Non-Pivotal PRELAPSE Study

PRELAPSE Study: Non-pivotal investigator-initiated study

Non-pivotal investigator-initiated study

The PRELAPSE study analyzed the time to first psychiatric hospitalization with ABILIFY MAINTENA® (aripiprazole) vs clinician’s choice over 2 years1

This study was an investigator-initiated project funded by Lundbeck and Otsuka America Pharmaceutical, Inc. The funders participated in the design of the study but had no influence on the conduct of the trial and were not involved in data collection or analysis, in the writing of the manuscript, or in the decision to submit for publication.1

The Prevention of Relapse in Schizophrenia (PRELAPSE) study was an investigator-initiated, multicenter, cluster-randomized clinical trial that randomized 41 sites in the US to receive either ABILIFY MAINTENA or clinician’s choice.1

Study site randomization1

ABILIFY MAINTENAClinician’s Choice19 sites analyzed
n=23419 sites analyzed
n=234††20 sites analyzed
n=25520 sites analyzed
n=255††20 sites randomized to ABILIFY MAINTENA21 sites randomized to clinician’s choiceClinicians at the sites were required to use ABILIFY MAINTENA in accordance with FDA-approved labeling, but were not otherwise restricted in treatmentClinicians at the sites offered treatment as usual, such as medication (including possible oral or LAI use), and other available services30.8%30.8% of patients were already receiving an LAI prior to enrollment of patients were already receiving an LAI prior to enrollment**27.4%27.4% of patients were already receiving an LAI prior to enrollment of patients were already receiving an LAI prior to enrollment‡‡41 sites randomized41 sites randomized
41 sites randomized41 sites randomizedClinicians at the sites were required to use 
ABILIFY MAINTENA in accordance with FDA-approved labeling, but were not otherwise restricted in treatment of patients were already receiving an LAI prior to enrollment of patients were already receiving an LAI prior to enrollment30.8%30.8%**20 sites randomized to ABILIFY MAINTENAABILIFY MAINTENA19 sites analyzed
n=23419 sites analyzed
n=234††20 sites analyzed
n=25520 sites analyzed
n=255††Clinicians at the sites offered treatment as usual, such as medication (including possible oral or LAI use), 
and other available services of patients were already receiving an LAI prior to enrollment of patients were already receiving an LAI prior to enrollment27.4%27.4%‡‡Clinician’s Choice21 sites randomized to clinician’s choice

*LAIs included ABILIFY MAINTENA (15.4%) or another LAI (15.4%) at time of consent.

†1 site was withdrawn from each arm due to 0 recruited patients for a total of 39 sites analyzed.

‡LAIs included ABILIFY MAINTENA (3.9%) and another LAI (23.5%) at the time of consent.

LAI=long-acting injectable.

 

Study design1

Inclusion criteria

  • Schizophrenia diagnosis confirmed by the Structured Clinical Interview for DSM-5, Research Version (SCID-5)
  • <5 years of lifetime antipsychotic use
  • Age of 18 to 35 years
  • Ability to provide informed consent

Exclusion criteria

  • Primary DSM-5 diagnosis other than schizophrenia
  • Pregnant or lactating women
  • Unstable medical condition
  • Prior clozapine use
  • History of intolerance to aripiprazole (ABILIFY MAINTENA sites only)

IMPORTANT WARNING AND PRECAUTION REGARDING TARDIVE DYSKINESIA (TD)

Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. Prescribing should be consistent with the need to minimize TD. If antipsychotic treatment is withdrawn, TD may remit, partially or completely.

 

Study limitations1

  • Only one study medication (ABILIFY MAINTENA)
  • Clinicians at ABILIFY MAINTENA sites offered ABILIFY MAINTENA without charge to patients in addition to other available services
  • Clinician’s choice sites allowed the use of LAIs, and sites were required to have clinical support; therefore, clinician’s choice sites had higher use of LAIs at baseline and during the study than US statistics would suggest
  • 51% of patients (n=130) at clinician’s choice sites received an LAI at some point during the study

Risk of first hospitalization was significantly reduced for patients taking ABILIFY MAINTENA in a 2-year study of adults with early-phase schizophrenia.

Clinicians’ choice was defined as treatment as usual, such as medication, including possible oral or LAI antipsychotics, and other available services.

Primary endpoint: Time to first psychiatric hospitalization with ABILIFY MAINTENA vs clinician’s choice over 2 years1

44%Reduced risk of first hospitalization(HR=0.56 [95% CI, 0.34-0.92], =0.02)§PDays from randomizationNumber of patients at risk23418315714712725518614811693Survival probability1.00.80.60.40.20.00180360540720ABILIFY MAINTENA (n=234) Clinician’s choice (n=255)Adapted from Kane JM, et al. . 2020;77(12):1217-1224.JAMA Psychiatry
ABILIFY MAINTENA (n=234) Clinician’s choice (n=255)Survival probability1.00.80.60.40.20.00720540360180Days from randomization44%Reduced risk of first hospitalization§(HR=0.56 [95% CI, 0.34-0.92], =0.02)P23418315714712725518614811693Number of patients at riskAdapted from Kane JM, et al. . 2020;77(12):1217-1224.JAMA Psychiatry

Medications allowed at clinician's choice sites per protocol included2||

Oral antipsychotics

Included but not limited to:

  • Aripiprazole
  • Lurasidone HCl
  • Olanzapine
  • Quetiapine fumarate
  • Risperidone
  • Ziprasidone HCl

LAI antipsychotics

Included but not limited to:

  • Aripiprazole
  • Fluphenazine decanoate
  • Haloperidol decanoate
  • Olanzapine
  • Paliperidone palmitate
  • Risperidone

§22.2% of ABILIFY MAINTENA patients met criteria for first hospitalization vs 36.0% of clinician’s choice patients.

||The percentage of patients on each of the different medications was not reported.

Administered via IM injection.

CI=confidence interval; HCl=hydrochloride; HR=hazard ratio; IM=intramuscular.

IMPORTANT WARNING AND PRECAUTION REGARDING METABOLIC CHANGES

Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes mellitus should be regularly monitored for worsening of glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes), should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
  • Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
  • Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

PRELAPSE: Adverse events reported after baseline assessment in ≥5% of patients1

PERCENTAGE OF PATIENTS REPORTING REACTION
ADVERSE
EVENT		 ABILIFY MAINTENA
(n=222)		 CLINICIAN’S CHOICE#
(n=241)
Worsening of psychotic symptoms 23.0 40.2
Weight gain 14.4 19.5
Suicidal ideation without suicide attempt** 8.6 9.5
Depression 10.4 8.3
Anxiety 12.2 6.2
Hyperprolactinemia 4.1 12.9
Elevated cholesterol levels 6.8 10.0
Hepatic enzyme abnormalities 6.8 9.1
Insomnia 8.6 7.1
Hypertension 5.4 7.5
Somnolence 7.2 4.6
Hostility/aggression 7.2 2.9
Tachycardia 3.2 5.0
Restlessness 6.3 0.8

#Clinician’s choice was defined as treatment as usual, such as medication, including possible oral or LAI antipsychotics, and other available services.

**Does not include the 1 patient in the clinician’s choice group who died by suicide. Patients who made suicide attempts concurrent with recorded suicidal ideation are not included; patients who made suicide attempts but also had suicidal ideation not concurrent with an attempt are included.

IMPORTANT WARNING AND PRECAUTION REGARDING PATHOLOGICAL GAMBLING AND OTHER COMPULSIVE BEHAVIORS

Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking aripiprazole. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping aripiprazole if such urges develop.

See the efficacy data of ABILIFY MAINTENA in the maintenance treatment of bipolar I disorder.

Bipolar I Disorder Maintenance