Characterization of Intramuscular Injections of Risperidone 4 Week Long-acting Injectable (LAI) Formulation in the Buttock of Patients With Schizophrenia

Official Title: “Single-Dose, Open-Label Pilot Study to Explore the Pharmacokinetics, Safety and Tolerability of a Gluteal Intramuscular Injection of a 4-Week Long-Acting Injectable Formulation of Risperidone in Patients With Chronic Stable Schizophrenia”

The purpose of this study is to explore the pharmacokinetics, safety and tolerability of a 4-week long-acting injectable (LAI) formulation of risperidone after single intramuscular (i.m.) injection of 75 mg risperidone LAI in the gluteal muscle.

An intramuscular injectable formulation of risperidone long-acting formulation is under development with the aim to provide a sustained and stable level of risperidone during each treatment cycle given every 4 weeks. As this formulation is a long acting formulation, patients will be treated with a 1 mg immediate release (IR) formulation in the first week to confirm that the patient does not develop an allergic reaction to the drug before receiving the long acting injectable (LAI) formulation. Each patient receives a total of two injections. The first one is the immediate release formulation and the second one, which is given at least a week later, is the new long acting formulation. Eligible patients can stay on their previous oral medication, no tapering of medication is needed. Blood samples will be collected to determine the levels of risperidone and its major metabolite in plasma.

Blood samples will be obtained by venipuncture (needle stick) immediately before (pre-dose) and at 5, 10, 20, 30, 45 min, 1, 1.5, 2, 4, 6, 8,12, 16, 24, 36, 48, 72, 96 hours after the 1st injection and at 2, 6, 12, 24, 48, 96 hrs, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 39, 43, 50, 57, 64, 71, 78, 85 days after the second injection of risperidone. Safety will assessed at visits throughout the study by monitoring scores of the Clinical Global Impression - Severity (CGI-S), scores of Extrapyramidal Symptom Rating Scale (ESRS), adverse events (AE), changes in clinical laboratory results, changes in physical examinations (PE), changes in electrocardiograms (ECGs), as well as patient and investigator evaluation of the injection site. The study has two periods. In the first period all patients will receive one injection of 1 mg risperidone IR (immediate release) solution (liquid). The follow-up duration is 96 hours. In the second period, patients will receive one injection of risperidone 4-week formulation of 75 mg. The follow-up duration is 85 days.

The injections, administered in the muscle of the buttocks, will be given 7 to 14 days apart.

Intervention(s) in this Clinical Trial

• Drug: risperidone IR and LAI formulation
  • 1 mg risperidone IR single injection, followed after 7 to 14 days with 75mg risperidone 4-week-LAI single injection

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 001
  • risperidone IR and LAI formulation 1 mg risperidone IR single injection followed after 7 to 14 days with 75mg risperidone 4-week-LAI single injection

Primary Measures

• To explore the pharmacokinetics of a 4-week long acting injectable (LAI) formulation of risperidone after single intramuscular (IM) injection of 75 mg in the gluteal muscle.
  • Time Frame: Up to 85 days for 4-week LAI formulation of risperidone and up to 96 hrs for immediate release (IR) formulation
    Safety Issue?: No

Secondary Measures

• To explore safety and tolerability of a 4-week LAI formulation of risperidone by monitoring scores on CGI-S, scores on ESRS, AEs, PE, lab values, ECG values and injection site reactions.
  • Time Frame: Up to 85 days
    Safety Issue?: No

Inclusion Criteria:

• Patients with a diagnosis of schizophrenia
• Clinically stable with no change in current antipsychotic medications
• Meet Positive and Negative Symptom Score (PANSS) and Clinical Global Impression (CGI) score criteria
• Have a body mass index (BMI) between 18 and 35 kilogram (kg)/meter (m)2
• If a woman, is postmenopausal surgically sterile, abstinent, or, if sexually active, is practicing before entry into the study and agrees to practice throughout the study an effective method of birth control
• If a man, agrees to use an adequate contraception method as deemed appropriate by the investigator

Exclusion Criteria:

• Alcohol or substance dependence, with the exception of nicotine or caffeine dependence
• Involuntarily-committed or unable to provide an informed consent
• Has tardive dyskinesia, History of Neuroleptic Malignant Syndrome
• History of or current clinically significant medical illness
• Treatment with any protocol disallowed therapies
• Clinically significant result from screening laboratory or ECG

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Industry

Overall Clinical Trial Officials and Contacts

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Study Director Johnson & Johnson Pharmaceutical Research & Development, L.L.C.  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00821600

Study ID Number: CR015742

ClinicalTrials.gov Identifier: NCT00821600

Health Authority: United States: Food and Drug Administration

Single Dose, Open Label Pilot Study to Explore the Pharmacokinetics, Safety and Tolerability of a Gluteal Intramuscular Injection of a 4 Week Long Acting Injectable Formulation of Risperidone in Subjects With Chronic Stable Schizophrenia