Aripiprazole, Abilify Maintena Collaborative Clinical Protocol

• ClinicalTrials.gov Identifier: NCT02717130
• Recruitment Status: Unknown
• First Posted: March 23, 2016
• Last Update Posted: March 23, 2016
• Sponsor: Florida Atlantic University
• Collaborators: Washington University School of Medicine; University of Missouri-Columbia; University of Missouri, Kansas City; Burrell Behavioral Health
• Information provided by (Responsible Party): Florida Atlantic University

Tracking Information

• First Submitted Date: March 4, 2016
• First Posted Date: March 23, 2016
• Last Update Posted Date: March 23, 2016
• Study Start Date: March 2016
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 17, 2016): Psychiatric re-hospitalization rates will be assessed using hospital admission records [ Time Frame: 30 days ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: March 17, 2016)

• Unscheduled psychiatric emergency department visits will be assessed using hospital records [ Time Frame: 30 days ]
• Psychiatric emergency department visits plus hospitalizations will be assessed using hospital records [ Time Frame: 30 days ]
• Total psychiatric hospitalization days will be assessed using hospital admission records [ Time Frame: 180 days ]
• The effects of aripiprazole once monthly will be assessed using the Clinical Global Impression-Severity (CGI-S) score. [ Time Frame: 30 days ]
• The effects of aripiprazole once monthly will be assessed using the Clinical Global Impression-Improvement (CGI-I) score. [ Time Frame: 30 days ]
• Evaluate changes from baseline for weight (kg) [ Time Frame: 180 days ]
• Evaluate changes from baseline for body mass index (BMI) (kg/m^2) [ Time Frame: 180 days ]
• Evaluate changes from baseline for fasting glucose concentrations [ Time Frame: 180 days ]
• Evaluate changes from baseline for HbA1c concentrations [ Time Frame: 180 days ]
• Evaluate changes from baseline for fasting triglycerides [ Time Frame: 180 days ]
• Evaluate changes from baseline for fasting total cholesterol [ Time Frame: 180 days ]
• Evaluate changes from baseline for fasting high-density lipoprotein (HDL) cholesterol [ Time Frame: 180 days ]
• Evaluate changes from baseline for fasting low-density lipoprotein (LDL) cholesterol [ Time Frame: 180 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Aripiprazole, Abilify Maintena Collaborative Clinical Protocol
• Official Title: Aripiprazole, Abilify Maintena Collaborative Clinical Protocol
• Brief Summary: 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.

Detailed Description

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

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Schizophrenia
• Intervention: Drug: Aripiprazole

Study Arms

Experimental: Aripiprazole (Abilify Maintena)

Aripiprazole once monthly (300-400 mg for entire study duration) plus 14 days oral antipsychotic medication (first injection only) (dosage according to package inserts). After the 14 day oral lead-in, after the first injection of aripiprazole once monthly, only oral aripiprazole will be allowed as a rescue medication.

