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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Varenicline
Drug: Placebo
Enrollment 66
Recruitment Details  
Pre-assignment Details Each participant was to complete a 3-week placebo run-in period then receive a treatment sequence of either varenicline followed by placebo, or placebo followed by varenicline, separated by a 3-week placebo washout period. Of 92 participants screened, 66 participants were randomized to treatment.
Arm/Group Title Varenicline Then Placebo Placebo Then Varenicline
Hide Arm/Group Description Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks; then placebo once daily for 1 week followed by placebo BID for 5 weeks. Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks; then varenicline 0.5 mg once daily for 1 week followed by 0.5 mg BID for 1 week followed by 1 mg BID for 4 weeks.
Period Title: Period 1
Started 32 34
Treated 31 33
Completed 26 29
Not Completed 6 5
Reason Not Completed
Lost to Follow-up             1             0
Withdrawal by Subject             0             2
Other             0             2
Adverse Event             4             0
Randomized but not Treated             1             1
Period Title: Placebo Washout
Started 26 29
Completed 26 29
Not Completed 0 0
Period Title: Period 2
Started 26 29
Completed 26 28
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Arm/Group Title Varenicline Then Placebo Placebo Then Varenicline Total
Hide Arm/Group Description Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks; then placebo once daily for 1 week followed by placebo BID for 5 weeks. Placebo twice a day (BID) initiated with a 2-week titration regimen (Week 1: once a day [QD]; Week 2: BID), followed by varenicline 1 mg BID initiated with a 2-week titration regimen (Week 1: 0.5 mg QD; Week 2: 0.5 mg BID). Total of all reporting groups
Overall Number of Baseline Participants 32 34 66
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 34 participants 66 participants
71.5  (8.7) 73.9  (5.8) 72.7  (7.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 34 participants 66 participants
Female
21
  65.6%
21
  61.8%
42
  63.6%
Male
11
  34.4%
13
  38.2%
24
  36.4%
1.Primary Outcome
Title Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): all participants who were randomized and took at least 1 dose of randomized study medication. N = number of participants with ADAS-Cog 75 results at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 53 55
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
18.07  (0.942) 18.49  (0.939)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo. Analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3873
Comments ANCOVA model using unstructured covariance structure; Type I error rate for primary hypothesis was 5%; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-1.37 to 0.53
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Alzheimer's Disease Assessment Scale-Cognitive Subscale 75 (ADAS-Cog 75) at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with ADAS-Cog 75 results at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
19.87  (0.935) 19.31  (0.941)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo. Analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2465
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
-0.39 to 1.49
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. N = number of participants with ADAS-Cog 70 results at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
19.60  (0.880) 19.01  (0.885)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2092
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
-0.33 to 1.50
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. N = number of participants with ADAS-Cog 70 results at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 53 55
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
17.86  (0.886) 18.23  (0.884)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4339
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-1.30 to 0.56
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Clinical Global Impression - Improvement (CGI-I) Score at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CGI-I score at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 54 55
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.71  (0.103) 3.70  (0.102)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects linear model with subject (nested within sequence) as a random effect, and stratum, site, period, sequence, and treatment as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9745
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.26 to 0.27
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Neuropsychiatric Inventory (NPI) Total Score at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. N = number of participants with a NPI total score at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 59 54
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
2.97  (0.845) 2.29  (0.858)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2852
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
-0.57 to 1.92
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Neuropsychiatric Inventory (NPI) Total Score at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. N = number of participants with a NPI total score at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 54 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
3.82  (0.857) 2.55  (0.855)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0468
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.02 to 2.53
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Detection at Week 1
Hide Description 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.
Time Frame Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Detection at Week 1.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 59 56
Least Squares Mean (Standard Error)
Unit of Measure: log10 millisecond
2.65  (0.015) 2.64  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8811
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.02 to 0.03
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Detection at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Detection at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: log10 millisecond
2.65  (0.015) 2.63  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0830
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.00 to 0.05
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Detection at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Detection at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 53 55
Least Squares Mean (Standard Error)
Unit of Measure: log10 millisecond
2.64  (0.015) 2.65  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7226
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.03 to 0.02
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Continuous Paired Associate Learning (CPAL) at Week 1
Hide Description 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.
Time Frame Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Continuous Paired Associate Learning at Week 1.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 59 56
Least Squares Mean (Standard Error)
Unit of Measure: errors
38.52  (2.586) 40.05  (2.626)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Week 1: difference from placebo. Analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5588
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.53
Confidence Interval (2-Sided) 95%
-6.68 to 3.62
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Continuous Paired Associate Learning (CPAL) at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Continuous Paired Associate Learning at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: errors
39.43  (2.600) 43.57  (2.656)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1173
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.15
Confidence Interval (2-Sided) 95%
-9.34 to 1.05
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Continuous Paired Associate Learning (CPAL) at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Continuous Paired Associate Learning at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 53 55
Least Squares Mean (Standard Error)
Unit of Measure: errors
41.67  (2.668) 42.98  (2.641)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6251
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.31
Confidence Interval (2-Sided) 95%
-6.58 to 3.96
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: One Back Working Memory at Week 1
Hide Description 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.
