Cariprazine for Adolescent Schizophrenia

Recruiting at 11 trial locations

Overseen By Balázs Lázár

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Allergan

Disqualifiers: Bipolar, Schizoaffective, Substance-related, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of cariprazine, an antipsychotic medication, for treating schizophrenia in teens. Participants will receive either cariprazine or a placebo (a pill with no active drug) to compare results. Teens diagnosed with schizophrenia and experiencing symptoms like delusions or hallucinations might be suitable for this trial. The study seeks to improve treatment options for young people living with this condition. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for schizophrenia in teens.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that cariprazine is likely to be safe for adolescents with schizophrenia?

Research has shown that cariprazine is generally safe and well-tolerated in teenagers. Studies with young people indicate that cariprazine has a safety profile similar to that in adults, with doses ranging from 1.5 to 6 mg. Side effects, which are unexpected problems that can occur during a study, were similar to those seen in other age groups. One study found it safe for children aged 10 to 17 years. This suggests that cariprazine could be a safe treatment option for teenagers with schizophrenia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Researchers are excited about cariprazine for adolescent schizophrenia because it offers a unique approach compared to current treatments like risperidone, aripiprazole, and olanzapine. Cariprazine works by targeting dopamine D3 and D2 receptors with a preference for D3, which is thought to play a crucial role in treating the negative symptoms and cognitive deficits associated with schizophrenia. This mechanism is different from most standard treatments, which primarily focus on D2 receptor antagonism. Additionally, cariprazine has shown potential for a better side-effect profile, particularly regarding weight gain and metabolic issues, which are significant concerns with many existing antipsychotics.

What evidence suggests that cariprazine might be an effective treatment for adolescent schizophrenia?

Studies have shown that cariprazine helps treat schizophrenia symptoms in teenagers. In one study, cariprazine significantly improved overall symptoms, as measured by the PANSS score, which rates the severity of schizophrenia. Another report showed a 29.8% reduction in negative symptoms and a 29.5% improvement in overall functioning after 18 months of treatment. Research indicates that cariprazine is generally well-tolerated and can be an effective option for young people with psychotic disorders. These findings suggest that cariprazine may help manage schizophrenia symptoms in adolescents. Participants in this trial will receive either cariprazine at different dosages or a placebo to evaluate its effectiveness and safety in this population. ^{6 7 8 9 10}

Who Is on the Research Team?

Paul Yeung

Principal Investigator

Allergan

Are You a Good Fit for This Trial?

Adolescents aged 13-17 with a confirmed diagnosis of schizophrenia can join this trial. They must be moderately ill or worse and have certain levels of symptoms like delusions or hallucinations. Those with intellectual disabilities, other psychotic disorders, or recent substance-related issues cannot participate.

Inclusion Criteria

You have a moderate level of illness according to the CGI-S scale at both the screening and baseline visits.

I have been diagnosed with schizophrenia.

My PANSS score is 70 or more with moderate symptoms in at least 2 areas.

Exclusion Criteria

You have a condition that causes difficulty with learning and problem-solving, and your IQ score is below 70.

Participant has a history of meeting DSM-5 diagnosis for any substance-related disorder (except caffeine- and tobacco-related) within the 3 months before Visit 1.

I have been diagnosed with a specific psychotic or bipolar disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cariprazine or placebo for 6 weeks to evaluate efficacy and safety in treating schizophrenia

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cariprazine
• Placebo

Trial Overview The study is testing the effectiveness and safety of Cariprazine compared to a placebo in treating schizophrenia in teenagers. Participants will randomly receive either the actual drug or a placebo to see if there's an improvement in their condition.

How Is the Trial Designed?

Group I: Cariprazine 4.5 mg/d Experimental Treatment 1 Intervention

Cariprazine capsules, oral administration, once daily.

Group II: Cariprazine 1.5 mg/d Experimental Treatment 1 Intervention

Cariprazine capsules, oral administration, once daily.

Group III: Placebo Placebo Group 1 Intervention

Matching placebo capsules, oral administration, once daily.

