Medication + Cognitive Training for Schizophrenia

Overseen By Gabriela Vargas, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Miami

Must be taking: Long-acting injectables

Must not be taking: Clozapine, Strong CYP inhibitors

Disqualifiers: Pregnancy, Suicide risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the role of clinical stability in functional recovery. in first episode schizophrenia.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that strongly affect specific liver enzymes (CYP 2D6 or CYP 3A4) at least 14 days before starting the trial. If you're on these medications, discuss with your doctor.

What data supports the effectiveness of the drug Aripiprazole Lauroxil for treating schizophrenia?

Research shows that Aripiprazole Lauroxil, a long-acting injectable antipsychotic, is effective in reducing severe psychotic symptoms in schizophrenia patients, with significant improvements in symptom scores over 12 weeks. It has been shown to be safe and effective in both short-term and long-term studies, with a consistent safety profile. ^{1 2 3 4 5}

Is the combination of Aripiprazole Lauroxil and cognitive training safe for humans?

Aripiprazole Lauroxil, a long-acting injectable medication used for schizophrenia, has been studied for safety over long periods, showing it is generally safe for humans. Common side effects include restlessness, headache, trouble sleeping, and anxiety, which are consistent with the known safety profile of aripiprazole. ^{1 3 4 6 7}

What makes the drug Aripiprazole Lauroxil unique for treating schizophrenia?

Aripiprazole Lauroxil is unique because it is a long-acting injectable form of the antipsychotic aripiprazole, which means it can be administered less frequently, every four weeks, compared to daily oral medications. It also has a unique mechanism as a partial dopamine D2 receptor agonist, which may help improve cognitive functions in schizophrenia, a benefit not seen with all antipsychotics. ^{1 3 8 9 10}

Research Team

Dante Durand, MD

Principal Investigator

University of Miami Miller School

Eligibility Criteria

This trial is for adults with schizophrenia who have been hospitalized or relapsed as outpatients fewer than four times. They must be willing to take long-acting injectable medication and participate in rehabilitation but cannot have had prior treatment resistance, previous long-acting injections, or be unable to consent.

Inclusion Criteria

I have been diagnosed with schizophrenia.

I am willing to get long-acting injections and join a rehab program.

Fewer than four previous admissions

Exclusion Criteria

I have previously received long-acting injectable treatments.

Current Suicide Risk

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive long-acting injectable aripiprazole every 2 months for 12 months and undergo computerized cognitive and functional skills training for the first 12 weeks

12 months

6 visits (in-person) for injections, additional visits for training

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Aripiprazole Lauroxil
• Computerized cognitive and functional skills training

Trial Overview The study tests whether Aripiprazole Lauroxil (a long-acting injectable antipsychotic) combined with computerized cognitive training can help patients with early-stage schizophrenia recover functionally when they are clinically stable.

Participant Groups

Group I: Aripiprazole and Computerized Cognitive and Functional Skills Training Group Experimental Treatment 2 Interventions

Participants in this arm will receive long-acting injectable aripiprazole every 2 months formulation for 12 consecutive months. Participants in this arm will also receive Computerized cognitive and functional skills training during the first 12 weeks of study participation.

Aripiprazole Lauroxil is already approved in United States for the following indications:

Approved in United States as Aristada for:

• Schizophrenia

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Alkermes, Inc.

Industry Sponsor

Trials

118

Recruited

27,200+

Richard Pops

Alkermes, Inc.

Chief Executive Officer since 1991

BA in Economics from Stanford University

Dr. Craig Hopkinson

Alkermes, Inc.

Chief Medical Officer since 2017

MD

Findings from Research

Aripiprazole lauroxil (Aristada) is an injectable medication used for treating schizophrenia, providing a long-acting option for patients.

Clinical studies have shown that Aripiprazole lauroxil effectively reduces symptoms of schizophrenia, offering a reliable alternative to daily oral medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole Lauroxil (Aristada): An Extended-Release, Long-Acting Injection For the Treatment of Schizophrenia. Cruz, MP.[2020]

In a Phase 3 study involving 622 patients with acute schizophrenia, aripiprazole lauroxil (AL) significantly improved symptoms compared to placebo, with notable improvements in various scales by Day 85, including the Clinical Global Impression-Severity (CGI-S) and Positive and Negative Syndrome Scale (PANSS).

Both doses of AL (441 mg and 882 mg) showed significantly higher treatment response rates than placebo, with improvements observable as early as Day 8, indicating its robust efficacy in managing schizophrenia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale-supportive analyses from a Phase 3 study. Citrome, L., Risinger, R., Cutler, AJ., et al.[2019]

In a 12-week trial involving 309 patients with severe psychotic symptoms, aripiprazole lauroxil (AL) showed significant improvements in schizophrenia symptoms, with placebo-adjusted reductions in PANSS Total scores of -14.7 for the 441mg dose and -16.6 for the 882mg dose (p<0.0001).

