A Study of RO4917838 in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia (NN25310)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01192867

Collaborator

(none)

629

Enrollment

122

Locations

Arms

41.5

Actual Duration (Months)

5.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multi-center, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4917838 in participants with persistent, predominant negative symptoms of schizophrenia. Participants, on stable treatment with antipsychotics, will be randomized to receive daily oral doses of RO4917838 or matching placebo for 56 weeks (treatment period 1 of 24 weeks and treatment period 2 of 32 weeks), followed by an optional treatment extension for up to 3 years. After 52 weeks, participants who were originally randomized to an active treatment will be randomly assigned to receive either placebo or continue on the originally assigned study treatment for 4 weeks washout period (Week 52 to Week 56) for the assessment of potential withdrawal effects in a blinded manner using participants staying on active treatment as a control. Participants initially randomized to placebo will remain on placebo. After 56 weeks, participants who were switched to placebo in the washout period will return to their blinded, active treatment arm.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Placebo Drug: RO4917838 Drug: Antipshychotics (Standard of Care)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

629 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase III, Multi-Center, Randomized, 24 Week, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate Efficacy and Safety of RO4917838 in Stable Patients With Persistent, Predominant Negative Symptoms of Schizophrenia Treated With Antipsychotics Followed by a 28 Week, Double-Blind Treatment Period

Actual Study Start Date :

Dec 11, 2010

Actual Primary Completion Date :

May 26, 2014

Actual Study Completion Date :

May 26, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RO4917838 20 milligrams (mg) Participants, on stable antipsychotics, will receive RO4917838 orally at 20 mg once daily (QD) up to 56 weeks followed by an optional treatment extension for up to 3 years.	Drug: RO4917838 RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks. Drug: Antipshychotics (Standard of Care) Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.
Experimental: RO4917838 10 mg Participants, on stable antipsychotics, will receive RO4917838 orally at 10 mg QD up to 56 weeks followed by an optional treatment extension for up to 3 years.	Drug: RO4917838 RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks. Drug: Antipshychotics (Standard of Care) Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.
Placebo Comparator: Placebo Participants, on stable antipsychotics, will receive RO4917838 matching placebo orally QD up to 56 weeks.	Drug: Placebo Placebo will be administered orally QD for 56 weeks Drug: Antipshychotics (Standard of Care) Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.

Arm

Intervention/Treatment

Experimental: RO4917838 20 milligrams (mg)

Participants, on stable antipsychotics, will receive RO4917838 orally at 20 mg once daily (QD) up to 56 weeks followed by an optional treatment extension for up to 3 years.

Drug: RO4917838

RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks.

Drug: Antipshychotics (Standard of Care)

Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.

Experimental: RO4917838 10 mg

Participants, on stable antipsychotics, will receive RO4917838 orally at 10 mg QD up to 56 weeks followed by an optional treatment extension for up to 3 years.

Drug: RO4917838

RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks.

Drug: Antipshychotics (Standard of Care)

Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.

Placebo Comparator: Placebo

Participants, on stable antipsychotics, will receive RO4917838 matching placebo orally QD up to 56 weeks.

Drug: Placebo

Placebo will be administered orally QD for 56 weeks

Drug: Antipshychotics (Standard of Care)

Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.

Outcome Measures

Primary Outcome Measures

Change From Baseline in the Positive and Negative Symptoms Scales (PANSS) Negative Symptoms Factor Score at Week 24 (All-Participant Population) [Baseline, Week 24]
Percentage of Participants With Adverse Events (All-Participant Population) [Week 24]

