An Efficacy and Safety Study of Paliperidone Palmitate in Participants With Schizophrenia

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose, Multicenter Study of JNS010 (Paliperidone Palmitate) in Patients With Schizophrenia

The purpose of this study is to evaluate the efficacy and safety of paliperidone palmitate as compared with placebo in the treatment of participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions [a false belief held in the face of strong differing evidence, especially as a symptom of psychiatric disorder] and hallucinations [imagining things], and withdrawal into the self).

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Paliperidone palmitate; Drug: Placebo

Detailed Description

This is a randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel-group (comparing the response in two groups of participants receiving different treatments), fixed-dose, multi-center (when more than one hospital or medical school team work on a medical research study) study of paliperidone palmitate in participants with schizophrenia. The study will consist of 3 periods: an up to 2-week pre-observation (screening) period, a double-blind period from Day 1 (baseline) to Week 13 (end of double-blind period) assessment, and a post-observation period starting after the Week 13 assessment to Week 21. For participants who discontinue the study before the last assessment in Week 13, the post-observation period will start after the discontinuation from double-blind period assessment with follow-up visits at 4, 8, and 12 weeks after the last injection. After completion of the double-blind period (Week 13), discontinuation of double-blind period treatment or withdrawal from the study, participants may receive treatment consistent with the usual standard of care. The total duration of the study will be 21 weeks, including the double-blind and post-observation periods. Participants will be randomly assigned to 1 of 2 treatment groups in a 1:1 ratio (intramuscular injections of either paliperidone palmitate or matching placebo). Injections of paliperidone palmitate or placebo will be given at Day 1 and at Weeks 1, 5, and 9 by a study drug manager and/or injector. For those participants receiving paliperidone palmitate, the Day 1 injection will be 150 milligram equivalent (mg eq.) paliperidone palmitate, followed by 100 mg eq. injections of paliperidone palmitate at Week 1, and 75 mg eq. injections of paliperidone palmitate at Weeks 5 and 9. Participants randomly assigned to placebo will receive injections matching the paliperidone palmitate injections on the same days. Efficacy will be assessed using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression - Severity (CGI-S). Participant's safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fujioka, Japan
  • Fujisawa, Japan
  • Fukui, Japan
  • Fukuoka, Japan
  • Hadano, Japan
  • Ichikawa, Japan
  • Itoman, Japan
  • Kanzaki, Japan
  • Kashihara, Japan
  • Kasuya, Japan
  • Kawasaki, Japan
  • Kitagunma, Japan
  • Kitakyushu, Japan
  • Kobe, Japan
  • Kodaira, Japan
  • Koshigaya, Japan
  • Kumagaya, Japan
  • Kumamoto, Japan
  • Kurayoshi, Japan
  • Kure, Japan
  • Kurume, Japan
  • Mitaka, Japan
  • Miyazaki, Japan
  • Moriguchi, Japan
  • Nanyo, Japan
  • Nishinomiya, Japan
  • Ohta, Japan
  • Okinawa, Japan
  • Oyabe, Japan
  • Sakai, Japan
  • Shibukawa, Japan
  • Takatsuki, Japan
  • Tamana, Japan
  • Tokyo, Japan
  • Toyama, Japan
  • Toyoake, Japan
  • Urasoe, Japan
  • Yatsushiro, Japan
  • Yokkaichi, Japan
  • Yokohama, Japan
• Korea, Republic of
  • Busan, Korea, Republic of
  • Chonju, Korea, Republic of
  • Chungcheongbuk-Do, Korea, Republic of
  • Daegu, Korea, Republic of
  • Deajun, Korea, Republic of
  • Incheon, Korea, Republic of
  • Inchun, Korea, Republic of
  • Seongnam, Korea, Republic of
  • Seoul, Korea, Republic of
• Taiwan
  • Bali Township, Taipei County, Taiwan
  • Changhua, Taiwan
  • Hua Lian, Taiwan
  • Hualien, Taiwan
  • Kaohsiung, Taiwan
  • Tainan, Taiwan
  • Taipei, Taiwan
  • Taoyuan, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants meeting Diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision
• Women had to be: postmenopausal (for at least 2 years), surgically sterile (had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (as judged by the investigator; per local regulations), or if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel], male partner sterilization) as local regulations permitted, before entry, and had to agree to continue to use the same method of contraception throughout the study
• A Positive and Negative Syndrome Scale (PANSS) total score at screening and at baseline (Day 1) of 60 to 120
• Documented history of exposure to either a risperidone formulation or a paliperidone formulation and known to be tolerated before baseline (Day 1) (Even if the participant's experience of taking risperidone or paliperidone cannot be confirmed at the time of informed consent, the participant will be able to meet this criterion if the participant takes oral risperidone 2 mg/day or more or paliperidone ER 6 mg/day or more for at least 4 days between the day of informed consent and the day before baseline, and it is possible to confirm that there is no lack of tolerability in the participant)
• Women of childbearing potential must have a negative beta human chorionic gonadotropin pregnancy test at the screening urine pregnancy test

