Cariprazine for Cocaine and Opioid Use Disorder

Overseen By Megan Ivey, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kyle Kampman

Must be taking: BUP-NX

Must not be taking: Antidepressants, Benzodiazepines, CYP3A4 drugs

Disqualifiers: Schizophrenia, Bipolar, Severe AUD, others

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: 2

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low dose of cariprazine, an antipsychotic medication, can reduce cocaine use in individuals with opioid use disorder who are stable on their current treatment. Participants will receive either cariprazine or a placebo to determine the medication's effect on cocaine cravings and use. It suits those who haven't recently used cocaine, are stable on buprenorphine/naloxone (a medication for opioid use disorder), and have struggled with cocaine use. The study will also examine brain responses in some participants to assess how the treatment might affect cravings and impulse control. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue taking BUP-NX (buprenorphine/naloxone) at a stable dose. You cannot take medications that interact with cariprazine or BUP-NX, and you should not be on psychoactive medications, except for occasional Benadryl for sleep.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cariprazine is generally well-tolerated. Studies have found that doses between 1.5 to 3 mg per day can improve conditions like depression and anxiety without major side effects. For example, one report noted that cariprazine helped patients with symptoms of psychosis and addiction and was well-tolerated, meaning patients experienced few unwanted effects.

Cariprazine is also approved for conditions like bipolar disorder, indicating it has passed strict safety tests for those uses. Although direct data on its use for cocaine and opioid use disorders is limited, the safety record from other studies is encouraging.

Prospective trial participants should discuss any concerns with the study team. They can provide detailed information about what to expect during the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cocaine and opioid use disorder?

Cariprazine is unique because it targets dopamine receptors, which play a crucial role in the brain's reward system. Most treatments for cocaine and opioid use disorders focus on managing withdrawal symptoms or reducing cravings through different pathways. However, Cariprazine directly influences the brain's reward mechanisms, potentially offering a new way to reduce drug-seeking behavior. Researchers are excited about Cariprazine because it could offer a more targeted approach, possibly leading to better outcomes for individuals struggling with these addictions.

What evidence suggests that cariprazine might be an effective treatment for cocaine and opioid use disorder?

Research has shown that cariprazine, which participants in this trial may receive, can reduce the chances of relapse in individuals with addiction issues. One study found that only 24.8% of patients taking cariprazine experienced a relapse, compared to 47.5% of those who took a placebo, a pill with no active medicine. Cariprazine also alleviates symptoms of psychosis and addiction, and most people tolerate it well with few side effects. This suggests it could be beneficial for individuals dealing with cocaine and opioid use problems. While early results are promising, further research is needed to confirm its effects specifically for cocaine addiction. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-65 with both cocaine and moderate to severe opioid use disorders, on stable doses of BUP-NX for at least a week, not pregnant or breastfeeding, able to understand English and provide informed consent. Excluded are those with certain mental health conditions, significant medical issues like severe kidney problems or liver damage, current high suicide risk, or taking conflicting medications.

Inclusion Criteria

I am not pregnant or breastfeeding, and I either cannot have children or use effective birth control.

An informed consent document understood, voluntarily signed and dated by the subject

Subject must provide a urine that is cocaine-negative and buprenorphine-positive on the day of enrollment

Exclusion Criteria

Any pending legal action that could prohibit participation and/or compliance in study procedures

My anemia is not severe, staying below grade 2.

Significant medical or psychiatric symptoms or dementia which in the opinion of the investigators would preclude compliance with the protocol, adequate cooperation in the study, or obtaining informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline

Includes baseline assessments, behavioral tasks/fNIRS session, and randomization

1-2 visits

Outpatient Treatment

Participants receive daily cariprazine (or placebo) and daily BUP-NX, with imaging and behavioral tasks at steady-state

8 weeks

2 visits per week

Follow-up

A follow-up visit to assess medical and psychological status

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Cariprazine
• Placebo

Trial Overview The study tests if low-dose cariprazine (1.5mg daily) affects cocaine use in patients already on BUP-NX. It's randomized and placebo-controlled; some participants will also undergo brain imaging (fMRI). Over approximately 11 weeks including screening and follow-up phases, urine and blood tests monitor drug compliance.

How Is the Trial Designed?

Group I: Cariprazine Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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?

Kyle Kampman

Lead Sponsor

Trials

4

Recruited

480+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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]

In a 12-week clinical trial involving 94 patients, both amantadine and desipramine showed initial reductions in reported cocaine abuse compared to placebo, but this effect diminished by week 8, indicating limited long-term efficacy.

Despite good treatment retention and compliance, there were no significant differences in cocaine-free urine samples between the medicated groups and placebo, suggesting that these medications may not effectively sustain abstinence in cocaine-abusing methadone-maintained patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. Kosten, TR., Morgan, CM., Falcione, J., et al.[2019]

Cariprazine, an antipsychotic approved for schizophrenia, has shown significant efficacy in clinical trials, with responder rates of 31% compared to 21% for placebo, and a lower relapse rate in long-term studies (24.8% vs. 47.5% for placebo).