Secondary Outcome Measures

Change From Baseline in the PANSS Negative Symptoms Factor Score at Week 24 (Complement Factor H Related Protein 1 High [CFHR1-High] Subgroup Population) [Baseline, Week 24]
Change From Baseline in the Personal and Social Performance (PSP) Total Score at Week 24 (All-Participant Population) [Baseline, Week 24]
Change From Baseline in the PSP Total Score at Week 24 (CFHR1-High Subgroup Population) [Baseline, Week 24]
Change From Baseline in the PANSS Total Score at Week 24 (All-Participant Population) [Baseline, Week 24]
Change From Baseline in the PANSS Total Score at Week 24 (CFHR1-High Subgroup Population) [Baseline, Week 24]
Change From Baseline in the PANSS Factor Score at Week 24 (All-Participant Population) [Baseline, Week 24]
Change From Baseline in the PANSS Factor Score at Week 24 (CFHR1-High Subgroup Population) [Baseline, Week 24]
Change From Baseline in the PANSS Subscale Scores at Week 24 (All-Participant Population) [Baseline, Week 24]
Change From Baseline in the PANSS Subscale Scores at Week 24 (CFHR1-High Subgroup Population) [Baseline, Week 24]
Percentage of Participants Who Have at least 20 Percent (%) Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 (All-Participant Population) [Baseline, Week 24]
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 (CFHR1-High Subgroup Population) [Baseline, Week 24]
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score for Two out of Three Assessments During 24 Weeks (All-Participant Population) [Baseline up to Week 24]
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score for Two out of Three Assessments During 24 Weeks (CFHR1-High Subgroup Population) [Baseline up to Week 24]
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on Clinical Global Impression - Improvement (CGI-I) Score (All-Participant Population) [Baseline, Week 24]
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score (CFHR1 Subgroup Population) [Baseline, Week 24]
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score for Two out of Three Assessments During 24 Weeks (All-Participant Population) [Baseline up to Week 24]
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score for Two out of Three Assessments During 24 Weeks (CFHR1 Subgroup Population) [Baseline up to Week 24]
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population) [Baseline, Week 24]
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population) [Baseline, Week 24]
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score for Two out of Three Assessments During 24 Weeks (All-Participant Population) [Baseline up to Week 24]
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score for Two out of Three Assessments During 24 Weeks (CFHR1 Subgroup Population) [Baseline up to Week 24]
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 and Improvement in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population) [Baseline, Week 24]
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 and Improvement in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population) [Baseline, Week 24]
Change From Baseline in Severity of Illness Based on Clinical Global Impression - Severity (CGI-S) Overall Score (All-Participant Population) [Baseline, Week 24]
Change From Baseline in Severity of Illness Based on CGI-S Overall Score (CFHR1 Subgroup Population) [Baseline, Week 24]
Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (All-Participant Population) [Baseline, Week 24]
Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (CFHR1 Subgroup Population) [Baseline, Week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of schizophrenia of paranoid, disorganized, residual, undifferentiated or catatonic subtype
Predominant negative symptoms
With the exception of clozapine, participants are on any of the available marketed atypical or typical antipsychotics (treatment with a maximum of two antipsychotics)

Exclusion Criteria:

Evidence that participant has clinically significant, uncontrolled and unstable disorder (e.g. cardiovascular, renal, hepatic disorder)
Body Mass Index (BMI) of less than (<) 17 or greater than (>) 40 kilograms per meter square (kg/m^2)
Depressive symptoms, defined as a score of 9 or greater on the Calgary Depression Rating Scale for Schizophrenia (CDSS)
A severity score of 3 or greater on the Parkinsonism item of the Exrapyramidal Symptoms Rating Scale-Abbreviated (ESRS-A) (Clinical Global Impression, Parkinsonism)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	K&S Professional Research Services LLC	Little Rock	Arkansas	United States	72201
2	Advanced Research Center Inc.	Anaheim	California	United States	92805
3	Comprehensive Clinical Development- Cerritos CA	Cerritos	California	United States	90703
4	Diligent Clinical Trials Inc	Downey	California	United States	90241
5	Care Research Center	La Palma	California	United States	90623
6	Pasadena Research Institute	Pasadena	California	United States	91106
7	CNRI - Los Angeles, LLC	Pico Rivera	California	United States	90660
8	Pharmax Research Clinic Inc.	Miami	Florida	United States	33126
9	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
10	American Medical Research, Inc	Oak Brook	Illinois	United States	60523
11	University of Iowa College of Medicine; Psychiatry Research	Iowa City	Iowa	United States	52242
12	Clinical Insights, Inc.	Glen Burnie	Maryland	United States	21061
13	St Louis Clinical Trials	Saint Louis	Missouri	United States	63141
14	Ocean Rheumatology	Toms River	New Jersey	United States	08775
15	CRI Worldwide LLC	Willingboro	New Jersey	United States	08046
16	Raymond G. Murphy VA Medical Center	Albuquerque	New Mexico	United States	87108
17	Behavioral Medical Research of Brooklyn	Brooklyn	New York	United States	11201
18	Comprehensive NeuroScience	Fresh Meadows	New York	United States	11366
19	North Carolina Psychiatric Research Center	Raleigh	North Carolina	United States	27603
20	UC Health Clinical Trials Office	Cincinnati	Ohio	United States	45267
21	Belmont Center for Comprehensive Treatment; Research	Philadelphia	Pennsylvania	United States	19131
22	Claghorn-Lesem Research Clinic, Inc.	Bellaire	Texas	United States	77401
23	FutureSearch Clinical Trials, LP	Dallas	Texas	United States	75231
24	Pillar Clinical Research LLC	Dallas	Texas	United States	75243
25	Family Psychiatry of the Woodlands P.A.	The Woodlands	Texas	United States	77381
26	Pacific Institute of Medical Sciences	Bothell	Washington	United States	98011
27	Eastside Therapeutic Resource	Kirkland	Washington	United States	98033
28	Centro SERES	Buenos Aires		Argentina	1425
29	Fundacion para el Estudio y Tratamiento des las Enfi Mentales	Buenos Aires		Argentina	C1425AHQ
30	Mulieris	Caba		Argentina	C1022AAO
31	Facene Fund.Argentina Contra Enferm.Neur.Del Envejecimiento	Ciudad Autonoma Bs As		Argentina	1117
32	Instituto Nacional de Psicopatologia	Ciudad Autonoma Bs As		Argentina	1405
33	Resolution Psicopharmacology Research Institute	Ciudad de Mendoza		Argentina	5500
34	Instituto DAMIC - Fundación Rusculleda	Cordoba		Argentina	5003
35	Sanatorio Prof.Leon.S.Morra S.A	Cordoba		Argentina	X5009BIN
36	Instituto de Neurociencias San Agustín S.A.	La Plata		Argentina	1900
37	Centro de Psiquiatria Biologica Professor Julio J. Herrera; Psiquiatria	Mendoza		Argentina	5500
38	Centro de Asistencia e Investigación en Neurociencias	Mendoza		Argentina
39	CIAP - Centro de Investigacion y Asistencia en Psiquiatria	Rosario		Argentina	S2000QJI
40	Centro de Investigacion Clinica Farmacologica en Psiquiatria	Santiago del Estero		Argentina	4200
41	Westmead Hospital; Department of Psychiatry	Westmead	New South Wales	Australia	2145
42	Monash Medical Centre-Clayton Campus; School of Psychology and Psychiatry	Clayton	Victoria	Australia	3168
43	Frankston Hospital; Mental Health Service	Frankston	Victoria	Australia	3199
44	The Alfred Hospital; Monash Alfred Psychiatry Research Centre (MAP-RC)	Melbourne	Victoria	Australia	3004
45	Centro de Investigaciones y Proyectos en Neurociencias CIPNA	Barranquilla		Colombia
46	E.S.E. Hospital Mental de Antioquia	Bello		Colombia
47	Centro de Investigaciones del Sistema Nervioso Limitada - Gr	Bogota		Colombia
48	Privater	Kuopio		Finland	70100
49	Centre Hospitalier Universitaire Caen; Pôle Psychiatrie - Addictologie	Caen		France	14033
50	CHU Gabriel Montpied; Service de Psychiatrie	Clermont-ferrand		France	63000
51	Centre Hospitalier Specialise du Jura	Dole		France	39100
52	Cabinet Médical Ambroise Paré	Elancourt		France	78990
53	Hôpital de la Conception; Pôle Psychiatrique Centre	Marseille		France	13005
54	CHU Strasbourg Nouvel Hôpital Civil;Service de Psychiatrie I	Strasbourg		France	67091
55	Hopital Chalucet; Unite de Psychiatrie	Toulon		France	83000
56	Dr. Kenessey Albert Hospital; Psychiatry I.	Balassagyarmat		Hungary	2660
57	Fov.Onk.Szt Janos Korh. E-Budai Egyesitett Korhazai; Pszichiatriaci rehabilitacio	Budapest		Hungary	1032
58	Semmelweis Egyetem AOK; Pszichiatriai es Pszichoterapias Klinika	Budapest		Hungary	1082
59	Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichatria II	Budapest		Hungary	1135
60	Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichiatria I.	Budapest		Hungary	1135
61	UNO Medical Trials Kft.	Budapest		Hungary	1135
62	Petz Aladar Megyei Oktato Korhaz; Pszichiatria I.	Gyor		Hungary	9024