Cariprazine is already approved in United States for the following indications:

Approved in United States as Vraylar for:

• Schizophrenia
• Acute manic or mixed episodes associated with bipolar I disorder
• Depressive episodes associated with bipolar I disorder (bipolar depression)
• Adjunctive treatment with an antidepressant therapy (ADT) for major depressive disorder (MDD)

Who Is Running the Clinical Trial?

Allergan

Lead Sponsor

Trials

782

Recruited

277,000+

Brent Saunders

Allergan

Chief Executive Officer since 2015

JD and MBA from Temple University

Dr. David Nicholson

Allergan

Chief Medical Officer since 2015

MD from Harvard Medical School

Gedeon Richter Plc.

Lead Sponsor

Trials

17

Recruited

173,000+

Founded

1901

Headquarters

Budapest, Hungary

Known For

Women's Health Innovations

Top Products

Reagila (cariprazine), Pegfilgrastim (biosimilar), Estelle (contraceptive)

Published Research Related to This Trial

Cariprazine was found to be generally safe and well tolerated in both adolescent (49 patients) and elderly (17 patients) populations with schizophrenia, with adverse events similar to those seen in adults, except for less insomnia in adolescents and no akathisia in the elderly.

The study suggests that the approved adult dosage of cariprazine (1.5-6 mg) may also be appropriate for treating schizophrenia in younger and older patients, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine Safety in Adolescents and the Elderly: Analyses of Clinical Study Data. Szatmári, B., Barabássy, Á., Harsányi, J., et al.[2020]

Cariprazine is effective for treating schizophrenia and bipolar I disorder, showing a favorable side effect profile due to its selective affinity for D3 receptors, which helps address a range of symptoms including negative and cognitive symptoms.

It has a longer half-life and a delayed relapse time compared to other second-generation antipsychotics, making it a potentially better option for patients with high rates of non-adherence and frequent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine. Batinic, B., Ristic, I., Zugic, M., et al.[2021]

In a study involving 14 patients hospitalized for acute schizophrenia or schizoaffective disorder, cariprazine demonstrated significant effectiveness, with improvements in psychiatric symptoms measured by the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity (CGI-S) scales.

Despite patients being discharged on high doses of cariprazine (up to 9.0 mg/day), the medication was well-tolerated, with only a few experiencing side effects, indicating its safety in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful high dose antipsychotic treatment with cariprazine in patients on the schizophrenia spectrum: Real-world evidence from a Spanish hospital setting. Galmes, LN., Rancans, E.[2023]

Cariprazine, a D3-preferring partial agonist, has shown efficacy in treating not only the positive symptoms of schizophrenia but also negative symptoms and cognitive impairments, which are often difficult to manage with traditional antipsychotics.

In clinical trials involving both short-term and long-term studies, cariprazine was found to be generally safe and well tolerated, with no new safety concerns arising from extended use, indicating its potential as a broad-spectrum treatment for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety. Laszlovszky, I., Barabássy, Á., Németh, G.[2021]

In clinical trials, cariprazine significantly improved schizophrenia symptoms compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a longer time to relapse in a long-term study.

Cariprazine was more effective than risperidone in treating negative symptoms of schizophrenia, which are often challenging to address, and it was generally well tolerated with mostly mild to moderate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine: A Review in Schizophrenia. Garnock-Jones, KP.[2018]

In patients with acute schizophrenia experiencing moderate to severe negative symptoms, cariprazine demonstrated significant efficacy in improving these symptoms compared to placebo, with response rates of 54.3% and 69.7% for lower and higher doses, respectively.

Cariprazine was also more effective than aripiprazole in reducing negative symptoms, suggesting it could be a valuable treatment option for this unmet need in schizophrenia management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cariprazine on negative symptoms in patients with acute schizophrenia: A post hoc analysis of pooled data. Earley, W., Guo, H., Daniel, D., et al.[2020]

Cariprazine (Vraylar) is an atypical antipsychotic that acts as a partial agonist at dopamine D3 and D2 receptors, with a preference for D3, and also affects serotonin 5-HT1A receptors, which contributes to its therapeutic effects.

Approved in the USA in September 2015, cariprazine is used to treat schizophrenia and acute manic or mixed episodes in bipolar I disorder, and is being explored for additional uses in treating negative symptoms of schizophrenia and bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine: First Global Approval. McCormack, PL.[2018]

Cariprazine is a novel antipsychotic medication that has shown efficacy in treating acute psychosis in schizophrenia and mania in bipolar disorder, making it a promising option for these conditions.