While cariprazine can cause side effects like extrapyramidal symptoms and akathisia, it does not significantly affect metabolic variables or cause major weight gain, making it a relatively safe option for treating schizophrenia and bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine for the Treatment of Schizophrenia: A Review of this Dopamine D3-Preferring D3/D2 Receptor Partial Agonist. Citrome, L.[2016]

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]

Cariprazine is a new medication approved by the FDA in 2015 for treating schizophrenia and type I bipolar disorder, showing efficacy in addressing positive, negative, and cognitive symptoms of schizophrenia without causing significant extrapyramidal side effects in animal models.

While cariprazine has a unique mechanism of action as a biased agonist at dopamine receptors, it can still cause mild to moderate side effects in humans, including akathisia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine:New dopamine biased agonist for neuropsychiatric disorders. De Deurwaerdère, P.[2017]

Cariprazine, a D₃-preferring dopamine receptor partial agonist, has shown potential in reducing the rewarding effects of cocaine and preventing relapse in cocaine-seeking behavior in rats, indicating its possible use in treating substance abuse disorders alongside schizophrenia and bipolar mania.

In comparison to aripiprazole and bifeprunox, cariprazine demonstrated effective doses for reducing cocaine's effects and preventing relapse, suggesting it may be a promising candidate for addressing both psychiatric and substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine (RGH-188), a D₃-preferring dopamine D₃/D₂ receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats. Román, V., Gyertyán, I., Sághy, K., et al.[2021]

This review highlights that certain drugs, including L-type calcium channel blockers (isradipine and nifedipine) and serotonin-3 receptor antagonists (MDL72222 and ICS205-930), can effectively block the positive place preference induced by cocaine in rats, suggesting their potential in treating cocaine addiction.

Additionally, the study discusses the blockade of other cocaine-related behaviors by these drugs, indicating their broader implications for understanding cocaine's effects and developing effective treatment strategies for addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of cocaine-induced conditioned place preference: relevance to cocaine abuse therapeutics. Calcagnetti, DJ., Keck, BJ., Quatrella, LA., et al.[2019]

Buprenorphine significantly reduced the preference for remifentanil in squirrel monkeys, indicating its potential effectiveness in decreasing opioid use during the five-day treatment evaluation.

Cariprazine and methadone did not show a significant impact on drug preference, suggesting that cariprazine may not alter opioid reward in non-dependent primates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buprenorphine, methadone, and cariprazine on economic choice between remifentanil and food in squirrel monkeys. Amirali, AS., Hecker, JC., Figueroa, HM., et al.[2023]

Buprenorphine, a mixed opioid agonist/antagonist, shows promise in reducing cocaine abuse among individuals with concurrent opioid and cocaine dependence, although it has not been proven superior to methadone in clinical trials.

The effectiveness of buprenorphine in reducing cocaine use appears to be dose-dependent, with higher doses (6 mg daily) associated with greater reductions in cocaine abuse compared to lower doses (2 mg daily).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine for cocaine and opiate dependence. Kosten, TR., Rosen, MI., Schottenfeld, R., et al.[2013]

A 56 mg/kg dose of naltrexone, administered 4 hours before conditioning, significantly reduced the reinforcing effects of cocaine, suggesting its potential as a treatment for cocaine addiction.

In contrast, an 8 mg/kg dose of methadone given 1 hour prior to conditioning increased cocaine's reinforcing properties, which may explain higher cocaine use among heroin addicts receiving methadone treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioidergic modulation of cocaine conditioned place preferences. Bilsky, EJ., Montegut, MJ., Delong, CL., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05063201

Cariprazine for Comorbid Cocaine and Opioid Use Disorder The primary clinical outcome measure is the impact of cariprazine (v. placebo) on cocaine use (percentage of cocaine-positive/missing urines across weeks 3-8). ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377451/

Case Report: Functional and Symptomatic Improvement ... Cariprazine is a good treatment option for patients with symptoms of psychosis and addiction; is well-tolerated without the induction of side effects.

3. withpower.com withpower.com/trial/phase-3-opioid-related-disorders-9-2021-b3f70

Cariprazine for Cocaine and Opioid Use Disorder In a 12-week clinical trial involving 94 patients, both amantadine and desipramine showed initial reductions in reported cocaine abuse compared to placebo, but ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03430544

Cariprazine Effects on Brain and Behavior in Cocaine Use ... This is a phase II, randomized, single-blind, placebo-controlled study to examine whether cariprazine (1.5 or 3 mg/d) 1) alters brain and/or behavioral ...

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

Cariprazine in Psychiatry: A Comprehensive Review of ... Specifically, relapse occurred in only 24.8% of cariprazine-treated patients, in contrast to 47.5% of those treated with placebo [37,38]. In ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601772/

Clinical Review - Cariprazine (Vraylar) - NCBI - NIH A numerical reduction in the HAM-A score at week 6 indicating an improvement of symptoms of anxiety was observed in all treatment groups, with no difference ...

7. mdpi.com mdpi.com/1424-8247/17/11/1464

Cariprazine in Bipolar Disorder and Substance Use In several studies, cariprazine at doses of 1.5 to 3 mg/day significantly improved depressive symptoms as measured by the Montgomery–Åsberg Depression Rating ...