A Study of Paliperidone Palmitate 3 Month Formulation for the Treatment of Patients With Schizophrenia

A Randomized, Multicenter, Double-Blind, Relapse Prevention Study of Paliperidone Palmitate 3 Month Formulation for the Treatment of Subjects With Schizophrenia

The purpose of this study is to evaluate the efficacy of paliperidone palmitate 3 month formulation (PP3M) compared with placebo in delay of the time to first occurrence of relapse of the symptoms of schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: PP3M 175 mg eq.; Drug: PP3M 263 mg eq.; Drug: PP3M 350 mg eq.; Drug: PP3M 525 mg eq.; Drug: Placebo (20% Intralipid emulsion)

Detailed Description

This is a randomized (the study drug is assigned by chance), double blind (neither physician nor patient knows the treatment that the patient receives), parallel group (each group of patients will be treated at the same time), placebo-controlled (an inactive substance is compared with a drug to test whether the drug has a real effect in a clinical trial) multicenter study. The study consists of 4 phases: a Screening Phase (up to 3 weeks); a 17-week flexible dose open-label Transition Phase (open-label phase means that all people know the identity of the intervention); a 12-week fixed dose open-label Maintenance Phase; and a randomized, double-blind, fixed dose, placebo-controlled relapse prevention phase (referred to as the Double-blind Phase). Patients who meet specific stabilization criteria will enter the Double-blind Phase at Week 29. Patients will be randomly assigned, in a 1:1 ratio, to receive either a fixed dose of PP3M or placebo. The Double-blind Phase will be of variable duration; patients will remain in the study until they experience a relapse event or meet discontinuation criteria.

