Effectiveness and Safety of 3 Fixed Doses (25 mg eq., 100 mg eq., and 150 mg eq.) of Paliperidone Palmitate in Patients With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Paliperidone palmitate 25 mg eq.; Paliperidone palmitate 150 mg eq.; Placebo; Paliperidone palmitate 100 mg eq.
Intervention description: Paliperidone palmitate 150 mg eq. i.m. Day 1 and 25 mg eq. i.m. Days 8, 36, 64; Paliperidone palmitate 150 mg eq. i.m. Days 1, 8, 36, 64; Placebo i.m. Days 1, 8, 36, 64; Paliperidone palmitate 150 mg eq. i.m. Day 1 and 100 mg eq. i.m. Days 8, 36, 64
Intervention MeSH terms: Paliperidone Palmitate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 652.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Schizophrenia; Long-acting injectable antipsychotic medication

Summary:

      The primary objectives of this study are to evaluate the efficacy and safety of 3 fixed doses
      of paliperidone palmitate administered i.m. after an initial loading dose of 150 mg eq. in
      the deltoid muscle followed by either deltoid or gluteal injections for a total of 13 weeks
      of treatment as compared with placebo in patients with schizophrenia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Met diagnostic criteria for schizophrenia according to Diagnostic and Statistical
             Manual of Mental Disorders, Fourth Edition (DSM IV) for at least 1 year before
             screening. Prior medical records, written documentation or verbal information obtained
             from previous psychiatric providers obtained by the investigator must be consistent
             with the diagnosis of schizophrenia

          -  A total PANSS score at screening of between 70 and 120, inclusive and at baseline of
             between 60 and 120, inclusive

          -  Body mass index (BMI)

          -  i.e., [weight (kg)]/[height (m)]², of >17.0 kg/m2

          -  Women must be postmenopausal for at least 2 years, surgically sterile, abstinent, or
             agree to practice an effective method of birth control if they are sexually active
             before entry and throughout the study. Effective methods of birth control include:
             prescription hormonal contraceptives, intrauterine device, double-barrier method, and
             male partner sterilization. Women of childbearing potential must have a negative urine
             pregnancy test at baseline, before receiving a dose of study drug

          -  Is able and willing to meet or perform study requirements (e.g., answer
             self-administered questionnaires). If a patient is unable to read the questions, study
             personnel may read documents and the patient may then mark his or her choice

          -  Patients in the US must be able to understand spoken English to permit adequate
             ratings by the blinded central rater

        Exclusion Criteria:

          -  Primary diagnosis other than schizophrenia

          -  Patients who are unable to provide their own consent or who are currently
             involuntarily committed to psychiatric hospitalization

          -  DSM-IV diagnosis of active substance dependence within 3 months before the screening
             evaluation (nicotine and caffeine dependence are not exclusionary)

          -  History of treatment resistance as defined by failure to respond to 2 adequate studies
             of different antipsychotic medications

          -  an adequate study is defined as a minimum of 4 weeks at the patient's maximum
             tolerated dose

          -  Relevant history of or current presence of any significant or unstable cardiovascular,
             respiratory, neurological (including seizures or significant cerebrovascular), renal,
             hepatic, hematologic, endocrine, immunologic, morbid obesity (BMI>=40), or other
             systemic disease

          -  History of any severe preexisting gastrointestinal narrowing (pathologic or
             iatrogenic) or inability to swallow the oral tolerability medication whole with the
             aid of water for patients requiring oral tolerability testing

          -  Biochemistry, hematology or urinalysis test results that are not within the
             laboratory's normal reference range and are deemed to be clinically significant by the
             investigator

          -  History or evidence of clinically significant hepatic disease (including aspartate
             aminotransferase [AST] or alanine aminotransferase [ALT] >2 times the upper limit of
             normal) at screening

          -  History of neuroleptic malignant syndrome

          -  Significant risk of suicidal, homicidal or violent ideation or behavior as clinically
             assessed by the investigator

          -  History of life threatening allergic reaction to any drug

          -  Known or suspected hypersensitivity or intolerance of risperidone, paliperidone,
             Intralipid (placebo) or any of their excipients (e.g., soybean oil, egg yolks,
             phospholipids, glycerol)

          -  Exposure to an experimental drug, experimental biologic, or experimental medical
             device within 6 months before screening or prior randomization into this study

          -  Enrollment in 2 or more clinical research studies in the previous year or one or more
             clinical research studies in the previous 6 months (non intervention, observational,
             and retrospective studies excluded)

          -  History of any active malignancy within the previous 5 years, with the exception of
             excised basal cell carcinomas

          -  A woman who is pregnant, breast-feeding, or planning to become pregnant during the
             study period

          -  Employee of the investigator or study center, with direct involvement in the proposed
             study or other studies under the direction of that investigator or study center, as
             well as family members of the employees or the investigator

          -  Treatment with any of the following disallowed therapies: an injectable antipsychotic
             within 1 injection cycle before screening, an injection of RISPERDAL CONSTA within 6
             weeks of screening, electroconvulsive therapy within 60 days before screening,
             previous injection of paliperidone palmitate within the past 10 months before
             baseline, use of clozapine within 3 months before baseline, nonselective or
             irreversible monoamine oxidase inhibitor antidepressants within 30 days before
             screening: other antidepressants unless patient has been on a stable dose for at least
             30 days before screening, mood stabilizers and beta-blockers must be washed out by the
             beginning of the study

          -  History or presence of circumstances that may increase the risk of the occurrence of
             serious illness or death in association with the use of drugs that affect heart rhythm