NCT01677754

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 Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
542

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2012

Geographic Reach
12 countries

142 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 30, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 3, 2012

Completed
2 months until next milestone

Study Start

First participant enrolled

October 24, 2012

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 12, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 12, 2015

Completed
Last Updated

May 30, 2017

Status Verified

May 1, 2017

Enrollment Period

2.6 years

First QC Date

August 30, 2012

Last Update Submit

May 25, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12

    Baseline, Month 12

Secondary Outcomes (18)

  • Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (<=) 4 Points in ADAS-Cog-11

    Baseline, Month 12

  • Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12

    Baseline, Month 12

  • Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12

    Baseline, Month 12

  • Percentage of Participants With Worsening in BEHAVE-AD-FW Score

    Baseline to Month 12

  • Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months

    Baseline, Month 12

  • +13 more secondary outcomes

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: PlaceboDrug: DonepezilDrug: MemantineDrug: RivastigmineDrug: Galantamine

RO4602522 1 milligram (mg)

EXPERIMENTAL

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.

Drug: RO4602522Drug: DonepezilDrug: MemantineDrug: RivastigmineDrug: Galantamine

RO4602522 5 mg

EXPERIMENTAL

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.

Drug: RO4602522Drug: DonepezilDrug: MemantineDrug: RivastigmineDrug: Galantamine

Interventions

Participants will receive RO4602522 orally once daily for 12 months.

RO4602522 1 milligram (mg)RO4602522 5 mg

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

Placebo

Stable dose as background medication

PlaceboRO4602522 1 milligram (mg)RO4602522 5 mg

Stable dose as background medication in combination with AChEIs

PlaceboRO4602522 1 milligram (mg)RO4602522 5 mg

Stable dose as background medication

PlaceboRO4602522 1 milligram (mg)RO4602522 5 mg

Stable dose as background medication

PlaceboRO4602522 1 milligram (mg)RO4602522 5 mg

Eligibility Criteria

Age50 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • Participation at any time in an active Alzheimer's disease vaccine study
  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (142)

Advanced Research Center, Inc.;In-Patient Unit

Anaheim, California, 92801, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

Torrance Clinical Research

Lomita, California, 90717, United States

Location

Artemis Institute for Clinical Research, LLC

San Diego, California, 92103, United States

Location

Sharp Mesa Vista Hospital

San Diego, California, 92123, United States

Location

San Francisco Clinical Research Center

San Francisco, California, 94109, United States

Location

Neurological Research Inst

Santa Monica, California, 90025, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06510, United States

Location

Research Center for Clinical Studies, Inc.

Norwalk, Connecticut, 06851, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Meridien Research

Brooksville, Florida, 34601, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Neurologic Consultants, P.A.

Fort Lauderdale, Florida, 33308, United States

Location

Galiz Research, LLC

Hialeah, Florida, 33016, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 3273, United States

Location

Compass Research East, LLC

Orlando, Florida, 32806, United States

Location

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

St. Petersburg, Florida, 33716, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, 33609, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

iResearch Atlanta

Decatur, Georgia, 30030, United States

Location

NeuroStudies.net, LLC

Decatur, Georgia, 30033, United States

Location

Alexian Brothers Neurosci Inst

Elk Grove Village, Illinois, 60007, United States

Location

Louisiana Research Associates

New Orleans, Louisiana, 70114, United States

Location

Booker, J. Gary, MD, APMC

Shreveport, Louisiana, 71104-2136, United States

Location

Northern Michigan Neurology

Traverse City, Michigan, 49684, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, 63141, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

Albuquerque Neuroscience Inc.

Albuquerque, New Mexico, 87109, United States

Location

New York University Medical Center;Child Study Center

New York, New York, 10016, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607-6520, United States

Location

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, 19046, United States

Location

Radiant Research, Inc.

Wyomissing, Pennsylvania, 19610, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Alzheimer's Research & Clinical Programs

Charleston, South Carolina, 29425, United States

Location

University of North Texas Health Science Center

Fort Worth, Texas, 76107, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Central Coast Neurosciences Research

Erina, New South Wales, 2250, Australia

Location

Southern Neurology

Kogarah, New South Wales, 2217, Australia

Location

Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Box Hill Hospital; Eastern Clinical Research Unit

Box Hill, Victoria, 3128, Australia

Location

A.G.Mander Pty Ltd

Geelong, Victoria, 3220, Australia

Location

Heidelberg Repatriation Hospital

Heidelberg, Victoria, 3084, Australia

Location

Hollywood Specialist Centre

Nedlands, Western Australia, 6009, Australia

Location

Neurodegenerative Disorders Research

Subiaco, Western Australia, 6008, Australia

Location

The Medical Arts Health Research Group

Powell River, British Columbia, V8A 3B6, Canada

Location

Vancouver Hospital - UBC Hospital Site

Vancouver, British Columbia, V6T 2B5, Canada

Location

Vancouver Island Health Authority

Victoria, British Columbia, V8R 1J8, Canada

Location

Capitol District Health Authority

Halilfax, Nova Scotia, B3H 2E1, Canada

Location

True North Clinical Research Kentville

Kentville, Nova Scotia, B4N 4K9, Canada

Location

Jbn Medical Diagnostic Services Inc.

Burlington, Ontario, L7M 4Y1, Canada

Location

Bruyere Continuing Care

Ottawa, Ontario, K1N 5C8, Canada

Location

Ingram, Jennifer MD

Peterborough, Ontario, K9H 3S1, Canada

Location

Toronto Memory Program (Neurology Research Inc.)

