Clinical trial NCT00490971: A Study to Evaluate the Effectiveness and Safety of Extended-Release (ER) Paliperidone Compared With Placebo in Delaying the Recurrence of Symptoms in Bipolar I Disorder
Official title: A Randomized, Double-Blind, Active- and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Extended-Release Paliperidone as Maintenance Treatment After an Acute Manic or Mixed Episode Associated With Bipolar I Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder
Mania
Depression
Manic-Depressive Disorder
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2007-06-25
Enrollment: 768
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness and safety of oral extended-release (ER) paliperidone compared with placebo in the prevention of the recurrence of mood symptoms in patients with Bipolar I Disorder who initially respond to treatment of an acute manic or mixed episode with paliperidone ER. Olanzapine was included as an active control arm, although the study is not designed to allow for a direct comparison of olanzapine with paliperidone.

Detailed description: This is a randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken), active- and placebo-controlled, parallel-group, multicenter study to evaluate the efficacy (effectiveness) and safety of paliperidone ER relative to placebo in the prevention of recurrent mood symptoms associated with Bipolar I Disorder.

There are 5 phases in this study: a screening phase (lasting up to 7 days) to establish a subject's eligibility for the study,; a 3-week double-blind acute treatment phase to treat the acute or manic episode; a 12-week double-blind treatment continuation phase to establish a patient's clinical stability,; a double-blind treatment maintenance phase to measure the time to symptom recurrence that will last until the patient experiences a recurrence,; and a follow-up phase consisting of a visit approximately 1 week after the last study visit. All antipsychotic drugs and all mood stabilizers other than study drug must be discontinued before the first study drug administration.

Hospitalization is required for at least the first 7 days of the acute treatment phase. At the beginning of the acute treatment phase, patients will be randomly assigned to receive ER paliperidone or olanzapine in a 4:1 ratio. Patients in the ER paliperidone group who have a clinical response at the end of the acute treatment phase, remain clinically stable throughout the continuation phase, and achieve remission for each of the last 3 weeks of the continuation phase will again be randomly assigned: they will be assigned in a 1:1 ratio to receive ER paliperidone or placebo in the maintenance phase. Patients in the olanzapine treatment group who fulfill the same criteria will continue receiving double-blind treatment with olanzapine in the maintenance phase.

Measures of efficacy used are the Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression - Bipolar Disorder - Severity of Illness Scale (CGI-BP-S), Global Assessment of Functioning (GAF), the Short Form-36 to measure health-related functional status, and the sleep visual analog scale (VAS).

Safety evaluations include monitoring of adverse events, clinical laboratory tests (including urine pregnancy testing and hemoglobin A1c), 12-lead ECG, vital signs measurements, measurement of orthostatic changes in pulse and blood pressure, physical examinations (including height, body weight, and waist circumference), and monitoring of extrapyramidal symptoms using the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Rating Scale (BARS), and the Simpson Angus Scale (SAS). In addition, the Scale for Suicidal Ideation will be administered to assess suicidality.

The primary hypothesis for this study is that, during the long-term treatment of patients with Bipolar I Disorder who maintain clinical stability after an acute manic or mixed episode, ER paliperidone is superior to placebo in delaying the time to recurrence of any mood symptoms associated with Bipolar I Disorder. Patients begin the acute treatment phase at 6.0 mg/day of oral ER paliperidone or 10 mg/day of oral olanzapine. Dosages may be adjusted, as needed, between 3 to 12 mg/day of ER paliperidone or 5 to 20 mg/day of olanzapine, through the end of the continuation phase. Then, in the maintenance phase, patients receive the dosage of ER paliperidone (or ER paliperidone placebo) or olanzapine reached at the end of the continuation phase. They remain on those dosages until the end of the study.

Eligibility criteria: Inclusion Criteria:

* Meet DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for Bipolar I Disorder Most Recent Episode Manic or Mixed (with or without psychotic features)
* have a history of at least 2 previously documented mood episodes associated with Bipolar I Disorder (1 of which must be a manic or mixed episode) that required medical treatment within the past 3 years
* a total score of at least 20 on the YMRS at screening and at Day 1 of the study.

