A Study of RO4602522 in Participants With Moderate Severity Alzheimer Disease on Background Alzheimer Disease Therapy
- Conditions
- Interventions
- Registration Number
- NCT01677754
- Lead Sponsor
- Hoffmann-La Roche
- 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 bef...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 542
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RO4602522 1 milligram (mg) Memantine 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. RO4602522 5 mg Rivastigmine 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. RO4602522 1 milligram (mg) RO4602522 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. RO4602522 1 milligram (mg) Galantamine 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. Placebo Donepezil Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. RO4602522 5 mg RO4602522 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. Placebo Placebo Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. Placebo Rivastigmine Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. Placebo Memantine Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. RO4602522 1 milligram (mg) Donepezil 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. Placebo Galantamine Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. RO4602522 1 milligram (mg) Rivastigmine 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. RO4602522 5 mg Memantine 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. RO4602522 5 mg Donepezil 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. RO4602522 5 mg Galantamine 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12 Baseline, Month 12
- Secondary Outcome Measures
Name Time Method Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months Baseline, Month 12 Percentage of Participants with Adverse Events Baseline up to 13 months Percentage of Participants with Change in Lens Opacity Grading Baseline; Months 6, and 12 Maximum Plasma Concentration of RO4602522 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 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 Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months Baseline, Month 12 Percentage of Participants With Worsening in ADCS-CGIC Score Baseline to Month 12 Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months Baseline, Month 12 Percentage of Participants with Abnormal Visual Acuity Test Results Baseline, Months 6, and 12 Change From Baseline in Michigan Neuropathy Screening Instrument Score Baseline, Weeks 8, 18, 30, 44, 52, and at the last follow-up visit (12 weeks after last dose, up to 64 weeks) Percentage of Participants Receiving Concomitant Medications Baseline to 13 Months Apparent Total Clearance of the Drug From Plasma After Administration of RO4602522 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 Area Under the Plasma Concentration-Time Curve of RO4602522 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 Apparent Volume of Distribution at Steady State after Administration of RO4602522 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
Trial Locations
- Locations (142)
Research Center for Clinical Studies, Inc.
🇺🇸Norwalk, Connecticut, United States
Vancouver Island Health Authority
🇨🇦Victoria, British Columbia, Canada
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
🇵🇱Poznan, Poland
Hospital Virgen del Puerto
🇪🇸Plasencia, Palencia, Spain
Università degli studi di Perugia
🇮🇹Perugia, Umbria, Italy
Advanced Research Center, Inc.;In-Patient Unit
🇺🇸Anaheim, California, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Neurology Center of North Orange County
🇺🇸Fullerton, California, United States
Neurological Research Inst
🇺🇸Santa Monica, California, United States
Meridien Research
🇺🇸Brooksville, Florida, United States
Compass Research East, LLC
🇺🇸Orlando, Florida, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
NeuroStudies.net, LLC
🇺🇸Decatur, Georgia, United States
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
Northern Michigan Neurology
🇺🇸Traverse City, Michigan, United States
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Millennium Psychiatric Associates, LLC
🇺🇸Creve Coeur, Missouri, United States
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
Bruyere Continuing Care
🇨🇦Ottawa, Ontario, Canada
NEUROHK s.r.o.
🇨🇿Chocen, Czechia
Albuquerque Neuroscience Inc.
🇺🇸Albuquerque, New Mexico, United States
Jbn Medical Diagnostic Services Inc.
🇨🇦Burlington, Ontario, Canada
Hôpital Maison Blanche
🇫🇷Reims, France
Hopital Cimiez; CMRR
🇫🇷Nice, France
P-P Klinika
🇨🇿Kladno, Czechia
Supervize s.r.o.
