A Study to Assess the Cognitive Effects of Fesoterodine in Elderly Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01161472
First received: July 12, 2010
Last updated: May 25, 2012
Last verified: May 2012
Results First Received: May 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Condition: Healthy
Interventions: Drug: 4mg fesoterodine
Drug: 8mg fesoterodine
Drug: alprazolam 1mg
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg Fesoterodine 4 milligram (mg) tablet administered orally once daily (OD) for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the first intervention period; followed by placebo matched to fesoterodine 4 mg or 8 mg tablet orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the second intervention period; then fesoterodine 4 mg tablet administered orally OD for the first 3 days followed by fesoterodine 8 mg tablet orally OD for the next 3 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the third intervention period; and placebo matched to fesoterodine 4 mg or 8 mg tablet administered orally OD for 6 days along with a single oral dose of alprazolam 1 mg capsule on Day 6 in the fourth intervention period. A washout period of at least 3 to 6 days was maintained between each treatment period.
Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo Fesoterodine 4 mg tablet administered orally OD for the first 3 days followed by fesoterodine 8 mg tablet orally OD for the next 3 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the first intervention period; then fesoterodine 4 mg tablet administered orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the second intervention period; followed by placebo matched to fesoterodine 4 mg or 8 mg tablet administered orally OD for 6 days along with a single oral dose of alprazolam 1 mg capsule on Day 6 in the third intervention period; and placebo matched to fesoterodine 4 mg or 8 mg tablet orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the fourth intervention period. A washout period of at least 3 to 6 days was maintained between each treatment period.
Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg Placebo matched to fesoterodine 4 mg or 8 mg tablet administered orally OD for 6 days along with a single oral dose of alprazolam 1 mg capsule on Day 6 in the first intervention period; followed by fesoterodine 4 mg tablet administered orally OD for the first 3 days followed by fesoterodine 8 mg tablet orally OD for the next 3 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the second intervention period; then placebo matched to fesoterodine 4 mg or 8 mg tablet orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the third intervention period; and fesoterodine 4 mg tablet administered orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the fourth intervention period. A washout period of at least 3 to 6 days was maintained between each treatment period.
Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg Placebo matched to fesoterodine 4 mg or 8 mg tablet orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the first intervention period; followed by placebo matched to fesoterodine 4 mg or 8 mg tablet administered orally OD for 6 days along with a single oral dose of alprazolam 1 mg capsule on Day 6 in the second intervention period; then fesoterodine 4 mg tablet administered orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the third intervention period; and fesoterodine 4 mg tablet administered orally OD for the first 3 days followed by fesoterodine 8 mg tablet orally OD for the next 3 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in the fourth intervention period. A washout period of at least 3 to 6 days was maintained between each treatment period.

Participant Flow for 7 periods

Period 1:   First Intervention Period
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     5     5     5     5  
Treated     5     5     5     5  
COMPLETED     5     5     5     5  
NOT COMPLETED     0     0     0     0  

Period 2:   Washout Period (At Least 3 to 6 Days)
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     5     5     5     5  
COMPLETED     5     5     5     5  
NOT COMPLETED     0     0     0     0  

Period 3:   Second Intervention Period
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     5     5     5     5  
COMPLETED     5     5     5     5  
NOT COMPLETED     0     0     0     0  

Period 4:   Washout Period (At Least 3 to 6 Days)
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     5     5     5     5  
COMPLETED     4     5     5     5  
NOT COMPLETED     1     0     0     0  
Withdrawal by Subject                 1                 0                 0                 0  

Period 5:   Third Intervention Period
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     4     5     5     5  
COMPLETED     4     5     5     5  
NOT COMPLETED     0     0     0     0  

Period 6:   Washout Period (At Least 3 to 6 Days)
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     4     5     5     5  
COMPLETED     4     5     5     5  
NOT COMPLETED     0     0     0     0  

Period 7:   Fourth Intervention Period
    Fesoterodine 4 mg, Placebo, Fesoterodine 8 mg, Aplrazolam 1 mg     Fesoterodine 8 mg, Fesoterodine 4 mg, Aplrazolam 1 mg, Placebo     Aplrazolam 1 mg, Fesoterodine 8 mg, Placebo, Fesoterodine 4 mg     Placebo, Aplrazolam 1 mg, Fesoterodine 4 mg, Fesoterodine 8 mg  
STARTED     4     5     5     5  
COMPLETED     4     5     5     5  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Entire Study Population All participants randomized to any treatment (fesoterodine 4 mg tablet first, fesoterodine 8 mg tablet first, alprazolam 1 mg capsule first and placebo first).

