Schizoaffective Disorder, Depressive Type, Schizophrenia, Schizophreniform Disorder
Conditions
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.
Interventions
12 month longitudinal aripiprazole lauroxil treatment and assessment follow-through
DRUGARI-ORAL
oral aripiprazole
DRUGAL-NCD
Aripiprazole Lauroxil 675 MG/2.4 ML Intramuscular Suspension, Extended Release
Sponsors
Alkermes, Inc.
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open label
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exacerbation or Relapse of Psychotic Symptoms | 12 months | Number of participants who experienced an exacerbation and/or relapse following a period of absence or relative low levels of psychotic symptoms based on the expanded 24-item version of the Brief Psychiatric Rating Scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Role Ratings on the Global Functioning Scale From Baseline to 12 Months | mean change from baseline to the 12 month point | The groups will be compared on change in this measure of role functioning. Scores range from 1 to 10, with higher indicating better role functioning. Change scores can theoretically range from 0 to 9 |
| Change From Baseline to One-Year in the MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Score. | 12 months | The change from Baseline to One-year on the MATRICS Consensus Cognitive Battery Overall Composite score. MATRICS is the abbreviation for Measurement and Treatment Research to Improve Cognition in Schizophrenia. T scores do not have an absolute minimum or maximum. Higher scores represent better cognition. The sex and age adjusted T-score was used. The T-Score has a population mean of 50 and standard deviation of 10. Fewer subjects analyzed than enrolled because only 9 subjects reached the 12 month point by study discontinuation and had MCCB data. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
Aripiprazole Lauroxil: 12 month longitudinal aripirprazole lauroxil treatment and assessment follow-through
AL-NCD: Aripiprazole Lauroxil 675 MG/2.4 ML Intramuscular Suspension, Extended Release | 6 |
| 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.
ARI-ORAL: oral aripiprazole | 9 |
| Total | 15 |
Baseline characteristics
| Characteristic | Total | AL-LAI: Long-Acting Injectable Antipsychotic | ARI-ORAL: Aripiprazole Oral Antipsychotic |
|---|---|---|---|
| Age, Continuous | 24.5 years STANDARD_DEVIATION 5.9 | 22.2 years STANDARD_DEVIATION 2.6 | 25.9 years STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 15 participants | 6 participants | 9 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 0 / 6 | 0 / 9 |
| serious Total, serious adverse events | 0 / 6 | 1 / 9 |
Outcome results
Primary
Exacerbation or Relapse of Psychotic Symptoms
Number of participants who experienced an exacerbation and/or relapse following a period of absence or relative low levels of psychotic symptoms based on the expanded 24-item version of the Brief Psychiatric Rating Scale
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AL-LAI: Long-Acting Injectable Antipsychotic | Exacerbation or Relapse of Psychotic Symptoms | 2 Participants |
| ARI-ORAL: Aripiprazole Oral Antipsychotic | Exacerbation or Relapse of Psychotic Symptoms | 2 Participants |
Secondary
Change From Baseline to One-Year in the MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Score.
The change from Baseline to One-year on the MATRICS Consensus Cognitive Battery Overall Composite score. MATRICS is the abbreviation for Measurement and Treatment Research to Improve Cognition in Schizophrenia. T scores do not have an absolute minimum or maximum. Higher scores represent better cognition. The sex and age adjusted T-score was used. The T-Score has a population mean of 50 and standard deviation of 10. Fewer subjects analyzed than enrolled because only 9 subjects reached the 12 month point by study discontinuation and had MCCB data.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL-LAI: Long-Acting Injectable Antipsychotic | Change From Baseline to One-Year in the MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Score. | 9.3 Change score: change in T scores | Standard Error 2.2 |
| ARI-ORAL: Aripiprazole Oral Antipsychotic | Change From Baseline to One-Year in the MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Score. | 4.6 Change score: change in T scores | Standard Error 2.5 |
Secondary
Change in Role Ratings on the Global Functioning Scale From Baseline to 12 Months
The groups will be compared on change in this measure of role functioning. Scores range from 1 to 10, with higher indicating better role functioning. Change scores can theoretically range from 0 to 9
Time frame: mean change from baseline to the 12 month point
Population: Fewer subjects analyzed than enrolled because only 6 subjects reached the 12 month point and had role functioning data availabe prior to study discontinuation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL-LAI: Long-Acting Injectable Antipsychotic | Change in Role Ratings on the Global Functioning Scale From Baseline to 12 Months | 4.3 score on a scale | Standard Error 0.97 |
| ARI-ORAL: Aripiprazole Oral Antipsychotic | Change in Role Ratings on the Global Functioning Scale From Baseline to 12 Months | .06 score on a scale | Standard Error 0.97 |