Clinical trial NCT00791232: A Study of Extended Release Extended-release (ER) OROS Paliperidone Tolerability, as Compared to Immediate-release (IR)Risperidone, in Patients With Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Extended-release paliperidone
Schizophrenia, Mood disorders, Antipsychotic drugs
ER OROS paliperidone
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2008-11-14
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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 outcomes:
measure: 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
Other outcomes:
Locations:
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: