A Study of RO4602522 in Participants With Moderate Severity Alzheimer Disease on Background Alzheimer Disease Therapy

NCT ID: NCT01677754

Last Updated: 2017-05-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

542 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-24

Study Completion Date

2015-06-12

Brief Summary

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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.

Detailed Description

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Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive placebo for RO4602522 orally once daily for 12 months.

Donepezil

Intervention Type DRUG

Stable dose as background medication

Memantine

Intervention Type DRUG

Stable dose as background medication in combination with AChEIs

Rivastigmine

Intervention Type DRUG

Stable dose as background medication

Galantamine

Intervention Type DRUG

Stable dose as background medication

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.

Group Type EXPERIMENTAL

RO4602522

Intervention Type DRUG

Participants will receive RO4602522 orally once daily for 12 months.

Donepezil

Intervention Type DRUG

Stable dose as background medication

Memantine

Intervention Type DRUG

Stable dose as background medication in combination with AChEIs

Rivastigmine

Intervention Type DRUG

Stable dose as background medication

Galantamine

Intervention Type DRUG

Stable dose as background medication

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.

Group Type EXPERIMENTAL

RO4602522

Intervention Type DRUG

Participants will receive RO4602522 orally once daily for 12 months.

Donepezil

Intervention Type DRUG

Stable dose as background medication

Memantine

Intervention Type DRUG

Stable dose as background medication in combination with AChEIs

Rivastigmine

Intervention Type DRUG

Stable dose as background medication

Galantamine

Intervention Type DRUG

Stable dose as background medication

Interventions

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RO4602522

Participants will receive RO4602522 orally once daily for 12 months.

Intervention Type DRUG

Placebo

Participants will receive placebo for RO4602522 orally once daily for 12 months.

Intervention Type DRUG

Donepezil

Stable dose as background medication

Intervention Type DRUG

Memantine

Stable dose as background medication in combination with AChEIs

Intervention Type DRUG

Rivastigmine

Stable dose as background medication

Intervention Type DRUG

Galantamine

Stable dose as background medication

Intervention Type DRUG

Eligibility Criteria

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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

* 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

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)
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Advanced Research Center, Inc.;In-Patient Unit

Anaheim, California, United States

Site Status

Neurology Center of North Orange County

Fullerton, California, United States

Site Status

Torrance Clinical Research

Lomita, California, United States

Site Status

Artemis Institute for Clinical Research, LLC

San Diego, California, United States

Site Status

Sharp Mesa Vista Hospital

San Diego, California, United States

Site Status

San Francisco Clinical Research Center

San Francisco, California, United States

Site Status

Neurological Research Inst

Santa Monica, California, United States

Site Status

Yale University School Of Medicine

New Haven, Connecticut, United States

Site Status

Research Center for Clinical Studies, Inc.

Norwalk, Connecticut, United States

Site Status

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Site Status

Meridien Research

Brooksville, Florida, United States

Site Status

Brain Matters Research, Inc.

Delray Beach, Florida, United States

Site Status

Neurologic Consultants, P.A.

Fort Lauderdale, Florida, United States

Site Status

Galiz Research, LLC

Hialeah, Florida, United States

Site Status

Miami Jewish Health Systems

Miami, Florida, United States

Site Status

Medical Research Group of Central Florida

Orange City, Florida, United States

Site Status

Compass Research East, LLC

Orlando, Florida, United States

Site Status

Comprehensive Clinical Development, Inc.- St. Petersburg, FL

St. Petersburg, Florida, United States

Site Status

Axiom Clinical Research of Florida

Tampa, Florida, United States

Site Status

Premiere Research Institute

West Palm Beach, Florida, United States

Site Status

iResearch Atlanta

Decatur, Georgia, United States

Site Status

NeuroStudies.net, LLC

Decatur, Georgia, United States

Site Status

Alexian Brothers Neurosci Inst

Elk Grove Village, Illinois, United States

Site Status

Louisiana Research Associates

New Orleans, Louisiana, United States

Site Status

Booker, J. Gary, MD, APMC

Shreveport, Louisiana, United States

Site Status

Northern Michigan Neurology

Traverse City, Michigan, United States

Site Status

Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Site Status

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, United States

Site Status

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States

Site Status

Albuquerque Neuroscience Inc.

