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

NCT ID: NCT00391222

Last Updated: 2014-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 585 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2009-04-30

Brief Summary

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.

Detailed Description

This is a randomized, double-blind, double-dummy multicenter study with 3 parallel arms (risperidone long-acting injectable (LAI), placebo, and olanzapine) to evaluate the efficacy and safety of risperidone LAI versus placebo in the prevention of a mood episode (recurrence event). The primary objective of this study is to evaluate the efficacy of risperidone LAI monotherapy 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. This study includes 3 periods - the screening period (Period I, lasting up to 2 weeks); the open-label treatment period (Period II, lasting 12 weeks); and the double-blind treatment period (Period III, lasting up to 18 months and at least 9 months). In the open -label treatment period (Period II) treatment with risperidone LAI will be started with injection of a recommended dose of 25 mg every 14 days in patients entering Period II. If judged clinically appropriate, patients may start with 37.5 mg every 14 days. Dosage can only be increased (up to a maximum dose of 50 mg every 14 days) if the Clinical Global Impression - Severity (CGI-S) score has increased by => 1 over 2 consecutive assessments at least 2 weeks apart and if there is symptom exacerbation that cannot be treated adequately with short-term (14 days) benzodiazepine medication. If an increase in risperidone LAI dosage is necessary, oral risperidone (1 to 2 mg/day) needs to be added for 3 weeks after the first injection of the higher dosage. Washout of all psychotropics other than risperidone long acting must be completed by the end of the first week. Non-acute patients on an antipsychotic or mood stabilizer for at least 4 weeks will continue their previous treatment for the first 3 weeks. No changes will be made in the regimens of non-acute patients receiving an antipsychotic or mood stabilizer unless there is concern about efficacy or safety.Patients experiencing an acute manic or mixed episode will additionally be treated with oral risperidone at whole-milligram dosages between 1 and 6 mg/day as needed to treat the symptoms of the acute episode for the first 3 weeks, in order to cover the 3 weeks lag period of Risperidone long acting. Patients experiencing an acute episode who do not respond to treatment within 4 weeks will be discontinued from the study. Patients who do not show a response (acute patients at baseline) or do not maintain the efficacy (non-acute patients at baseline and acute patients after initial response) during the 12-week (3 month) open-label risperidone LAI stabilization period (Period II), will be discontinued from the study as soon as any one of the following criteria is met: The patient meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, text revised (DSM-IV-TR) criteria for a hypomanic, manic, mixed, or depressive episode; the patient needs treatment intervention with any mood stabilizer, antipsychotic medication (other than study drug), benzodiazepine (beyond the dosage allowed), or antidepressant medication; the patient requires hospitalization for any bipolar mood episode; the patient either has a Young Mania Rating Scale (YMRS) score >12 in combination with CGI-S score =>4 or a Montgomery-Åsberg Depression Rating Scale (MADRS) score >12 in combination with a CGI-S score =>4. (If either of these criteria is fulfilled at an assessment but if the investigator assumes that this is only a temporary state that requires no action, the investigator is allowed to postpone the decision about maintenance or response by a maximum of 4 days. If after 4 days, the criteria are still met, the patient must be withdrawn from Period II.) Patients who show initial and maintained response (acute patients at baseline) or who maintain the efficacy (non-acute patients at baseline) during the 12-week (3-month) open-label risperidone LAI stabilization period (Period II), will be eligible for entering the double-blind treatment period (Period III). Patients who enter Period III will be randomized to receive intramuscular injections of risperidone LAI every 14 days (at the dosage achieved at the end of Period II) and oral placebo daily, or placebo injections every 14 days and oral placebo daily, or placebo injections every 14 days and oral olanzapine 10 mg/day. No supplementation with oral risperidone and no dosage titration will be allowed during this period of the study. Using the double-dummy design, all patients will receive an intramuscular injection every 14 days and will take oral medication every day. Patients who present with a recurrence during Period III, will be considered as meeting the end point of the study. Patients will remain in the double-blind treatment period until they meet recurrence criteria, until they withdraw consent, or are lost to follow-up, until the last patient completed at least 9 months without a mood episode in Period III, or until the study ends. The study will end when 158 patients have presented with a mood episode in Period III, or if the study is terminated based on the decision of the sponsor. Approximately 860 patients meeting the inclusion and exclusion criteria will be enrolled in this study, with the goal of observing at least 158 recurrence events in Period III. Safety evaluations will include adverse events, clinical laboratory tests - including blood glucose/lipid profile (fasting), prolactin, TSH, and urinalysis - vital signs (pulse and blood pressure) and ECG, physical examination, body weight and height, the Extrapyramidal Symptom Rating Scale, pregnancy testing, and urine drug screen. The patients will receive risperidone LAI (25, 37.5 or 50 mg (period II)) every 14 days during the 12 week long open-label period (Period II). Patients who enter the double-blind period (Period III) will be randomized to receive intramuscular injections of risperidone LAI every 14 days and oral placebo daily, or placebo injections every 14 days and oral placebo daily, or placebo injections every 14 days and oral olanzapine 10 mg/day.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

