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Trial record 4 of 1588 for:    Alzheimer's Disease

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:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00744978
First received: August 29, 2008
Last updated: October 12, 2011
Last verified: October 2011
  Purpose
  1. Assess the efficacy of varenicline, relative to placebo, on a performance based measure of cognition in patients with mild to moderate Alzheimer's disease
  2. Evaluate the effects of varenicline on clinically relevant measures including attention and executive function, behavior, and clinician rated global change.
  3. Evaluate the safety and tolerability of varenicline, relative to placebo, in patients with mild to moderate Alzheimer's disease
  4. 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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Dementia
Tauopathies
Varenicline
Cholinergic Agents
Cholinergic Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014