Albuquerque, New Mexico, United States

Site Status

New York University Medical Center;Child Study Center

New York, New York, United States

Site Status

Richmond Behavioral Associates

Staten Island, New York, United States

Site Status

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Site Status

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, United States

Site Status

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Site Status

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Site Status

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, United States

Site Status

Radiant Research, Inc.

Wyomissing, Pennsylvania, United States

Site Status

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Alzheimer's Research & Clinical Programs

Charleston, South Carolina, United States

Site Status

University of North Texas Health Science Center

Fort Worth, Texas, United States

Site Status

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Central Coast Neurosciences Research

Erina, New South Wales, Australia

Site Status

Southern Neurology

Kogarah, New South Wales, Australia

Site Status

Queen Elizabeth Hospital

Woodville, South Australia, Australia

Site Status

Box Hill Hospital; Eastern Clinical Research Unit

Box Hill, Victoria, Australia

Site Status

A.G.Mander Pty Ltd

Geelong, Victoria, Australia

Site Status

Heidelberg Repatriation Hospital

Heidelberg, Victoria, Australia

Site Status

Hollywood Specialist Centre

Nedlands, Western Australia, Australia

Site Status

Neurodegenerative Disorders Research

Subiaco, Western Australia, Australia

Site Status

The Medical Arts Health Research Group

Powell River, British Columbia, Canada

Site Status

Vancouver Hospital - UBC Hospital Site

Vancouver, British Columbia, Canada

Site Status

Vancouver Island Health Authority

Victoria, British Columbia, Canada

Site Status

Capitol District Health Authority

Halilfax, Nova Scotia, Canada

Site Status

True North Clinical Research Kentville

Kentville, Nova Scotia, Canada

Site Status

Jbn Medical Diagnostic Services Inc.

Burlington, Ontario, Canada

Site Status

Bruyere Continuing Care

Ottawa, Ontario, Canada

Site Status

Ingram, Jennifer MD

Peterborough, Ontario, Canada

Site Status

Toronto Memory Program (Neurology Research Inc.)

Toronto, Ontario, Canada

Site Status

The Centre for Memory and Aging

Toronto, Ontario, Canada

Site Status

Toronto Sunnybrook Hospital

Toronto, Ontario, Canada

Site Status

Recherches Neuro-Hippocame

Gatineau, Quebec, Canada

Site Status

Clinique Neuro Rive-Sud

Greenfield Park, Quebec, Canada

Site Status

Institut Universitaire de gériatrie de Sherbrooke; Service de gériatrie/pavillon Argyll

Sherbrooke, Quebec, Canada

Site Status

McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric

Verdun, Quebec, Canada

Site Status

CHU de Quebec - Hôpital de l' Enfant Jésus

Québec, , Canada

Site Status

NEUROHK s.r.o.

Choceň, , Czechia

Site Status

P-P Klinika

Kladno, , Czechia

Site Status

Supervize s.r.o.

Kutna Hora - Vnitrni Mesto, , Czechia

Site Status

Clintrial,s.r.o.

Prague, , Czechia

Site Status

AD71 s.r.o.

Prague, , Czechia

Site Status

Psychiatry Trial s.r.o.

Prague, , Czechia

Site Status

Neurologicka ambulance

Prague, , Czechia

Site Status

FORBELI s.r.o.