• Study Type: Interventional
• Enrollment (Actual): 509
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Barranquilla, Colombia
  • Bogota, Colombia
  • Medellin, Colombia
  • Pereira, Colombia
• Korea, Republic of
  • Deajun, Korea, Republic of
  • Gyeongsangnam-Do, Korea, Republic of
  • Incheon, Korea, Republic of
  • Seongnam, Korea, Republic of
• Malaysia
  • Johor Bahru, Malaysia
  • Kuala Lumpur, Malaysia
  • Tanjong Rambutan, Malaysia
• Mexico
  • Guadajalara, Mexico
  • Mexico City, Mexico
  • Monterrey, Mexico
  • San Luis Potosi, Mexico
  • Zapopan, Mexico
• Romania
  • Arad, Romania
  • Craiova, Romania
  • Iasi, Romania
  • Sibiu, Romania
  • Tg Mures, Romania
• Turkey
  • Diyarbakir, Turkey
  • Sakarya, Turkey
• Ukraine
  • Donetsk, Ukraine
  • Evpatoriya, Ukraine
  • Glevakha, Ukraine
  • Ivano-Frankivsk, Ukraine
  • Kerch, Ukraine
  • Kharkiv, Ukraine
  • Kharkov, Ukraine
  • Kherson, Ukraine
  • Kiev, Ukraine
  • Lviv, Ukraine
  • Lvov, Ukraine
  • Odesa, Ukraine
  • Odessa, Ukraine
  • Poltava, Ukraine
  • Smela, Ukraine
  • Ternopil, Ukraine
  • Uzhgorod, Ukraine
  • Vinnitsa, Ukraine
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • San Fran Cisco, California, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Lauderhill, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
    • Hoffman Estates, Illinois, United States
  • Kansas
    • Topeka, Kansas, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Mississippi
    • Flowood, Mississippi, United States
  • New Jersey
    • Marlton, New Jersey, United States
  • New York
    • Cedarhurst, New York, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Texas
    • Austin, Texas, United States
    • Dallas, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with schizophrenia for more than 1 year
• A total score in the Positive and Negative Syndrome Scale (PANSS) < 120
• Signed informed consent
• Women must not be pregnant, breastfeeding, and if capable of pregnancy must practice an effective method of birth control
• Men must agree to use a double-barrier method of birth control
• Be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs, and electrocardiogram (ECG) Exclusion Criteria:
• A diagnosis other than schizophrenia, e.g., dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, primary substance-induced psychotic disorder, dementia-related psychosis
• Relevant history or current presence of any significant or unstable medical condition(s) determined to be clinically significant by the Investigator (ie, obesity, diabetes, heart disease etc)
• A diagnosis of substance dependence within 6 months before screening
• History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia
• Clozapine use in the last 2 months when used for treatment-resistant or treatment-refractory illness
• Clinically significant findings in biochemistry, hematology, ECG or urinalysis results
• Any other disease or condition that, in the opinion of the investigator, would make participation not in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo (20% Intralipid emulsion); Form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.
Experimental: Paliperidone palmitate 3-month (PP3M)	Drug: PP3M 175 mg eq.; Type= exact number, unit= mg eq., number= 175, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.; Drug: PP3M 263 mg eq.; Type= exact number, unit= mg eq., number= 263, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.; Drug: PP3M 350 mg eq.; Type= exact number, unit= mg eq., number= 350, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.; Drug: PP3M 525 mg eq.; Type= exact number, unit= mg eq., number= 525, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Relapse During the Double-Blind Phase	Time to relapse defined as the time between participant randomization into the double blind Phase and the first documentation of a relapse event. Median time to relapse was estimated by the Kaplan-Meier method.	Approximately Week 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase	The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each item is rated 1 (absent) to 7 (extreme). The total score ranging from 30 to 210. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia.	Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase	The CGI-S rating scale is used to rate the severity of a participant's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe).	Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase	The PSP scale measures personal and social functioning in the domains of: a) Socially useful activities, b) Personal and social relationships, c) Self-care, and d) Disturbing and aggressive behavior. The results of the assessment were converted to a numerical score which ranges from 1 to 100. A score lying between 71 and 100 indicates a mild degree of dysfunction; scores between 31 and 70 indicate varying degrees of difficulty, and a participant with a score of <=30 had functioning so poor that he or she required intensive supervision.	Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.
• 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.
• Savitz AJ, Xu H, Gopal S, Nuamah I, Mathews M, Soares B. Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies. Braz J Psychiatry. 2019 Nov-Dec;41(6):499-510. doi: 10.1590/1516-4446-2018-0153.
• Magnusson MO, Samtani MN, Plan EL, Jonsson EN, Rossenu S, Vermeulen A, Russu A. Population Pharmacokinetics of a Novel Once-Every 3 Months Intramuscular Formulation of Paliperidone Palmitate in Patients with Schizophrenia. Clin Pharmacokinet. 2017 Apr;56(4):421-433. doi: 10.1007/s40262-016-0459-3.
• Gopal S, Vermeulen A, Nandy P, Ravenstijn P, Nuamah I, Buron Vidal JA, Berwaerts J, Savitz A, Hough D, Samtani MN. Practical guidance for dosing and switching from paliperidone palmitate 1 monthly to 3 monthly formulation in schizophrenia. Curr Med Res Opin. 2015 Nov;31(11):2043-54. doi: 10.1185/03007995.2015.1085849. Epub 2015 Oct 2.
• Berwaerts J, Liu Y, Gopal S, Nuamah I, Xu H, Savitz A, Coppola D, Schotte A, Remmerie B, Maruta N, Hough DW. Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Aug;72(8):830-9. doi: 10.1001/jamapsychiatry.2015.0241.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 8, 2012
• First Posted (Estimate): February 9, 2012

Study Record Updates

• Last Update Posted (Estimate): May 11, 2016
• Last Update Submitted That Met QC Criteria: May 2, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Schizophrenia; R092670; Paliperidone Palmitate; Paliperidone palmitate 3 month formulation (PP3M)
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: CR100717; R092670PSY3012 (Other Identifier: Janssen Research & Development, LLC); 2011-004676-11 (EudraCT Number); U1111-1135-1969 (Other Identifier: Universal Trial Number)