular disease
- Subjects with pulmonary disease or evidence of clinically significant pulmonary symptoms
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00744978
Locations
| Korea, Republic of | |
| Pfizer Investigational Site | |
| Seongnam, Gyunggido, Korea, Republic of, 463-707 | |
| Pfizer Investigational Site | |
| Busan, Korea, Republic of, 602-715 | |
| Pfizer Investigational Site | |
| Daegu, Korea, Republic of, 700-721 | |
| Pfizer Investigational Site | |
| Incheon, Korea, Republic of, 400-711 | |
| Pfizer Investigational Site | |
| Seoul, Korea, Republic of, 138-736 | |
| Pfizer Investigational Site | |
| Seoul, Korea, Republic of, 158-710 | |
| Pfizer Investigational Site | |
| Seoul, Korea, Republic of, 136-705 | |
| Pfizer Investigational Site | |
| Suwon, Korea, Republic of, 443-721 | |
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
More Information
Additional Information:
No publications provided
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT00744978 History of Changes |
| Other Study ID Numbers: | A3051101 |
| Study First Received: | August 29, 2008 |
| Results First Received: | October 12, 2011 |
| Last Updated: | October 12, 2011 |
| Health Authority: | Korea: Food and Drug Administration |
Keywords provided by Pfizer:
|
Efficacy Safety Pharmacokinetics Alzheimer's disease |
Additional relevant MeSH terms:
|
Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders |
Varenicline Nicotinic Agonists Cholinergic Agonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 16, 2013