001

Risperidone Long Acting Injectable (LAI) Intramuscular injections of risperidone LAI (25 37.5 or 50 mg) every 2 weeks and oral placebo daily

Group Type: EXPERIMENTAL

Risperidone Long Acting Injectable (LAI)

Intervention Type: DRUG

Intramuscular injections of risperidone LAI (25, 37.5, or 50 mg) every 2 weeks and oral placebo daily

002

Placebo Intramuscular injections of placebo every 2 weeks and oral placebo daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intramuscular injections of placebo every 2 weeks and oral placebo daily

003

Olanzapine Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily

Group Type: ACTIVE_COMPARATOR

Olanzapine

Intervention Type: DRUG

Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily

Interventions

Olanzapine

Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily

Intervention Type: DRUG

Placebo

Intramuscular injections of placebo every 2 weeks and oral placebo daily

Intervention Type: DRUG

Risperidone Long Acting Injectable (LAI)

Intramuscular injections of risperidone LAI (25, 37.5, or 50 mg) every 2 weeks and oral placebo daily

Intervention Type: DRUG

Eligibility 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

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceutica N.V., Belgium

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Pharmaceutica N.V. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Pharmaceutica N.V.

Locations

Baoding, , China

Beijing, , China

Guangzhou, , China

Nanjing, , China

Shanghai, , China

Suozhou, , China

Wuhan, , China

Barranquilla Atlantico, , Colombia

Bello Antioquia, , Colombia

Bogotá, , Colombia

Bogotá S/N, , Colombia

Medellin Antioquia, , Colombia

Pereira Risaralda, , Colombia

Freiburg im Breisgau, , Germany

Hildesheim, , Germany

Oranienburg, , Germany

Athens, , Greece

Ahmedabad, , India

Bangalore, , India

Chennai, , India

Hyderabad, , India

Ludhiana, , India

Mangalore, , India

Mumbai, , India

New Delhi, , India

Pune, , India

Varanasi, , India

Jakarta, , Indonesia

Amman, , Jordan

Beirut, , Lebanon

Johor Bahru, , Malaysia

Kuala Lumpur, , Malaysia

Mexico City, , Mexico

Mérida, , Mexico

Monterrey, , Mexico

Puebla City, , Mexico

Tabasco, , Mexico

Tampico, , Mexico

Zapopan, , Mexico

Lima, , Peru

Lima Lima, , Peru

Iloilo City, , Philippines

Mandaluyong, , Philippines

Mandaue City, , Philippines

Arkhangelsky District, , Russia

Chelyabinsk, , Russia

Izhevsk, , Russia

Kazan’, , Russia

Moscow, , Russia

Moscow Region, , Russia

Nizny Novgorod, , Russia

Orenburg, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Stavropol Na, , Russia

Tomsk Na, , Russia

Voronezh, , Russia

Bloemfontein, , South Africa

Cape Town, , South Africa

Durban, , South Africa

Pretoria, , South Africa

Tainan City, , Taiwan

Taipei, , Taiwan

Countries

China; Colombia; Germany; Greece; India; Indonesia; Jordan; Lebanon; Malaysia; Mexico; Peru; Philippines; Russia; South Africa; Taiwan

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=26&filename=CR012145_CSR.pdf

A randomized, double-blind, placebo and active-controlled, parallel-group study to evaluate the efficacy and safety of risperidone long-acting injectable for the prevention of mood episodes in the treatment of subjects with bipolar I disorder

Other Identifiers

CR012145

Identifier Type: -

Identifier Source: org_study_id

NCT01205113

Identifier Type: -

Identifier Source: nct_alias