Aripiprazole, Abilify Maintena Collaborative Clinical Protocol

Aripiprazole, Abilify Maintena Collaborative Clinical Protocol

An Open-label, Multi-center, Longitudinal, Within-subject Comparison Study to Evaluate the Effects of Aripiprazole Once Monthly in Subjects with Schizophrenia on 30-, 90-, and 180- day Re-hospitalization Rates Following Hospital Discharge Compared with Retrospective Re-hospitalization Rates while on Oral Antipsychotic Medication.

This is an open-label, multi-center, longitudinal, within-subject comparison study of the effects of aripiprazole once monthly on 30-, 90-, and 180-day psychiatric re-hospitalization rates following hospital discharge in subjects with schizophrenia compared with prior psychiatric hospitalization rates while on oral antipsychotics.

Prospective subjects will undergo screening for eligibility for entry into the study while hospitalized for symptoms due to schizophrenia.

Prospective subjects will be hospitalized for the necessary length of time as determined by the assigned treatment provider as clinically indicated, per the current standard of care. To be eligible, the anticipated duration of hospitalization should be long enough to accommodate the screening procedures, the 3-day Oral Tolerability Phase (if applicable), and initiation of treatment with aripiprazole once monthly.

During the Screening Period, subjects can be treated with any oral antipsychotic medication of the clinician's choice, with the exception of clozapine and olanzapine. However, oral olanzapine is permitted during the Screening Period only for subjects who are eligible for Phase A. Following the Screening Period, subjects who have no history of aripiprazole use will be entered into Phase A, the Oral Tolerability Phase. Subjects from Phase A that demonstrate tolerability to aripiprazole will then be entered into Phase B (i.e., the Treatment Phase). Subjects who already have a history of tolerating at least three consecutive oral doses of aripiprazole will be entered directly into Phase B. All eligible subjects will eventually enter Phase B.

Subjects who meet the inclusion and exclusion criteria and have no history of oral aripiprazole use will enter Phase A after the Screening Period while still hospitalized. Subjects in Phase A will be administered oral aripiprazole, as indicated in the product labeling, to determine tolerability. Dosage will be based on symptoms and the judgment of the investigator. The dose of oral aripiprazole may be titrated as needed. Prior antipsychotic medications will be tapered off and discontinued during the Screening Period and Phase A as clinically appropriate.

During Phase A, tolerability to oral aripiprazole will be evaluated daily for a minimum of 3 days using safety and tolerability measures (i.e., AIMS, BARS, and SAS) in conjunction with clinical judgment. If the subject shows tolerability to the oral aripiprazole, the Phase B baseline/Day 1 should occur with the first aripiprazole once monthly injection given immediately after the Phase B baseline/Day1 assessments. If a subject is unable to tolerate oral aripiprazole during the tolerability assessment in Phase A, he or she will be withdrawn from the study.

During Phase B, the subject will receive the first aripiprazole once monthly intramuscular (IM) injection, in conjunction with the first of 14 doses of concomitant oral aripiprazole, as indicated in the product labeling, after the baseline data are collected.

All subjects must attend scheduled visits at the Baseline Visit and Weeks 2, 4, 8, 12, 16, 20, and 24, totaling 180 days. Aripiprazole once monthly injections will occur at the Baseline Visit and every 28 ( -2, +5) days at Weeks 4, 8, 12, 16, 20, and 24, totaling seven injections. After the initial injection of 400 mg, the monthly dosage can be decreased to 300 mg, based on the clinical judgment of the investigator. All aripiprazole once monthly injections will be administered based on the investigator's judgment and the prescribing information.

For subjects who are psychiatrically stabilized and discharged prior to the completion of the required 14-day course of oral aripiprazole, a pre-discharge assignment will be given to a community support worker (CSW). The CSW will maintain regular contact with the subject until the first outpatient visit in Phase B (Week 2), when oral aripiprazole will be discontinued. Regular contact is defined as no less than weekly, but can be more frequent depending on the clinical judgment of the CSW and outpatient treatment team. Following the Week 2 Visit, subjects will have contact with their assigned CSW based on routine clinical care. Contact with the CSW can be in person or by telephone, as clinically appropriate.