Time Frame Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for One Back Working Memory at Week 1.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 59 56
Least Squares Mean (Standard Error)
Unit of Measure: arcsine proportion correct
0.94  (0.031) 0.94  (0.031)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9109
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.05 to 0.05
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: One Back Working Memory at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for One Back Working Memory at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: arcsine proportion correct
0.96  (0.031) 0.97  (0.032)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6632
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.06 to 0.04
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: One Back Working Memory at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for One Back Working Memory at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 53 55
Least Squares Mean (Standard Error)
Unit of Measure: arcsine proportion correct
0.95  (0.032) 0.96  (0.031)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5450
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.07 to 0.04
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Visual Learning at Week 1
Hide Description 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.
Time Frame Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Visual Learning at Week 1.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 59 56
Least Squares Mean (Standard Error)
Unit of Measure: arcsine proportion correct
0.83  (0.015) 0.81  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2799
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.02 to 0.05
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Visual Learning at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Visual Learning at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: arcsine proportion correct
0.82  (0.016) 0.82  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo aAnalyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9675
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.03 to 0.04
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Visual Learning at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Visual Learning at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 53 55
Least Squares Mean (Standard Error)
Unit of Measure: arcsine proportion correct
0.83  (0.016) 0.84  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5008
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.05 to 0.02
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Identification at Week 1
Hide Description 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.
Time Frame Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Identification at Week 1.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 59 56
Least Squares Mean (Standard Error)
Unit of Measure: log10 millisecond
2.79  (0.011) 2.80  (0.011)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2245
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.01
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Identification at Week 3
Hide Description 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.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Identification at Week 3.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 58 54
Least Squares Mean (Standard Error)
Unit of Measure: log10 millisecond
2.79  (0.011) 2.80  (0.011)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4974
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.01
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Computerized Test Battery for Cognition (CogState) Tasks: Identification at Week 6
Hide Description 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.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; N = number of participants with a CogState score for Identification at Week 6.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks.
Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
Overall Number of Participants Analyzed 52 55
Least Squares Mean (Standard Error)
Unit of Measure: log10 millisecond
2.79  (0.012) 2.79  (0.011)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Difference from placebo analyzed using a mixed effects longitudinal linear model with subject (nested within sequence) as a random effect and fixed effects stratum, site, period, sequence, treatment, week, and treatment by week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8525
Comments ANCOVA model using unstructured covariance structure; tested using a nominal 5% Type I error rate; no adjustments made for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.02 to 0.02
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description Varenicline 0.5 mg once daily for 1 week followed by 0.5 mg twice daily (BID) for 1 week followed by 1 mg BID for 4 weeks. Placebo once daily for 1 week followed by placebo twice daily (BID) for 5 weeks.
