Using cariprazine to treat patients with both cocaine and opioid use disorders

A Phase 2a Randomized, Single-blind, Placebo-controlled Pilot Study to Evaluate the Impact of Cariprazine (1.5mg) on Cocaine Use in OUD-CocUD Patients on Buprenorphine-naloxone.

This study is testing if a low dose of cariprazine can help people who are stable on opioid treatment and also struggle with cocaine use.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT05063201 on ClinicalTrials.gov

What this trial studies

This phase IIa pilot study investigates the effects of low-dose cariprazine (1.5mg/day) on cocaine use in patients with co-occurring opioid use disorder (OUD) and cocaine use disorder (CocUD) who are stable on buprenorphine-naloxone treatment. The study will randomly assign approximately 48 participants, stratified by the severity of cocaine use, to receive either cariprazine or a placebo. Additionally, a subset of participants will undergo fMRI scans to assess how cariprazine affects brain responses related to addiction. Eligible patients must have a cocaine-negative urine test at enrollment and meet specific inclusion criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with moderate to severe opioid use disorder and cocaine use disorder who are stable on buprenorphine-naloxone.

Not a fit: Patients who do not meet the inclusion criteria, such as those with a positive cocaine urine test or those not on stable buprenorphine-naloxone, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients struggling with both cocaine and opioid use disorders.

How similar studies have performed: While this approach is novel in combining treatment for both cocaine and opioid use disorders, similar studies have shown promise in addressing substance use disorders with pharmacological interventions.

Eligibility criteria

Inclusion Criteria:

* An informed consent document understood, voluntarily signed and dated by the subject.
* Males and females, aged 18-65 years old, who meet criteria for cocaine use disorder (CocUD) and moderate or severe opioid use disorder (OUD) (based on DSM-5 criteria), have been on a stable dose of BUP-NX for at least one week, and plan to continue taking BUP-NX for at least 12 weeks.
* Subject must provide a urine that is cocaine-negative and buprenorphine-positive on the day of enrollment.
* Females must be non-pregnant, non-lactating, and either be of non-childbearing potential (e.g., sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of childbearing potential, but practicing a highly-effective contraception method (failure rate \<1%, guided by CDC reference list).
* Subject must read at or above eighth grade level, and understand spoken and written English.
* IQ score of ≥ 80.
* Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, and must have access to a cellphone.

Exclusion Criteria:

* Current participation (or participation within 30 days prior to the research study) in clinical trial and receipt of investigational drug(s).
* Meets DSM-5 criteria for moderate to severe Substance Use Disorder for any substance other than opioids, cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. For Alcohol Use Disorder, subjects are excluded if they meet DSM-5 criteria for moderate to severe AUD within the past three months (patients in early or sustained remission are eligible).
* Meets current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, bipolar I or II disorder, or organic mental disorder, including dementia-related psychosis.
* Meets DSM-5 criteria for Major Depressive Disorder AND is currently taking or clinically requires, antidepressant therapy.
* Current comorbid GAD, Social Phobia, Specific Phobia are excluded if in current treatment and/or clinically unstable.
* Current and/or in treatment for Panic Disorder With or Without Agoraphobia, Agoraphobia Without Panic Disorder.
* Presence of any another psychiatric and/or medical disorder that in the opinion of the PI will interfere with completion of the study or place the patient at heightened risk through participation in the study.
* Actively suicidal, or present suicidal risk, or who reports a lifetime history of serious or recurrent suicidal behavior, or who has an SBQ-R total score ≥8 at Screening, and/or "yes" answers on items 4 or 5 of the C-SSRS, or in the investigator's clinical judgment present a suicidal risk.
* Currently homicidal to the extent that immediate attention is required.
* Has evidence of a history of significant active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (\>1.3), or, clinically significant levels (over 3x upper limit of normal) of aspartate aminotransferase (AST), or serum alanine aminotransferase (ALT).
* Has positive serology test results at screening for HIV1/HIV2 antibodies, hepatitis B surface antigen, or hepatitis C antibody. If a subject is hepatitis C antibody positive and RNA negative OR their liver function tests are \<2 times the upper limit of normal (ULN) range, and they have been treated for hepatitis C, the investigator may include the subject with the approval of the Medical Monitor.
* Anemia more severe than grade 2.
* Significant renal insufficiency (estimated creatinine clearance less than or equal to 30 ml/min).
* Current diagnosis of pain requiring opioids.
* Currently physically dependent on benzodiazepines.
* 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.
* Concurrent medical conditions (such as severe respiratory insufficiency) that may prevent the patient from safely participating in the study.
* History of seizures (excluding childhood febrile seizure) or uncontrolled seizure disorder.
* Has received medication that could interact adversely with VRAYLAR or BUP-NX within the time of administration of study agent based on the study physician's guidance.
* Needs treatment with any psychoactive medications (with the exception of Benadryl used sparingly, if necessary, for sleep).
* Has demonstrated hypersensitivity or allergy to cariprazine or any ingredients in VRAYLAR capsules or BUP-NX.
* Currently taking a CYP3A4 inhibitor/inducer or agent metabolized through the CYP3A4 pathway likely to interact with BUP-NX to produce clinically significant and/or unfavorable effects.
* Any pending legal action that could prohibit participation and/or compliance in study procedures.
* Living in unstable housing.

Exclusions for fMRI eligibility:

An individual who is deemed eligible for participation in the study based upon the criteria listed above, will be excluded from participation in the fMRI session if they meet any of the following criteria:

1. History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes and/or associated with skull fracture or intracranial bleeding or abnormal MRI.
2. Presence of magnetically active prosthetics, plates, pins, broken needles, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that its presence is unproblematic). An x-ray may be obtained to determine eligibility.
3. Claustrophobia or other medical condition that disables the participant from lying in the MRI for approximately 60 minutes.
4. Non-removable skin patches, at discretion of PI.

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Study coordinator: Megan Ivey, MS

Conditions: Opioid-use Disorder, Cocaine Use Disorder