A Study of the Effect of Carbamazepine on the Pharmacokinetics of Paliperidone Extended Release (ER) in Patients With Schizophrenia or Bipolar I Disorder

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00892125
First received: November 20, 2008
Last updated: May 17, 2011
Last verified: April 2010
  Purpose

The purposes of this study are to evaluate the effects of a potent metabolic enzyme inducer, carbamazepine, on the steady-state pharmacokinetics of orally administered paliperidone ER and to evaluate the safety and tolerability of the treatments in clinically stable patients with a diagnosis of schizophrenia or bipolar I disorder.


Condition Intervention Phase
Schizophrenia
Bipolar Disorder
Drug: paliperidone ER; Carbamazepine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Effect of Carbamazepine on the Steady-state Pharmacokinetics of Paliperidone Extended Release in Clinically Stable Subjects With Schizophrenia or Bipolar I Disorder

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • to evaluate the effects of a potent enzyme inducer, carbamazepine, on the steady-state pharmacokinetics of orally administered paliperidone ER

Secondary Outcome Measures:
  • to evaluate the safety and tolerability of the treatments in clinically stable patients with a diagnosis of schizophrenia or bipolar I disorder

Enrollment: 64
Study Start Date: September 2006
Study Completion Date: March 2007
Detailed Description:

The current study is designed as an open-label, multiple-center, multiple-dose, 2 treatment, 2 period sequential drug interaction study. It consists of 3 phases: a screening phase beginning within 21 days before the first study drug administration; an open label treatment phase consisting of 2 treatment periods (Period 1 and Period 2), during which patients will receive multiple oral doses of 6-mg paliperidone ER alone or in combination with multiple oral doses of carbamazepine, and end of study evaluations upon completion of all the study procedures in Period 2 or at early withdrawal. There is no washout period between treatment periods. Given the potential concomitant use of carbamazepine with antipsychotics, such as paliperidone ER, in the treatment of schizophrenia or bipolar I disorder, this study is designed to investigate the effect of carbamazepine on the steady-state pharmacokinetics of paliperidone ER. Safety and tolerability will be monitored throughout the study.. Period 1: 6 mg paliperidone ER once daily from Day 1 through Day 7, route oral; Period 2: 6 mg paliperidone ER once daily and carbamazepine 200 mg twice daily from Day 8 through Day 28, route oral.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of schizophrenia of any subtype (295.10
  • 295.20
  • 295.30
  • 295.60
  • 295.90) or bipolar I disorder (296.0x, 296.4x, 296.5x, 296.6x or 296.7), according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
  • Clinically stable with no psychiatric hospitalization or change in existing mood stabilizers, antipsychotic, or anti-manic drugs for 3 months before screening. A reduction in the dose of existing medication is acceptable if the subject remained clinically stable throughout the 3 month period. In addition, an increase or decrease in the dose of a mood stabilizer on the basis of therapeutic drug monitoring or the substitution of a specific mood stabilizer, antipsychotic, or anti-manic drug for another because of poor tolerability will be allowed within 3 months before screening
  • Have a CGI-S score of 3 or less at baseline and at screening
  • Body mass index (BMI, weight [kg]/height [m2]) of 18 to 35 kg/m2, inclusive
  • Have a supine (after 5 minutes rest) blood pressure between 100 and 140 mmHg systolic, inclusive, and 50 and 90 mmHg diastolic, inclusive
  • Apart from the above-mentioned diagnosis, otherwise healthy on the basis of a prestudy physical examination, medical history, 12-lead ECG, and the laboratory results of serum chemistry, hematology, and urinalysis performed within 21 days before the first dose. For renal function tests, the values must be within the normal laboratory reference ranges
  • Women must be postmenopausal for at least 2 years, surgically sterile, abstinent, or practicing or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study (effective methods of birth control include intrauterine devices, double-barrier method, and male partner sterilization). Prescription hormonal contraceptives must be used in combination with another method of birth control (e.g., double-barrier method) throughout the study. Women of childbearing potential must have a negative serum pregnancy test result at screening, and a negative urine test at baseline (Day 1).

Exclusion Criteria:

  • Diagnosis of schizoaffective disorder (295.70) according to the DSM-IV
  • Meet DSM-IV criteria for rapid cycling
  • DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within 12 months before screening. Intermittent substance abuse in the months before screening will not be exclusionary, depending upon the clinical judgment of the investigator, with the exception of barbiturates
  • Acute substance abuse, as evidenced by a positive urine drug screen at screening or baseline (Day 1)
  • Positive alcohol test at screening or baseline (Day 1)
  • Current suicidal ideation or violent tendencies at the time of screening
  • Involuntarily-hospitalized subjects
  • Moderate or severe tardive dyskinesia at the time of screening
  • History of neuroleptic malignant syndrome
  • History of bone marrow depression or acute intermittent porphyria
  • History of or a positive result at screening for any of the serology tests (hepatitis B, C, and human immunodeficiency virus [HIV])
  • History or presence of any relevant cardiovascular (including myocardial infarct or cardiac arrhythmia), respiratory, neurologic (including seizures), renal, hepatic, gastrointestinal (including surgeries, severe gastrointestinal narrowing, and malabsorption problems), endocrine, hematologic, or immunologic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892125

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00892125     History of Changes
Other Study ID Numbers: CR011440
Study First Received: November 20, 2008
Last Updated: May 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Schizophrenia
Bipolar I disorder
mood disorders
antipsychotic drugs
enzyme inducer
Paliperidone ER

Additional relevant MeSH terms:
Schizophrenia
Bipolar Disorder
Disease
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Affective Disorders, Psychotic
Mood Disorders
Pathologic Processes
9-hydroxy-risperidone
Carbamazepine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Anticonvulsants
Antimanic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014