The purpose is to compare solifenacin and oxybutynin with an inactive tablet and assess any potential effects on mental ability.
All subjects will receive each intervention during the course of the study. Subjects will complete a 21-day washout period between treatment periods and following last treatment period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
QUADRUPLE
Enrollment
26
Unnamed facility
Blackpool, Lancashire, United Kingdom
Unnamed facility
Manchester, Lancashire, United Kingdom
Unnamed facility
Bradford, Yorkshire, United Kingdom
Change From Baseline in Cognitive Function Composite Score - Power of Attention
Cognitive effects were assessed at the end of each treatment period using a computerized assessment system at time points close to the predicted time to attain maximum plasma concentration (Tmax) for solifenacin (6 hours) and oxybutynin (2 hours). Power of attention is calculated from the sum of three cognitive function speed tests: Simple Reaction Time, Choice Reaction Time and the Speed of Detections in Digit Vigilance task. A low score reflects a fast reaction time and a high intensity of concentration. A positive change from baseline reflects impairment compared to the baseline assessment.
Time frame: Assessed at each treatment period baseline visit (the day prior to the first dose of each treatment; Days -1, 42, 84) and at the end of each treatment period (Days 21, 63 and 105). At each visit, tests were performed at 2 and 6 hours post-dose.
Change From Baseline in Cognitive Function Composite Score - Continuity of Attention
Cognitive effects were assessed using a computerized assessment system at time points close to the predicted time of maximum plasma concentration for solifenacin and oxybutynin. For continuity of attention, the number of correct responses (out of 50) for choice reaction time was added to the total number of targets correctly identified (out of 45) digit vigilance minus the number of false alarms (total score of -45 to 95). A high score reflects someone able to keep his/her mind on a single task for a prolonged period. A negative change from baseline reflects impairment compared to baseline.
Time frame: Assessed at each treatment period baseline visit (the day prior to the first dose of each treatment; Days -1, 42, 84) and at the end of each treatment period (Days 21, 63 and 105). At each visit, tests were performed at 2 and 6 hours post-dose.
Change From Baseline in Cognitive Function Composite Score - Quality of Working Memory
Cognitive effects were assessed at the end of each treatment period using a computerized assessment system at time points close to the predicted time to attain maximum plasma concentration (Tmax) for solifenacin (6 hours) and oxybutynin (2 hours). Quality of working memory is calculated from the sum of two cognitive function sensitivity tests: Numeric Working Memory Sensitivity and Spatial Working Memory Sensitivity, and ranges from -2 to 2. A higher score reflects a good working memory and a negative change from baseline reflects impairment compared to the baseline assessment.
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Time frame: Assessed at each treatment period baseline visit (the day prior to the first dose of each treatment; Days -1, 42, 84) and at the end of each treatment period (Days 21, 63 and 105). At each visit, tests were performed at 2 and 6 hours post-dose.
Change From Baseline in Cognitive Function Composite Score - Quality of Episodic Secondary Memory
Cognitive effects were assessed at the end of each treatment period using a computerized assessment system at time points close to the predicted time of maximum plasma concentration for solifenacin and oxybutynin. Quality of episodic secondary memory is calculated from the sum of 4 tests: Immediate and delayed word recall, and word and picture recognition, and ranges from -200 to 400. A high score reflects a good ability to store, hold and retrieve information of an episodic nature (i.e. an event or a name) and a negative change from baseline reflects impairment compared to baseline.
Time frame: Assessed at each treatment period baseline visit (the day prior to the first dose of each treatment; Days -1, 42, 84) and at the end of each treatment period (Days 21, 63 and 105). At each visit, tests were performed at 2 and 6 hours post-dose.
Change From Baseline in Cognitive Function Composite Score - Speed of Memory
Cognitive effects were assessed at the end of each treatment period using a computerized assessment system at time points close to the predicted time to attain maximum plasma concentration for solifenacin and oxybutynin. Speed of Memory was calculated from the sum of 4 cognitive function speed tests: numeric and spatial working memory and word and picture recognition. A low score reflects that a person is able to recall a name, a face or any other item fast from the episodic secondary memory; a positive change from baseline reflects impairment compared to baseline.
Time frame: Assessed at each treatment period baseline visit (the day prior to the first dose of each treatment; Days -1, 42, 84) and at the end of each treatment period (Days 21, 63 and 105). At each visit, tests were performed at 2 and 6 hours post-dose.
Change From Baseline in Postural Stability Test
The postural stability test measures the ability to stand upright without moving, and was assessed at the end of each treatment period using a computerized assessment system at time points close to the predicted time to attain maximum plasma concentration for solifenacin and oxybutynin. Using apparatus modeled on the Wright Ataxia-meter, a cord from the meter is attached to the patient who is required to stand as still as possible with feet apart and eyes closed for 1 minute. The amount of sway is expressed as the total angular movement, summed regardless of sign, in the antero-posterior plane and calibrated in units of one-third degree of angle of sway. Wright (1971) described a range of 20-30 units as a normal range for adults with eyes wide open, increasing by 50 to 100% with eyes shut.
Time frame: Assessed at each treatment period baseline visit (the day prior to the first dose of each treatment; Days -1, 42, 84) and at the end of each treatment period (Days 21, 63 and 105). At each visit, tests were performed at 2 and 6 hours post-dose.