Intervention: Drug: Aripiprazole

Publications *

• Covell NH, Jackson CT, Evans AC, Essock SM. Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles. Schizophr Bull. 2002;28(1):17-29.
• Jablensky A, McGrath J, Herrman H, Castle D, Gureje O, Evans M, Carr V, Morgan V, Korten A, Harvey C. Psychotic disorders in urban areas: an overview of the Study on Low Prevalence Disorders. Aust N Z J Psychiatry. 2000 Apr;34(2):221-36.
• Barnes TR, Shingleton-Smith A, Paton C. Antipsychotic long-acting injections: prescribing practice in the UK. Br J Psychiatry Suppl. 2009 Nov;52:S37-42. doi: 10.1192/bjp.195.52.s37.
• Barnes TR, Paton C, Hancock E, Cavanagh MR, Taylor D, Lelliott P; UK Prescribing Observatory for Mental Health. Screening for the metabolic syndrome in community psychiatric patients prescribed antipsychotics: a quality improvement programme. Acta Psychiatr Scand. 2008 Jul;118(1):26-33. doi: 10.1111/j.1600-0447.2008.01203.x.
• Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002 Oct;106(4):286-90.
• Verdoux H, Lengronne J, Liraud F, Gonzales B, Assens F, Abalan F, van Os J. Medication adherence in psychosis: predictors and impact on outcome. A 2-year follow-up of first-admitted subjects. Acta Psychiatr Scand. 2000 Sep;102(3):203-10.
• Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry. 2006;67 Suppl 5:3-8. Review.
• Thornicroft G, Farrelly S, Szmukler G, Birchwood M, Waheed W, Flach C, Barrett B, Byford S, Henderson C, Sutherby K, Lester H, Rose D, Dunn G, Leese M, Marshall M. Clinical outcomes of Joint Crisis Plans to reduce compulsory treatment for people with psychosis: a randomised controlled trial. Lancet. 2013 May 11;381(9878):1634-41. doi: 10.1016/S0140-6736(13)60105-1. Epub 2013 Mar 26.
• Burns T, Rugkåsa J, Molodynski A, Dawson J, Yeeles K, Vazquez-Montes M, Voysey M, Sinclair J, Priebe S. Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial. Lancet. 2013 May 11;381(9878):1627-33. doi: 10.1016/S0140-6736(13)60107-5. Epub 2013 Mar 26.
• Gaebel W, Schreiner A, Bergmans P, de Arce R, Rouillon F, Cordes J, Eriksson L, Smeraldi E. Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial. Neuropsychopharmacology. 2010 Nov;35(12):2367-77. doi: 10.1038/npp.2010.111. Epub 2010 Aug 4. Erratum in: Neuropsychopharmacology. 2011 Jan;36(2):548.
• Olivares JM, Rodriguez-Martinez A, Burón JA, Alonso-Escolano D, Rodriguez-Morales A; e-STAR Study Group. Cost-effectiveness analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia : a 12- and 24-month follow-up from the e-STAR database in Spain. Appl Health Econ Health Policy. 2008;6(1):41-53.
• Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, Ali MW. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002 Sep;63(9):763-71.
• Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Stringfellow J, Ingenito G, Marder SR. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2003 Jul;60(7):681-90.
• Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, Archibald D, Ingenito G, Marcus R, Pigott T. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol. 2003 Dec;6(4):325-37.
• Kerwin R, Millet B, Herman E, Banki CM, Lublin H, Pans M, Hanssens L, L'Italien G, McQuade RD, Beuzen JN. A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study. Eur Psychiatry. 2007 Oct;22(7):433-43. Epub 2007 Jun 7.
• Tandon R, Devellis RF, Han J, Li H, Frangou S, Dursun S, Beuzen JN, Carson W, Corey-Lisle PK, Falissard B, Jody DN, Kujawa MJ, L'italien G, Marcus RN, McQuade RD, Ray S, Van Peborgh P; IAQ Validation Study Group. Validation of the Investigator's Assessment Questionnaire, a new clinical tool for relative assessment of response to antipsychotics in patients with schizophrenia and schizoaffective disorder. Psychiatry Res. 2005 Sep 15;136(2-3):211-21.
• Vieta E, Bourin M, Sanchez R, Marcus R, Stock E, McQuade R, Carson W, Abou-Gharbia N, Swanink R, Iwamoto T; Aripoprazole Study Group. Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial. Br J Psychiatry. 2005 Sep;187:235-42.
• Schulte RF, Boesiger P. ProFit: two-dimensional prior-knowledge fitting of J-resolved spectra. NMR Biomed. 2006 Apr;19(2):255-63.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 17, 2016): 177
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2018
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02717130
• Other Study ID Numbers: 031-104-0014
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Florida Atlantic University
• Study Sponsor: Florida Atlantic University

Collaborators

• Washington University School of Medicine
• University of Missouri-Columbia
• University of Missouri, Kansas City
• Burrell Behavioral Health

Investigators

• Principal Investigator: John Newcomer, MD; Florida Atlantic University
• Principal Investigator: Ginger Nicol, MD; Washington University School of Medicine

• PRS Account: Florida Atlantic University
• Verification Date: March 2016