PERFlexS: An Efficacy, Safety And Tolerability Study of Flexibly Dosed Paliperidone Extended Release (ER) in Participants With Schizophrenia

Sponsor

Janssen-Cilag International NV (Industry)

Overall Status

Completed

CT.gov ID

NCT00460512

Collaborator

(none)

1,814

Enrollment

236

Locations

Arm

154.3

Actual Duration (Months)

7.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to explore tolerability, safety and effectiveness of flexibly dosed paliperidone extended release (ER) in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) previously unsuccessfully treated with an oral antipsychotic medication.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Paliperidone ER	Phase 3

Detailed Description

This is a non-randomized (the study drug is not assigned by chance), single arm, multicenter (when more than one hospital or medical school team work on a medical research study) 6-month study. Participants can be transitioned to an effective dose of paliperidone ER from any oral antipsychotic medication due to lack of efficacy, lack of tolerability or safety, lack of compliance or other reason. A transition period of maximum 4 weeks will be allowed. Throughout the study, participants will receive flexible dose of 3 to 12 milligram (mg) of paliperidone once daily orally for 6 months. Adjustment of the dosage will be done at Investigator's discretion, based on the individual participant's clinical response and tolerability of the study drug dosages. Participants who complete this 6-month study and would like to continue will be eligible to be enrolled in an extension phase until paliperidone ER is available. The starting dose of the extension phase will be the same as at the end of the 6-month study and may be changed throughout the extension period. The extension phase will consist of a main extension phase (ending with an End of Main Extension Phase Visit) and a modified extension phase (ending with an End of Study Visit). Efficacy will primarily be evaluated by positive and negative syndrome scale (PANSS). Safety will primarily be evaluated by Extrapyramidal Symptom Rating Scale (ESRS).

Study Design

Study Type:

Interventional

Actual Enrollment :

1814 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Prospective Trial to Explore the Tolerability, Safety and Efficacy of Flexibly Dosed Paliperidone ER in Subjects With Schizophrenia

Actual Study Start Date :

Apr 25, 2007

Actual Primary Completion Date :

Jan 22, 2009

Actual Study Completion Date :

Mar 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paliperidone Extended Release (ER)	Drug: Paliperidone ER Paliperidone ER tablet in dose range of 3 to12 milligram (mg) per day was given orally for 6 months as per Investigator's discretion to participants who transitioned to Paliperidone ER from other oral antipsychotics due to lack of efficacy, lack of tolerability, lack of compliance or other reasons.

Arm

Intervention/Treatment

Experimental: Paliperidone Extended Release (ER)

Drug: Paliperidone ER

Paliperidone ER tablet in dose range of 3 to12 milligram (mg) per day was given orally for 6 months as per Investigator's discretion to participants who transitioned to Paliperidone ER from other oral antipsychotics due to lack of efficacy, lack of tolerability, lack of compliance or other reasons.

Outcome Measures

Primary Outcome Measures

Percentage of Participants With at Least 20 Percent Improvement in Total Positive and Negative Syndrome Scale (PANSS) Score in Those Participants who Transitioned due to Lack of Efficacy [Endpoint (up to Week 26)]
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.

Secondary Outcome Measures

Percentage of Participants With at Least 20 Percent Improvement in Total Positive and Negative Syndrome Scale (PANSS) Score [Endpoint (up to Week 26)]
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). Positive subscale score ranges from 7 (absent) to 49 (extreme psychopathology), negative subscale score ranges from 7 (absent) to 49 (extreme psychopathology) and general psychopathology subscale score ranges from 16 (absent) to 112 (extreme psychopathology).
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Marder PANSS subscales include positive symptoms subscale consisting of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consisting of 7 items with total score range of 7-49; and uncontrolled hostility/excitement subscale and anxiety/depression subscale, each consisting of 4 items with total score range of 4-28. Higher score indicates greater severity.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The CGI-S rating scale assesses the severity of a participant's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe).
Change From Baseline in Total Personal and Social Performance (PSP) Score at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The PSP scale assesses the degree of dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 6, very severe) in each of the 4 domains. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less or equal to 30, functioning so poorly as to require intensive supervision.
Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The SF-36 is a health status survey with 36 questions measuring 8 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) that are subsequently aggregated into 2 summary scales, Physical Component Summary (PCS) and Mental Component Summary (MCS). Each item is scored into on a 0-100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state.
Number of Participants With Satisfaction With the Study Treatment [Endpoint (up to Week 26)]
Participants will assess their satisfaction with paliperidone ER on a 5-point scale: 1 (very good), 2 (good), 3 (moderate), 4 (poor) and 5 (very poor).
Change From Baseline in Sleep and Daytime Drowsiness Evaluation Score at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The Sleep and Daytime Drowsiness Evaluation Scale is a self-administered scale that rates quality of sleep and daytime drowsiness. Participants indicate on an 11 point scale how well they have slept in the previous 7 days, score ranging from 0 (very badly) to 10 (very well) and how often they have felt drowsy within the previous 7 days, score ranging from 0 (not at all) to 10 (all the time).
Change From Baseline in Extrapyramidal Symptoms Rating Scale (ESRS) Total Score at Endpoint (up to Week 26) [Baseline and endpoint (up to Week 26)]
The ESRS scale assesses parkinsonism (slow movements), dystonia (abnormal muscle movement causing focal/generalized, sustained muscle contractions, postures, and involuntary movements) and dyskinetic (involuntary muscle contractions) movement subscale. Parkinsonism consists of 8 items rated on a 7-point scale (0=absent/normal and 6=worst score), Dystonia consists of 2 items rated on a 7-point scale (0=absent and 6=extremely severe) and Dyskinetic movements consists of 7 items rated on a 7-point scale (0=none and 6=worst score). Total score: 0-102. Lower scores indicate better condition.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant meets the Diagnostic and Statistical Manual of Mental Disorders (Edition

