A Study to Compare Two Medications With an Inactive Medic... | NCT01126424

NCT01126424

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2008-005966-29	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Solifenacin	Experimental	Participants received 21 days of treatment with 5 mg solifenacin, in tablet form once a day.	Drug: Solifenacin
Oxybutynin	Active Comparator	Participants received 21 days of treatment with 10 mg oxybutynin (1 x 5 mg twice daily) in capsule form.	Drug: Oxybutynin
Placebo	Placebo Comparator	Participants received 21 days of treatment with placebo.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Solifenacin	Drug	tablet	Solifenacin	YM905

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The subject has mild cognitive impairment as determined by mini-mental state examination (MMSE) ≥ grade 24
The subject conforms to the Stockholm criteria for mild cognitive impairment as assessed by the investigator
The subject has a body mass index (BMI) between 18.0 to 30.0 kg/m2 inclusive
The subject is available to complete the study

Exclusion Criteria:

The subject has moderate or severe cognitive impairment as determined by MMSE criteria at screening, ≤ grade 23
The subject has depression as determined by Geriatric Depression Scale (GDS) short form ≥ 5 at screening
The subject has a history of urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony or toxic megacolon or severe ulcerative colitis), myasthenia gravis, uncontrolled narrow angle glaucoma or shallow anterior chamber or deemed to be at risk for these conditions
The subject is undergoing hemodialysis or has severe renal impairment or moderate hepatic impairment and who are on treatment with a potent CYP3A4 inhibitor, e.g. Ketoconazole
The subject has uncontrolled diabetes mellitus
The subject has a positive pre-study hepatitis B surface antigen, hepatitis C antibody or HIV result at time of screening
The subject has a history of drug and / or alcohol abuse at time of screening
The subject has an average weekly alcohol intake of greater than 21 units (male) or 14 units (female) within ≤ 3 months prior to screening (1 unit is 270cc of beer, 40cc of spirits or 125cc of wine)
The subject has a history of smoking more than 10 cigarettes (or the equivalent amount of tobacco) per day within ≤ 3 months prior to screening
The subject has a history of known or suspected hypersensitivity to solifenacin succinate, oxybutynin hydrochloride, other anti-cholinergics or lactose, to any component of the dosage form
The subject has taken any unstable doses of prescribed medication within ≤ 1 month prior to screening or over-the-counter medicine (including vitamins and herbal remedies) within 48 hours prior to the first study day, which in the opinion of the Investigator, will interfere with the study procedures or compromise safety
The subject is currently dosing with medication(s) intended to treat overactive bladder symptoms or has history of non-drug treatment intended to treat overactive bladder symptoms within ≤ 3 months prior to screening
The subject has any clinically significant abnormality following Investigator review of the physical examination
The subject has any clinically significant abnormality following the Investigator's review of the ECG
The subject has mobility impairment that precludes the assessment of postural stability
The subject has any clinically significant abnormal heart rate or blood pressure measurements, at the screening visit (dBP > 90mmHg, sBP > 160mmHg or HR < 40bpm or > 100bpm)
The subject has any clinically significant abnormality following Investigator's review of the biochemistry & hematology results which, in the opinion of the Investigator, contraindicates their participation
The subject has donated blood or plasma within ≤ 3 months prior to screening or more than 500ml or 1 unit of blood or plasma within ≤ 6 months prior to screening
The subject, may find it difficult to adhere to the provisions of treatment and observation specified in the protocol
The subject has participated in any clinical study within ≤ 3 months prior to screening
The subject has any clinical condition, diagnosis, symptomatology or ongoing investigation, which, contraindicates their participation
The subject is an employee of Astellas Pharma, Cognitive Drug Research, and any other third party related to the study site

Name	Affiliation	Role
Use Central Contact	Astellas Pharma Europe Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Blackpool	Lancashire	FY2 0JH	United Kingdom

PubMed Identifier	Type	Citation	Retractions
5130616	Background	Wright BM. A simple mechanical ataxia-meter. J Physiol. 1971 Oct;218 Suppl:27P-28P. No abstract available.
23332882	Derived	Wagg A, Dale M, Tretter R, Stow B, Compion G. Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: the SENIOR study. Eur Urol. 2013 Jul;64(1):74-81. doi: 10.1016/j.eururo.2013.01.002. Epub 2013 Jan 11.

