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Evaluation of the Efficacy of Varenicline on Cognition, Safety, Tolerability and Pharmacokinetics in Subjects With Mild-to-Moderate Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT00744978
Recruitment Status : Completed
First Posted : September 1, 2008
Results First Posted : November 22, 2011
Last Update Posted : November 22, 2011
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE August 29, 2008
First Posted Date  ICMJE September 1, 2008
Results First Submitted Date  ICMJE October 12, 2011
Results First Posted Date  ICMJE November 22, 2011
Last Update Posted Date November 22, 2011
Study Start Date  ICMJE July 2009
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2011)
Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 6 [ Time Frame: Week 6 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 29, 2008)
Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 6 [ Time Frame: 6 weeks ]
Change History Complete list of historical versions of study NCT00744978 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2011)
  • Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 3 [ Time Frame: Week 3 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2008)
  • Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 3 [ Time Frame: 3 weeks ]
  • Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) [ Time Frame: 3 and 6 weeks ]
  • Clinical Global Impression - Improvement [ Time Frame: 6 Weeks ]
  • Neuropsychiatric Inventory [ Time Frame: 3 and 6 weeks ]
  • Computerized Test Battery for Cognition [ Time Frame: 1, 3 and 6 weeks ]
  • Adverse events, vital signs (blood pressure, pulse rate, respiration), body weight, electrocardiogram, physical exam, laboratory tests [ Time Frame: 1, 3 and 6 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Efficacy of Varenicline on Cognition, Safety, Tolerability and Pharmacokinetics in Subjects With Mild-to-Moderate Alzheimer's Disease
Official Title  ICMJE 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
Brief Summary
  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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo once daily for 1 week followed by placebo twice daily for 5 weeks.
Study Arms  ICMJE
  • Experimental: Varenicline
    Intervention: Drug: Varenicline
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Kim SY, Choi SH, Rollema H, Schwam EM, McRae T, Dubrava S, Jacobsen J. Phase II crossover trial of varenicline in mild-to-moderate Alzheimer's disease. Dement Geriatr Cogn Disord. 2014;37(3-4):232-45. doi: 10.1159/000355373. Epub 2013 Nov 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2010)
66
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2008)
60
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00744978
Other Study ID Numbers  ICMJE A3051101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP