A Pharmacokinetic Study of Risperidone and Topiramate Administered Alone and in Combination in Patients With Bipolar Disorder or Schizoaffective Disorders
Information source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bipolar Disorder
Intervention: topiramate (Drug); topiramate (Drug); risperidone (Drug); topiramate (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Official(s) and/or principal investigator(s): Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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.
Clinical Details
Official title: A Comparative Study of the Steady-state Pharmacokinetics of Risperidone and Topiramate on Monotherapy and During Combination Therapy in Patients With Bipolar or Schizoaffective Disorder
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To evaluate the potential pharmacokinetic interaction between topiramate and risperidone in patients with bipolar disorder or schizoaffective disorders.
Secondary outcome: Assess the safety of multiple doses of topiramate in combination with varying doses of risperidone
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).
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients meeting DSM-IV criteria for either Bipolar I Disorder, Bipolar II Disorder,
Cyclothymic Disorder, Bipolar Disorder NOS, or Schizoaffective Disorder (bipolar
type)
- Patients not in the midst of an acute manic, major depressive, or schizoaffective
episode and had not experienced an acute episode within the month prior to screening
- Women were to be postmenopausal for at least 1 year, or surgically incapable of
childbearing, or practicing an acceptable method of birth control (hormonal
contraception, intrauterine device, or barrier with spermicide were acceptable) and
not pregnant at baseline.
Exclusion Criteria:
- Patients with a history of an acquired or hereditary neurologic disease, e. g.,
epilepsy or significant brain trauma
- Patients using prescription medication, including psychotropic medications, within 14
days prior to the first day of Period I with the exception of hormonal contraceptives
(women), risperidone, or other medications approved by the sponsor
- Patients on depot medications (including but not limited to haloperidol decanoate)
- Patients who had taken acetazolamide, zonisamide, triamterene, dichlorphenamide,
chronic antacids, or calcium supplements, or any medication associated with
nephrolithiasis in the month prior to beginning TPM titration.
Locations and Contacts
Additional Information
A comparative study of the steady-state pharmacokinetics of risperidone and topiramate on monotherapy and during combination therapy in subjects with bipolar or schizoaffective disorders
Starting date: February 2001
Last updated: June 8, 2011
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