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  20  
Age  
[units: Years]
Mean ± Standard Deviation
  72.2  ± 5.2  
Gender  
[units: Participants]
 
Female     8  
Male     12  



  Outcome Measures
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1.  Primary:   Computer Based Objective Cognition Testing (CogState) Detection Speed   [ Time Frame: Baseline ]

2.  Primary:   Change From Baseline in Computer Based Objective Cognition Testing (CogState) Detection Speed on Day 6   [ Time Frame: Baseline and Day 6 ]

3.  Secondary:   CogState Identification Speed   [ Time Frame: Baseline ]

4.  Secondary:   Change From Baseline in CogState Identification Speed on Day 6   [ Time Frame: Baseline and Day 6 ]

5.  Secondary:   CogState One Card Learning   [ Time Frame: Baseline ]

6.  Secondary:   Change From Baseline in CogState One Card Learning on Day 6   [ Time Frame: Baseline and Day 6 ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Change From Baseline in CogState One Card Learning on Day 6
Measure Description One card learning: a cognitive test which assessed visual learning. Participants were to remember which cards were previously shown in a task. The outcome measure was accuracy of performance; arcsine transformation of the square root (sqrt) of the proportion of correct responses. Higher scores meant a better performance.
Time Frame Baseline and Day 6  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PP Analysis Set included all randomized participants who completed the study, received treatment in all 4 study periods until the end of treatment visit in the fourth study period and who were not serious protocol violators. 'N' (Number of participants analyzed) signifies participants evaluable for the outcome measure.

Reporting Groups
  Description
Fesoterodine 4 mg Fesoterodine 4 mg tablet administered orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in any of the intervention periods.
Fesoterodine 8 mg Fesoterodine 4 mg tablet administered orally OD for the first 3 days followed by fesoterodine 8 mg tablet orally OD for the next 3 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in any of the intervention periods.
Aplrazolam 1 mg Placebo matched to fesoterodine 4 mg or 8 mg tablet administered orally OD for 6 days along with a single oral dose of alprazolam 1 mg capsule on Day 6 in any of the intervention periods.
Placebo Placebo matched to fesoterodine 4 mg or 8 mg tablet orally OD for 6 days along with placebo matched to a single oral dose of alprazolam 1 mg capsule on Day 6 in any of the intervention periods.

Measured Values
    Fesoterodine 4 mg     Fesoterodine 8 mg     Aplrazolam 1 mg     Placebo  
Number of Participants Analyzed  
[units: participants]
  18     18     18     18  
Change From Baseline in CogState One Card Learning on Day 6  
[units: Arcsine¬†[(sqrt)¬†proportion¬†correct]]
Least Squares Mean ± Standard Error
  -0.0094  ± 0.0204     0.0151  ± 0.0203     -0.0880  ± 0.0204     -0.0058  ± 0.0205  


Statistical Analysis 1 for Change From Baseline in CogState One Card Learning on Day 6
Groups [1] Fesoterodine 4 mg vs. Placebo
Method [2] ANCOVA
P Value [3] 0.8944
LS Mean Difference [4] -0.0035
Standard Error of the mean ± 0.0265
95% Confidence Interval ( -0.0569 to 0.0498 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA was used to determine p-value for comparison of fesoterodine 4 mg vs placebo, with model terms: period and treatment as the fixed effect, participants as the random effect, and between and within participant baselines as the covariates.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in CogState One Card Learning on Day 6
Groups [1] Fesoterodine 8 mg vs. Placebo
Method [2] ANCOVA
P Value [3] 0.4308
LS Mean Difference [4] 0.0209
Standard Error of the mean ± 0.0263
95% Confidence Interval ( -0.0320 to 0.0738 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA was used to determine p-value for comparison of fesoterodine 8 mg vs placebo, with model terms: period and treatment as the fixed effect, participants as the random effect, and between and within participant baselines as the covariates.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   CogState Continuous Paired Associate Learning (CPAL)   [ Time Frame: Baseline ]

8.  Secondary:   Change From Baseline in CogState CPAL on Day 6   [ Time Frame: Baseline and Day 6 ]

9.  Secondary:   CogState Groton Maze Learning Task (GMLT)   [ Time Frame: Baseline ]

10.  Secondary:   Change From Baseline in CogState Groton Maze Learning Task on Day 6   [ Time Frame: Baseline and Day 6 ]

11.  Secondary:   Rey Auditory Verbal Learning Test (RAVLT)   [ Time Frame: Baseline ]

12.  Secondary:   Rey Auditory Verbal Learning Test (RAVLT) on Day 6   [ Time Frame: Baseline and Day 6 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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