The Impact of Cobenfy Maintenance on Cocaine's Effects

NCT07624227 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 105840
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if Cobenfy influences the effects of cocaine in people with cocaine use disorder. This trial will also provide information about the safety and tolerability of combining Cobenfy and cocaine. Researchers will compare Cobenfy to a placebo (a look-alike substance that contains no drug) to see if Cobenfy is a safe, tolerable and effective at blocking cocaine's effects in participants with cocaine use disorder. Participants will:

• Participate in an 11-day inpatient trial
• Take Cobenfy or placebo twice per day.
• Participate in experimental sessions to test the effects of Cobenfy (or placebo) on the response to cocaine and cocaine self-administration.

Conditions

Cocaine Use Disorder (CUD)

Outcome Measures

Primary Outcomes (1)

• Cocaine Self-Administration Choice Behavior

  Number of cocaine choices selected during progressive-ratio cocaine-versus-money choice sessions following Cobenfy or placebo maintenance.

  During Inpatient Experimental Sessions (Days 6-11)

Study Arms (2)

Cobenfy Maintenance

EXPERIMENTAL

Participants receive Cobenfy maintenance (100 mg xanomeline + 20 mg trospium twice daily) during the inpatient protocol, followed by IV cocaine self-administration and behavioral assessment sessions.

Drug: Cobenfy

Placebo Maintenance

PLACEBO COMPARATOR

Participants receive placebo maintenance during the inpatient protocol, followed by IV cocaine self-administration and behavioral assessment sessions.

Drug: Placebo

Interventions

Placebo DRUG

Participants receive matching placebo maintenance during the inpatient protocol prior to cocaine self-administration sessions.

Placebo Maintenance

Cobenfy DRUG

Participants receive Cobenfy maintenance (100 mg xanomeline + 20 mg trospium twice daily) during the inpatient protocol, prior to IV cocaine self-administration.

Cobenfy Maintenance

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Must meet criteria for cocaine use disorder - report past month smoked or IV cocaine use, and provide a urine sample positive for recent cocaine use during screening.
• Female subjects of childbearing potential must be using an effective form of birth control (e.g., birth control pills, surgical sterilization, IUD, cervical cap with a spermicide, or abstinence). Exceptions include women reporting 12 months of spontaneous amenorrhea, 6 months of spontaneous amenorrhea with a follicle stimulating hormone (FSH) level \> 40 mIU/mL, or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy. Urine pregnancy tests will be conducted prior to sessions to ensure that female subjects do not participate if pregnant.
• Able to speak and read English.

You may not qualify if:

• Chemistry values or screening outcomes including outside normal ranges that are deemed by the study physician to be clinically significant. Lipid levels are also included in this protocol as an additional check for cardiovascular health.
• Persistent hypertension \>140/90 mmHg or tachycardia \>100 bpm for three consecutive recordings during screening.
• AST, ALT or alkaline phosphatase \>3x ULN.
• Creatinine levels \>1.2x ULN will be repeated; subjects with creatinine re-test values remaining above this level will be excluded.
• Bilirubin levels \>1.5x ULN will be repeated to determine trends; subjects with bilirubin increasing over time will be excluded.
• Subjects presenting with anemia (hematocrit \< 36) or evidence of current infection (white blood cell count \> 5) are referred to their PCP. If urine protein is greater than trace, urinalysis is repeated, and subjects with continued elevation is referred to their PCP. Subjects can be reconsidered for enrollment if these issues are resolved.
• Electrocardiogram abnormalities, including:
• Atrial premature beats (\>= 2 consecutive)
• Ventricular premature beats (Lown's Grade 3 or higher; \>= 2 consecutive beats, multiform)
• Heart block (2nd or 3rd degree AV block or bundle branch block)
• Pre-excitation syndromes (Wolff-Parkinson-White or Lown-Ganong-Levine)
• QTc interval \> 450 msec
• History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of head trauma with prolonged loss of consciousness, seizures or CNS tumors, or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation.
• First degree family member with significant premature cardiac comorbidity.
• Meet diagnostic criteria for psychoactive substance use disorder for substances other than cocaine or nicotine/caffeine that would require detoxification (i.e., alcohol, opioids, benzodiazepines or barbiturates). Negative urine/breath samples for these substances, and the absence of withdrawal, will be required during screening.

Sponsors & Collaborators

• Joshua A. Lile, Ph.D.: lead

Study Sites (1)

Psychopharmacology of Addiction Laboratory

Lexington, Kentucky, 40502, United States

Location

Central Study Contacts

Joshua Lile

CONTACT

8593236034; jalile2@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 28, 2026
• First Posted: June 3, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: June 3, 2026

Record last verified: 2026-05

Locations

US (1)