Prevention of Relapse With Oral Antipsychotics Versus Injectable Paliperidone Palmitate (PROSIPAL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT01081769
First received: March 4, 2010
Last updated: March 15, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to assess the efficacy (how well the drug works; primarily through the time to relapse) of long-acting injectable paliperidone palmitate compared to treatment as usual with orally administered antipsychotics in monotherapy over 24 months in the treatment of recently diagnosed (1-5 years since diagnosis) schizophrenia.


Condition Intervention Phase
Schizophrenia
Drug: paliperidone palmitate injection
Drug: oral antipsychotics
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 24-month, Prospective, Randomized, Active-Controlled, Open-Label, Rater-Blinded, Multicenter, International Study of the Prevention of Relapse Comparing Long-Acting Injectable Paliperidone Palmitate to Treatment as Usual With Oral Antipsychotic Monotherapy in Adults With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • The primary outcome measure is time to a relapse event. [ Time Frame: Relapse is assessed from baseline (Day 1) up to maximally 24 months. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The percentage of treatment responders defined as achieving > or = 30% improvement in PANSS total score at endpoint versus baseline [ Time Frame: every visit: screening, day 1, 8, 38, 68, 98, 128, 158, 188, 278, 368, 458, 548, 638, 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  • Changes from baseline in total PANSS score and PANSS sub-domains/symptom factors [ Time Frame: every visit: screening, day 1, 8, 38, 68, 98, 128, 158, 188, 278, 368, 458, 548, 638, 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  • Changes from baseline in level of functioning (PSP) [ Time Frame: screening visit, days 1, 38, 68, 98, 188, 278 368 458 548 638 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  • Overall score and changes from baseline in global severity of illness (CGI-S, CGI C) [ Time Frame: every visit: screening, day 1, 8, 38, 68, 98, 128, 158, 188, 278, 368, 458, 548, 638, 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  • Measures of patient's mental health, well-being, treatment satisfaction and physician treatment satisfaction [ Time Frame: days 1, 188, 368 and 728 and at early withdrawal and relapse ] [ Designated as safety issue: No ]

Enrollment: 769
Study Start Date: February 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paliperidone Palmitate
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
Drug: paliperidone palmitate injection
injection with 150 mg equivalent on Day 1, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter
Active Comparator: Oral Antipsychotics
oral antipsychotics daily treatment according to local label for maximally 24 months
Drug: oral antipsychotics
daily treatment according to local label for maximally 24 months

Detailed Description:

This is a randomized (study drug assigned by chance), open-label (both physician and patient know the name of the assigned drug), rater-blinded (the person who assesses the condition of the patient does not know the name of the assigned drug), active-controlled, parallel-group, multicenter, prospective international study of paliperidone palmitate versus treatment as usual with oral antipsychotic agents in monotherapy in the prevention of relapse (return of symptoms). Patients who have been recently diagnosed with schizophrenia (within 5 years) and are suffering from a schizophrenic relapse (return of symptoms of schizophrenia) will be enrolled. This study consists of a 2-week initial acute oral treatment phase, followed by a treatment phase until relapse or up to maximally 24 months, whichever comes first. Prior to a 2-week oral treatment phase, patients will be randomly (by chance) assigned in a 1:1 ratio to receive treatment with paliperidone palmitate injection (once-monthly) or oral antipsychotic medication (daily). Patients randomized to paliperidone palmitate will first receive oral paliperidone ER once daily for 2 weeks followed by paliperidone palmitate injections at a dose of 150 mg eq. on Day 1, 100 mg eq. on Day 8 and 75 mg eq. on Day 38 and doses in a dose range of 25 to 150 mg eq. in either the deltoid or the gluteal muscle thereafter. Patients randomized to oral comparator arm will receive oral antipsychotics (haloperidol, paliperidone ER, risperidone, olanzapine, quetiapine and aripiprazole) as per investigator discretion and prescribed according to the label. Total treatment duration is maximally 24 months. During the 24 month treatment phase, investigators will be allowed to flexibly decrease or increase the dose of paliperidone palmitate with one dose level in the range of 25 to 150 mg eq. or the oral antipsychotic in the respective locally approved dose range, all according to the patient's clinical needs. The primary endpoint of the 24-month treatment phase will be the time to relapse. Safety will be monitored by evaluating Adverse Events (AEs), rating of extrapyramidal symptoms (symptoms like abnormal muscle movements, abnormal movements of the tongue or jaw, slow or sustained muscle contractions, muscle spasms, shaking, abnormal movements of the eyes, involuntary muscle contractions, slow movements, or restlessness), vital signs measurements (including heart rate and blood pressure), body weight and physical examination findings. A urine pregnancy test will be performed in females of childbearing potential. Adverse events (unintended, but not necessarily unexpected, results of therapy that can be unpleasant or dangerous), associated concomitant medications, and symptoms of relapse will be recorded as needed. Patients randomized to paliperidone palmitate will first receive oral paliperidone ER once daily for 2 weeks followed by paliperidone palmitate injections at a dose of 150 mg eq. on Day 1, 100 mg eq. on Day 8 and 75 mg eq. on Day 38 and doses in a dose range of 25 to 150 mg eq. in either the deltoid or the gluteal muscle thereafter. Patients randomized to oral medications will be treated daily with the prescribed drug according to the label. Total treatment duration is maximally 24 months.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have been meeting the diagnostic criteria for schizophrenia for 1 to 5 years before screening, and have a history of treatment with antipsychotics
  • Have a history of two or more relapses requiring psychiatric hospitalization in the preceding 24 months, which may include the current acute episode
  • Experiencing at screening an acute schizophrenic episode with a PANSS total score at screening between 70 and 120, inclusive
  • Be healthy on the basis of physical examination, medical history and vital signs performed at screening
  • Woman must be postmenopausal (for at least 1 year) or surgically sterile or abstinent or be practicing an effective method of birth control, must agree to continue to use the same method of contraception throughout the study and must have a negative urine pregnancy test at screening
  • be able to fill out questionnaires
  • Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:

  • Patients that have never been treated with antipsychotics before
  • Treatment resistant patient and/or currently (i.within the last 3 months) treated with clozapine
  • Substance dependence within 6 months prior to entry and current intravenous drug use or abuse
  • allergies, hypersensitivity, or intolerance to risperidone or paliperidone or excipients
  • treatment with a long-acting injectable antipsychotic within three injection cycles prior to screening
  • newly started psychotherapy program within the two months preceding the treatment phase baseline
  • evidence of clinically significant hepatic, renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances in the past 6 months (as determined by medical history, clinical laboratory or ECG results, or physical examination) that would increase the risk associated with taking study medication or would confound the interpretation of the study
  • history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome
  • involuntarily hospitalized patient
  • pregnant or breast-feeding females
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01081769

  Show 99 Study Locations
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV
  More Information

No publications provided

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT01081769     History of Changes
Other Study ID Numbers: CR015199, R092670SCH3005, 2008-002247-16
Study First Received: March 4, 2010
Last Updated: March 15, 2014
Health Authority: Czech Republic: State Institute for Drug Control
Egypt: Ministry of Health and Population
Estonia: The State Agency of Medicine
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Croatia: Ministry of Health and Social Care
Bulgaria: Bulgarian Drug Agency
Austria: Agency for Health and Food Safety
Israel: Ministry of Health
Italy: Ethics Committee
Korea: Food and Drug Administration
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Turkey: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Ethics Commission
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
United States: Food and Drug Administration

Keywords provided by Janssen-Cilag International NV:
Schizophrenia
paliperidone palmitate
Invega
Intramuscular injection
Oral antipsychotics
Relapse

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Antipsychotic Agents
9-hydroxy-risperidone
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 29, 2014