Cariprazine Effects on Brain and Behavior in Cocaine Use Disorder

Study Overview
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Brief Summary
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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 responses to probes of reward and inhibition and 2) decreases cocaine use in individuals with cocaine use disorder. Subjects will be tested as inpatients during fMRI sessions. After the 2-week inpatient/medication induction phase, study medication will continue for 8 outpatient weeks, during which time cocaine use will be tracked. Subjects will be monitored during a 4-wk followup phase thereafter.

Official Title
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A Randomized, Single-blind, Placebo-controlled Phase II Study to Assess the Effects of Cariprazine on Brain and Behavior in Subjects With Cocaine Use Disorder

Conditions
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Cocaine Use Disorder

Intervention / Treatment
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* Drug: Cariprazine Oral Capsule [Vraylar]
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (limited): An informed consent voluntarily signed and dated by the subject. Physically healthy males and females with cocaine use disorder. Ability to read at or above eighth grade level and speak, understand, and write in English. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Available for an inpatient stay, when applicable. Exclusion Criteria (limited): Certain psychological disorders that could put subjects at risk during participation in the study. Certain lifetime or current medical disorders or conditions that could put subjects at risk during participation in the study. Medical contraindications for MRI, when applicable. Has received medication that could interact adversely with cariprazine within the time of administration of study agent based on the study physician's guidance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo oral capsule<br>* PLACEBO Group: Visually identical placebo capsules will be supplied by the University of Pennsylvania Investigational Drug Service, with a dosing regimen matching the cariprazine groups.<br>|
| Experimental: 1.5 mg/d cariprazine<br> | Drug: Cariprazine Oral Capsule [Vraylar]<br>* Cariprazine Groups (1.5 or 3mg/d): Cariprazine (VRAYLAR) capsules will be administered orally, once per day. Subjects in the 1.5mg group will receive 1 VRAYLAR capsule containing 1.5 mg cariprazine each day that study drug is administered. Subjects in the 3 mg group will be gradually titrated up to full dose: they will receive 1 VRAYLAR capsule containing 1.5mg cariprazine on the first and second days that study drug is administered and will receive 1 VRAYLAR capsule containing 3mg cariprazine each day for the rest of the medication period. The study medication period begins during the inpatient/induction phase and ends on the last day of outpatient treatment week 8 (approx. 10 weeks total). All VRAYLAR capsules will be over-encapsulated by the University of Pennsylvania Investigational Drug Services (IDS).<br>|
| Experimental: 3.0 mg/d cariprazine<br> | Drug: Cariprazine Oral Capsule [Vraylar]<br>* Cariprazine Groups (1.5 or 3mg/d): Cariprazine (VRAYLAR) capsules will be administered orally, once per day. Subjects in the 1.5mg group will receive 1 VRAYLAR capsule containing 1.5 mg cariprazine each day that study drug is administered. Subjects in the 3 mg group will be gradually titrated up to full dose: they will receive 1 VRAYLAR capsule containing 1.5mg cariprazine on the first and second days that study drug is administered and will receive 1 VRAYLAR capsule containing 3mg cariprazine each day for the rest of the medication period. The study medication period begins during the inpatient/induction phase and ends on the last day of outpatient treatment week 8 (approx. 10 weeks total). All VRAYLAR capsules will be over-encapsulated by the University of Pennsylvania Investigational Drug Services (IDS).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary fMRI outcome measure - BOLD signal change during visual cocaine vs. neutral cues. | The primary fMRI outcome is the extracted BOLD signal change during visual stimuli reminiscent of cocaine (i.e., cocaine cues) in an a priori circuit-level ROI. | Collected during fMRI scan 1, which takes place approximately 12-13 days after subject enrollment. | 
| Primary clinical outcome measure - percentage of urines cocaine-positive or missing during outpatient phase. | The primary clinical outcome is percentage of urines cocaine-positive or missing (assessed by urines positive for benzoylecgonine (BE), a metabolite of cocaine) throughout the outpatient treatment phase [Urines are counted as BE-positive if BE exceeds 300 ng/ml or if they are missing (no sample provided for a time point)]. | Urines are collected 3x per week during the 8 week outpatient phase. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary fMRI outcome measure - BOLD signal change during attempted inhibition of cue-triggered drug craving. | The secondary fMRI outcome is the extracted BOLD signal change during attempted inhibition of cue-triggered drug craving in an a priori ROI . | Collected during fMRI scan 2, which takes place approximately 13-14 days after subject enrollment. | 
| Attentional bias scores | Attentional bias scores derived from reaction time (msec) during attentional bias task | Completed on approximately day 14-15 after subject enrollment. | 
| Affective bias scores | Affective bias scores derived from reaction time (msec) during affective bias task | Completed on approximately day 14-15 after subject enrollment. | 
| Balloon Analogue Risk Task scores | # of average adjusted pumps on BART | Completed on approximately day 14-15 after subject enrollment. | 
| Go-NoGo Task scores | # of errors of commission | Completed on approximately day 14-15 after subject enrollment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cariprazine, fMRI, D3 receptor, cocaine use disorder, urine