Exclusion Criteria:

• Primary active Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision Axis I diagnosis other than schizophrenia
• A Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary)
• Relevant history or current presence of any significant or unstable cardiovascular, respiratory, neurological (including seizures or significant cerebrovascular), renal, hepatic, hematologic, endocrine, immunologic, or other systemic disease
• History or current presence of neuroleptic malignant syndrome or tardive dyskinesia
• Known or suspected hypersensitivity or intolerance to risperidone, paliperidone, Intralipid, or any of their excipients (including egg yolks, soybean oil, phospholipids, and glycerol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Matching Placebo will be given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64. Participants who complete double-blind period or discontinued early from double-blind period will have follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants will not receive any study drug during post-observational period.
EXPERIMENTAL: Paliperidone palmitate	Drug: Paliperidone palmitate; Paliperidone palmitate will be given intramuscularly as an initial loading dose of 150 milligram (mg) equivalents (eq.) on Day 1 and 100 mg eq. on Day 8, followed by 75 mg eq. on Day 36 and Day 64. Participants who complete double-blind period or discontinued early from double-blind period will have follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants will not receive any study drug during post-observational period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 13 or Early Discontinuation	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210, higher scores indicate worsening.	Baseline and Week 13 or early discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 13 or Early Discontinuation	The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants", higher scores indicate worsening.	Baseline and Week 13 or early discontinuation
Participants With Response to the Treatment as Per PANSS Total Score.	Participants with response were defined as those participants who shows 30 percent or more and 20 percent or more reduction in PANSS total score.	up to Week 13 or early discontinuation
Change From Baseline in PANSS Marder Subscale Scores at Week 13 or Early Discontinuation	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). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28, higher score indicates greater severity.	Baseline and Week 13 or early discontinuation (ED)
Change From Baseline in PANSS Negative Subscale Score at Week 13 or Early Discontinuation	Negative Syndrome Scale (range 7-49): Sum of scores for items 1-7 in negative subscale: blunted effect, emotional withdrawal, poor rapport, passive apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking, higher scores indicate worsening.	Baseline and Week 13 or early discontinuation
Change From Baseline in PANSS Positive Subscale Score at Week 13 or Early Discontinuation	Positive Syndrome Scale (range 7-49): Sum of scores for items 1-7 in positive subscale: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility, higher scores indicate worsening.	Baseline and Week 13 or early discontinuation
Change From Baseline in PANSS General Psychopathology Subscale Score at Week 13 or Early Discontinuation	General Psychopathology (range 16-112): Sum of scores for somatic concern, anxiety, guilt feelings, tension, mannerisms/posturing, depression, motor retardation, uncooperativeness, unusual thought content, disoriented, poor attention, lack of judgment/insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance, higher scores indicate worsening.	Baseline and Week 13 or early discontinuation

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: January 27, 2011
• First Submitted That Met QC Criteria: February 17, 2011
• First Posted (ESTIMATE): February 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): June 17, 2013
• Last Update Submitted That Met QC Criteria: June 13, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; Paliperidone palmitate
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Paliperidone Palmitate
• Other Study ID Numbers: CR017026; PALM-JPN-4 (OTHER: Janssen Pharmaceutical K.K., Japan)