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

Alzheimer's Disease Clinical Trial

— MAyflOwer RoAD  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01677754
• Other study ID #: BP28248
• Secondary ID: 2012-000943-29
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2012
• Last updated: May 25, 2017
• Start date: October 24, 2012
• Est. completion date: June 12, 2015

Study information

• Verified date: May 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 542
• Est. completion date: June 12, 2015
• Est. primary completion date: June 12, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• RO4602522
Participants will receive RO4602522 orally once daily for 12 months.
• Placebo
Participants will receive placebo for RO4602522 orally once daily for 12 months.
• Donepezil
Stable dose as background medication
• Memantine
Stable dose as background medication in combination with AChEIs
• Rivastigmine
Stable dose as background medication
• Galantamine
Stable dose as background medication

Locations

Country	Name	City	State
Australia	Box Hill Hospital; Eastern Clinical Research Unit	Box Hill	Victoria
Australia	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	Heidelberg Repatriation Hospital	Heidelberg	Victoria
Australia	Southern Neurology	Kogarah	New South Wales
Australia	Hollywood Specialist Centre	Nedlands	Western Australia
Australia	Neurodegenerative Disorders Research	Subiaco	Western Australia
Australia	Queen Elizabeth Hospital	Woodville	South Australia
Canada	Jbn Medical Diagnostic Services Inc.	Burlington	Ontario
Canada	Recherches Neuro-Hippocame	Gatineau	Quebec
Canada	Clinique Neuro Rive-Sud	Greenfield Park	Quebec
Canada	Capitol District Health Authority	Halilfax	Nova Scotia
Canada	True North Clinical Research Kentville	Kentville	Nova Scotia
Canada	Bruyere Continuing Care	Ottawa	Ontario
Canada	Ingram, Jennifer MD	Peterborough	Ontario
Canada	The Medical Arts Health Research Group	Powell River	British Columbia
Canada	CHU de Quebec - Hôpital de l' Enfant Jésus	Quebec
Canada	Institut Universitaire de gériatrie de Sherbrooke; Service de gériatrie/pavillon Argyll	Sherbrooke	Quebec
Canada	The Centre for Memory and Aging	Toronto	Ontario
Canada	Toronto Memory Program (Neurology Research Inc.)	Toronto	Ontario
Canada	Toronto Sunnybrook Hospital	Toronto	Ontario
Canada	Vancouver Hospital - UBC Hospital Site	Vancouver	British Columbia
Canada	McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric	Verdun	Quebec
Canada	Vancouver Island Health Authority	Victoria	British Columbia
Czechia	NEUROHK s.r.o.	Chocen
Czechia	P-P Klinika	Kladno
Czechia	Supervize s.r.o.	Kutna Hora - Vnitrni Mesto
Czechia	Nemocnice Na Bulovce	Prague
Czechia	AD71 s.r.o.	Praha 10
Czechia	Clintrial,s.r.o.	Praha 10
Czechia	Thomayerova nemocnice	Praha 4 - Krc
Czechia	Psychiatry Trial s.r.o.	Praha 5
Czechia	FORBELI s.r.o.	Praha 6
Czechia	Neurologicka ambulance	Praha 6
France	Centre Hospitalier de la côte Basque	Bayonne
France	Hopital Neurologique Pierre Wertheimer	Bron
France	Hopital Nord Laënnec - CHU Nantes	Nantes
France	Hopital Cimiez; CMRR	Nice
France	Hôpital Lariboisière	Paris
France	Groupe Hospitalier Sud - Hôpital Xavier Arnozan	Pessac
France	Hôpital Maison Blanche	Reims
France	CHU Rennes - Hopital Hôtel Dieu	Rennes
France	CHU Toulouse - La Grave	Toulouse
France	CHU Tours - Hôpital Bretonneau	Tours
France	Hôpital de Brabois Adultes	Vandoeuvre-les-nancy
France	Hopital des Charpennes	Villeurbanne
Germany	Gemeinschaftspraxis	Ellwangen
Germany	Henriettenstiftung Hannover	Hannover
Germany	ISPG - Institut fuer Studien zur Psychischen Gesundheit	Mannheim
Germany	Klinikum rechts der Isar der Technischen Universität München	Munchen
Germany	Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung	Siegen
Italy	Ente Ospedaliero Ospedali Galliera	Genova	Liguria
Italy	Università degli Studi di Genova	Genova	Liguria
Italy	Nuovo Ospedale Civile S.Agostino - Estense	Modena	Emilia-Romagna
Italy	Università degli studi di Perugia	Perugia	Umbria
Italy	Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica	Pisa	Toscana
Italy	Fondazione Santa Lucia IRCCS	Roma	Lazio
Italy	Policlinico Universitario Agostino Gemelli; Farmacia	Roma	Lazio
Italy	Umberto I Policlinico di Roma-Università di Roma La Sapienza	Roma	Lazio
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Inha University Hospital; Pulmonary Medicine	Incheon
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Centrum Medyczne Dendryt	Katowice
Poland	Specjal. Praktyka Lekarska; Prof. Grzegorz Opala	Katowice
Poland	NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek	Poznan
Poland	NZOZ Syntonia	Pruszcz Gdanski
