A Pharmacokinetic Study of Lithium Before and During Topiramate Dosing in Bipolar Disorder Patients
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the initial (after 1-week of maintenance dosing)
      and extended (after 3-weeks of maintenance dosing) effect of topiramate, at doses up to 600
      mg/day, on the steady-state pharmacokinetics (absorption, distribution and excretion of the
      drug by the body) of lithium carbonate in patients with bipolar disorders.
    

Detailed description: 
      This was an open-label (both the investigator and the patient knew the identity of the study
      drug), sequential treatment, multicenter study evaluating the interaction of topiramate and
      lithium in patients with bipolar disorders. The study population included 24 patients (12
      patients per group) with complete data considered adequate to fully evaluate the extent of
      the effect of topiramate on lithium pharmacokinetics (PK). The study consisted of a screening
      phase, during which patients were maintained on a stable dose of an immediate release lithium
      carbonate formulation administered every 12 hours, for a minimum of 2 weeks prior to the
      start of the study, and an open-label treatment phase consisting of a topiramate titration
      phase and a lithium and topiramate maintenance phase, and 3 PK sampling periods (days when
      multiple blood and urine samples are taken to estimate the amount of topiramate and /or
      lithium in the patients blood or urine). The duration of all of the periods were determined
      by the investigator. Patients were sequestered for 48 hours for each of the 3 PK sampling
      periods. At each sampling period, blood and urine samples were collected for laboratory
      safety analyses at the same designated serial sampling times and collection intervals as for
      PK sampling. All doses of study medication were administered every 12 hours. During PK
      sampling Period 1, patients were maintained on their respective morning and evening doses of
      lithium carbonate. Serial blood and urine samples were collected through 12 hours postdose
      for estimation of lithium serum and urine concentrations. Patients continued their lithium
      regimens and subsequently were initiated on topiramate and assigned to either the low-dose
      Group 1 (200 mg/day) or high-dose Group 2 (up to 600 mg/day). During the topiramate titration
      phase, the initial dose of topiramate was 25 mg/day and was titrated upward until the target
      dose of 200 mg/day was reached (Group 1) or the target dose of 600 mg/day (or maximum
      tolerated dose greater than 200 mg/day) was reached (Group 2). Topiramate dose titration was
      conducted on study Days 2, 4, and 7 for Group 1 and on Days 2, 7, 12, 17, 22, and 27 for
      Group 2. Once the maximum dose of topiramate was reached, the lithium and topiramate
      maintenance phase began and lasted for 3 weeks, during which the patients were maintained on
      a constant daily dose of topiramate and lithium carbonate. One week after beginning
      maintenance on topiramate and lithium carbonate, patients entered PK sampling Period 2 of the
      study, during which serial blood and urine samples were collected through 12 hours postdose
      for estimation of lithium serum and urine concentrations and for estimation of topiramate
      plasma concentrations. At the end of the 3 weeks of lithium and topiramate maintenance,
      patients entered PK sampling Period 3 of the study, during which serial blood and urine
      samples were collected through 12 hours postdose for estimation of lithium serum and urine
      concentrations and for estimation of topiramate plasma concentrations. Throughout the
      topiramate titration phase and the lithium and topiramate maintenance phase, serum trough
      concentrations of lithium (the amount of lithium in the patients blood immediately before
      their next dose) were determined prior to the morning dose every 3 days, beginning on Day 3
      of the topiramate titration phase. Patients are maintained on a stable dose of an immediate
      release lithium carbonate formulation for 2 weeks prior to study start. In the titration
      phase, topiramate given every 12 hours starting at 25 mg/day. Patients are titrated to target
      doses of 200 mg/day (low-dose group) over a period of up to 10 days, or 600 mg/day (high-dose
      group) over a period of up to 30 days. The lithium and topiramate maintenance phase lasts for
      an additional 3 weeks after target doses are reached.
    

Intervention name(s): topiramate; topiramate
Intervention type(s): Drug; Drug
Intervention description(s): 100 mg tablet twice daily for 3 weeks; One 100 mg and one 200 mg tablet twice daily for 3 weeks
Intervention MeSH terms: Topiramate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Topiramate; Lithium; Bipolar disorder