A Study of the Efficacy (Effectiveness) of Paliperidone Palmitate in the Prevention of Recurrence of the Symptoms of Schizophrenia.

Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)

Overall Status

Completed

CT.gov ID

NCT00111189

Collaborator

Janssen-Cilag International NV (Industry)

414

Enrollment

Locations

Arms

Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of paliperidone palmitate compared with placebo in the prevention of recurrence of the symptoms of schizophrenia and to assess the safety and tolerability of paliperidone palmitate in patients with stable and symptomatic schizophrenia. The placebo used in this study was a nutritional substance known as 20% Intralipid emulsion given to patients requiring intravenous feedings.

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

Detailed Description

Many patients with schizophrenia have difficulty adhering to a daily oral treatment regimen. Long-acting injectable formulations, such as long-acting injectable paliperidone palmitate, may provide therapeutic plasma concentrations over several weeks, thereby eliminating the need for daily oral medication and making compliance easier. This study is a randomized (patients will be assigned to different treatment groups based solely on chance), double-blind (neither the patient nor the physician will know if placebo or drug is being given and at what dose), placebo-controlled, parallel-group, multicenter study followed by an open-label extension period in patients with schizophrenia. The study is designed to evaluate the efficacy of paliperidone palmitate (a long-acting injectable formulation) in delaying the time to and decreasing the rate of recurrence compared with placebo in patients with schizophrenia. The study will consist of 5 periods: an up to 7-day screening/washout/tolerability period, a 9-week open-label transition period, a 24-week open-label maintenance period, a randomized, variable-length double-blind, placebo-controlled recurrence prevention period, and an up to 52-week open-label extension period. Patients will have intramuscular (i.m.) study drug injections and efficacy and safety evaluations performed every 4 weeks throughout the study. Efficacy will be evaluated during the study using a recurrence assessment, the Positive and Negative Symptom Scale for Schizophrenia (PANSS), the Clinical Global Impression - Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Safety will be assessed throughout the study by monitoring adverse events; use of extrapyramidal symptoms (EPS) rating scales (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Rating Scale [BARS], Simpson Angus Scale [SAS]); clinical laboratory testing; vital signs (temperature, blood pressure, and heart rate) measurements; electrocardiograms (ECGs); and physical examinations. Additionally, the patients will assess the tolerability of the injections by evaluating the pain of the injection and the pain at the injection sites. Tolerability test: 3 mg/day of oral ER OROS paliperidone for 4 days. Transition (9 wks): 50 mg eq. paliperidone palmitate i.m. dose on Day 1, then i.m. injections (25, 50, or 100 mg eq.) once every 4 wks (q4wk). Maintenance (24-wks): paliperidone palmitate i.m. injections (25, 50, or 100 mg eq.) q4wk. Recurrence Prevention: paliperidone palmitate i.m. injections (25, 50, or 100 mg eq. or placebo) q4wk. Open-label paliperidone palmitate (25, 50, 75, or 100 mg eq.) q4wk for 12 dosing periods.

Study Design

Study Type:

Interventional

Actual Enrollment :

414 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

A Randomized Double-blind Placebo-controlled Parallel Group Study Evaluating Paliperidone Palmitate in the Prevention of Recurrence in Patients With Schizophrenia. Placebo Consists of 20% Intralipid (200 mg/mL) Injectable Emulsion.

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Feb 1, 2007

Actual Study Completion Date :

Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 Paliperidone Palmitate 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo	Drug: Paliperidone Palmitate 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo
Placebo Comparator: 002 Placebo Placebo every 4 wk up to 24 mo	Drug: Placebo Placebo every 4 wk up to 24 mo

Arm

Intervention/Treatment

Experimental: 001

Paliperidone Palmitate 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo

Drug: Paliperidone Palmitate

25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo

Placebo Comparator: 002

Placebo Placebo every 4 wk up to 24 mo

Drug: Placebo

Placebo every 4 wk up to 24 mo

Outcome Measures

Primary Outcome Measures

The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period [After 68 relapse events]

Secondary Outcome Measures

Changes from randomization to the end of the recurrence prevention period in PANSS (total and subscales), CGI-S, and PSP. Incidence of adverse events, labs and ECGs throughout study. [After 68 relapse events]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who meet the diagnostic criteria for schizophrenia according to DSM-IV-TM for at least 1 year before screening
have a PANSS score of <120
have a body mass index (BMI) >/=15.0 kilogram (kg)/meter (m)2
and have resided at the same address for at least 30 days

Exclusion Criteria:

Patients unable to provide their own consent
have been involuntarily committed to psychiatric hospitalization
have primary, active DSM-IV-TM diagnosis other than schizophrenia
who have a DSM-IV-TM diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary)
have a history of treatment resistance as defined by failure to respond to 2 adequate trials (minimum of 4 weeks at a therapeutic dose) of different antipsychotic medications
have a history of any severe preexisting gastrointestinal narrowing or inability to swallow the medication whole with water
have a history of neuroleptic malignant syndrome (NMS)
are at significant risk of suicidal or violent behavior
current presence of any significant or unstable medication condition
treatment with any protocol disallowed therapies
clinically significant result from screening laboratory or ECG.

Contacts and Locations

Locations

	City	State	Country
1	Little Rock	Arkansas	United States
2	Cerritos	California	United States
3	Santa Ana	California	United States
4	Hialeah	Florida	United States
5	Chicago	Illinois	United States
6	Granite City	Illinois	United States
7	Lake Charles	Louisiana	United States
8	Shreveport	Louisiana	United States
9	Flowood	Mississippi	United States
10	St. Louis	Missouri	United States
11	Clementon	New Jersey	United States
12	Cedarhurst	New York	United States
13	Cleveland	Ohio	United States
14	Oklahoma City	Oklahoma	United States
15	Conroe	Texas	United States
16	Desoto	Texas	United States
17	Irving	Texas	United States
18	San Antonio	Texas	United States
19	Costa Rica		Costa Rica
20	Gwangju		Korea, Republic of
21	Inchun		Korea, Republic of
22	Pusan		Korea, Republic of
23	Seoul		Korea, Republic of
24	Ciudad De Mexico		Mexico
25	Merida		Mexico
26	Monterrey		Mexico
27	Bucharest		Romania
28	Bucuresti		Romania
29	Cluj-Napoca		Romania
30	Iasi		Romania
31	Sibiu		Romania
32	Tg Mures		Romania
33	Timisoara		Romania
34	Arkhangelsk		Russian Federation
35	Moscow N/A		Russian Federation
36	Moscow Russia		Russian Federation
37	Moscow		Russian Federation
38	Samara N/A		Russian Federation
39	St Petersburg N/A		Russian Federation
40	Yaroslavl		Russian Federation
41	Cape Town		South Africa
42	Centurion Gauteng		South Africa
43	Florida Johannesburg Gauteng		South Africa
44	Johannesburg		South Africa
45	Changhua		Taiwan
46	Kaohsiung		Taiwan
47	Tainan		Taiwan
48	Taoyuan		Taiwan
49	Dnepropetrovsk		Ukraine
50	Glevakha		Ukraine
51	Kharkiv		Ukraine
52	Kiev		Ukraine
53	Kyiv		Ukraine
54	Lvov		Ukraine
55	Odessa		Ukraine
56	Simferopol		Ukraine
57	Vinnitsa		Ukraine

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Janssen-Cilag International NV

Investigators

Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.