A Study of Extended Release Extended-release (ER) OROS Paliperidone Tolerability, as Compared to Immediate-release (IR)Risperidone, in Patients With Schizophrenia

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00791232
First received: November 13, 2008
Last updated: June 6, 2011
Last verified: March 2010
  Purpose

The purpose of this study is a noninferiority comparison of the orthostatic tolerability of a dose of 12 mg extended-release (ER) OROS paliperidone with the current recommended initial titration dose (2 mg) of immediate-release (IR) risperidone in patients with schizophrenia. Other study objectives are 1) to compare the tolerability and safety of a clinically equivalent fixed dose of ER OROS paliperidone with the currently recommended dose of risperidone, 2) to compare the early tolerability of the 2 treatments with placebo, 3) to compare tolerability of the 2 treatments, using a population pharmacokinetic/pharmacodynamic (pop PK/PD) model, to 4) assess the relationship between genetic variability in drug metabolizing enzymes and interindividual variability in plasma exposure to paliperidone or risperidone within each treatment group.


Condition Intervention Phase
Schizophrenia
Drug: extended-release (ER) OROS paliperidone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, Phase 1 Study to Compare the Tolerability of OROS Paliperidone (Extended Release) With Immediate-release (IR) Risperidone in Subjects With Schizophrenia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • A non-inferiority comparison of the orthostatic tolerability of a higher initial dose of paliperidone OROS with the current recommended initial dose of risperidone in patients with schizophrenia

Secondary Outcome Measures:
  • To compare the tolerability and safety of a clinically equivalent fixed dose of paliperidone OROS with the recommended dose of risperidone; early tolerability of the two formulations with placebo; tolerability using a pop PK/PD model

Enrollment: 113
Study Start Date: March 2003
Study Completion Date: June 2003
Detailed Description:

This is a randomized, double-blind, placebo- and active-controlled, parallel group, Phase 1. The study in patients with schizophrenia consists of a 1 week, open-label, placebo washout period (Days -7 to -1) and a 6 day double-blind treatment period during which patients will receive 1 of 3 treatments: placebo on Day 1 and ER OROS paliperidone (12 mg) on Days 2 to 6, ER OROS paliperidone (12 mg) on Days 1 to 6, or IR risperidone 2 mg on Day 1 and 4 mg on Days 2 to 6. Safety and tolerability will be monitored throughout the study.. ER OROS paliperidone (12 mg, oral) on Days 2 to 6, ER OROS paliperidone (12 mg, oral) on Days 1 to 6, or IR risperidone (oral) 2 mg on Day 1 and 4 mg on Days 2 to 6

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willingness to spend 2 weeks as an in-patient during the washout and treatment period
  • Currently treated with oral risperidone antipsychotic monotherapy for at least 1 month prior to screening
  • DSM-IV diagnosis of schizophrenia (Patients with a diagnosis of schizophrenia [paranoid type (295.30), disorganized type (295.10), catatonic type (295.20), undifferentiated type (295.90), or residual type (295.60)] as defined by DSM-IV criteria
  • Absence of acute exacerbation for a minimum of 6 months prior to screening
  • Female patients must be postmenopausal for at least 1 year, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before screening and throughout the study, and have a negative urine pregnancy test at screening and baseline
  • The patient is otherwise healthy on the basis of a physical examination, medical history, electrocardiogram, and the results of blood biochemistry and hematology tests and a urinalysis performed within 30 days of the start of the treatment period. If the results of the biochemistry or hematology tests or the urinalysis testing are not within the laboratory's reference ranges, the patient may be included only on condition that the investigator judges that the deviations are not clinically significant.

Exclusion Criteria:

  • Involuntarily committed in-patients
  • Patients who have received long-acting depot antipsychotic medication (discontinued RISPERDAL CONSTA for less than 10 weeks or discontinued other depots for less than 2 cycles)
  • Any significant history of cardiovascular disease: atrial fibrillation or flutter, second and third degree heart block and equivalent, resting supraventricular tachycardia (>100 beats per minute), unstable atherosclerotic heart disease, valvular abnormality
  • Body Mass Index > = 35 kg/m2 or a history of or current hypertension
  • Use of disallowed concomitant therapy or patients likely to require prohibited concomitant therapy during participation in the study
  • Patients with a pacemaker
  • Concomitant disease of the central nervous system that would bias the study evaluations, e.g.
  • stroke, brain tumor, Parkinson's disease, significant brain trauma, Alzheimer's disease, epilepsy, multiple sclerosis, currently-treated migraine
  • A DSM-IV Axis I diagnosis other than schizophrenia or with a DSM-IV diagnosis of substance dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary)
  • Diabetes mellitus and/or repeated fasting blood glucose value during the washout period >126 mg/dl and /or HbA1C > 7. 5%, hypothalamo-hypophyse dysfunction, Cushing, Addison, thyrotoxicosis, or Anemia (as defined by hematocrit < 30%)
  • Suicidal or homicidal ideation
  • Positive drug screen at screening and at baseline
  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: NCT00791232

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: NCT00791232     History of Changes
Other Study ID Numbers: CR004273
Study First Received: November 13, 2008
Last Updated: June 6, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Extended-release paliperidone
Schizophrenia, Mood disorders, Antipsychotic drugs
ER OROS paliperidone

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
9-hydroxy-risperidone
Risperidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 21, 2014