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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01677754
• Collaborator: (none)
• Enrollment: 542
• Locations: 142
• Arms: 3
• Actual Duration (Months): 31.6
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: RO4602522; Drug: Placebo; Drug: Donepezil; Drug: Memantine; Drug: Rivastigmine; Drug: Galantamine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 542 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 24, 2012
• Actual Primary Completion Date: Jun 12, 2015
• Actual Study Completion Date: Jun 12, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

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

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

4. Percentage of Participants With Worsening in BEHAVE-AD-FW Score [Baseline to Month 12]

5. Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months [Baseline, Month 12]

6. Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months [Baseline, Month 12]

7. Percentage of Participants With Worsening in ADCS-CGIC Score [Baseline to Month 12]

8. Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months [Baseline, Month 12]

9. Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months [Baseline, Month 12]

10. Percentage of Participants with Adverse Events [Baseline up to 13 months]

11. Percentage of Participants with Change in Lens Opacity Grading [Baseline; Months 6, and 12]

12. Percentage of Participants with Abnormal Visual Acuity Test Results [Baseline, Months 6, and 12]

13. 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)]

14. Percentage of Participants Receiving Concomitant Medications [Baseline to 13 Months]

15. 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]

16. 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]

17. 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]

18. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Research Center, Inc.;In-Patient Unit	Anaheim	California	United States	92801
2	Neurology Center of North Orange County	Fullerton	California	United States	92835
3	Torrance Clinical Research	Lomita	California	United States	90717
4	Artemis Institute for Clinical Research, LLC	San Diego	California	United States	92103
5	Sharp Mesa Vista Hospital	San Diego	California	United States	92123
6	San Francisco Clinical Research Center	San Francisco	California	United States	94109
7	Neurological Research Inst	Santa Monica	California	United States	90025
8	Yale University School Of Medicine	New Haven	Connecticut	United States	06510
9	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut	United States	06851
10	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
11	Meridien Research	Brooksville	Florida	United States	34601
12	Brain Matters Research, Inc.	Delray Beach	Florida	United States	33445
13	Neurologic Consultants, P.A.	Fort Lauderdale	Florida	United States	33308
14	Galiz Research, LLC	Hialeah	Florida	United States	33016
15	Miami Jewish Health Systems	Miami	Florida	United States	33137
16	Medical Research Group of Central Florida	Orange City	Florida	United States	3273
17	Compass Research East, LLC	Orlando	Florida	United States	32806
18	Comprehensive Clinical Development, Inc.- St. Petersburg, FL	Saint Petersburg	Florida	United States	33716
19	Axiom Clinical Research of Florida	Tampa	Florida	United States	33609
20	Premiere Research Institute	West Palm Beach	Florida	United States	33407
21	iResearch Atlanta	Decatur	Georgia	United States	30030
22	NeuroStudies.net, LLC	Decatur	Georgia	United States	30033
23	Alexian Brothers Neurosci Inst	Elk Grove Village	Illinois	United States	60007
24	Louisiana Research Associates	New Orleans	Louisiana	United States	70114
25	Booker, J. Gary, MD, APMC	Shreveport	Louisiana	United States	71104-2136
26	Northern Michigan Neurology	Traverse City	Michigan	United States	49684
27	Hattiesburg Clinic	Hattiesburg	Mississippi	United States	39401
28	Millennium Psychiatric Associates, LLC	Creve Coeur	Missouri	United States	63141
