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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well people with early schizophrenia can recover daily functioning through a combination of medication and cognitive training. Participants will receive a long-acting injection of Aripiprazole Lauroxil, a medication that manages schizophrenia symptoms, every two months for a year. They will also engage in computerized training to enhance cognitive and functional skills. This trial suits individuals with schizophrenia who are currently hospitalized or have recently relapsed and have had fewer than four hospital admissions. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for Aripiprazole Lauroxil and Computerized cognitive and functional skills training?

Research has shown that aripiprazole lauroxil is generally safe for treating schizophrenia. After 52 weeks of use, studies found no new safety issues, indicating that doctors are already familiar with its safety profile.

In one long-term study, only about 5.9% of patients discontinued use due to side effects, suggesting most people tolerate it well.

Computerized cognitive and functional skills training has improved thinking skills in people with schizophrenia. This training is evidence-based, having been tested and shown to be effective, with no major safety concerns.

Overall, both treatments in this study have a strong safety record. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike typical treatments for schizophrenia that primarily involve daily oral medications, Aripiprazole Lauroxil is unique because it is a long-acting injectable form of aripiprazole administered every two months. This delivery method can improve adherence by reducing the frequency of dosing, which is a significant challenge for many patients. Researchers are also excited about the combination of this medication with computerized cognitive and functional skills training, offering a holistic approach that not only targets symptoms but also enhances cognitive functioning. This dual approach aims to improve overall quality of life for individuals with schizophrenia.

What evidence suggests that this trial's treatments could be effective for schizophrenia?

Research has shown that Aripiprazole Lauroxil can reduce symptoms of schizophrenia. Studies indicate that this medication manages sudden episodes and decreases the risk of relapse and hospitalization. Long-term research confirms that it improves symptoms and the overall severity of the illness. In this trial, participants will receive Aripiprazole Lauroxil alongside computerized cognitive and functional skills training. This training has been shown to enhance mental skills like memory and attention, which schizophrenia often affects. Together, these treatments offer a promising way to manage symptoms and improve daily life. ^{3 5 6 7 8}

Who Is on the Research Team?

Dante Durand, MD

Principal Investigator

University of Miami Miller School

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5013847/

Aripiprazole Lauroxil (Aristada): Long-Acting Atypical ... Clinical data demonstrate that aripiprazole lauroxil extended-release injectable suspension is an effective and safe alternative for the treatment of adults ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11921517/

Aripiprazole Lauroxil: Development and Evidence-Based ... LAIs offer reliable efficacy for the management of acute exacerbations of schizophrenia, reduce the risk of relapse and hospitalization, and provide consistent ...

3. psychiatrist.com psychiatrist.com/jcp/long-term-safety-of-aripiprazole-lauroxil/

Long-Term Outcomes of Aripiprazole Lauroxil for Patients ... Continuous efficacy data examined post hoc demonstrated that schizophrenia symptoms and severity of illness improved over the course of the ...

4. aristadahcp.com aristadahcp.com/pivotal-trial

Pivotal Trial of ARISTADA® (aripiprazole lauroxil) | HCP ARISTADA® (aripiprazole lauroxil) was clinically proven to reduce symptoms of schizophrenia.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01469039

A Study to Evaluate the Efficacy and Safety of ALKS 9072 ... The study will determine the efficacy of ALKS 9072 (also known as aripiprazole lauroxil or ALKS 9070) for the treatment of schizophrenia in subjects ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32841554/

Long-Term Outcomes of Aripiprazole Lauroxil for Patients ... After the first 52 weeks, safety assessments revealed no new safety concerns and were consistent with the known safety profile of aripiprazole.

7. aristadahcp.com aristadahcp.com/52-week-safety-study

Long-Term Safety Study of ARISTADA® (aripiprazole ... Long-term safety and tolerability of ARISTADA® (aripiprazole lauroxil) over 52 weeks in patients with schizophrenia · 5.9% of patients discontinued therapy due ...

8. dovepress.com dovepress.com/aripiprazole-lauroxil-development-and-evidence-based-review-of-a-long--peer-reviewed-fulltext-article-NDT

Aripiprazole Lauroxil: Development and Evidence-Based ... Beyond 52-week long-term safety: long-term outcomes of aripiprazole lauroxil for patients with schizophrenia continuing in an extension study.