A Pharmacokinetic Study of Risperidone and Topiramate Administered Alone and in Combination in Patients With Bipolar Disorder or Schizoaffective Disorders
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder; Psychotic Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the potential pharmacokinetic (absorption,
      distribution and excretion of the drug by the body) interaction between, and the safety of,
      topiramate and risperidone administered in combination in patients with a history of either
      bipolar spectrum or schizoaffective (bipolar type) disorders as defined by DSM-IV criteria.
    

Detailed description: 
      This was an open-label (both the investigator and the patient knew the identity of the study
      drug), nonrandomized pharmacokinetic (PK) study evaluating the interaction of topiramate and
      risperidone in patients with bipolar disorder. The study enrolled a sufficient number of
      patients to obtain 24 completed patients. Patients were men or women aged 18 to 55 years,
      inclusive, with a diagnosis of Bipolar Spectrum or Schizoaffective Disorder, who were not in
      the midst of an acute episode, and had not experienced an acute manic, major depressive, or
      schizoaffective episode for a minimum of 30 days prior to screening (enrollment was monitored
      to ensure that at least one-third of the study sample was of the same sex.) The study
      consisted of a screening phase and 3 treatment periods. In Period I, patients were stabilized
      to a clinically appropriate dose of risperidone within the range of 1 to 6 mg/day,
      administered in divided doses every 12 hours during a 2- to 3-week period (or longer as
      clinically necessary). Upon risperidone stabilization, serial blood and urine samples were
      obtained through 12 hours postdose for estimation of risperidone and its metabolite
      9-OH-risperidone (metabolites are formed by metabolism of the drug) concentrations in Period
      I. In Period II, which lasted up to 6 weeks or longer as clinically necessary, topiramate was
      gradually escalated to 3 steady-state target doses, while risperidone therapy continued
      unchanged. There were up to 3 PK sampling periods (days when multiple blood and urine samples
      are taken to estimate the amount of topiramate and /or risperidone and its metabolite
      9-OH-risperidone in blood or urine) when the patient achieved steady state at 100 mg/day
      topiramate (consistent amount of drug in blood with each dose); when/if the patient achieved
      steady state at 250 mg/day topiramate or maximum tolerated dose (MTD); and when/if the
      patient achieved steady state at 400 mg/day topiramate or MTD. During each PK sampling visit
      in Period II, serial blood and urine samples were obtained through 12 hours postdose for
      estimation of risperidone, 9-OH risperidone, and topiramate concentrations. In Period III,
      risperidone was gradually tapered while the 400-mg/day dose (or MTD) of topiramate was
      maintained. There were 2 PK sampling visits: when patients had attained steady state at a
      dose of 50% of the maximal risperidone dose reached in Period I; and when risperidone was
      discontinued for 7 days and patients were maintained on topiramate 400 mg/day or their
      respective MTD. During each PK sampling visit in Period III, serial blood and urine samples
      were obtained through 12 hours postdose for estimation of risperidone, 9-OH risperidone, and
      topiramate concentrations. Period I (risperidone stabilization): risperidone 1-6 mg/day for 2
      to 3 weeks. Period II (topiramate dose escalation): topiramate administered for approximately
      6 weeks titrated up to 3 potential target doses (100 mg/day, 250 mg/day and 400 mg/day), and
      risperidone continues unchanged. Period III (risperidone dose reduction): risperidone dose
      tapered to zero over a 4-week period while topiramate maintained at the target dose of 400
      mg/day (or MTD).
    

Intervention name(s): topiramate; topiramate; risperidone; topiramate
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 1-25 mg plus 1-100 mg tablet twice daily for 2 weeks (250 mg/day); 2-100 mg tablets twice daily for 2 weeks (400 mg/day); Twice daily, individualized dosing to stabilization at 1-6 mg/day.; 2-25 mg tablets twice daily for 2 weeks (100 mg/day)
Intervention MeSH terms: Topiramate; Risperidone
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: topiramate; risperidone, bipolar disorder