A Drug Interaction Study of Valproic Acid and Single-dose Paliperidone Extended-Release (ER) in Healthy Men
Condition: Schizophrenia; Epilepsy
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the effect of valproic acid (VPA) on the
      pharmacokinetics (blood levels) of a single oral dose of an extended-release formulation of
      paliperidone in healthy male volunteers.
    

Detailed description: 
      This is an open-label (patient will know the identity of the study drug they are taking)
      study in healthy volunteers (only healthy men will be asked to participate in the study). The
      primary purpose of the study is to determine how paliperidone (a schizophrenia medication)
      and divalproex sodium (an epilepsy medication also referred to as valproic acid [VPA])
      interact with each other to affect the absorption, distribution, metabolism, and elimination
      by the body. Other purposes of the study are to learn about the safety of the two study drugs
      when taken together and to learn how healthy volunteers tolerate the two drugs when taken
      together. Approximately 24 healthy men (referred to as healthy volunteers) will take part in
      the study. The study will last about 40 days and will consist of a screening period beginning
      up to 21 days before the first study drug administration followed by an open label treatment
      period that will last approximately 20 days (Day -1 through Day 19). The purpose of the
      screening visit is to see if healthy volunteers meet all of the requirements to participate
      in the study. During the screening period which may require more than one visit to the study
      clinic, the following procedures will be performed: 1) signed informed consent will be
      obtained from healthy volunteers to document that they agree to participate in the study, 2)
      medical history and demographic information including age, date of birth, sex, race, etc will
      be collected, 3) a physical examination will be performed, 4) vital signs (pulse rate, blood
      pressure, and temperature) will be measured, 5) a blood sample will be collected for routine
      laboratory tests as well as to test for hepatitis B, hepatitis C, and human immunodeficiency
      virus (HIV), and 6) a urine sample will be collected for routine laboratory testing including
      testing for drugs of abuse and alcohol. Healthy volunteers who meet the entry criteria for
      enrollment at screening will be asked to check in to the study clinic the evening before the
      first administration of study drug (Day -1) and will stay overnight in the clinic until Day
      19. During the 20 days at the study clinic, healthy volunteers will be asked to refrain from
      the consumption of food or beverages containing alcohol, grapefruit juice, Seville oranges,
      or quinine (such as tonic water), use of any caffeine/xanthine-containing products (coffee,
      tea, chocolate, cola, other soda with caffeine), and food containing poppy seeds. Healthy
      volunteers will also be asked to refrain from jogging, strenuous exercise of all types, and
      sunbathing while confined to the study center and for 48 hours before admission to the study
      center. Healthy volunteers will be provided with standard meals during the 20 days of
      confinement at the study center and may smoke throughout the study with a limit of 10
      cigarettes or 2 cigars, or 2 pipes of tobacco per day. If a healthy volunteer has an illness
      with a fever within 2 days of a scheduled dose of study drug, the dose of study drug will be
      postponed until their body temperature is normal for at least 72 hours (3 days). All healthy
      volunteers will take each study drug orally (by mouth) in the following order on the days
      specified: 1 extended release (ER) tablet of 12 mg paliperidone on Day 1 followed by two
      500-mg ER tablets of divalproex sodium once daily from Day 5 to 18, and 1 tablet of 12 mg
      paliperidone ER on Day 15. Paliperidone ER tablets will be taken by healthy volunteers after
      an overnight fast (having nothing to eat or drink except water) of at least 10 hours.
      Divalproex sodium ER tablets can be taken at any time between 1 hour before and 1 hour after
      a meal (except for Days 14 and 15); the morning dose on Days 14 and 15 will be administered
      after a 10 hour fast. All study drug tablets will be swallowed whole with a glass of water
      (tablets must not chewed, divided, dissolved, or crushed). The shells of the paliperidone ER
      tablets are non-disintegrating and may leave the body intact. Therefore, healthy volunteers
      may see the shells of the tablets in their stools but there is no reason for alarm. During
      the study, healthy volunteers will have blood samples taken from a vein in their arm using a
      needle. Each blood sample will consist of approximately 1 teaspoonful of blood. Over the
      course of the study a total of 53 blood samples will be collected which is about a total of 9
      ounces or just a little over a cup of blood. The blood samples will be used to evaluate the
      primary outcome measure in the study which is the pharmacokinetics (blood levels) of a single
      dose of orally administered paliperidone ER before and during the administration of VPA at
      steady-state (steady state is achieved when the rate of drug absorption equals that of the
      drug elimination and drug concentrations in blood are stable). Healthy volunteers will also
      be monitored for safety throughout the study. Safety assessments include monitoring of
      adverse events (side effects) and findings from clinical laboratory tests (including
      hematology, serum chemistry, and urinalysis), 12-lead electrocardiograms (ECGs) (ECGs are
      used to trace the electrical activity of the heart), vital signs measurements, and physical
      examinations. A review of concomitant medications/therapies taken by healthy volunteers
      during the study will also be performed. Healthy volunteers will complete the study after the
      final blood sample is collected on Day 19. Before leaving the study center, end of study
      procedures performed will include a physical examination, vital signs measurements, routine
      clinical laboratory tests, and an ECG. All healthy volunteers will receive a single oral (by
      mouth) dose of one 12 mg paliperidone extended release (ER) tablet on Day 1 followed by two
      500-mg divalproex sodium ER tablets (each tablet equivalent to 500 mg of valproic acid) for
      oral administration once daily from Day 5 to 18 and a single oral dose of one 12 mg
      paliperidone ER tablet on Day 15. All drugs will be swallowed with 240 mL of noncarbonated
      water and must be swallowed whole, not chewed, divided, dissolved, or crushed.
    

Intervention name(s): paliperidone ER; divalproex sodium ER
Intervention type(s): Drug; Drug
Intervention description(s): 1 tablet of 500 mg once daily on Day 1 and Day 15; 2 tablets of 500 mg once daily from Days 5 through 18
Intervention MeSH terms: Valproic Acid; Paliperidone Palmitate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: Paliperidone ER; INVEGA; Divalproex sodium; Depakote ER; Pharmacokinetics; Valproic Acid; Human Experimentation