🇨🇿Kutna Hora - Vnitrni Mesto, Czechia
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Box Hill Hospital; Eastern Clinical Research Unit
🇦🇺Box Hill, Victoria, Australia
Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
Heidelberg Repatriation Hospital
🇦🇺Heidelberg, Victoria, Australia
Hollywood Specialist Centre
🇦🇺Nedlands, Western Australia, Australia
Ingram, Jennifer MD
🇨🇦Peterborough, Ontario, Canada
Recherches Neuro-Hippocame
🇨🇦Gatineau, Quebec, Canada
ISPG - Institut fuer Studien zur Psychischen Gesundheit
🇩🇪Mannheim, Germany
Toronto Sunnybrook Hospital
🇨🇦Toronto, Ontario, Canada
Nemocnice Na Bulovce
🇨🇿Prague, Czechia
Henriettenstiftung Hannover
🇩🇪Hannover, Germany
CHU de Quebec - Hôpital de l' Enfant Jésus
🇨🇦Quebec, Canada
Neurologicka ambulance
🇨🇿Praha 6, Czechia
FORBELI s.r.o.
🇨🇿Praha 6, Czechia
Psychiatry Trial s.r.o.
🇨🇿Praha 5, Czechia
CHU Toulouse - La Grave
🇫🇷Toulouse, France
Clintrial,s.r.o.
🇨🇿Praha 10, Czechia
AD71 s.r.o.
🇨🇿Praha 10, Czechia
Groupe Hospitalier Sud - Hôpital Xavier Arnozan
🇫🇷Pessac, France
Karolinska Universitetssjukhuset Huddinge
🇸🇪Stockholm, Sweden
CHU Tours - Hôpital Bretonneau
🇫🇷Tours, France
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Podlaskie Centrum Psychogeriatrii
🇵🇱Bialystok, Poland
CAE Oroitu
🇪🇸BaraKaldo, Vizcaya, Spain
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Cognitive Treatment & Research Unit
🇬🇧Crowborough, United Kingdom
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
CHU Rennes - Hopital Hôtel Dieu
🇫🇷Rennes, France
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Nuovo Ospedale Civile S.Agostino - Estense
🇮🇹Modena, Emilia-Romagna, Italy
Ente Ospedaliero Ospedali Galliera
🇮🇹Genova, Liguria, Italy
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
mMED Maciej Czarnecki
🇵🇱Warszawa, Poland
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Inha University Hospital; Pulmonary Medicine
🇰🇷Incheon, Korea, Republic of
NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog
🇵🇱Sopot, Poland
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Fundació ACE
🇪🇸BArcelon, Barcelona, Spain
NZOZ Syntonia
🇵🇱Pruszcz Gdanski, Poland
Institute of Psychiatry
🇬🇧London, United Kingdom
Hospital Universitario Virgen Macarena
🇪🇸Seville, Sevilla, Spain
Hospital Perpetuo Socorro, Servicio de Geriatria
🇪🇸Albacete, Spain
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
Norwich Medical School
🇬🇧Norwich, United Kingdom
Artemis Institute for Clinical Research, LLC
🇺🇸San Diego, California, United States
Sharp Mesa Vista Hospital
🇺🇸San Diego, California, United States
San Francisco Clinical Research Center
🇺🇸San Francisco, California, United States
Miami Jewish Health Systems
🇺🇸Miami, Florida, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Cutting Edge Research Group
🇺🇸Oklahoma City, Oklahoma, United States
West London Cognitive Disorders Treatment and Research Unit; Lakeside Metal Health Unit
🇬🇧Isleworth, United Kingdom
Memory Service North
🇬🇧Sheffield, United Kingdom
The Centre for Memory and Aging
🇨🇦Toronto, Ontario, Canada
Hôpital Lariboisière
🇫🇷Paris, France
Torrance Clinical Research
🇺🇸Lomita, California, United States
Galiz Research, LLC
🇺🇸Hialeah, Florida, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Neurologic Consultants, P.A.
