Efficacy
Once-monthly ABILIFY MAINTENA® (aripiprazole): Demonstrated efficacy and safety for adult patients living with schizophrenia
Establish tolerability with oral aripiprazole before initiating therapy. For patients already stable on oral aripiprazole or another oral antipsychotic, after the first injection, continue treatment with the antipsychotic for 14 consecutive days.
12-week study
Study design
Primary endpoint: Mean change in PANSS total score from baseline to Week 101
A 12-week, randomized, double-blind, placebo-controlled study in which acutely relapsed adult patients* living with schizophrenia were randomized to either ABILIFY MAINTENA or intramuscular placebo.1 Safety was assessed throughout the duration of the study.
*Baseline characteristics: PANSS total score ≥80 and PANSS score >4 on each of four specific psychotic symptoms (conceptual disorganization, hallucinatory behavior, suspiciousness/persecution, and unusual thought content).1
PANSS=Positive and Negative Syndrome Scale.
ABILIFY MAINTENA showed a statistically significant reduction in PANSS total score vs placebo as early as Week 1 through Week 121
*Baseline characteristics: PANSS total score ≥80 and PANSS score >4 on each of four specific psychotic symptoms (conceptual disorganization, hallucinatory behavior, suspiciousness/persecution, and unusual thought content).1
PANSS=Positive and Negative Syndrome Scale.
Study design
A 12-week, randomized, double-blind, placebo-controlled study in which acutely relapsed adult patients with schizophrenia were randomized to either ABILIFY MAINTENA (n=168) or intramuscular placebo (n=172). After initial injection, patients received 14 days of oral aripiprazole or oral placebo based on treatment arm.1
- Primary endpoint was mean change in PANSS total score from baseline to Week 101
- Safety was assessed throughout the duration of the study1
| Patients were receiving a range of medications prior to study enrollment2† | |
|---|---|
| Risperidone | 21.5% |
| Quetiapine | 15.3% |
| Olanzapine | 8.2% |
| Aripiprazole | 6.5% |
| Another antipsychotic | 22.0% |
| No antipsychotic | 26.5% |
†Percentages provided were patient-reported estimations. All patients underwent a seven-day washout period at trial entry.
Screening phase
93.5% of patients were treated with an antipsychotic other than aripiprazole or no antipsychotic prior to study entry2
Patients without prior exposure received oral aripiprazole to establish tolerability.1
Patients had a mean PANSS total score of 103 (range 82 to 144) and a CGI-S score of 5.2 (markedly ill) at baseline.
CGI-S=Clinical Global Impressions-Severity of Illness.
IMPORTANT WARNING AND PRECAUTION REGARDING CEREBROVASCULAR ADVERSE EVENTS, INCLUDING STROKE
Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with oral aripiprazole.
52-week maintenance study
Study design
In a 52-week, multiphase maintenance study of adult patients living with schizophrenia diagnosed ≥3 years with a history of symptom exacerbation or relapse when not receiving antipsychotic treatment.‡ Phases consisted of an open-label phase 1 (conversion to oral aripiprazole), an open-label phase 2 (stabilization on oral aripiprazole 10 mg to 30 mg once daily), a single-blind phase 3 (conversion and stabilization on ABILIFY MAINTENA 400 mg; patients continued on oral aripiprazole 10 mg to 20 mg for the first 14 days following the initial ABILIFY MAINTENA dose), and a double-blind, placebo-controlled, randomized phase 4 in which patients received either ABILIFY MAINTENA (n=269) or placebo IM depot (n=134).3
The hazard ratio was used to calculate the reduction in risk of relapse for patients on ABILIFY MAINTENA vs placebo.
‡DSM-IV-TR criteria.
§Relapse was defined as one or more of the following: clinical worsening, psychiatric hospitalization, risk of suicide, or violent behavior.
||This figure is based on a total of 80 relapse events.
CI=confidence interval; DSM-IV-TR=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; HR=hazard ratio; IM=intramuscular.
ABILIFY MAINTENA (n=269) significantly delayed time to relapse§ vs placebo (n=134) in a 52-week study (HR=0.199 [95% CI, 0.1-0.3], P<0.0001)3,4||
Primary endpoint:
Time from randomization to relapse
‡DSM-IV-TR criteria.
§Relapse was defined as one or more of the following: clinical worsening, psychiatric hospitalization, risk of suicide, or violent behavior.
||This figure is based on a total of 80 relapse events.
CI=confidence interval; DSM-IV-TR=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; HR=hazard ratio; IM=intramuscular.
The placebo-controlled, 52-week maintenance study evaluated the time
to relapse for adult patients with schizophrenia
Study design
A multiphase study that included open-label stabilization on oral aripiprazole, single-blind stabilization on ABILIFY MAINTENA (along with oral aripiprazole for the first 14 days), and a 52-week, randomized, double-blind, placebo-controlled study in which adult patients with schizophrenia were randomized to either ABILIFY MAINTENA (n=269) or intramuscular placebo (n=134).3
The study enrolled patients with schizophrenia diagnosed ≥3 years and a history of symptom exacerbation
or relapse when not receiving antipsychotic treatment.3¶
PHASE 1
4-6 weeks
ORAL ARIPIPRAZOLE
PHASE 2
2-8 weeks
ORAL ARIPIPRAZOLE
15 mg to 30 mg
once daily
PHASE 3
12-36 weeks
ABILIFY MAINTENA® (aripiprazole)
400 mg
Patients continued on oral aripiprazole 10 mg to 20 mg for the first 14 days following the initial ABILIFY MAINTENA dose.
PLACEBO-CONTROLLED, RANDOMIZED
PHASE 4
Up to 52 weeks
Patients were randomized at baseline to receive either ABILIFY MAINTENA or placebo.
Primary endpoint: Time from randomization to relapse3
Relapse was defined as one or more of the following3:
- Clinical worsening
- CGI-Improvement score ≥5 and an increase on any of the 4 specific PANSS# items to a score >4:
with an absolute increase of ≥2 on that specific item since randomization or with an absolute increase
of ≥4 on the combined score of these items since randomization
- CGI-Improvement score ≥5 and an increase on any of the 4 specific PANSS# items to a score >4:
- Psychiatric hospitalization
- Due to worsening of psychotic symptoms
- Risk of suicide
- CGI-SS score of 4 (severely suicidal) or 5 (attempted suicide) on part 1 or CGI-SS score of 6 (much worse) or 7 (very much worse) on part 2
- Violent behavior
- Clinically significant self-injury, injury to another person, or property damage
¶DSM-IV-TR criteria.
#PANSS items were conceptual disorganization, hallucinatory behavior, suspiciousness, or unusual thought content.3
CGI=Clinical Global Impression; CGI-SS=Clinical Global Impression of Severity of Suicidality.
IMPORTANT WARNING AND PRECAUTION REGARDING NEUROLEPTIC MALIGNANT SYNDROME (NMS)
NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including aripiprazole. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of aripiprazole, intensive symptomatic treatment, and monitoring.
See the efficacy data of ABILIFY MAINTENA in the maintenance treatment
of bipolar I disorder.
ABILIFY MAINTENA® (aripiprazole): Demonstrated efficacy and safety for maintenance monotherapy for appropriate adult patients living with bipolar I disorder
52-week study design
In a 52-week multiphase maintenance study of adult patients living with bipolar I disorder with a history of ≥1 manic or mixed episode with manic symptoms that required hospitalization and/or treatment with either a mood stabilizer and/or antipsychotic (N=266).1
The placebo-controlled, 52-week maintenance study evaluated the time to recurrence for adult patients living with bipolar I disorder.1
Maintenance study of adult patients living with bipolar I disorder consisted of four phases.1
*Including those patients entering the trial on oral aripiprazole.
IM=intramuscular.
Recurrence was defined as one or more of the following1:
Clinical worsening
- YMRS total score ≥15
OR - MÅDRS total score ≥15
OR - CGI-BP-S overall score >4
OR - Serious AE of worsening BP-I
OR - Discontinuation due to lack of efficacy or due to an AE of worsening BP-I
OR - Clinical worsening with the need for addition of a mood stabilizer, antidepressant treatment, antipsychotic medication, and/or increase greater than the allowed benzodiazepine doses for treatment of symptoms of an underlying mood disorder
Psychiatric hospitalization
- For any mood episode
Increased risk of suicide
- Score ≥4 on the MÅDRS item 10
OR - Answer of YES on question 4 or 5 on the
C-SSRS
AE=adverse event; BP-I=bipolar I disorder; CGI-BP-S=Clinical Global
Impression-Bipolar Version-Severity; C-SSRS=Columbia-Suicide Severity Rating Scale; MÅDRS=Montgomery-Åsberg Depression Rating Scale; YMRS=Young Mania Rating Scale.
ABILIFY MAINTENA significantly delayed time to recurrence† of any mood episode vs placebo over one year (HR=0.45 [95% CI, 0.30-0.68], P<0.0001)1‡
Significantly delayed time to recurrence for a manic episode (52 episodes; P<0.0001) and mixed episodes (11 episodes; P=0.06). No substantial difference in the time to a depressive episode (39 episodes; P=0.864).2
†Recurrence was defined as clinical worsening, psychiatric hospitalization, or increased risk of suicide.1
‡This figure is based on a total of 103 recurrences.
CI=confidence interval; HR=hazard ratio.
ABILIFY MAINTENA significantly delayed time to recurrence† of any mood episode vs placebo over one year (HR=0.45 [95% CI, 0.30-0.68], P<0.0001)1‡
Primary endpoint: Time from randomization to recurrence†
of any mood episode1
IMPORTANT WARNING AND PRECAUTION REGARDING CEREBROVASCULAR ADVERSE EVENTS, INCLUDING STROKE
Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with oral aripiprazole.
ABILIFY MAINTENA significantly reduced the risk of recurrence of manic or mixed mood episodes over one year vs placebo2
No substantial difference in the time to a depressive episode (HR=0.932 [95% CI, 0.497-1.747], P=0.8247)2
The HR was used to calculate the reduction in risk of recurrence for patients on ABILIFY MAINTENA vs placebo.
IMPORTANT WARNING AND PRECAUTION REGARDING NEUROLEPTIC MALIGNANT SYNDROME (NMS)
NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including aripiprazole. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of aripiprazole, intensive symptomatic treatment, and monitoring.
See safety and tolerability data for ABILIFY MAINTENA.