A Drug Interaction Study of Valproic Acid and Paliperidone Extended-Release (ER) in Patients With Schizophrenia, Bipolar I Disorder, or Schizoaffective Disorder
Condition: Schizophrenia; Bipolar Disorder; Psychotic Disorders
MeSH terms: Schizophrenia; Bipolar Disorder; Psychotic Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the potential effect of multiple oral doses of an
      extended release formulation of paliperidone on the pharmacokinetics (blood levels) of
      valproic acid (VPA) in patients with schizophrenia, bipolar I disorder, or schizoaffective
      disorder.
    

Detailed description: 
      This is an open-label (patient will know the identity of the study drug they are taking)
      study in patients diagnosed with either schizophrenia, bipolar I disorder, or schizoaffective
      disorder who currently receive treatment with valproic acid, sodium valproate, or divalproex
      sodium. The primary purpose of the study is to determine the effect, if any, that multiple
      doses of paliperidone extended release (ER) tablets has on the pharmacokinetics (ie, blood
      levels) of valproic acid administered in the study as divalproex sodium extended release
      (ER). Divalproex sodium consists of a compound of sodium valproate and valproic acid in a 1:1
      molar relationship in an enteric coated form. Approximately 16 patients will take part in the
      study. The study will last approximately 41 days and participation in this study will require
      a minimum of 5 overnight stays up to a maximum of 13 overnight stays during study drug
      treatment. The study will consist of a screening period that will occur up to 21 days before
      study treatment, a 13-day treatment period, and a posttreatment period that will include a
      follow-up visit 1 week after end-of-treatment procedures are performed. The purpose of the
      screening visit is to see patients meet all of the requirements to participate in the study.
      At the screening visit, after patients read and provide written informed consent
      acknowledging their willingness to participate in the study, the following procedures will be
      performed: 1) information regarding medical, psychiatric, and surgical history and
      medications currently taken will be collected, 2) a physical examination will be performed,
      3) vital signs (blood pressure) and an electrocardiogram (ECG, a painless test to measure the
      electrical activity of the heart) will be assessed, 4) a blood sample for routine laboratory
      tests as well as to test for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)
      (and to check for pregnancy in women of child-bearing potential) will be collected, 5) a
      urine sample will be collected for routine laboratory testing including testing for drugs of
      abuse, and 6) an alcohol breath test will be performed. Patients who meet entry criteria for
      the study will be asked to check-in at the study clinic the evening before the first
      administration of study drug and will stay overnight at the clinic for at least 5 days or
      through Day 13 (approximately 2 weeks). During overnight stays at the clinic, patients will
      be required to eat and drink only the meals and beverages provided at the clinic. Patients
      will take each study drug orally (by mouth) in the following order on the days specified:
      divalproex sodium ER once daily for 7 days (Day 1 through Day 7) followed by divalproex
      sodium ER once daily in combination with paliperidone ER once daily for 7 days (ie, Days 8
      through Day 12). During the study, patients will have blood samples taken from a vein in
      their arm using a needle (or flexible tube) at specified times during the study to determine
      the concentration of drugs in their blood. On Day 13 (or at the time of early withdrawal from
      the study) after the last blood sample for drug levels has been collected, patients will
      undergo end-of-study procedures that will include a physical examination, measurement of
      vital signs, and an ECG. A blood and urine sample for routine laboratory testing will also be
      collected during the end-of-study procedures to check the patients general health (and to
      check for pregnancy in women of child-bearing potential). After all end-of-study procedures
      have been completed, patients will leave the study clinic and return in about 1 week for a
      posttreatment follow-up visit where their overall general condition and the occurrence of any
      adverse events will be assessed. The primary objective of this study is to assess the
      potential effect of multiple doses of paliperidone ER tablets on the steady state
      pharmacokinetics of VPA. Steady state is achieved when drug concentrations in the blood are
      stable (ie, when the rate of drug absorption equals the rate of drug elimination in the
      body). Patients will also be monitored for safety from the time that they sign the informed
      consent form through to the end of the study (ie, posttreatment follow up visit). Safety will
      include monitoring adverse events, changes in clinical laboratory test results, ECG
      parameters, vital signs measurements, physical examination findings, the severity of the
      patients general condition, and concomitant medications (medications other than study drugs
      taken by patients) throughout the study period. All patients will receive a single oral (by
      mouth) daily dose of divalproex sodium ER (dose depended on the patients prescreening
      therapeutic dose) on Days 1 through 7 and divalproex sodium ER once daily in combination with
      one 12mg tablet of paliperidone ER once daily on Days 8 through 12. All study drugs are to be
      swallowed whole with water.
    

Intervention name(s): divalproex sodium ER/paliperidone ER
Intervention type(s): Drug
Intervention description(s): Divalproex sodium ER (dose determined from the patients prescreening therapeutic dose) once daily from Day 1 through Day 7 and once daily in combination with paliperidone ER 12 mg from Day 8 through Day 12
Intervention MeSH terms: Valproic Acid; Paliperidone Palmitate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: Paliperidone ER; INVEGA; Divalproex sodium; Depakote ER; Valproic acid; Pharmacokinetics; R076477BIM1004