The primary objective of the double blind phase of this study is to evaluate the efficacy and safety of 3 fixed dosages of extended release (ER) OROS paliperidone (6, 9, and 12 mg/day) compared with placebo in subjects with schizophrenia. The efficacy response will be measured by the change in the Positive and Negative Syndrome Scale (PANSS) total score from start of treatment to the end of double blind phase.

Condition	Treatment or Intervention	Phase
Schizophrenia	Drug: Paliperidone	Phase III

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Double-Blind phase:

• Subjects can be male or female
• Age must be 18 years or older
• Subjects must have been diagnosed with shizophrenia according to DSM - IV (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year prior to screening
• Subjects must have signed an informed consent document, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Subjects must be experiencing an acute episode, with a total PANSS score at screening between 70 and 120.
• Female subjects of child-bearing potential must agree to use an acceptable form of contraception (e.g., prescription oral contraceptives patch, male partner sterilization) before entry and thorought the study, and must have a negative serum b-human chorionic gonadotropin (b-hCG) pregnancy test at screening.
• Subjects must agree to voluntary hospitalization for a minimum of 14 days.
• Subjects must be willing and able to fill out self administered questionnaires.
• Subjects must be able to be compliant with self-administration of medication, or have consistent help/support available.

Open Label Extension phase:

• Subjects must have signed the Informed Consent Form for the open-label phase.
• Subjects must have completed the 6 weeks of double-blind treatment or completed at least 21 days of treatment and discontinued due to lack of efficacy.
• Subjects and investigator must agree that open-label treatment is in the best interest of the subjects.
• Female subjects of child-bearing potential must agree to use an acceptable form of contraception (e.g., prescription oral contraceptives patch, male partner sterilization) throughout the open-label extension and must have a negative urine pregnancy test at open-label baseline.

Exclusion Criteria

Double-blind phase:

• A DSM-IV axis I diagnosis other than schizophrenia
• A DSM-IV diagnosis of substance dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary)
• Any medical condition that could potentially alter the absorbtion, metabolism, or excretion of the study medication, such as Crohn's disease, liver disease, or renaldisease.
• Relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases
• History of tardive dyskinesia or neuroleptic malignant syndrome (NMS)
• Known allergic reaction (rash)to phenytoin, carbamazepine, barbiturantes, lamotrigine
• Other significant and/or unstable systemic illnesses
• Allergy or hypersensitivity to risperidone, paliperidone, or olanzapine
• History of any severe preexisting gastrointestinal narrowing (pathologic or iatrogenic)
• Inability to swallow the study medication whole with the aid of water(subjects may not chew, divide, dissolve, or crush the study medication, as this may affect the release profile)
• Previous history of lack of response (2 adequate trials) to any antipsychotic
• Exposure to an experimental drug or experimental medical device within 90 days before screening
• Significant risk of suicidal or viloent behavior
• Female subjects who are pregnant or breastfeeding
• Alanine aminotransferase or aspartate aminotranferase levels more than 2 times the upper limit of normal
• Other biochemistry, hematology, or urinalysis results that are not within the laboratory's reference range, and that are deemed by the investigator to be clinically significant
• Use of beta-blockers (if used for any indication other than hypertension and still present at baseline)
• Injection of a depot antipsychotic within 120 days before screening, or use of paliperidone palmitate within 10 months before screening
• Use of monoamine oxidase inhibitors within 4 weeks before screening
• Use of another antidepressants (unless subject has been on a stable dosage for at least 3 months prior to screening) or mood stabilizers (e.g., antiepileptics, lithium) within 2 weeks before screening
• Received electroconvulsive therapy within 3 months before screening
• Employees of the investigator or study center, persons with direct involvment in the proposed study or other studies under the direction of the investigator or study center, or family members of the employees or the investigator

Open-Lable Phase:

• Subjects believed by the investigator to be at significant risk for suicidal or violent behaviour during the open-label extension
• Female subjects who have become pregnant
• Subjects who have received an injection of a depot antipsychotic since entry into the preceding double-blind phase