29	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey	United States	07724
30	Albuquerque Neuroscience Inc.	Albuquerque	New Mexico	United States	87109
31	New York University Medical Center;Child Study Center	New York	New York	United States	10016
32	Richmond Behavioral Associates	Staten Island	New York	United States	10312
33	Raleigh Neurology Associates	Raleigh	North Carolina	United States	27607-6520
34	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina	United States	27103
35	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
36	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
37	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
38	Radiant Research, Inc.	Wyomissing	Pennsylvania	United States	19610
39	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island	United States	02914
40	Rhode Island Hospital	Providence	Rhode Island	United States	02903
41	Alzheimer's Research & Clinical Programs	Charleston	South Carolina	United States	29425
42	University of North Texas Health Science Center	Fort Worth	Texas	United States	76107
43	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
44	Central Coast Neurosciences Research	Erina	New South Wales	Australia	2250
45	Southern Neurology	Kogarah	New South Wales	Australia	2217
46	Queen Elizabeth Hospital	Woodville	South Australia	Australia	5011
47	Box Hill Hospital; Eastern Clinical Research Unit	Box Hill	Victoria	Australia	3128
48	A.G.Mander Pty Ltd	Geelong	Victoria	Australia	3220
49	Heidelberg Repatriation Hospital	Heidelberg	Victoria	Australia	3084
50	Hollywood Specialist Centre	Nedlands	Western Australia	Australia	6009
51	Neurodegenerative Disorders Research	Subiaco	Western Australia	Australia	6008
52	The Medical Arts Health Research Group	Powell River	British Columbia	Canada	V8A 3B6
53	Vancouver Hospital - UBC Hospital Site	Vancouver	British Columbia	Canada	V6T 2B5
54	Vancouver Island Health Authority	Victoria	British Columbia	Canada	V8R 1J8
55	Capitol District Health Authority	Halilfax	Nova Scotia	Canada	B3H 2E1
56	True North Clinical Research Kentville	Kentville	Nova Scotia	Canada	B4N 4K9
57	Jbn Medical Diagnostic Services Inc.	Burlington	Ontario	Canada	L7M 4Y1
58	Bruyere Continuing Care	Ottawa	Ontario	Canada	K1N 5C8
59	Ingram, Jennifer MD	Peterborough	Ontario	Canada	K9H 3S1
60	Toronto Memory Program (Neurology Research Inc.)	Toronto	Ontario	Canada	M3B 2S7
61	The Centre for Memory and Aging	Toronto	Ontario	Canada	M4G 3E8
62	Toronto Sunnybrook Hospital	Toronto	Ontario	Canada	M4N 3M5
63	Recherches Neuro-Hippocame	Gatineau	Quebec	Canada	J8T 8J1
64	Clinique Neuro Rive-Sud	Greenfield Park	Quebec	Canada	J4V 2J2
65	Institut Universitaire de gériatrie de Sherbrooke; Service de gériatrie/pavillon Argyll	Sherbrooke	Quebec	Canada	J1J 3H5
66	McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric	Verdun	Quebec	Canada	H4H 1R3
67	CHU de Quebec - Hôpital de l' Enfant Jésus	Quebec		Canada	G1J 1Z4
68	NEUROHK s.r.o.	Chocen		Czechia	565 01
69	P-P Klinika	Kladno		Czechia	272 80
70	Supervize s.r.o.	Kutna Hora - Vnitrni Mesto		Czechia	284 01
71	Nemocnice Na Bulovce	Prague		Czechia	180 01
72	Clintrial,s.r.o.	Praha 10		Czechia	100 00
73	AD71 s.r.o.	Praha 10		Czechia	102 00
74	Thomayerova nemocnice	Praha 4 - Krc		Czechia	140 59
75	Psychiatry Trial s.r.o.	Praha 5		Czechia	158 00
76	Neurologicka ambulance	Praha 6		Czechia	16000
77	FORBELI s.r.o.	Praha 6		Czechia	165 00
78	Centre Hospitalier de la côte Basque	Bayonne		France	64109
79	Hopital Neurologique Pierre Wertheimer	Bron		France	69500
80	Hopital Nord Laënnec - CHU Nantes	Nantes		France	44093
81	Hopital Cimiez; CMRR	Nice		France	06003
82	Hôpital Lariboisière	Paris		France	75475
83	Groupe Hospitalier Sud - Hôpital Xavier Arnozan	Pessac		France	33604
84	Hôpital Maison Blanche	Reims		France	51092
85	CHU Rennes - Hopital Hôtel Dieu	Rennes		France	35064
86	CHU Toulouse - La Grave	Toulouse		France	31059
87	CHU Tours - Hôpital Bretonneau	Tours		France	37044
88	Hôpital de Brabois Adultes	Vandoeuvre-les-nancy		France	54511
89	Hopital des Charpennes	Villeurbanne		France	69100
