Aripiprazole Lauroxil for Preventing Psychotic Relapse After an Initial Schizophrenia Episode (APPRAISE)

• ClinicalTrials.gov Identifier: NCT04203056
• Recruitment Status: Terminated
• First Posted: December 18, 2019
• Last Update Posted: October 12, 2022
• Sponsor: University of California, Los Angeles
• Collaborator: Alkermes, Inc.
• Information provided by (Responsible Party): Kenneth L. Subotnik, PhD, University of California, Los Angeles

Tracking Information

• First Submitted Date: December 16, 2019
• First Posted Date: December 18, 2019
• Last Update Posted Date: October 12, 2022
• Actual Study Start Date: December 16, 2019
• Actual Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2019)

Exacerbation or relapse of positive psychotic symptoms [ Time Frame: 12 months ]

Time to first positive symptom exacerbation and/or relapse following a period of absence or relatively low levels of psychotic symptoms based on the expanded 24-item version of the Brief Psychiatric Rating Scale.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 17, 2019)

• Role ratings on the Global Functioning Scale [ Time Frame: 12 months ]
  The groups will be compared on this measure of role functioning. Scores range from 1 to 10, with higher indicating better role functioning.
• Overall Composite T-score of the MATRICS Consensus Cognitive Battery [ Time Frame: 12 months ]
  The groups will be compared on this standardized measure of cognition. T scores do not have an absolute minimum or maximum. Higher scores represent better cognition.

Original Secondary Outcome Measures (submitted: December 16, 2019)

• Role ratings on the Global Functioning Scale (GFS: Role) [ Time Frame: 12 months ]
  The groups will be compared on this measure of role functioning.
• Overall Composite T-score of the MATRICS Consensus Cognitive Battery (MCCB) [ Time Frame: 12 months ]
  The groups will be compared on this standardized measure of cognition.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Aripiprazole Lauroxil for Preventing Psychotic Relapse After an Initial Schizophrenia Episode
• Official Title: Aripiprazole Lauroxil for Preventing Psychotic Relapse After an Initial Schizophrenia Episode
• Brief Summary: This 12-month study will evaluate the efficacy of aripiprazole lauroxil compared to oral aripiprazole in preventing the re-emergence of psychotic symptoms in patients with a recent onset of schizophrenia.
• Detailed Description: This is a single-site 12-month open-label randomized study comparing the efficacy of the FDA-approved long-acting formulation of aripiprazole lauroxil to the efficacy of oral aripiprazole among patients with a recent onset of schizophrenia, schizophreniform, or schizoaffective (depressed) disorder. All assessments and treatment will take place at the UCLA Aftercare Research Program (300 UCLA Medical Plaza, Los Angeles, CA 90095), which is a program that specializes in the treatment and study of individuals with a recent onset of schizophrenia. The primary goal is to evaluate the efficacy of aripiprazole lauroxil compared to oral aripiprazole in preventing the re-emergence of psychotic symptoms in patients with a recent onset of schizophrenia. All patients on oral medications will, at least initially, be treated with oral aripiprazole.
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized Controlled Trial; 12-month longitudinal follow-through study (anticipate enrolling at least 128 patients of whom 90 will be randomized to one of the two arms)

Masking: None (Open Label)
Masking Description:

open label

Primary Purpose: Treatment

Condition

• Schizophrenia
• Schizoaffective Disorder, Depressive Type
• Schizophreniform Disorder

Intervention

• Drug: Aripiprazole Lauroxil
  12 month longitudinal aripirprazole lauroxil treatment and assessment follow-through
  Other Name: Aristada
• Drug: ARI-ORAL
  oral aripiprazole
  Other Names:

  • aripiprazole
  • Abilify
• Drug: AL-NCD
  Aripiprazole Lauroxil 675 MG/2.4 ML Intramuscular Suspension, Extended Release
  Other Name: Aristada Initio

Study Arms

• Experimental: AL-LAI: Long-Acting Injectable Antipsychotic
  Patients successfully completing the Stabilization period will be randomized to one of the two medications groups: For patients assigned to the AL-LAI (aripiprazole lauroxil- long-acting injections), initiation of AL-LAI will begin with a one-day initiation regimen (using AL-NCD IM (aripiprazole lauroxil NanoCrystal Dispersion)). Subsequent dosing of AL-LAI will be flexible based on clinician judgment. Treatment with AL-LAI can be initiated at a dose of 441mg or 661mg (administered monthly), 882mg (administered monthly or every 6 weeks), or 1064mg (administered every 2 months).
  Interventions:

  • Drug: Aripiprazole Lauroxil
  • Drug: AL-NCD
• Active Comparator: ARI-ORAL: Aripiprazole Oral Antipsychotic
  Patients successfully completing the Stabilization period will be randomized to one of the two medications groups: Patients assigned to the oral medication condition will continue with ARI-ORAL. ARI-ORAL dosage will be flexible and dosage will be at the discretion of the treating psychiatrist. Patients discontinuing ARI-ORAL study drug after Randomization to oral antipsychotic medication, can remain in active treatment and follow-up within the study, and may be prescribed any of a number of first-line oral antipsychotics.
  Intervention: Drug: ARI-ORAL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 7, 2022): 20
• Original Estimated Enrollment (submitted: December 16, 2019): 128
• Actual Study Completion Date: October 1, 2022
• Actual Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Is between 18 and 45 years of age, inclusive, at Screening.
2. Has a diagnosis of schizophreniform disorder, schizophrenia, or schizoaffective disorder, depressed type.
3. Has a first episode of a psychotic illness that occurred within the 24 months before entry.
4. Fluency (oral and written) in the English language.
5. Exhibits tolerability to ARI ORAL during the Stabilization period.
6. Resides within commuting distance of the UCLA Aftercare Research Program in a stable living situation where the patient can be located.
7. Agrees to abide by the contraceptive requirements of the protocol.
8. Additional criteria may apply

Exclusion Criteria:

1. Evidence of a known neurological disorder (e.g., epilepsy) or significant head injury.
2. Premorbid IQ less than 70.
3. Is currently pregnant or breastfeeding, or is planning to become pregnant during the study.
4. Is currently on a long-acting injectable antipsychotic medication and it is clinically contra-indicated to switch to oral aripiprazole.
5. History of poor or inadequate response to an adequate trial of oral or injectable aripiprazole.
6. Has received AL-LAI or IM depot aripiprazole within two months prior to Randomization.
7. Has alcohol or substance abuse as a prominent clinical problem or makes the primary diagnosis not possible to confirm.
8. Is currently being treated with clozapine.
9. Has participated in a clinical drug trial involving any drug within the past two months.
10. Has a current DSM-5 diagnosis of bipolar disorder, or schizoaffective disorder, bipolar type, based on the screening SCID.
11. Patient is an imminent danger to himself/herself.
12. History of neuroleptic malignant syndrome, malignant hyperthermia, or clinically significant tardive dyskinesia.
13. Additional criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (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: NCT04203056
• Other Study ID Numbers: PATS 20184225
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Kenneth L. Subotnik, PhD, University of California, Los Angeles
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, Los Angeles
• Original Study Sponsor: Same as current
• Collaborators: Alkermes, Inc.

Investigators

• Principal Investigator: Kenneth L Subotnik, PhD; University of California, Los Angeles

• PRS Account: University of California, Los Angeles
• Verification Date: October 2022