Bulgaria
      Clinic of Psychiatry, Medical University, Plodiv,  4002,  Bulgaria; Recruiting
      City Psychiatric Dispensary, Sofia,  1000,  Bulgaria; Recruiting
      District Dispensary for Psychiatric Diseases, Bourgas,  8000,  Bulgaria; Recruiting
      State Psychiatric Hospital, Radnevo,  6260,  Bulgaria; Recruiting
Croatia
      Psychiatric Hospital Vrapce, Zagreb,  10090,  Croatia; Recruiting
Estonia
      Psychaitric Hospital, Tallin,  10614,  Estonia; Recruiting
      Psychiatric Clinic, Parnu,  80012,  Estonia; Recruiting
      Ahtme Hospital, Hotla-Jarve,  31027,  Estonia; Recruiting
France
      Psychiatrie, Nimes,  30000,  France; Recruiting
      Clinique Universitaire, Psychiatrie, Marseille,  13005,  France; Recruiting
      Psychiatire, Clermont,  63001,  France; Recruiting
      Psychiatire, Poitiers,  86021,  France; Recruiting
      Centre Hospitalier Specialise de Saint-Ylie, Dole,  39100,  France; Recruiting
      Centre Hospitalier de Toulon, Toulon,  3000,  France; Recruiting
Greece
      Dept. of Psychiatry of Athens University, Athens,  11528,  Greece; Recruiting
      3rd Psychiatric Clinic Aristotle University of Thessaloniki, THESSALONIKI,  54636,  Greece; Recruiting
      14th Psychiatric Section, Athens,  12462,  Greece; Recruiting
      Dept. of Psychaitry, Athens,  15100,  Greece; Recruiting
India
      Asha Hospital, Hyderabad,  500034,  India; Recruiting
      Nair Hospital, Mumbai,  400034,  India; Recruiting
      National Institute of Mental Health & Neuro Sciences, Bangalore,  560029,  India; Recruiting
      K.S. Hegde Medical Academy, Mangalore,  574160,  India; Recruiting
      K.E.M. Hospital, Mumbai,  400012,  India; Recruiting
      Kasturba Medical College, Manipal,  576119,  India; Recruiting
Netherlands
      Mediant, ENSCHEDE,  7546TA,  Netherlands; Recruiting
      GGZ Winschoten, Winschoten,  9675 AA,  Netherlands; Recruiting
      Stichting Adhesie, Deventer,  7416 SB,  Netherlands; Recruiting
Poland
      II Klinika Chorob Psychicznych AMG, Gdansk,  80-282,  Poland; Recruiting
      Klinika Psychiatrii AMB, Choroszcz,  16-070,  Poland; Recruiting
      Szpital dla Nerwowo i Psychicznie Chorych, Starogard Gdanski,  83-200,  Poland; Recruiting
      Samodzielny Publiczny Szpital Kliniczny Nr 1, Lublin,  20-439,  Poland; Recruiting
      Specjalistyczny Psychiatryczny ZOZ, Lodz,  91-229,  Poland; Recruiting
      Wojewodzki Szpital Psychiatryczny, Swiecie,  86-100,  Poland; Recruiting
      NZOZ Wolmed, Dubie 1,  97-720,  Poland; Recruiting
      SP ZOZ Lipno, Lipno,  87-600,  Poland; Recruiting
      Wojewodzki Osrodek Lecznictw Psychiatrycznego, Torun,  87-100,  Poland; Recruiting
      Wojewodzki Szpital Neuropsychiatryczny, Lubliniec,  42-700,  Poland; Recruiting
      Szpital Psychiatryczny, Ciborz,  66-213,  Poland; Recruiting
Russian Federation
      Serbsky National Research Center, Moscow,  123367,  Russian Federation; Recruiting
      Bekhterev Psychopharmacological Research Institute, St Petersburg,  193019,  Russian Federation; Recruiting
      Mental Health Research Center, Moscow,  115522,  Russian Federation; Recruiting
      City Psychiatric Hospital #6, St Petersburg,  193167,  Russian Federation; Recruiting
      Saratov Hospital #2, Saratov,  410028,  Russian Federation; Recruiting
      Samara Regional Psychiatric Hospital #1, Samara,  443016,  Russian Federation; Recruiting
      Mental Health Research Center, Moscow,  115552,  Russian Federation; Recruiting
      Psychiatric Hospital #6, St Petersburg,  194314,  Russian Federation; Recruiting
      City Psychiatric Hospital #14, Moscow,  115516,  Russian Federation; Recruiting
      Psychiatric Hospital #1, Moscow,  113152,  Russian Federation; Recruiting
Slovakia
      Psychiatricke Oddelenie NsP Petrzalka, Bratislava,  85107,  Slovakia; Not yet recruiting
      Psychiatricke Oddelenie Msp, Rimavska Sobota,  97912,  Slovakia; Recruiting
      Psychiatricak Klinika SZU, Bratislava,  82606,  Slovakia; Not yet recruiting
      Association for Mental Health "Hope for Health", Michalovice,  07101,  Slovakia; Recruiting
      Psychiatricka Nemocnica P.Pinela, Pezinok,  Slovakia; Recruiting
Spain
      H. Psychiatrico De Madrid, Madrid,  28049,  Spain; Recruiting
      H. Infanta Cristina, Badjoz,  6080,  Spain; Recruiting
      Centro Asistencial Dr. Emili Mir y Lopez, Santa Coloma,  8921,  Spain; Recruiting

Study ID Numbers:  R076477-SCH-303/ 703
Record last reviewed:  October 2004
Last Updated:  October 21, 2004
Record first received:  February 17, 2004
ClinicalTrials.gov Identifier:  NCT00078039
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08