A Study to Compare Two Medications With an Inactive Medication and Look at the Effect on a Person's Mental Ability

NCT01126424 | Completed Phase 4 Results

• 2 other identifiers: 905-EC-0082008-005966-29
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Cognition

Keywords

Anti-muscarinics; Anti-cholinergics; Cognition; Solifenacin

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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 (1)

• Change From Baseline in Postural Stability Test

  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.

Study Arms (3)

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

Interventions

Solifenacin DRUG

tablet

Also known as: YM905

Solifenacin

Oxybutynin DRUG

capsule

Oxybutynin

Placebo DRUG

tablet

Placebo

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (3)

Unknown Facility

Blackpool, Lancashire, FY2 0JH, United Kingdom

Location

Unknown Facility

Manchester, Lancashire, M50 2GY, United Kingdom

Location

Unknown Facility

Bradford, Yorkshire, BD3 0DQ, United Kingdom

Location

Related Publications (2)

• Wright BM. A simple mechanical ataxia-meter. J Physiol. 1971 Oct;218 Suppl:27P-28P. No abstract available.

  PMID: 5130616 BACKGROUND

• 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.

  PMID: 23332882 DERIVED

Related Links

• Link to Prescribing Information

MeSH Terms

Interventions

Solifenacin Succinate; oxybutynin

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

Results Point of Contact

• Title: Associate Medical Director Urology
• Organization: Astellas Pharma Europe Ltd.

clinicaltrials@us.astellas.com

Study Officials

• Use Central Contact

  Astellas Pharma Europe Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2010
• First Posted: May 19, 2010
• Study Start: April 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: October 15, 2012
• Results First Posted: October 15, 2012

Record last verified: 2012-09

Locations

GB (3)