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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01677754




Registration number
NCT01677754
Ethics application status
Date submitted
30/08/2012
Date registered
3/09/2012
Date last updated
30/05/2017

Titles & IDs
Public title
A Study of RO4602522 in Participants With Moderate Severity Alzheimer Disease on Background Alzheimer Disease Therapy
Scientific title
A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of RO4602522 Added to Background Alzheimer's Disease Therapy in Patients With Moderate Severity Alzheimer's Disease
Secondary ID [1] 0 0
2012-000943-29
Secondary ID [2] 0 0
BP28248
Universal Trial Number (UTN)
Trial acronym
MAyflOwer RoAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RO4602522
Treatment: Drugs - Placebo
Treatment: Drugs - Donepezil
Treatment: Drugs - Memantine
Treatment: Drugs - Rivastigmine
Treatment: Drugs - Galantamine

Placebo comparator: Placebo - Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.

Experimental: RO4602522 1 milligram (mg) - Participants will receive RO4602522 1 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.

Experimental: RO4602522 5 mg - Participants will receive RO4602522 5 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.


Treatment: Drugs: RO4602522
Participants will receive RO4602522 orally once daily for 12 months.

Treatment: Drugs: Placebo
Participants will receive placebo for RO4602522 orally once daily for 12 months.

Treatment: Drugs: Donepezil
Stable dose as background medication

Treatment: Drugs: Memantine
Stable dose as background medication in combination with AChEIs

Treatment: Drugs: Rivastigmine
Stable dose as background medication

Treatment: Drugs: Galantamine
Stable dose as background medication
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [1] 0 0
Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (<=) 4 Points in ADAS-Cog-11
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [2] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12
Timepoint [2] 0 0
Baseline, Month 12
Secondary outcome [3] 0 0
Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12
Timepoint [3] 0 0
Baseline, Month 12
Secondary outcome [4] 0 0
Percentage of Participants With Worsening in BEHAVE-AD-FW Score
Timepoint [4] 0 0
Baseline to Month 12
Secondary outcome [5] 0 0
Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months
Timepoint [5] 0 0
Baseline, Month 12
Secondary outcome [6] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months
Timepoint [6] 0 0
Baseline, Month 12
Secondary outcome [7] 0 0
Percentage of Participants With Worsening in ADCS-CGIC Score
Timepoint [7] 0 0
Baseline to Month 12
Secondary outcome [8] 0 0
Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months
Timepoint [8] 0 0
Baseline, Month 12
Secondary outcome [9] 0 0
Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months
Timepoint [9] 0 0
Baseline, Month 12
Secondary outcome [10] 0 0
Percentage of Participants with Adverse Events
Timepoint [10] 0 0
Baseline up to 13 months
Secondary outcome [11] 0 0
Percentage of Participants with Change in Lens Opacity Grading
Timepoint [11] 0 0
Baseline; Months 6, and 12
Secondary outcome [12] 0 0
Percentage of Participants with Abnormal Visual Acuity Test Results
Timepoint [12] 0 0
Baseline, Months 6, and 12
Secondary outcome [13] 0 0
Change From Baseline in Michigan Neuropathy Screening Instrument Score
Timepoint [13] 0 0
Baseline, Weeks 8, 18, 30, 44, 52, and at the last follow-up visit (12 weeks after last dose, up to 64 weeks)
Secondary outcome [14] 0 0
Percentage of Participants Receiving Concomitant Medications
Timepoint [14] 0 0
Baseline to 13 Months
Secondary outcome [15] 0 0
Apparent Total Clearance of the Drug From Plasma After Administration of RO4602522
Timepoint [15] 0 0
Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Secondary outcome [16] 0 0
Apparent Volume of Distribution at Steady State after Administration of RO4602522
Timepoint [16] 0 0
Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Secondary outcome [17] 0 0
Area Under the Plasma Concentration-Time Curve of RO4602522
Timepoint [17] 0 0
Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Secondary outcome [18] 0 0
Maximum Plasma Concentration of RO4602522
Timepoint [18] 0 0
Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364