criteria for schizophrenia

Participant is previously non-acute (on the same antipsychotic medication used for the treatment of schizophrenia and Clinical Global Impression-Severity [CGI-S] change less than or equal to 1 in the past 4 weeks before enrollment) and has been given an adequate dose of an appropriate oral antipsychotic for an adequate period of time prior to enrollment, but previous treatment is considered unsuccessful due to one or more of the following reasons: lack of effectiveness, lack of tolerability or safety, lack of compliance and/or other reasons to switch to another antipsychotic medication
Participant is healthy on the basis of a physical examination and vital signs at screening
Female participants must be postmenopausal for at least 1 year, surgically sterile, abstinent, or, if sexually active, agree to practice an effective method of birth control before entry and throughout the study
Participants must be willing and able to fill out self-administered questionnaires

Exclusion Criteria:

Participants on clozapine, any conventional depot neuroleptic or risperidone long-acting injection during the last 3 months
Participants with serious unstable medical condition, including known clinically relevant laboratory abnormalities
Participants with history or current symptoms of tardive dyskinesia (twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body) and neuroleptic malignant syndrome (high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness)
Participants judged to be at high risk for adverse events, violence or self-harm
Participants with a current use or known history (over the past 6 months) of substance dependence according to Diagnostic and Statistical Manual of Mental Disorders (Edition