Both doses of AL were effective in increasing overall responder rates, with 49% for 441mg and 61% for 882mg compared to only 18% for placebo, while maintaining a safety profile consistent with aripiprazole, including common side effects like akathisia and insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation. Potkin, SG., Risinger, R., Du, Y., et al.[2018]

In a study involving 478 patients over 180 weeks, the long-acting injectable antipsychotic aripiprazole lauroxil (AL) demonstrated a consistent safety profile with no new safety concerns, and adverse events were reported by 57.5% of patients, primarily related to the higher dose.

Significant improvements in schizophrenia symptoms were observed over time, with both the Positive and Negative Syndrome Scale (PANSST) and Clinical Global Impressions-Severity of Illness (CGI-S) scores showing continued therapeutic efficacy throughout the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond 52-Week Long-Term Safety: Long-Term Outcomes of Aripiprazole Lauroxil for Patients With Schizophrenia Continuing in an Extension Study. Lauriello, J., Claxton, A., Du, Y., et al.[2020]

In a study involving 181 patients with schizophrenia, long-term treatment with aripiprazole lauroxil showed a high retention rate, with 73% of patients on the 441 mg dose and 66% on the 882 mg dose completing the 52-week treatment.

Both dosage groups demonstrated significant and continued improvements in symptoms, with 74% of the 441 mg group and 68% of the 882 mg group achieving remission, indicating the sustained efficacy of aripiprazole lauroxil after initial stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durability of Therapeutic Response With Long-Term Aripiprazole Lauroxil Treatment Following Successful Resolution of an Acute Episode of Schizophrenia. McEvoy, JP., Risinger, R., Mykhnyak, S., et al.[2021]

In a 52-week study involving 478 patients with schizophrenia, long-acting aripiprazole lauroxil (AL) was found to be generally well tolerated, with 50.4% of patients experiencing adverse events, most of which were mild to moderate.

The treatment showed minimal weight gain (average of 0.8 kg) and no significant changes in metabolic parameters, indicating that AL is a safe and effective long-term option for managing schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia. Nasrallah, HA., Aquila, R., Du, Y., et al.[2020]

In a phase 3b study involving 200 patients with schizophrenia, the 2-month formulation of aripiprazole lauroxil (AL) showed significant improvement in symptoms and caregiver burden, with high patient satisfaction rates (70.8%-74.7%) throughout the treatment period.

Both AL and paliperidone palmitate (PP) demonstrated similar efficacy in reducing schizophrenia symptoms and improving quality of life, indicating that either long-acting injectable can be effectively initiated in a hospital setting and continued as outpatient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study. Nasrallah, HA., Weiden, PJ., Walling, DP., et al.[2023]

Cognitive disturbances often persist in patients with psychoses, particularly schizophrenia, despite antipsychotic treatment, highlighting the need for therapies that address cognitive deficits.

Aripiprazole, a third-generation antipsychotic, shows promise in improving cognitive functions based on a review of studies, suggesting it may enhance memory and learning processes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Impairment in Schizophrenia, Neurotransmitters and the New Atypical Antipsychotic Aripiprazole. Topolov, MK., Getova, DP.[2022]

Aripiprazole, an atypical antipsychotic, showed a tendency for reduced performance in executive functioning tasks compared to haloperidol and placebo, suggesting it may not enhance cognitive function as intended.

While aripiprazole produced stronger activation in certain brain areas (frontal and temporal gyri, putamen) compared to haloperidol, these differences were not statistically significant after correcting for multiple comparisons, indicating similar effects on brain activation between the two drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol. Bolstad, I., Andreassen, OA., Groote, IR., et al.[2022]

Aripiprazole lauroxil is a long-acting injectable antipsychotic approved by the FDA in 2015, designed to treat schizophrenia with dosing options of 4, 6, or 8 weeks, which helps improve patient compliance.

The medication works by partially activating D2 and 5-HT1A receptors while blocking 5-HT2A receptors, and it has been shown to be safe and effective, although it may cause side effects like weight gain and tardive dyskinesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review. Maini, K., Gould, H., Hicks, J., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Aripiprazole Lauroxil (Aristada): An Extended-Release, Long-Acting Injection For the Treatment of Schizophrenia. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale-supportive analyses from a Phase 3 study. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Beyond 52-Week Long-Term Safety: Long-Term Outcomes of Aripiprazole Lauroxil for Patients With Schizophrenia Continuing in an Extension Study. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Durability of Therapeutic Response With Long-Term Aripiprazole Lauroxil Treatment Following Successful Resolution of an Acute Episode of Schizophrenia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study. [2023]

8. Bulgaria pubmed.ncbi.nlm.nih.gov

Cognitive Impairment in Schizophrenia, Neurotransmitters and the New Atypical Antipsychotic Aripiprazole. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review. [2023]