Eligibility
Key inclusion criteria
* Probable Alzheimer disease, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV-TR) criteria
* Mini-Mental State Exam (MMSE) score at screening between 13 and 20, inclusive
* Body mass index (BMI) between 18 and 36 kilograms per square meter (kg/m^2) (inclusive) at screening
* Modified Hachinski Ischemia Score of less than or equal to (</=) 4
* Participants with Cornell Scale for Depression in Dementia (CSDD) scores </= 13 at screening
* Receiving treatment with donepezil, rivastigmine, galantamine or any AChEIs in combination with memantine for at least 4 months before screening, with their dose and formulation stabilized at least 3 months before screening. All formulation and dosages are allowed except donezepil 23 mg (alone or in combination)
* Females of childbearing potential must have a negative pregnancy test and must agree to use effective contraception
* Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane)
* Have a reliable caregiver or some other identified responsible person who has frequent contact with the participant
Minimum age
50 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any neurological or psychiatric condition that may occur currently or during the course of the study that can impair cognition or functioning that is not associated with Alzheimer's disease
* Background of mental retardation
* Uncontrolled behavioral symptoms incompatible with compliance or evaluability
* Alcohol and/or substance abuse or dependence (DSM-IV-TR) in the past 2 years, except nicotine use which is allowed. However, smokers treated with nicotine replacement therapy or bupropion are excluded
* Unstable or poorly controlled hypertension as assessed by the investigator regardless of whether or not the participant is taking antihypertensive medications
* Unstable or clinically significant cardiovascular disease that could be expected to progress, recur, or change during study period to such an extent that it could bias the assessment of the clinical or mental status of the participant
* Inadequate hepatic, renal or thyroid function
* Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
* Poorly controlled diabetes (glycosylated hemoglobin [HbA1c] greater than or equal to [>/=] 9 percent at screening)
* Requiring nursing home care. Participants living in assisted living facilities are allowed if a reliable caregiver is available (see inclusion criteria)
* Current treatment for Alzheimer's disease other than those listed in inclusion criteria
* Participation at any time in an active Alzheimer's disease vaccine study
* Participation in a passive Alzheimer's disease immunization study less than 1 year before screening except for a) participants where documented medical history indicate that they were randomized to the placebo group in these studies, b) participants treated with bapineuzumab where a 6-month exclusion period applies
* Recent (</= 12 weeks) or concomitant use of other Monoamine oxidase inhibitors (selective or not) including selegiline or rasagiline
* Antidepressant treatments are not allowed except for citalopram up to 20 mg daily, escitalopram up to 10 mg daily, paroxetine up to 30 mg daily, sertraline up to 100 mg daily and trazodone up to 100 mg daily. If treated with one of these antidepressants, the treatment should be present for at least 6 weeks at screening. All other antidepressants including other SSRIs, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), St. John's wort and bupropion are excluded
* Anti-psychotic use within 4 weeks before screening is not permitted except risperidone up to 1.5 mg/day, quetiapine up to 100 milligrams per day (mg/day), olanzapine up to 5 mg/day, and aripiprazole up to 10 mg daily
* Anxiolytics/ hypnotics use is not permitted except for benzodiazepines of short or intermediate half-life for anxiety/sleeping disorders. Zolpidem (up to 5 mg/day), zopiclone (up to 7.5 mg/day), eszopiclone (up to 2 mg/day), trazodone (up to 50 mg/day, at bedtime) or zaleplon (up to 5 mg/day) is permitted for insomnia
* Anti-Parkinson's agents within 2 weeks before screening are not permitted
* Recent (less than 4 weeks prior to screening) or concomitant use of anticonvulsants
* Anticholinergics/ antihistaminics within 2 weeks before screening are not permitted, except i) if used episodically more than 3 days before the screening cognitive measurement, ii) non-sedating antihistaminic medications (without anticholinergic effects such as cetirizine) or peripheral anticholinergics without central anticholinergic effects (such as, trospium for the treatment of hyperactive bladder), which are permitted
* Recent (less than 1 week prior to screening) or concomitant use of opioid drugs (tramadol, methadone, propoxyphene, or meperidine), cyclobenzaprine and dextromethorphan
* Concomitant use of sympathomimetic drugs, including sympathomimetics in local anesthetics and ephedra supplements

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/06/2015
Sample size
Target
Accrual to date
Final
542
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Central Coast Neurosciences Research - Erina
Recruitment hospital [3] 0 0
Southern Neurology - Kogarah
Recruitment hospital [4] 0 0
Queen Elizabeth Hospital - Woodville
Recruitment hospital [5] 0 0
Box Hill Hospital; Eastern Clinical Research Unit - Box Hill
Recruitment hospital [6] 0 0
A.G.Mander Pty Ltd - Geelong
Recruitment hospital [7] 0 0
Heidelberg Repatriation Hospital - Heidelberg
Recruitment hospital [8] 0 0
Hollywood Specialist Centre - Nedlands
Recruitment hospital [9] 0 0
Neurodegenerative Disorders Research - Subiaco
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2250 - Erina
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment postcode(s) [9] 0 0
6008 - Subiaco
Recruitment outside Australia
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United States of America
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California
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Connecticut
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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Louisiana
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Michigan
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Mississippi
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Missouri
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New Jersey
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New Mexico
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North Carolina
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Oklahoma
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Rhode Island
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South Carolina
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Texas
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British Columbia
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Nova Scotia
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Ontario
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Quebec
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Czechia
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Chocen
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Kladno
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Prague
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Siegen
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Lazio
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Liguria
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Italy
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Toscana
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Umbria
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Korea, Republic of
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Gyeonggi-do
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Incheon
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Seoul
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Bialystok
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Gdansk
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Katowice
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Poznan
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Pruszcz Gdanski
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Sopot
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Warszawa
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Spain
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Alicante
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Barcelona
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Madrid
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Palencia
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Sevilla
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Vizcaya
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Spain
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Albacete
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Spain
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Valencia
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Sweden
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Malmö
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Sweden
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Stockholm
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United Kingdom
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Crowborough
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United Kingdom
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Dundee
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United Kingdom
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Glasgow
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United Kingdom
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Isleworth
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United Kingdom
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London
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United Kingdom
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Norwich
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United Kingdom
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Plymouth
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United Kingdom
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Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4602522 in participants with moderate severity Alzheimer's disease. Participants who are taking background therapy of acetylcholinesterase inhibitors (AChEI) alone or in combination with memantine for at least 4 months before screening will be randomized to receive either one of two doses of RO4602522 or placebo for 12 months.
Trial website
https://clinicaltrials.gov/study/NCT01677754
Trial related presentations / publications
Nave S, Doody RS, Boada M, Grimmer T, Savola JM, Delmar P, Pauly-Evers M, Nikolcheva T, Czech C, Borroni E, Ricci B, Dukart J, Mannino M, Carey T, Moran E, Gilaberte I, Muelhardt NM, Gerlach I, Santarelli L, Ostrowitzki S, Fontoura P. Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD). J Alzheimers Dis. 2017;58(4):1217-1228. doi: 10.3233/JAD-161309.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01677754