Prague, , Czechia

Site Status

Nemocnice Na Bulovce

Prague, , Czechia

Site Status

Thomayerova nemocnice

Praha 4 - Krc, , Czechia

Site Status

Centre Hospitalier de la côte Basque

Bayonne, , France

Site Status

Hopital Neurologique Pierre Wertheimer

Bron, , France

Site Status

Hopital Nord Laënnec - CHU Nantes

Nantes, , France

Site Status

Hopital Cimiez; CMRR

Nice, , France

Site Status

Hôpital Lariboisière

Paris, , France

Site Status

Groupe Hospitalier Sud - Hôpital Xavier Arnozan

Pessac, , France

Site Status

Hôpital Maison Blanche

Reims, , France

Site Status

CHU Rennes - Hopital Hôtel Dieu

Rennes, , France

Site Status

CHU Toulouse - La Grave

Toulouse, , France

Site Status

CHU Tours - Hôpital Bretonneau

Tours, , France

Site Status

Hôpital de Brabois Adultes

Vandœuvre-lès-Nancy, , France

Site Status

Hopital des Charpennes

Villeurbanne, , France

Site Status

Gemeinschaftspraxis

Ellwangen, , Germany

Site Status

Henriettenstiftung Hannover

Hanover, , Germany

Site Status

ISPG - Institut fuer Studien zur Psychischen Gesundheit

Mannheim, , Germany

Site Status

Klinikum rechts der Isar der Technischen Universität München

München, , Germany

Site Status

Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung

Siegen, , Germany

Site Status

Nuovo Ospedale Civile S.Agostino - Estense

Modena, Emilia-Romagna, Italy

Site Status

Policlinico Universitario Agostino Gemelli; Farmacia

Rome, Lazio, Italy

Site Status

Fondazione Santa Lucia IRCCS

Rome, Lazio, Italy

Site Status

Umberto I Policlinico di Roma-Università di Roma La Sapienza

Rome, Lazio, Italy

Site Status

Ente Ospedaliero Ospedali Galliera

Genoa, Liguria, Italy

Site Status

Università degli Studi di Genova

Genoa, Liguria, Italy

Site Status

Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica

Pisa, Tuscany, Italy

Site Status

Università degli studi di Perugia

Perugia, Umbria, Italy

Site Status

Podlaskie Centrum Psychogeriatrii

Bialystok, , Poland

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

Specjal. Praktyka Lekarska; Prof. Grzegorz Opala

Katowice, , Poland

Site Status

Centrum Medyczne Dendryt

Katowice, , Poland

Site Status

NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek

Poznan, , Poland

Site Status

NZOZ Syntonia

Pruszcz Gdański, , Poland

Site Status

NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog

Sopot, , Poland

Site Status

mMED Maciej Czarnecki

Warsaw, , Poland

Site Status

Instytut Psychiatrii i Neurologii

Warsaw, , Poland

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Site Status

Ajou University Hospital

Gyeonggi-do, , South Korea

Site Status

Inha University Hospital; Pulmonary Medicine

Incheon, , South Korea

Site Status

Kyung Hee University Hospital

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Konkuk University Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital General Universitario de Elche; Servicio de Farmacia

Elche, Alicante, Spain

Site Status

Fundació ACE

BArcelon, Barcelona, Spain

Site Status

Hospital General De Catalunya; Servicio de Neurologia

Sant Cugat del Vallès, Barcelona, Spain

Site Status

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Site Status

Hospital Virgen del Puerto

Plasencia, Palencia, Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Site Status

CAE Oroitu

Barakaldo, Vizcaya, Spain

Site Status

Hospital Perpetuo Socorro, Servicio de Geriatria

Albacete, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo

Malmo, , Sweden

Site Status

Karolinska Universitetssjukhuset Huddinge

Stockholm, , Sweden

Site Status

Cognitive Treatment & Research Unit

Crowborough, , United Kingdom

Site Status

Ninewells Hospital

Dundee, , United Kingdom

Site Status

Glasgow Memory Clinic

Glasgow, , United Kingdom

Site Status

West London Cognitive Disorders Treatment and Research Unit; Lakeside Metal Health Unit

Isleworth, , United Kingdom

Site Status

Institute of Psychiatry

London, , United Kingdom

Site Status

Norwich Medical School

Norwich, , United Kingdom

Site Status

Derriford Hospital

Plymouth, , United Kingdom

Site Status

Memory Service North

Sheffield, , United Kingdom

Site Status

Countries

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United States Australia Canada Czechia France Germany Italy Poland South Korea Spain Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 28550255 (View on PubMed)

Other Identifiers

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2012-000943-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP28248

Identifier Type: -

Identifier Source: org_study_id

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