While cariprazine has been approved by the FDA, it can cause side effects such as extrapyramidal symptoms and gastrointestinal issues, which are important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on schizophrenia and bipolar disorder: focus on cariprazine. Roberts, RJ., Findlay, LJ., El-Mallakh, PL., et al.[2020]

In a 6-week study involving patients with acute schizophrenia, low-dose cariprazine (1.5-4.5 mg/day) showed significant improvements in overall and negative symptoms compared to placebo, indicating potential efficacy in treating schizophrenia.

While the overall treatment effect of cariprazine was not statistically significant across all doses, it was generally well tolerated, with common side effects including akathisia and tremor, suggesting a favorable safety profile for low-dose treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine in the treatment of schizophrenia: a proof-of-concept trial. Durgam, S., Litman, RE., Papadakis, K., et al.[2018]

Cariprazine, a new antipsychotic, was found to be effective in reducing overall symptoms of acute schizophrenia compared to placebo, with both low and high doses showing superiority in all symptom domains across four studies involving 2144 patients.

The drug demonstrated a particularly strong effect on negative symptoms, outperforming many other antipsychotics, especially at lower doses, and may be especially beneficial for younger patients with a shorter duration of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine specificity profile in the treatment of acute schizophrenia: a meta-analysis and meta-regression of randomized-controlled trials. Corponi, F., Serretti, A., Montgomery, S., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11421304/

Cariprazine in Psychiatry: A Comprehensive Review of ... The study conducted by Riccobene et al showed the effectiveness of cariprazine in pediatric patients with schizophrenia (13–17 years old) or ...

2. vraylarhcp.com vraylarhcp.com/efficacy/schizophrenia-efficacy

VRAYLAR® (cariprazine) Efficacy for Schizophrenia VRAYLAR significantly improved overall schizophrenia symptoms1-4* ; Study 1 · Line graph showing PANSS total score in schizophrenia study 1. · 97.3. Placebo (n=148).

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1155518/full

Case series: Cariprazine in early-onset schizophrenia In this case, after 18 months of treatment with Cariprazine, there was a 29.8% reduction in negative symptoms, 29.5% improvement in global functioning, and 25% ...

4. liebertpub.com liebertpub.com/doi/full/10.1089/cap.2019.0106

Cariprazine in Youth with Bipolar and Psychotic Disorders Overall, the findings presented herein suggest that cariprazine may be a well-tolerated, effective, and adjunctive medication for treating bipolar and psychotic ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03817502?term=AREA%5BSponsorSearch%5D(COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Gedeon%20Richter%20Plc.%22))&rank=4

NCT03817502 | Efficacy and Safety of Cariprazine in the ... Study Overview​​ The purpose of this study is to evaluate the efficacy and safety of cariprazine in the treatment of schizophrenia in the adolescent population.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32194443/

Cariprazine Safety in Adolescents and the Elderly Results indicate that cariprazine was generally safe and well tolerated. Adverse events in the marginal age populations were comparable to the ...

7. vraylarhcp.com vraylarhcp.com/safety

VRAYLAR® (cariprazine) Tolerability and Safety Well-established tolerability across weight and metabolics. In 6-week MDD studies, VRAYLAR + ADT-treated patients demonstrated mean weight change of 1.5 lb ...

8. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00061/full

Cariprazine Safety in Adolescents and the Elderly Cariprazine in the approved adult dose-range of 1.5–6 mg might be a safe treatment option also in adolescent and elderly patients with schizophrenia.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7062963/

Cariprazine Safety in Adolescents and the Elderly In conclusion, cariprazine in the approved adult dose-range of 1.5–6 mg might be a safe treatment option also in adolescent and elderly patients ...

10. liebertpub.com liebertpub.com/doi/10.1089/cap.2021.0139

Pharmacokinetics, Safety, and Tolerability of Cariprazine in ... Cariprazine appeared to be safe and well-tolerated in a pediatric population aged 10–17 years. The psychiatric symptom improvement provides support for future ...