Toronto, Ontario, M3B 2S7, Canada

Location

The Centre for Memory and Aging

Toronto, Ontario, M4G 3E8, Canada

Location

Toronto Sunnybrook Hospital

Toronto, Ontario, M4N 3M5, Canada

Location

Recherches Neuro-Hippocame

Gatineau, Quebec, J8T 8J1, Canada

Location

Clinique Neuro Rive-Sud

Greenfield Park, Quebec, J4V 2J2, Canada

Location

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

Sherbrooke, Quebec, J1J 3H5, Canada

Location

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

Verdun, Quebec, H4H 1R3, Canada

Location

CHU de Quebec - Hôpital de l' Enfant Jésus

Québec, G1J 1Z4, Canada

Location

NEUROHK s.r.o.

Choceň, 565 01, Czechia

Location

P-P Klinika

Kladno, 272 80, Czechia

Location

Supervize s.r.o.

Kutna Hora - Vnitrni Mesto, 284 01, Czechia

Location

Clintrial,s.r.o.

Prague, 100 00, Czechia

Location

AD71 s.r.o.

Prague, 102 00, Czechia

Location

Psychiatry Trial s.r.o.

Prague, 158 00, Czechia

Location

Neurologicka ambulance

Prague, 16000, Czechia

Location

FORBELI s.r.o.

Prague, 165 00, Czechia

Location

Nemocnice Na Bulovce

Prague, 180 01, Czechia

Location

Thomayerova nemocnice

Praha 4 - Krc, 140 59, Czechia

Location

Centre Hospitalier de la côte Basque

Bayonne, 64109, France

Location

Hopital Neurologique Pierre Wertheimer

Bron, 69500, France

Location

Hopital Nord Laënnec - CHU Nantes

Nantes, 44093, France

Location

Hopital Cimiez; CMRR

Nice, 06003, France

Location

Hôpital Lariboisière

Paris, 75475, France

Location

Groupe Hospitalier Sud - Hôpital Xavier Arnozan

Pessac, 33604, France

Location

Hôpital Maison Blanche

Reims, 51092, France

Location

CHU Rennes - Hopital Hôtel Dieu

Rennes, 35064, France

Location

CHU Toulouse - La Grave

Toulouse, 31059, France

Location

CHU Tours - Hôpital Bretonneau

Tours, 37044, France

Location

Hôpital de Brabois Adultes

Vandœuvre-lès-Nancy, 54511, France

Location

Hopital des Charpennes

Villeurbanne, 69100, France

Location

Gemeinschaftspraxis

Ellwangen, 73479, Germany

Location

Henriettenstiftung Hannover

Hanover, 30559, Germany

Location

ISPG - Institut fuer Studien zur Psychischen Gesundheit

Mannheim, 68165, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung

Siegen, 57072, Germany

Location

Nuovo Ospedale Civile S.Agostino - Estense

Modena, Emilia-Romagna, 41126, Italy

Location

Policlinico Universitario Agostino Gemelli; Farmacia

Rome, Lazio, 00168, Italy

Location

Fondazione Santa Lucia IRCCS

Rome, Lazio, 00179, Italy

Location

Umberto I Policlinico di Roma-Università di Roma La Sapienza

Rome, Lazio, 00185, Italy

Location

Ente Ospedaliero Ospedali Galliera

Genoa, Liguria, 16128, Italy

Location

Università degli Studi di Genova

Genoa, Liguria, 16132, Italy

Location

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

Pisa, Tuscany, 56126, Italy

Location

Università degli studi di Perugia

Perugia, Umbria, 06126, Italy

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-732, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Specjal. Praktyka Lekarska; Prof. Grzegorz Opala

Katowice, 40-588, Poland

Location

Centrum Medyczne Dendryt

Katowice, 40-684, Poland

Location

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

Poznan, 61-289, Poland

Location

NZOZ Syntonia

Pruszcz Gdański, 83-000, Poland

Location

NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog

Sopot, 81-717, Poland

Location

mMED Maciej Czarnecki

Warsaw, 01-697, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, 02-957, Poland

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Ajou University Hospital

Gyeonggi-do, 443-380, South Korea

Location

Inha University Hospital; Pulmonary Medicine

Incheon, 400-711, South Korea

Location

Kyung Hee University Hospital

Seoul, 02447, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital General Universitario de Elche; Servicio de Farmacia

Elche, Alicante, 03203, Spain

Location

Fundació ACE

BArcelon, Barcelona, 08034, Spain

Location

Hospital General De Catalunya; Servicio de Neurologia

Sant Cugat del Vallès, Barcelona, 8195, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Virgen del Puerto

Plasencia, Palencia, 10600, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41071, Spain

Location

CAE Oroitu

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Perpetuo Socorro, Servicio de Geriatria

Albacete, 2006, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo

Malmo, 205 02, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, 171 64, Sweden

Location

Cognitive Treatment & Research Unit

Crowborough, TN6 1HB, United Kingdom

Location

Ninewells Hospital

Dundee, DD12 9SY, United Kingdom

Location

Glasgow Memory Clinic

Glasgow, G20 0XA, United Kingdom

Location

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

Isleworth, TW7 6FY, United Kingdom

Location

Institute of Psychiatry

London, SE5 8AF, United Kingdom

Location

Norwich Medical School

Norwich, NR4 7UY, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Memory Service North

Sheffield, S35 8QS, United Kingdom

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Alzheimer Disease

Interventions

sembragilineDonepezilMemantineRivastigmineGalantamine

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

IndansIndenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPolycyclic CompoundsAmantadineAdamantaneBridged-Ring CompoundsPhenylcarbamatesCarbamatesAcids, AcyclicCarboxylic AcidsAmaryllidaceae AlkaloidsAlkaloidsBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 30, 2012

First Posted

September 3, 2012

Study Start

October 24, 2012

Primary Completion

June 12, 2015

Study Completion

June 12, 2015

Last Updated

May 30, 2017

Record last verified: 2017-05

Locations