Exclusion Criteria:

* Meet DSM-IV criteria for any type of episode associated with bipolar disorder other than Bipolar I Disorder Most Recent Episode Manic or Mixed
* Meet DSM-IV criteria for rapid cycling
* Meet DSM-IV criteria for schizoaffective disorder
* Known or suspected borderline or antisocial personality disorder
* be, in the opinion of the investigator, at significant immediate risk for suicidal or violent behavior during the course of the study based on current status or prior history (e.g., suicide attempts during previous episodes).

Primary outcomes:
measure: Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder
timeFrame: Date of randomization into the maintenance phase until the first occurrence of recurrence of any symptoms or discontinuation from the study, assessed over a period of 41 months.
Secondary outcomes:
measure: Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder
timeFrame: Date of randomization into the maintenance phase until the first occurrence of recurrence of manic symptoms or discontinuation from the study, assessed over a period of 41 months.
measure: Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder
timeFrame: Date of randomization into the maintenance phase until the first occurrence of recurrence of depressive symptoms or discontinuation from the study, assessed over a period of 41 months.
Other outcomes:
measure: Young Mania Rating Scale (YMRS): Change From Baseline
timeFrame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
measure: Global Assessment of Functioning (GAF): Change From Baseline
timeFrame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
measure: Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline
timeFrame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Riverside
country: United States
state: California
city: San Diego
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Hoffman Estates
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Willingboro
country: United States
state: New Jersey
city: Cincinnati
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Bellevue
country: United States
state: Washington
city: Bulgaria
country: Bulgaria
city: Radnevo N/A
country: Bulgaria
city: Sofia
country: Bulgaria
city: Baoding
country: China
city: Beijing
country: China
city: Guangzhou
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Suzhou
country: China
city: Xi'An
country: China
city: San Jose
country: Costa Rica
city: San José
country: Costa Rica
city: Casablanca
country: France
city: Manouba
country: France
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Chemnitz
country: Germany
city: Düsseldorf
country: Germany
city: Göttingen
country: Germany
city: Jena
country: Germany
city: Lübeck
country: Germany
city: Bangalore
country: India
city: Calicut
country: India
city: Coimbatore
country: India
city: Hyderabad
country: India
city: Ludhiana
country: India
city: Pune
country: India
city: Varanasi
country: India
city: Kuala Lumpur
country: Malaysia
city: Panama Panama
country: Panama
city: Panama
country: Panama
city: Gdansk N/A
country: Poland
city: Krakow N/A
country: Poland
city: Leszno N/A
country: Poland
city: Skape
country: Poland
city: Swiecie Poland
country: Poland
city: Torun N/A
country: Poland
city: Tuszyn N/A
country: Poland
city: Bucharest
country: Romania
city: Craiova
country: Romania
city: Iasi
country: Romania
city: Tg Mures
country: Romania
city: Timisoara
country: Romania
city: Krasnodar N/A
country: Russian Federation
city: Nizny Novgorod
country: Russian Federation
city: Perm
country: Russian Federation
city: Smolensk Region N/A
country: Russian Federation
city: Yaroslavl N/A
country: Russian Federation
city: Belgrade
country: Serbia
city: Beograd
country: Serbia
city: Gornja Toponica
country: Serbia
city: Kragujevac
country: Serbia
city: Novi Knezevac
country: Serbia
city: Cape Town
country: South Africa
city: Durban Kn
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria
country: South Africa
city: Ankara
country: Turkey
city: Manisa
country: Turkey
city: Dnepropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kiev
country: Ukraine
city: Lvov
country: Ukraine
city: Vinnitsa
country: Ukraine
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Berwaerts J, Melkote R, Nuamah I, Lim P. A randomized, placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode. J Affect Disord. 2012 May;138(3):247-58. doi: 10.1016/j.jad.2012.01.047. Epub 2012 Feb 27.