Poland	NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog	Sopot
Poland	Instytut Psychiatrii i Neurologii	Warszawa
Poland	mMED Maciej Czarnecki	Warszawa
Spain	Hospital Perpetuo Socorro, Servicio de Geriatria	Albacete
Spain	CAE Oroitu	BaraKaldo	Vizcaya
Spain	Fundació ACE	BArcelon	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital General Universitario de Elche; Servicio de Farmacia	Elche	Alicante
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Virgen del Puerto	Plasencia	Palencia
Spain	Hospital General De Catalunya; Servicio de Neurologia	Sant Cugat del Valles	Barcelona
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Sweden	Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo	Malmö
Sweden	Karolinska Universitetssjukhuset Huddinge	Stockholm
United Kingdom	Cognitive Treatment & Research Unit	Crowborough
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Glasgow Memory Clinic	Glasgow
United Kingdom	West London Cognitive Disorders Treatment and Research Unit; Lakeside Metal Health Unit	Isleworth
United Kingdom	Institute of Psychiatry	London
United Kingdom	Norwich Medical School	Norwich
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Memory Service North	Sheffield
United States	Albuquerque Neuroscience Inc.	Albuquerque	New Mexico
United States	Advanced Research Center, Inc.;In-Patient Unit	Anaheim	California
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Meridien Research	Brooksville	Florida
United States	Alzheimer's Research & Clinical Programs	Charleston	South Carolina
United States	Millennium Psychiatric Associates, LLC	Creve Coeur	Missouri
United States	iResearch Atlanta	Decatur	Georgia
United States	NeuroStudies.net, LLC	Decatur	Georgia
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Alexian Brothers Neurosci Inst	Elk Grove Village	Illinois
United States	Neurologic Consultants, P.A.	Fort Lauderdale	Florida
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	Neurology Center of North Orange County	Fullerton	California
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Galiz Research, LLC	Hialeah	Florida
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	Torrance Clinical Research	Lomita	California
United States	Miami Jewish Health Systems	Miami	Florida
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Louisiana Research Associates	New Orleans	Louisiana
United States	New York University Medical Center;Child Study Center	New York	New York
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	Compass Research East, LLC	Orlando	Florida
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Comprehensive Clinical Development, Inc.- St. Petersburg, FL	Saint Petersburg	Florida
United States	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	Neurological Research Inst	Santa Monica	California
United States	Booker, J. Gary, MD, APMC	Shreveport	Louisiana
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Northern Michigan Neurology	Traverse City	Michigan
United States	Premiere Research Institute	West Palm Beach	Florida
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina
United States	Radiant Research, Inc.	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12		Baseline, Month 12
Secondary	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
Secondary	Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12		Baseline, Month 12
Secondary	Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12		Baseline, Month 12
Secondary	Percentage of Participants With Worsening in BEHAVE-AD-FW Score		Baseline to Month 12
Secondary	Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months		Baseline, Month 12
Secondary	Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months		Baseline, Month 12
Secondary	Percentage of Participants With Worsening in ADCS-CGIC Score		Baseline to Month 12
Secondary	Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months		Baseline, Month 12
Secondary	Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months		Baseline, Month 12
Secondary	Percentage of Participants with Adverse Events		Baseline up to 13 months
Secondary	Percentage of Participants with Change in Lens Opacity Grading		Baseline; Months 6, and 12
Secondary	Percentage of Participants with Abnormal Visual Acuity Test Results		Baseline, Months 6, and 12
Secondary	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)
Secondary	Percentage of Participants Receiving Concomitant Medications		Baseline to 13 Months
Secondary	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
Secondary	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
Secondary	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
Secondary	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