90	Gemeinschaftspraxis	Ellwangen		Germany	73479
91	Henriettenstiftung Hannover	Hannover		Germany	30559
92	ISPG - Institut fuer Studien zur Psychischen Gesundheit	Mannheim		Germany	68165
93	Klinikum rechts der Isar der Technischen Universität München	Munchen		Germany	81675
94	Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung	Siegen		Germany	57072
95	Nuovo Ospedale Civile S.Agostino - Estense	Modena	Emilia-Romagna	Italy	41126
96	Policlinico Universitario Agostino Gemelli; Farmacia	Roma	Lazio	Italy	00168
97	Fondazione Santa Lucia IRCCS	Roma	Lazio	Italy	00179
98	Umberto I Policlinico di Roma-Università di Roma La Sapienza	Roma	Lazio	Italy	00185
99	Ente Ospedaliero Ospedali Galliera	Genova	Liguria	Italy	16128
100	Università degli Studi di Genova	Genova	Liguria	Italy	16132
101	Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica	Pisa	Toscana	Italy	56126
102	Università degli studi di Perugia	Perugia	Umbria	Italy	06126
103	Dong-A University Hospital	Busan		Korea, Republic of	49201
104	Seoul National University Bundang Hospital	Gyeonggi-do		Korea, Republic of	13620
105	Ajou University Hospital	Gyeonggi-do		Korea, Republic of	443-380
106	Inha University Hospital; Pulmonary Medicine	Incheon		Korea, Republic of	400-711
107	Kyung Hee University Hospital	Seoul		Korea, Republic of	02447
108	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
109	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
110	Konkuk University Medical Center	Seoul		Korea, Republic of	05030
111	Samsung Medical Center	Seoul		Korea, Republic of	06351
112	Podlaskie Centrum Psychogeriatrii	Bialystok		Poland	15-732
113	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
114	Specjal. Praktyka Lekarska; Prof. Grzegorz Opala	Katowice		Poland	40-588
115	Centrum Medyczne Dendryt	Katowice		Poland	40-684
116	NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek	Poznan		Poland	61-289
117	NZOZ Syntonia	Pruszcz Gdanski		Poland	83-000
118	NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog	Sopot		Poland	81-717
119	mMED Maciej Czarnecki	Warszawa		Poland	01-697
120	Instytut Psychiatrii i Neurologii	Warszawa		Poland	02-957
121	Hospital General Universitario de Elche; Servicio de Farmacia	Elche	Alicante	Spain	03203
122	Fundació ACE	BArcelon	Barcelona	Spain	08034
123	Hospital General De Catalunya; Servicio de Neurologia	Sant Cugat del Valles	Barcelona	Spain	8195
124	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
125	Hospital Virgen del Puerto	Plasencia	Palencia	Spain	10600
126	Hospital Universitario Virgen Macarena	Seville	Sevilla	Spain	41071
127	CAE Oroitu	BaraKaldo	Vizcaya	Spain	48903
128	Hospital Perpetuo Socorro, Servicio de Geriatria	Albacete		Spain	2006
129	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
130	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
131	Hospital Universitario Clínico San Carlos	Madrid		Spain	28040
132	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
133	Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo	Malmö		Sweden	205 02
134	Karolinska Universitetssjukhuset Huddinge	Stockholm		Sweden	171 64
135	Cognitive Treatment & Research Unit	Crowborough		United Kingdom	TN6 1HB
136	Ninewells Hospital	Dundee		United Kingdom	DD12 9SY
137	Glasgow Memory Clinic	Glasgow		United Kingdom	G20 0XA
138	West London Cognitive Disorders Treatment and Research Unit; Lakeside Metal Health Unit	Isleworth		United Kingdom	TW7 6FY
139	Institute of Psychiatry	London		United Kingdom	SE5 8AF
140	Norwich Medical School	Norwich		United Kingdom	NR4 7UY
141	Derriford Hospital	Plymouth		United Kingdom	PL6 8DH
142	Memory Service North	Sheffield		United Kingdom	S35 8QS

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01677754
• Other Study ID Numbers: BP28248; 2012-000943-29
• First Posted: Sep 3, 2012
• Last Update Posted: May 30, 2017
• Last Verified: May 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease; Memantine; Rivastigmine; Donepezil; Galantamine

Study Results

No Results Posted as of May 30, 2017