Clinical trial NCT01126424: A Study to Compare Two Medications With an Inactive Medication and Look at the Effect on a Person's Mental Ability
Official title: A Study to Compare the Cognitive Effect of Solifenacin 5mg Once-daily and Oxybutynin 5mg Twice-daily After Chronic Dosing Versus Placebo in Subjects 75 Years and Over With Mild Cognitive Impairment - A Double-blind, Randomized, Multi-center Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cognition
Keywords: Anti-muscarinics
Anti-cholinergics
Cognition
Solifenacin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2010-05-19
Enrollment: 26
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The purpose is to compare solifenacin and oxybutynin with an inactive tablet and assess any potential effects on mental ability.

Detailed description: 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.

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

Primary outcomes:
measure: Change From Baseline in Cognitive Function Composite Score - Power of Attention
timeFrame: 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.
measure: Change From Baseline in Cognitive Function Composite Score - Continuity of Attention
timeFrame: 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.
measure: Change From Baseline in Cognitive Function Composite Score - Quality of Working Memory
timeFrame: 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.
measure: Change From Baseline in Cognitive Function Composite Score - Quality of Episodic Secondary Memory
timeFrame: 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.
measure: Change From Baseline in Cognitive Function Composite Score - Speed of Memory
timeFrame: 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.
Secondary outcomes:
measure: Change From Baseline in Postural Stability Test
timeFrame: 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.
Other outcomes:
Locations:
city: Blackpool
country: United Kingdom
state: Lancashire
city: Manchester
country: United Kingdom
state: Lancashire
city: Bradford
country: United Kingdom
state: Yorkshire
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Use Central Contact
role: STUDY_DIRECTOR
References:
citation: Wright BM. A simple mechanical ataxia-meter. J Physiol. 1971 Oct;218 Suppl:27P-28P. No abstract available.
citation: 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.