Official Title: “High Dose Risperidone Consta for Patients With Schizophrenia With Unsatisfactory Response to Standard Dose Risperidone or Long-Acting Injectable”

The purpose of this study is to look at two doses of long-acting injectable risperidone (Risperdal Consta). The study will use a usual dose of Risperdal Consta (50 mg given every two weeks) or a higher dose (75 mg-100 mg given every two weeks) to see which one is better at improving symptoms of schizophrenia or schizoaffective disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Historical Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2010

This six month double-blind,randomized trial is designed to compare the efficacy of high dose long acting risperidone ( 75 mg-100 mg q2 weeks or its equivalent) with standard doses of long acting risperidone (≤50 mg/q 2weeks) for Total Psychopathology, positive, negative, and depressive symptoms, and cognition in patients who are considered to be poor responders by themselves, significant others, or clinicians. This will include two types of inadequately responding patients—those who are treatment resistant by research criteria (Kane et al., 1988) and those with inadequate response

Intervention(s) in this Clinical Trial

• Drug: long-acting injectable risperidone
  • Subjects will be randomized to conventional dose Consta or high dose Consta. All of those who are randomized to the conventional Consta dose will receive it in the form of Consta at a starting dose of 50 mg q 2 weeks. Those who are randomized to high dose Consta will receive a Consta 50 mg injection plus 25 mg injection (total dose 75 mg) q 2 weeks as the starting dose.Oral risperidone will be given up to Week 4 along with the injections for both groups to provide a transition phase.At Week 6, psychopathology will be assessed with a PANSS. If no improvement from baseline is shown, the randomized dose of Consta will be increased to 100 mg q 2 weeks (given as two 50 mg injections ) for those in the high dose Consta group. The dose for those randomized to the conventional dose group will remain the same (50 mg plus placebo).
• Drug: long acting injectable risperidone
  • Study dose remains 50 mg for the length of the study.
• Drug: long acting injectable risperidone
  • Beginning dose 75 mg. Can be increased to 100 mg at Week 6.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Conventional dose
  • All of those who are randomized to the conventional Consta dose will receive it in the form of Consta at a starting dose of 50 mg q 2 weeks (given as two injections - active 50 mg plus placebo injection).As advised by the package insert for Consta, oral risperidone will be given (3-4 mg qd x 3 days followed by 6mg qd up to Week 3 unless symptoms warrant a quicker titration) along with the injections.Any oral risperidone the patients receive will be discontinued after Week 4.At Week 6, psychopathology will be assessed with a PANSS. Dose will remain at 50 mg q 2 weeks for those in the conventional Consta dose group.
• Active Comparator: High Dose group
  • Those who are randomized to high dose Consta will receive Consta 50 mg injection plus 25 mg injection (total dose 75 mg) q 2 weeks as the starting dose after consent. As advised by the package insert for Consta, oral risperidone will be given (3-4 mg qd x 3 days followed by 6mg qd up to Week 4 unless symptoms warrant a quicker titration) along with the injections. Any oral risperidone the patients receive will be discontinued after Week 4.Psychopathology will be assessed with a PANSS at Week 6. If no improvement since baseline, dose will be increased to two 50 mg injections q 2 weeks for the remainder of the study.

Primary Measures

• The primary end point will be change in PANSS Positive Subscale Score in the high dose group using a mixed model ANOVA
  • Time Frame: six months
    Safety Issue?: No

Secondary Measures

• change in PANSS; time to discontinuation for lack of efficacy and tolerability; change in cognitive domain scores; comparative incidence and time course of EPS, hyperprolactinemia, plasma lipids, weight gain, and other side effects between treatments
  • Time Frame: six months
    Safety Issue?: Yes

Inclusion Criteria:

• Patients diagnosed with schizophrenia or schizoaffective disorder
• Able to give written informed consent.
• Moderate psychosis persists although compliant with medication
• Patients must have an inadequate response to two antipsychotic medications (can be risperidone, oral or long acting - but not required), at doses that are within the upper end of the standard dosage range
• Patients must have a Clinical Global Impression - Severity (CGI-S) scale score at screening of at least moderate severity and a PSP score of 60 or below.
• At the time of screening, eligible patients will be receiving or have received treatment with risperidone oral or Consta, or a combination that does not exceed 50 mg q 2 weeks of Consta or oral risperidone 8 mg/day for at least 6 weeks within seven years of study entry without satisfactory response as documented in the medical record Risperidone
• Patients who have received Consta injectable medication within the specified dose range for no more than a month prior to the onset of the study will be eligible.
• Patients receiving mood stabilizers or antidepressants, or both, in addition to risperidone oral or Consta, will be eligible
• Patients may initially be inpatients or outpatients
• Females of child bearing potential will be admitted only if they are on stable birth control medication and understand that they should not get pregnant during the course of the study.
• All patients must have stable housing at the current time or plans for housing following hospital discharge, if an inpatient.
• Patients must be willing to receive injectable medication

Exclusion Criteria:

• Patients with a diagnosis other than schizophrenia or schizoaffective disorder.
• Patients previously treated with doses of these agents higher than those allowed for at least six months and who failed to have an adequate response will be excluded
• Patients currently taking clozapine or have failed an adequate trial of clozapine which lasted at least 3 months
• Pregnant females. Females who are currently breastfeeding will be excluded.
• Patients with a diagnosis of substance dependence at screening or up to one year prior to enrollment.
• Patient with worse than mild tardive dyskinesia or history of marked EPS at screening
• Patients who have had neuroleptic malignant syndrome
• Patients with a history of galactorrhea
• Patients with uncontrolled medical condition(s)
• Patients with a history of non-compliance to oral or injectable medication.
• Patients unwilling to have injectable medication

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Vanderbilt University

Overall Clinical Trial Officials and Contacts

Herbert Meltzer, M.D. Principal Investigator Vanderbilt University  

Overall Contact: Kara Watts, M.A. 615-343-9717 kara.l.watts@vanderbilt.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00539071

Study ID Number: 070580

ClinicalTrials.gov Identifier: NCT00539071

Health Authority: United States: Institutional Review Board