Note: All long-acting antipsychotics are excluded from use during the study; however, aripiprazole once monthly is allowed

Inclusion Criteria:

• Are able to provide written informed consent.
• Are male and female subjects 18 to 65 years of age, inclusive, at time of informed consent
• Have a current diagnosis of schizophrenia as defined by DSM-5 criteria and a history of the illness for at least 6 months prior to screening from a reliable source (e.g., subject, family member, friend, caregiver, healthcare provider, or medical records)
• Present at one of the selected inpatient units with acute psychotic symptoms for hospitalization at study entry
• Have a clinically indicated need for a change in current antipsychotic therapy
• Are on Medicaid with searchable claims data
• Have at least one inpatient psychiatric hospitalization or psychiatric ED visit within the 6 months prior to screening
• Have been previously prescribed oral antipsychotic treatment for the 6 consecutive months prior to screening
• Have a history of response to antipsychotic treatment, with no history of clozapine treatment
• Are able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, aripiprazole once monthly injection, and discontinuation of prohibited concomitant medications
• Are able to read and understand the written word in order to complete subject-reported outcomes measures
• Are willing to accept a monthly injection
• Are male and female subjects who are surgically sterile (i.e., have undergone orchiectomy or hysterectomy, respectively); female subjects who have been postmenopausal for at least 12 consecutive months; or male and female subjects who agree to use an approved form of birth control during study participation

Exclusion Criteria:

• Has a current DSM-5 diagnosis other than schizophrenia, including schizophreniform disorder, schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also excluded are subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
• Prisoners or subjects who are involuntarily incarcerated, or have been incarcerated in the past 7 months for any reason
• Require potent cytochrome P450 (CYP)2D or CYP3A4 inhibitors or CYP3A4 inducers
• Are allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones or has a history of hypersensitivity to antipsychotic agents
• Have received electroconvulsive therapy within the 6 months prior to screening
• Have a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator
• Have current diagnosis of diabetes or known fasting triglyceride levels consistent with risk for pancreatitis
• Meets DSM-5 criteria for current substance use disorder within 3 months prior to screening
• Received treatment with long-acting injectable antipsychotics (e.g., haloperidol decanoate, fluphenazine decanoate, risperidone long-acting injection [Risperdal Consta®], paliperidone palmitate extended-release injectable suspension [Invega® Sustenna®], olanzapine for extended-release injectable suspension [Zyprexa® Relprevv™]), in which the last dose was within 7 months prior to screening
• Have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on Question 4 or Question 5 within the last 30 days on the baseline version of the C-SSRS
• Have a history or evidence of a medical condition that would expose them to an undue risk of a significant AE or interfere with assessments of safety or efficacy during the course of the study, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as determined by the clinical judgment of the investigator
• Have results from one or more of the following laboratory test, vital sign, and ECG tests at screening that are exclusionary (laboratory testing and ECGs will be performed locally): Platelets ≤ 75,000/mm3; Hemoglobin ≤ 9 g/dL; Fasting blood glucose > 126 mg/dL or HbA1c > 7.0%; Fasting triglyceride > 500 mg/dL; Neutrophils, absolute ≤ 1000/mm3; Aspartate transaminase (AST) > 3x ULN; Alanine transaminase (ALT) > 3x ULN; Creatinine ≥ 2 mg/dL; Diastolic blood pressure > 105 mmHg; QTc > 475 msec on either the QTcB (Bazett) or QTcF (Fridericia) corrections on ECG, confirmed by a second tracing; Any other abnormal laboratory tests, vital sign results, or ECG findings that, in the judgment of the investigator, are medically significant and would affect the safety of the subject or the interpretation of the study results. Abnormal results for laboratory parameters or vital signs should be repeated to ensure reproducibility of the abnormality before excluding a subject based on the criteria noted above.
• Have been previously enrolled in an aripiprazole once monthly clinical study
• Have participated in any clinical study with an investigational agent within the past 30 days
• Are pregnant or lactating