63	Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek	Gyula		Hungary	5703
64	Samvedna Hospitals; Samvedana Psychiatry and Sex Therapy Hospital	Ahmedabad		India	380006
65	Sneh Clinic	Ahmedabad		India	380008
66	Gujarat Institute of Psychological Research (GIPS)	Ahmedabad		India	380015
67	Mental Health Care & Research	Jaipur		India	302017
68	R. K.Yadav Memorial Mental Health & De-Addiction Hospital	Jaipur		India	302021
69	Manav Neuropsychiatric Hospital Pvt. Ltd.	Kalyan		India	421301
70	Kasturba Medical College & Hospital	Mangalore		India	575001
71	K. S. Hegde Medical Academy	Mangalore		India	575018
72	Poona Hospital and Research Centre	Pune		India	411030
73	Brij Psychiatry Hospital & Muskaan Research Centre; Maanav Health Foundation	Vadodara		India	390001
74	Inje University Busan Paik Hospital	Busan		Korea, Republic of	47392
75	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
76	Korea University Ansan Hospital	Gyeonggi-do		Korea, Republic of	15355
77	Inha University Hospital	Incheon		Korea, Republic of	22332
78	Gil Hospital. Gachon University	Incheon		Korea, Republic of	405-760
79	Chonbuk National Uni Hospital	Jeollabuk-do		Korea, Republic of	561-712
80	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
81	Seoul National University Hospital	Seoul		Korea, Republic of	03080
82	The Catholic University of Korea St.Mary's Hospital	Seoul		Korea, Republic of	150-713
83	Arete Proycectos y Administracion S.C	Mexico		Mexico	05300
84	Centro de Investigacion Medica S.C; Hospital Santa Cecilia de Monterrey S.A. de C.V.	Monterrey		Mexico	64000
85	Medikalink	Monterrey		Mexico	64060
86	Instituto de informacion e investigacion en salud mental AC	Monterrey		Mexico	64710
87	Hospital Lomas de San Luis Internacional	San Luis Potosi		Mexico	72818
88	Spitalul Clinic Judetean Arad; Departamentul de Psihiatrie	Arad		Romania	310022
89	Spit Univ Urgenta Militar Dr. Carol Davila; Sectia Psihiatrie	Bucuresti		Romania	010825
90	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Clinical III Psihiatrie	Bucuresti		Romania	041914
91	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Comunitara si Reintegrare Psihosociala	Bucuresti		Romania	041914
92	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Sectia Clinica XIII Psihiatrie	Bucuresti		Romania	041914
93	Spitalul Clinic Judetean de Urgenta Cluj; Sectia Clinica de Psihiatrie III	Cluj-Napoca		Romania	400012
94	Spitalul Universitar de Psihiatrie Socola	Lasi		Romania	700282
95	Spitalul Clinic Municipal Dr. Gavril Curteanu; Sectia Clinica Psihiatrie I	Oradea		Romania	410154
96	Spitalul de Psihiatrie Dr. Gh. Preda Sibiu;CSM Adulti Sibiu	Sibiu		Romania	550082
97	Cabinet Medical S.C. Lorentina 2102 S.R.L.; Psihiatrie	Targouiste		Romania	130081
98	Kemerovo Regional Clinical Psychiatric Hospital	Kemerovo		Russian Federation	650036
99	GUZ Lipetsk Regional psychoneurological Hospital #1; Dispansary Department	Lipetsk		Russian Federation	399313
100	Moscow Region Psychiatric Hospital #5	Moscow Region		Russian Federation	142601
101	Scientifically Research Institute of Psychiatry of Ministry of Health of the Russian Federation	Moscow		Russian Federation	107076
102	Institution of RAMS (Mental Health Research Center of RAMS)	Moscow		Russian Federation	115522
103	Federal State Institution Moscow SRI of Psychiatry of Minzdravsocrazvitia	Moscow		Russian Federation	117995
104	Central Moscow Regional Clinical Psychiatric Hospital	Moscow		Russian Federation	127083
105	City Clinical Psychiatry Hospital #1	Nizhny Novgorod		Russian Federation	603155
106	Military Medical Academy	Saint Petersburg		Russian Federation	194044
107	Samara Psychiatric Hospital	Samara		Russian Federation	443016
108	Mhi City Clinical Hospital #2 Named After v.i. Razumousky	Sartatov		Russian Federation	410028
109	St. Petersburg State Healthcare Institution	St Petersbourg		Russian Federation	190005
110	St. Petersburg GUZ City Psychiatric Hospital #6	St Petersburg		Russian Federation	193167
111	St. Petersburg State Healthcare Institution "City Mental Hospital #3; I.I. Skvortsov-Stepanov	St Petersburg		Russian Federation	197341
112	City Psychiatric Hospital #2 of St. Nikolay Chudotvorets	St. Petersburg		Russian Federation	190121
113	Saint Petersburg Psychoneurological Research Institute of Roszdrav n.a. Bekhterev	St. Petersburg		Russian Federation	192019
114	Arkhangelsk Regional Clinical Psychiatric Hospital	Talagi		Russian Federation	163530
115	Tomsk Clinical Psychiatric Hospital	Tomsk		Russian Federation	634014
116	Integrerad Närsjukvård i Malmö	Malmö		Sweden	21135
117	Karolinska Universitetssjukhuset Huddinge, Psykiatri Sydväst	Stockholm		Sweden	14186
118	Danderyds Sjukhus AB; PRIMA Vuxenpsykiatri	Stockholm		Sweden	18288
119	Akademiska Sjukhuset; Psykosvård och rättspsykiatrisk vård	Uppsala		Sweden	75185
120	Royal Edinburgh Hospital; Psychiatry	Edinburgh		United Kingdom	EH10 5HF
121	Institute of Pyschiatry	London		United Kingdom	SE5-8AF
122	Wareneford Hospital	Oxford		United Kingdom	OX3 7JX

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:

NCT01192867

Other Study ID Numbers:

NN25310
2010-020370-42

First Posted:

Sep 1, 2010

Last Update Posted:

Jun 26, 2017

Last Verified:

Jun 1, 2017

Additional relevant MeSH terms:

Schizophrenia

Study Results

No Results Posted as of Jun 26, 2017