Clinical trial NCT00111189: A Study of the Efficacy (Effectiveness) of Paliperidone Palmitate in the Prevention of Recurrence of the Symptoms of Schizophrenia.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
Paliperidone palmitate
R092670
antipsychotic
recurrence prevention
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Janssen-Cilag International NV
First posted: 2005-05-18
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period
timeFrame: After 68 relapse events
Secondary outcomes:
measure: 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.
timeFrame: After 68 relapse events
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Cerritos
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Hialeah
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Granite City
country: United States
state: Illinois
city: Lake Charles
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Flowood
country: United States
state: Mississippi
city: St. Louis
country: United States
state: Missouri
city: Clementon
country: United States
state: New Jersey
city: Cedarhurst
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Conroe
country: United States
state: Texas
city: Desoto
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Costa Rica
country: Costa Rica
city: Gwangju
country: Korea, Republic of
city: Inchun
country: Korea, Republic of
city: Pusan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Ciudad De Mexico
country: Mexico
city: Merida
country: Mexico
city: Monterrey
country: Mexico
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Sibiu
country: Romania
city: Tg Mures
country: Romania
city: Timisoara
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Moscow Russia
country: Russian Federation
city: Moscow
country: Russian Federation
city: Samara N/A
country: Russian Federation
city: St Petersburg N/A
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Cape Town
country: South Africa
city: Centurion Gauteng
country: South Africa
city: Florida Johannesburg Gauteng
country: South Africa
city: Johannesburg
country: South Africa
city: Changhua
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Tainan
country: Taiwan
city: Taoyuan
country: Taiwan
city: Dnepropetrovsk
country: Ukraine
city: Glevakha
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Lvov
country: Ukraine
city: Odessa
country: Ukraine
city: Simferopol
country: Ukraine
city: Vinnitsa
country: Ukraine
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Ceraso A, Lin JJ, Schneider-Thoma J, Siafis S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM, Leucht S. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2020 Aug 11;8(8):CD008016. doi: 10.1002/14651858.CD008016.pub3.
citation: Mathews M, Gopal S, Singh A, Nuamah I, Pungor K, Tan W, Soares B, Kim E, Savitz AJ. Comparison of Relapse Prevention with 3 Different Paliperidone Formulations in Patients with Schizophrenia Continuing versus Discontinuing Active Antipsychotic Treatment: A Post-Hoc Analysis of 3 Similarly Designed Randomized Studies. Neuropsychiatr Dis Treat. 2020 Jun 19;16:1533-1542. doi: 10.2147/NDT.S221242. eCollection 2020.
citation: Emsley R, Nuamah I, Gopal S, Hough D, Fleischhacker WW. Relapse After Antipsychotic Discontinuation in Schizophrenia as a Withdrawal Phenomenon vs Illness Recurrence: A Post Hoc Analysis of a Randomized Placebo-Controlled Study. J Clin Psychiatry. 2018 Jun 19;79(4):17m11874. doi: 10.4088/JCP.17m11874.
citation: Weiden PJ, Kim E, Bermak J, Turkoz I, Gopal S, Berwaerts J. Does Half-Life Matter After Antipsychotic Discontinuation? A Relapse Comparison in Schizophrenia With 3 Different Formulations of Paliperidone. J Clin Psychiatry. 2017 Jul;78(7):e813-e820. doi: 10.4088/JCP.16m11308.
citation: Kozma CM, Slaton T, Dirani R, Fastenau J, Gopal S, Hough D. Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE). Curr Med Res Opin. 2011 Aug;27(8):1603-11. doi: 10.1185/03007995.2011.595000. Epub 2011 Jun 22.
citation: Hough D, Gopal S, Vijapurkar U, Lim P, Morozova M, Eerdekens M. Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2010 Feb;116(2-3):107-17. doi: 10.1016/j.schres.2009.10.026. Epub 2009 Dec 2.