An Efficacy and Safety Study of One Dosage of Paliperidone Extended Release (ER) in Treating Patients With Schizophrenia

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Information provided by (Responsible Party): Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy and safety of 1.5 mg/day dose of paliperidone Extended Release (ER) as compared with placebo when used to treat patients with schizophrenia.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Paliperidone ER; Drug: Placebo	Phase 4

Detailed Description:

Currently, treatment of acute symptoms in schizophrenia is less than ideal, up to one-third of patients with schizophrenia do not respond to current treatments, and poor drug tolerability can decrease a patient's ability to remain on treatment. Paliperidone ER doses in the range of 3 mg/day to 12 mg/day have been approved for the treatment of patients with schizophrenia. A lower dosage form of paliperidone ER be efficacious and may reduce the risk of certain adverse effects. This study will evaluate the efficacy of 1 fixed (ie, it does not change during the study) dosage of paliperidone ER (1.5 mg/day) compared with placebo. One fixed dosage of paliperidone ER (6.0 mg/day) will be given to some patients as an active (it has already been shown to have efficacy) control. This is a multicenter, double-blind (neither the patient nor the study-site personnel know which treatment the patient is receiving), randomized (patients are assigned to a treatment group by chance), placebo-controlled (some patients will receive placebo and no active drug), parallel-group (patients in all groups follow the same study design) study in adults who were diagnosed with schizophrenia at least 1 year before screening and who are experiencing an acute episode. The study starts with an up-to-5-day screening phase to find out if the patient is eligible for the study. The screening phase includes a 3- to 5-day washout (the medication dosage is tapered down and finally stopped) of any medications that are being taken by a patient but that are not allowed during the study. A 6-week double-blind treatment phase follows and finishes with an end-of-study visit. A post-study visit to collect additional safety data will be scheduled for 1 week after a patient receives his or her last dose of study drug. The length of the entire study is about 8 weeks. Patients who withdraw from the study before completing the double-blind treatment phase will complete the end-of-study visit procedures at the time they withdraw and the post-study visit 1 week after receiving their last dose of study drug. For all patients leaving the study, the investigator will make every effort to see that they receive adequate continuity of care. At baseline (the visit just before a patient takes the first dose of study drug), all patients will be randomly assigned to 1 of the 3 possible treatment groups to receive paliperidone ER 1.5 mg/day, paliperidone ER 6 mg/day, or placebo once daily for 6 weeks. Patients must be voluntary inpatients at the time of randomization, and they must remain in the hospital for a minimum of 8 days. Efficacy will be measured using the following rating scales: the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S), the Personal and Social Performance Scale (PSP), and the Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36). Safety will be evaluated using physical examinations, ECGs, clinical laboratory testing (hematology, serum chemistry, and urinalysis), testings for pregnancy, and monitoring for adverse events including extrapyramidal symptoms (EPS) using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Rating Scale (SAS). The study hypothesis is that Paliperidone ER at 1.5 mg per day will be effective in the treatment of schizophrenia as measured by the change in total PANSS score between baseline and endpoint in comparison with placebo. Oral paliperidone ER 1.5 mg or 6.0 mg tablets or matching oral placebo tablets taken once daily in the morning for 6 weeks.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	201 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Fixed Dosage of 1.5 mg/Day of Paliperidone Extended Release (ER) in the Treatment of Subjects With Schizophrenia
Study Start Date :	September 2007
Actual Primary Completion Date :	November 2008
Actual Study Completion Date :	November 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 001; Paliperidone ER 1.5 mg tablet once daily for 6 weeks	Drug: Paliperidone ER; 1.5 mg tablet once daily for 6 weeks
Active Comparator: 002; Paliperidone ER 6 mg tablet once daily for 6 weeks	Drug: Paliperidone ER; 6 mg tablet once daily for 6 weeks
Placebo Comparator: 003; Placebo Once daily for 6 weeks	Drug: Placebo; Once daily for 6 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in PANSS Total Score at the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment). [ Time Frame: Baseline, 6 weeks ]
   The Positive and Negative Syndrome Scale (PANSS) is a tool used by psychiatrists to measure the symptoms of psychosis experienced by a patient with schizophrenia. It includes 30 items that produce a total score ranging from a minimum of 30 (indicating least severe symptoms of illness) to a maximum of 120 (indicating most severe symptoms of illness). A negative change in score from baseline to end point indicates improvement in the symptoms of illness.

Secondary Outcome Measures :

1. Change From Baseline to the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment) in CGI-S [ Time Frame: Baseline, 6 weeks ]
   The Clinical Global Impression-Severity (CGI-S) rating scale is used by psychiatrists to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). The scale permits a global evaluation of the patient's condition at a given time.
2. Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in PSP Score [ Time Frame: Baseline, 6 weeks ]
   The Personal and Social Performance (PSP) scale assesses the degree of difficulty (ranging from i [absent] to vi [very severe]) a patient exhibits over a 1-month period in socially useful activities, personal and social relationships, self care, and disturbing and aggressive behavior. The overall score ranges from 1 to 100. Patients with scores of 71 to 100 have a mild degree of difficulty; patients with scores from 31 to 70 have various degrees of disability; and patients with scores of 30 or less function so poorly as to require intensive supervision.
3. Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Physical Component Summary Scale Score [ Time Frame: Baseline, 6 weeks ]
   The Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36) is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 subscale scores: the Physical Component Summary and the Mental Component Summary.
4. Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Mental Component Summary Scale Score [ Time Frame: Baseline, 6 weeks ]
   The MOS SF-36 is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year before screening
• Experiencing an acute episode with a total PANSS score at screening of between 70 and 120
• Are otherwise physically healthy
• Agree to at least 8 days of voluntary hospitalization.

Exclusion Criteria:

• Active comorbid DSM-IV axis I diagnosis other than schizophrenia (nicotine and caffeine dependence are not exclusionary)
• Treatment with antidepressants (unless a subject has been on a stable dosage for at least 3 months before baseline) other than monoamine oxidase inhibitors
• DSM-IV diagnosis of substance dependence within 6 months before screening evaluation (nicotine and caffeine dependence are not exclusionary)
• Any medical condition that could potentially alter the absorption, metabolism, or excretion of the study medication, such as Crohn's disease, liver disease, or renal disease
• Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic disease.

Contacts and Locations

Locations

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United States, California
Cerritos, California, United States
Torrance, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Bradenton, Florida, United States
Leesburg, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Maryland
Rockville, Maryland, United States
United States, New Jersey
Nutley, New Jersey, United States
United States, New York
Cedarhurst, New York, United States
Hollis, New York, United States
United States, Oklahoma
Moore, Oklahoma, United States
United States, Texas
Austin, Texas, United States
India
Calicut, India
Hyderabad, India
Mumbai, India
Pune, India
Varanasi, India
Taiwan
Hualien, Taiwan
Tainan, Taiwan
Taipei, Taiwan

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

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

More Information

Additional Information:

A Study of the Efficacy and Safety of One Dosage of Paliperidone Extended Release (ER) in Treating Patients With Schizophrenia 

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Responsible Party:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00524043 History of Changes
Other Study ID Numbers:	CR013771; R076477SCH4012
First Posted:	September 3, 2007
Results First Posted:	February 26, 2010
Last Update Posted:	June 4, 2014
Last Verified:	May 2014

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Schizophrenia

Additional relevant MeSH terms:

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Paliperidone Palmitate; Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs	Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Dopamine Agents