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
Information source: Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bipolar Disorder
Intervention: Olanzapine (Drug); Placebo (Drug); Risperidone Long Acting Injectable (LAI) (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Janssen Pharmaceutica N.V., Belgium Official(s) and/or principal investigator(s): Janssen Pharmaceutica N.V. Clinical Trial, Study Director, Affiliation: Janssen Pharmaceutica N.V.
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Time to Recurrence of a Mood Episode (Risperidone LAI Versus Placebo)
Secondary outcome: Time to Recurrence of an Elevated Mood (Hypomanic, Manic, or Mixed) EpisodeTime to Recurrence of a Depressive Episode Time to Early Study Discontinuation for Any Reason Change From Double-blind Baseline to Endpoint in Young Mania Rating Scale (YMRS) Change From Double-blind Baseline to Endpoint in Montgomery Åsberg Depression Rating Scale (MADRS) Time to Recurrence of a Mood Episode (Exploratory/Olanzapine)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Baoding, China
Beijing, China
Guangzhou, China
Nanjing, China
Shanghai, China
Suozhou, China
Wuhan, China
Barranquilla Atlantico, Colombia
Bello Antioquia, Colombia
Bogota, Colombia
Bogotá S/N, Colombia
Medellin Antioquia, Colombia
Pereira Risaralda, Colombia
Freiburg, 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
Ciudad De Mexico, Mexico
Merida, Mexico
Monterrey, Mexico
Puebla, Mexico
Tabasco, Mexico
Tampico, Mexico
Zapopan, Mexico
Lima Lima, Peru
Lima, Peru
Iloilo, Philippines
Mandaluyong, Philippines
Mandaue, Philippines
Arkhangelsky District, Russian Federation
Chelyabinsk, Russian Federation
Izhevsk, Russian Federation
Kazan N/A, Russian Federation
Moscow Region, Russian Federation
Moscow, Russian Federation
Nizny Novgorod, Russian Federation
Orenburg, Russian Federation
Saratov N/A, Russian Federation
St Petersburg N/A, Russian Federation
St-Petersburg, Russian Federation
Stavropol Na, Russian Federation
Tomsk Na, Russian Federation
Voronezh, Russian Federation
Bloemfontein, South Africa
Cape Town, South Africa
Durban, South Africa
Pretoria, South Africa
Tainan, Taiwan
Taipei, Taiwan
Additional Information
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
Starting date: November 2006
Last updated: April 24, 2014
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