🇺🇸Fort Lauderdale, Florida, United States
Medical Research Group of Central Florida
🇺🇸Orange City, Florida, United States
Alexian Brothers Neurosci Inst
🇺🇸Elk Grove Village, Illinois, United States
Booker, J. Gary, MD, APMC
🇺🇸Shreveport, Louisiana, United States
iResearch Atlanta
🇺🇸Decatur, Georgia, United States
Comprehensive Clinical Development, Inc.- St. Petersburg, FL
🇺🇸Saint Petersburg, Florida, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Louisiana Research Associates
🇺🇸New Orleans, Louisiana, United States
New York University Medical Center;Child Study Center
🇺🇸New York, New York, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Raleigh Neurology Associates
🇺🇸Raleigh, North Carolina, United States
The Clinical Trial Center, LLC
🇺🇸Jenkintown, Pennsylvania, United States
University of North Texas Health Science Center
🇺🇸Fort Worth, Texas, United States
Alzheimer's Research & Clinical Programs
🇺🇸Charleston, South Carolina, United States
Radiant Research, Inc.
🇺🇸Wyomissing, Pennsylvania, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Central Coast Neurosciences Research
🇦🇺Erina, New South Wales, Australia
A.G.Mander Pty Ltd
🇦🇺Geelong, Victoria, Australia
Neurodegenerative Disorders Research
🇦🇺Subiaco, Western Australia, Australia
Capitol District Health Authority
🇨🇦Halilfax, Nova Scotia, Canada
The Medical Arts Health Research Group
🇨🇦Powell River, British Columbia, Canada
True North Clinical Research Kentville
🇨🇦Kentville, Nova Scotia, Canada
Toronto Memory Program (Neurology Research Inc.)
🇨🇦Toronto, Ontario, Canada
Institut Universitaire de gériatrie de Sherbrooke; Service de gériatrie/pavillon Argyll
🇨🇦Sherbrooke, Quebec, Canada
Clinique Neuro Rive-Sud
🇨🇦Greenfield Park, Quebec, Canada
McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
🇨🇦Verdun, Quebec, Canada
Hopital Nord Laënnec - CHU Nantes
🇫🇷Nantes, France
Hopital Neurologique Pierre Wertheimer
🇫🇷Bron, France
Thomayerova nemocnice
🇨🇿Praha 4 - Krc, Czechia
Centre Hospitalier de la côte Basque
🇫🇷Bayonne, France
Hopital des Charpennes
🇫🇷Villeurbanne, France
Hôpital de Brabois Adultes
🇫🇷Vandoeuvre-les-nancy, France
Gemeinschaftspraxis
🇩🇪Ellwangen, Germany
Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung
🇩🇪Siegen, Germany
Policlinico Universitario Agostino Gemelli; Farmacia
🇮🇹Roma, Lazio, Italy
Klinikum rechts der Isar der Technischen Universität München
🇩🇪Munchen, Germany
Fondazione Santa Lucia IRCCS
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
🇮🇹Pisa, Toscana, Italy
Università degli Studi di Genova
🇮🇹Genova, Liguria, Italy
Ajou University Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Specjal. Praktyka Lekarska; Prof. Grzegorz Opala
🇵🇱Katowice, Poland
Centrum Medyczne Dendryt
🇵🇱Katowice, Poland
Hospital General De Catalunya; Servicio de Neurologia
🇪🇸Sant Cugat del Valles, Barcelona, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo
🇸🇪Malmö, Sweden
Hospital Universitario Clínico San Carlos
🇪🇸Madrid, Spain
Umberto I Policlinico di Roma-Università di Roma La Sapienza
🇮🇹Roma, Lazio, Italy
Instytut Psychiatrii i Neurologii
🇵🇱Warszawa, Poland
Hospital General Universitario de Elche; Servicio de Farmacia
🇪🇸Elche, Alicante, Spain
Vancouver Hospital - UBC Hospital Site
🇨🇦Vancouver, British Columbia, Canada
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States