Criteria

Contacts and Locations

Locations

	City	Country
1	Antwerpen	Belgium
2	Bertrix	Belgium
3	Dave	Belgium
4	Diest	Belgium
5	Duffel	Belgium
6	Kortenberg	Belgium
7	Liège	Belgium
8	Montignies-sur-Sambre	Belgium
9	Mortsel	Belgium
10	Roeselare	Belgium
11	Saint Denijs-Westrem	Belgium
12	Saint-Servais	Belgium
13	Sint-Truiden	Belgium
14	Tielt	Belgium
15	Waregem	Belgium
16	Bulgaria	Bulgaria
17	Sofia N/a	Bulgaria
18	Tzerova Korya	Bulgaria
19	Osijek	Croatia
20	Rijeka	Croatia
21	Split	Croatia
22	Zagreb	Croatia
23	Aalborg	Denmark
24	Helsingør	Denmark
25	Risskov N/a	Denmark
26	Viby J	Denmark
27	Helsinki	Finland
28	Raahe	Finland
29	Tammisaari	Finland
30	Tampere	Finland
31	Bar Le Duc	France
32	Bordeaux	France
33	Bourg En Bresse	France
34	Bully Les Mines	France
35	Caen	France
36	Chambery	France
37	Clermont Ferrand Cedex 1	France
38	Creteil Cedex	France
39	Dijon Cedex	France
40	Dole	France
41	Henin Baumont	France
42	Jarnac	France
43	La Roche Sur Yon	France
44	La Seyne Sur Mer	France
45	Mont St Martin	France
46	Montpellier	France
47	Nimes Cedex 9	France
48	Paris	France
49	Pau	France
50	Rennes	France
51	Roubaix	France
52	Saint Avé	France
53	Saint-Cyr Au Mont D'or N/a	France
54	St Germain En Laye	France
55	Villejuif Cedex	France
56	Aalen	Germany
57	Achim	Germany
58	Augsburg	Germany
59	Bamberg	Germany
60	Bergfelde	Germany
61	Bergheim	Germany
62	Berlin	Germany
63	Bochum	Germany
64	Butzbach	Germany
65	Chemnitz	Germany
66	Coesfeld	Germany
67	Darmstadt	Germany
68	Dillingen	Germany
69	Dresden	Germany
70	Duisburg	Germany
71	Düsseldorf	Germany
72	Ebensfeld	Germany
73	Eberbach	Germany
74	Ellwangen	Germany
75	Elmshorn	Germany
76	Essen	Germany
77	Ettlingen	Germany
78	Freiburg	Germany
79	Gelnhausen	Germany
80	Gelsenkirchen	Germany
81	Gießen	Germany
82	Göttingen	Germany
83	Haina	Germany
84	Halle	Germany
85	Hamburg	Germany
86	Hannover	Germany
87	Hattingen	Germany
88	Hemer	Germany
89	Hemmoor	Germany
90	Heppenheim	Germany
91	Idar-oberstein	Germany
92	Jena	Germany
93	Kaufbeuren	Germany
94	Krefeld	Germany
95	Köln	Germany
96	Königsbrück	Germany
97	Leipzig	Germany
98	Liebenburg	Germany
99	Lüdenscheid	Germany
100	Mainz	Germany
101	Mannheim	Germany
102	Mittweida	Germany
103	München	Germany
104	Münster	Germany
105	Naumburg	Germany
106	Norden	Germany
107	Nürnberg	Germany
108	Ober-Ramstadt	Germany
109	Oldenburg	Germany
110	Oranienburg	Germany
111	Ostfildern	Germany
112	Potsdam	Germany
113	Rostock	Germany
114	Saalfeld	Germany
115	Salzgitter	Germany
116	Schlüchtern	Germany
117	Siegen	Germany
118	Spremberg	Germany
119	Stralsund	Germany
120	Straubing	Germany
121	Ulm	Germany
122	Viersen	Germany
123	Wasserburg	Germany
124	Wiesbaden	Germany
125	Wiesloch	Germany
126	Wilhelmshaven	Germany
127	Wismar	Germany
128	Würzburg	Germany
129	Athens	Greece
130	Chios	Greece
131	Herakleion	Greece
132	Larisa	Greece
133	Thessalonikis	Greece
134	Balassagyarmat N/a	Hungary
135	Budapest N/a	Hungary
136	Kecskemet	Hungary
137	Sopron	Hungary
138	Bat-Yam	Israel
139	Be'er Ya'acov	Israel
140	Jerusalem	Israel
141	Pardesia	Israel
142	Daugavpils	Latvia
143	Jelgava	Latvia
144	Liepaja	Latvia
145	Riga	Latvia
146	Strenci	Latvia
147	Kaunas	Lithuania
148	Panevezys	Lithuania
149	Vilnius	Lithuania
150	's-Gravenhage	Netherlands
151	Assen	Netherlands
152	Beilen	Netherlands
153	Bennebroek	Netherlands
154	Enschede	Netherlands
155	Groningen	Netherlands
156	Hoofddorp	Netherlands
157	Leeuwarden	Netherlands
158	Tilburg	Netherlands
159	Zwolle	Netherlands
160	Bydgoszcz N/a	Poland
161	Gdynia Na	Poland
162	Krakow Na	Poland
163	Lubliniec	Poland
164	Skorzewo Na	Poland
165	Angra Do Heroísmo	Portugal
166	Braga	Portugal
167	Castelo Viegas N/a	Portugal
168	Coimbra	Portugal
169	Lisboa N/a	Portugal
170	Lisboa	Portugal
171	Porto N/a	Portugal
172	Porto	Portugal
173	Kazan	Russian Federation
174	Krasnodar	Russian Federation
175	Moscow N/a	Russian Federation
176	Moscow Russia	Russian Federation
177	Moscow	Russian Federation
178	Saint-Petersburg	Russian Federation
179	Saratov	Russian Federation
180	St Peterburg Na	Russian Federation
181	St Petersburg	Russian Federation
182	Yaroslavl	Russian Federation
183	Beograd	Serbia
184	Kragujevac	Serbia
185	Novi Sad	Serbia
186	Alicante	Spain
187	Barcelona	Spain
188	Bunyola Illes Balears	Spain
189	Burgos	Spain
190	Oviedo	Spain
191	Pontevedra	Spain
192	Sama De Langreo Asturias	Spain
193	Valencia	Spain
194	Zamora	Spain
195	Zaragoza	Spain
196	Bromma	Sweden
197	Göteborg	Sweden
198	Hudiksvall	Sweden
199	Karlskrona	Sweden
200	Malmö	Sweden
201	Mölndal	Sweden
202	Norrtälje	Sweden
203	Nyköping	Sweden
204	Simrishamn	Sweden
205	Skövde	Sweden
206	Solna	Sweden
207	Trollhättan	Sweden
208	Västra Frölunda	Sweden
209	Aarau	Switzerland
210	Basel Bs	Switzerland
211	Basel	Switzerland
212	Bienne	Switzerland
213	Geneve	Switzerland
214	Lenzburg	Switzerland
215	Liestal	Switzerland
216	Marsens	Switzerland
217	Montreux	Switzerland
218	Munsingen	Switzerland
219	Oetwil Am See	Switzerland
220	Riehen	Switzerland
221	Sarnen	Switzerland
222	Solothurn	Switzerland
223	Viganello	Switzerland
224	Zurich	Switzerland
225	Zürich	Switzerland
226	Ankara N/a	Turkey
227	Denizli	Turkey
228	Diyarbakir	Turkey
229	Gaziantep	Turkey
230	Izmir	Turkey
231	Barnet	United Kingdom
232	Birmingham	United Kingdom
233	Clacton On Sea	United Kingdom
234	Devon	United Kingdom
235	Exeter	United Kingdom
236	Glasgow	United Kingdom