Label	URL
Link to Prescribing Information	View source

Arm/Group Information

ID	Title	Description
FG000	Solifenacin / Oxybutynin / Placebo	Participants received 21 days of each treatment in the following order: 5 mg solifenacin, 10 mg oxybutynin, placebo. There was a 21-day washout period between each treatment period.
FG001	Solifenacin / Placebo / Oxybutynin	Participants received 21 days of each treatment in the following order: 5 mg solifenacin, placebo, 10 mg oxybutynin. There was a 21-day washout period between each treatment period.
FG002	Oxybutynin / Placebo / Solifenacin	Participants received 21 days of each treatment in the following order: 10 mg oxybutynin, placebo, 5 mg solifenacin. There was a 21-day washout period between each treatment period.
FG003	Oxybutynin / Solifenacin / Placebo	Participants received 21 days of each treatment in the following order: 10 mg oxybutynin, 5 mg solifenacin, placebo. There was a 21-day washout period between each treatment period.
FG004	Placebo / Solifenacin / Oxybutynin	Participants received 21 days of each treatment in the following order: placebo, 5 mg solifenacin, 10 mg oxybutynin. There was a 21-day washout period between each treatment period.
FG005	Placebo / Oxybutynin / Solifenacin	Participants received 21 days of each treatment in the following order: placebo, 10 mg oxybutynin, 5 mg solifenacin. There was a 21-day washout period between each treatment period.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjectsAll randomized patients who took at least 1 dose of study drug FG0014 subjectsAll randomized patients who took at least 1 dose of study drug FG0025 subjectsAll randomized patients who took at least 1 dose of study drug FG0036 subjectsAll randomized patients who took at least 1 dose of study drug FG0044 subjectsAll randomized patients who took at least 1 dose of study drug FG0054 subjectsAll randomized patients who took at least 1 dose of study drug
Safety Analysis Subset 1 (SAF 1)		FG0003 subjectsTook at least 1 dose of study drug and completed cognitive function tests for at least 2 treatments. FG0014 subjectsTook at least 1 dose of study drug and completed cognitive function tests for at least 2 treatments. FG0024 subjectsTook at least 1 dose of study drug and completed cognitive function tests for at least 2 treatments. FG003
COMPLETED		FG0003 subjects FG0014 subjects FG0024 subjects FG0033 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0021 subjects FG0033 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0020 subjects FG003

ID	Title	Description
BG000	Solifenacin / Oxybutynin / Placebo	Participants received 21 days of each treatment in the following order: 5 mg solifenacin, 10 mg oxybutynin, placebo. There was a 21-day washout period between each treatment period.
BG001	Solifenacin / Placebo / Oxybutynin

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	The number of participants analyzed represents the Safety Analysis Subset 1 (SAF1), consisting of all randomized patients who took at least one dose of the study medication and who completed the cognitive function tests for at least two treatment periods. The number of participants per arm is consistent for all categories / rows of the data table.	Posted		Mean	Standard Deviation	msec		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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Solifenacin	Participants received 21 days of treatment with 5 mg solifenacin, in tablet form once a day.

ID	Term
D000069464	Solifenacin Succinate
C005419	oxybutynin

ID	Term
D011812	Quinuclidines
D006572	Heterocyclic Compounds, Bridged-Ring
D006571	Heterocyclic Compounds
D044005	Tetrahydroisoquinolines

ID	Title	Description
OG000	Solifenacin	Participants received 21 days of treatment with 5 mg solifenacin, in tablet form once a day.
OG001	Oxybutynin	Participants received 21 days of treatment with 10 mg oxybutynin (1 x 5 mg twice daily) in capsule form.
OG002	Placebo	Participants received 21 days of treatment with placebo.