All-Cause Mortality
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/60 (3.33%)   0/59 (0.00%) 
General disorders     
Asthenia  1  1/60 (1.67%)  0/59 (0.00%) 
Injury, poisoning and procedural complications     
Fracture  1  1/60 (1.67%)  0/59 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1  1/60 (1.67%)  0/59 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   56/60 (93.33%)   37/59 (62.71%) 
Ear and labyrinth disorders     
External ear inflammation  1  1/60 (1.67%)  1/59 (1.69%) 
Tinnitus  1  1/60 (1.67%)  1/59 (1.69%) 
Eye disorders     
Cataract  1  1/60 (1.67%)  1/59 (1.69%) 
Conjunctival haemorrhage  1  1/60 (1.67%)  0/59 (0.00%) 
Eye disorder  1  1/60 (1.67%)  0/59 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort  1  2/60 (3.33%)  0/59 (0.00%) 
Abdominal pain  1  1/60 (1.67%)  0/59 (0.00%) 
Abdominal pain lower  1  0/60 (0.00%)  1/59 (1.69%) 
Abdominal pain upper  1  2/60 (3.33%)  2/59 (3.39%) 
Constipation  1  3/60 (5.00%)  2/59 (3.39%) 
Diarrhoea  1  2/60 (3.33%)  1/59 (1.69%) 
Dry mouth  1  2/60 (3.33%)  0/59 (0.00%) 
Duodenal ulcer  1  0/60 (0.00%)  1/59 (1.69%) 
Dyspepsia * 1  4/60 (6.67%)  1/59 (1.69%) 
Gastric disorder  1  1/60 (1.67%)  0/59 (0.00%) 
Gastritis haemorrhagic  1  0/60 (0.00%)  1/59 (1.69%) 
Inguinal hernia  1  1/60 (1.67%)  1/59 (1.69%) 
Nausea  1  17/60 (28.33%)  2/59 (3.39%) 
Stomatitis  1  1/60 (1.67%)  1/59 (1.69%) 
Vomiting  1  12/60 (20.00%)  0/59 (0.00%) 
General disorders     
Asthenia  1  2/60 (3.33%)  1/59 (1.69%) 
Fatigue  1  2/60 (3.33%)  1/59 (1.69%) 
Feeling abnormal  1  1/60 (1.67%)  1/59 (1.69%) 
Hunger  1  1/60 (1.67%)  1/59 (1.69%) 
Malaise  1  1/60 (1.67%)  0/59 (0.00%) 
Oedema peripheral  1  0/60 (0.00%)  1/59 (1.69%) 
Pyrexia  1  1/60 (1.67%)  0/59 (0.00%) 
Infections and infestations     
Bronchitis  1  2/60 (3.33%)  0/59 (0.00%) 
Nasopharyngitis  1  2/60 (3.33%)  4/59 (6.78%) 
Upper respiratory tract infection  1  1/60 (1.67%)  0/59 (0.00%) 
Urinary tract infection  1  2/60 (3.33%)  2/59 (3.39%) 
Injury, poisoning and procedural complications     
Fall  1  1/60 (1.67%)  1/59 (1.69%) 
Scratch  1  0/60 (0.00%)  1/59 (1.69%) 
Skin laceration  1  1/60 (1.67%)  0/59 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  1/60 (1.67%)  1/59 (1.69%) 
Aspartate aminotransferase increased  1  1/60 (1.67%)  1/59 (1.69%) 
Urine analysis abnormal  1  1/60 (1.67%)  0/59 (0.00%) 
Weight decreased  1  1/60 (1.67%)  1/59 (1.69%) 
White blood cells urine positive  1  1/60 (1.67%)  1/59 (1.69%) 
Metabolism and nutrition disorders     
Decreased appetite  1  13/60 (21.67%)  6/59 (10.17%) 
Hypercholesterolaemia  1  1/60 (1.67%)  1/59 (1.69%) 
Hypokalaemia  1  2/60 (3.33%)  1/59 (1.69%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/60 (0.00%)  1/59 (1.69%) 
Arthritis  1  0/60 (0.00%)  1/59 (1.69%) 
Back pain  1  0/60 (0.00%)  1/59 (1.69%) 
Muscle spasms  1  1/60 (1.67%)  0/59 (0.00%) 
Musculoskeletal pain  1  2/60 (3.33%)  2/59 (3.39%) 
Myalgia  1  1/60 (1.67%)  0/59 (0.00%) 
Osteoporosis  1  1/60 (1.67%)  1/59 (1.69%) 
Pain in extremity  1  1/60 (1.67%)  1/59 (1.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to spine  1  1/60 (1.67%)  0/59 (0.00%) 
Nervous system disorders     
Dementia Alzheimer’s type  1  1/60 (1.67%)  0/59 (0.00%) 
Dizziness  1  8/60 (13.33%)  0/59 (0.00%) 
Headache  1  7/60 (11.67%)  4/59 (6.78%) 
Intention tremor  1  1/60 (1.67%)  1/59 (1.69%) 
Lethargy  1  1/60 (1.67%)  0/59 (0.00%) 
Paraesthesia  1  1/60 (1.67%)  0/59 (0.00%) 
Somnolence  1  1/60 (1.67%)  1/59 (1.69%) 
Psychiatric disorders     
Anxiety  1  2/60 (3.33%)  0/59 (0.00%) 
Depressed mood  1  0/60 (0.00%)  1/59 (1.69%) 
Depression  1  0/60 (0.00%)  1/59 (1.69%) 
Insomnia  1  2/60 (3.33%)  0/59 (0.00%) 
Sleep disorder  1  1/60 (1.67%)  1/59 (1.69%) 
Renal and urinary disorders     
Renal impairment  1  0/60 (0.00%)  1/59 (1.69%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/60 (3.33%)  0/59 (0.00%) 
Epistaxis  1  0/60 (0.00%)  1/59 (1.69%) 
Hiccups  1  1/60 (1.67%)  0/59 (0.00%) 
Oropharyngeal discomfort  1  1/60 (1.67%)  0/59 (0.00%) 
Productive cough  1  1/60 (1.67%)  0/59 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  0/60 (0.00%)  1/59 (1.69%) 
Dermatitis contact  1  0/60 (0.00%)  1/59 (1.69%) 
Ecchymosis  1  0/60 (0.00%)  2/59 (3.39%) 
Erythema nodosum  1  1/60 (1.67%)  0/59 (0.00%) 
Hyperhidrosis  1  1/60 (1.67%)  0/59 (0.00%) 
Pruritus  1  0/60 (0.00%)  1/59 (1.69%) 
Rash pruritic  1  0/60 (0.00%)  1/59 (1.69%) 
Skin irritation  1  1/60 (1.67%)  1/59 (1.69%) 
Vascular disorders     
Hypertension  1  2/60 (3.33%)  0/59 (0.00%) 
Intermittent claudication  1  1/60 (1.67%)  1/59 (1.69%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00744978     History of Changes
Other Study ID Numbers: A3051101
First Submitted: August 29, 2008
First Posted: September 1, 2008
Results First Submitted: October 12, 2011
Results First Posted: November 22, 2011
Last Update Posted: November 22, 2011