A Study to Evaluate the Efficacy and Safety of Risperidone for the Prevention of Mood Episodes in the Treatment of Patients With Bipolar I Disorder
This study has been completed.
Sponsor:
Janssen Pharmaceutica N.V., Belgium
Information provided by:
Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier:
NCT00391222
First received: October 20, 2006
Last updated: May 19, 2011
Last verified: May 2011
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
The purpose of this randomized, double blind, double dummy, multicenter study was to evaluate the efficacy of risperidone long-acting injectable (LAI) monotherapy in comparison with placebo in the prevention of a mood episode in treatment of patients with bipolar I disorder. Oral olanzapine was used to assess the validity of the study design. The primary objective of this study is to evaluate the efficacy of risperidone LAI versus placebo in the prevention of a mood episode (recurrence event) in patients with bipolar I disorder after a 12-week (3 month) stabilization period on risperidone LAI, as measured by the time to recurrence of any mood episode. Risperidone LAI has been approved by the FDA in the USA for the treatment of patients with schizophrenia and for the prevention of mood recurrences in bipolar I disorder, as monotherapy or add-on treatment. It is approved at EMEA and other European and non-European health authorities for the treatment of patients with schizophrenia, too.
| Condition | Intervention | Phase |
|---|---|---|
|
Bipolar Disorder |
Drug: Risperidone Long Acting Injectable (LAI) Drug: Olanzapine Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | A Randomized, Double Blind, Placebo and Active Controlled Parallel Group Study to Evaluate the Efficacy and Safety of Risperidone Long-acting Injectable (LAI) for the Prevention of Mood Episodes in the Treatment of Subjects With Bipolar I Disorder |
Resource links provided by NLM:
Further study details as provided by Janssen Pharmaceutica N.V., Belgium:
Primary Outcome Measures:
- Time to Recurrence of a Mood Episode (Risperidone LAI Versus Placebo) [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]Recurrence was estimated using the Kaplan-Meier method and defined as meeting any of the following: DSM-IV-TR criteria for a hypomanic, manic, mixed, or depressive episode; in need of mood stabilizer, antipsychotic medication, benzodiazepine or antidepressant; requiring hospitalization for mood episode; either Young Mania Rating Scale (YMRS) >12 or Montgomery-Åsberg Depression Rating Scale (MADRS) >12 combined with Clinical Global Impression - Severity (CGI-S) >=4; in need of increase in study medication dose or supplementation with oral risperidone or another antipsychotic or mood stabilizer.
Secondary Outcome Measures:
- Time to Recurrence of an Elevated Mood (Hypomanic, Manic, or Mixed) Episode [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]Recurrences were classified as elevated mood or depressive by the investigator based on the patient's data at the time of the event. Time to recurrence of an elevated mood episode was estimated by means of the same survival analysis method as for the primary outcome.
- Time to Recurrence of a Depressive Episode [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]Recurrences were classified as elevated mood or depressive by the investigator based on the patient's data at the time of the event. Time to recurrence of a depressive episode was estimated by means of the same survival analysis method as for the primary outcome.
- Time to Early Study Discontinuation for Any Reason [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]The robustness of the primary outcome analysis was tested by means of a sensitivity analysis: patients who discontinued the study during Period III for any reason were analyzed as having a recurrence of a mood episode at the time of their study discontinuation. The same survival analysis method as for the primary outcome was applied.
- Change From Double-blind Baseline to Endpoint in Young Mania Rating Scale (YMRS) [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]The 11-item YMRS was administered by an adequately trained clinician who did not provide psychotherapy or psycho-education to the patient. A severity rating was assigned to each of the items, based on the patient's subjective report of his or her condition over the previous 7 days or since the last visit (whichever was shorter) and the clinician's behavioral observations during the interview, with emphasis on the latter. The total YMRS score included the score of all 11 items ranging from 0 to 60, a higher score indicating a more severe condition.
- Change From Double-blind Baseline to Endpoint in Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]The MADRS was assessed by an adequately trained clinician who did not provide psychotherapy or psycho-education to the patient. The scale consists of 10 items that cover all of the core depressive symptoms. Each item is scored from 0 to 6 and a total score is calculated by adding the scores of all 10 items. For each individual item as well as for the total score, a higher score represents a more severe condition.
- Time to Recurrence of a Mood Episode (Exploratory/Olanzapine) [ Time Frame: Assessed at every visit from the moment of randomization to a treatment arm (baseline Period III) until the end of treatment (Month 21 or earlier) ] [ Designated as safety issue: No ]Recurrence was defined as for the risperidone LAI and placebo arms (meeting any of 5 criteria). Since the study was designed to compare the efficacy of risperidone LAI versus placebo, this olanzapine analysis was exploratory in nature.
| Enrollment: | 585 |
| Study Start Date: | November 2006 |
| Study Completion Date: | April 2009 |
| Primary Completion Date: | April 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 001
Risperidone Long Acting Injectable (LAI) Intramuscular injections of risperidone LAI (25 37.5 or 50 mg) every 2 weeks and oral placebo daily
|
Drug: Risperidone Long Acting Injectable (LAI)
Intramuscular injections of risperidone LAI (25, 37.5, or 50 mg) every 2 weeks and oral placebo daily
|
|
Placebo Comparator: 002
Placebo Intramuscular injections of placebo every 2 weeks and oral placebo daily
|
Drug: Placebo
Intramuscular injections of placebo every 2 weeks and oral placebo daily
|
|
Active Comparator: 003
Olanzapine Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily
|
Drug: Olanzapine
Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of bipolar I disorder as defined by DSM-IV-TR criteria. All diagnoses will be confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.). Patients who present with additional signs or symptoms compatible with Axis I diagnoses of social anxiety disorder or generalized anxiety disorder are acceptable. All other comorbid or active Axis I diagnoses are excluded. Personality disorders as defined by DSM IV TR criteria are acceptable, with the exception of antisocial and borderline personality disorders
- Must be currently experiencing a manic or mixed episode (acute
- YMRS >20 and CGI-S =>4 [moderate]) or must be between mood episodes (non-acute
- YMRS <12 and CGI-S=<3 [mild])
- Must have had at least 2 bipolar mood (manic, mixed manic, or depressed) episodes, exclusive of the current episode (if applicable), during the last year. For non-acute subjects (YMRS <12 and CGI-S=<3 [mild]), one manic episode must have occurred within 4 months of enrollment
- Patients who are non-acute (YMRS <12 and CGI-S =<3 [mild]) and are currently receiving an antipsychotic other than risperidone or a mood stabilizer must have received this other medication at the same dosage for a minimum of 4 weeks and must be either experiencing problems of safety or tolerability with the antipsychotic or mood stabilizer or request a change of medication
Exclusion Criteria:
- No history of more than 4 mood episodes each year (rapid cycling) during the last 2 years prior to screening
- No history of ADHD, anxiety disorder, or panic disorder as the primary diagnosis
- Not meeting DSM-IV-TR criteria for a hypomanic or depressive episode
- Not meeting DSM-IV-TR criteria for any comorbid or active Axis I disorder other than those specifically allowed in the Inclusion Criteria
- Not meeting DSM-IV-TR criteria for antisocial or borderline personality disorder
- Not having a chronic or serious general medical illness, including hepatic, renal, respiratory, cardiovascular, endocrine, neurologic (including seizure disorder), or hematologic disease as determined by the clinical judgment of the investigator
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | EMEA Medical Affairs Director, Janssen-Cilag S.A., Spain |
| ClinicalTrials.gov Identifier: | NCT00391222 History of Changes |
| Obsolete Identifiers: | NCT01205113 |
| Other Study ID Numbers: | CR012145 |
| Study First Received: | October 20, 2006 |
| Results First Received: | April 19, 2010 |
| Last Updated: | May 19, 2011 |
| Health Authority: | Belgium: Ministry of Social Affairs, Public Health and the Environment |
Keywords provided by Janssen Pharmaceutica N.V., Belgium:
|
Bipolar I Disorder Intramuscular injection prevention of mood episodes long acting injectable risperidone |
Additional relevant MeSH terms:
|
Bipolar Disorder Affective Disorders, Psychotic Mood Disorders Mental Disorders Risperidone Olanzapine Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Antipsychotic Agents |
Tranquilizing Agents Central Nervous System Depressants Central Nervous System Agents Therapeutic Uses Psychotropic Drugs Dopamine Antagonists Dopamine Agents Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents |
ClinicalTrials.gov processed this record on May 16, 2013