Positron Emission Tomography (PET) Trial to Evaluate Target Occupancy of CVL-354 at Kappa and Mu Opioid Receptors in Brain Following Oral Dosing

NCT05547542 | Completed Phase 1 FDA Drug

• 2 other identifiers: CVL-354-10024UH3DA052166-02
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purpose of this study is to assess the target occupancy at kappa and mu opioid receptors in the brain after single oral doses of CVL-354 in healthy adult participants.

Conditions

Opioid Use Disorder

Keywords

Healthy adult participants

Outcome Measures

Primary Outcomes (2)

• Kappa Opioid Receptor Occupancy in the Brain Following Single Oral Doses of CVL-354 in Healthy Adult Participants

  Day 1

• Mu Opioid Receptor Occupancy in the Brain Following Single Oral Doses of CVL-354 in Healthy Adult Participants

  Day 1

Secondary Outcomes (9)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Up to 18 days

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results

  Up to Day 2

• Number of Participants With Clinically Significant Changes in Vital Sign Measurements

  Up to Day 2

• Number of Participants Clinically Significant Changes in Clinical Laboratory Assessments

  Up to Day 2

• Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results

  Up to Day 2

Study Arms (2)

Part A: Kappa Opioid Receptor (KOR) Cohort

EXPERIMENTAL

Participants will receive single dose of CVL-354, 25 mg, orally, on Day 1 along with \[11C\]-LY2795050, intravenous (IV) bolus injection of up to 20 millicurie (mCi) before the baseline and post-dose PET scans. Based on the KOR receptor occupancy (RO) results from this cohort, dosing may be explored further in subsequent cohorts.

Drug: CVL-354; Drug: [11C]-LY2795050

Part B: Mu Opioid Receptor (MOR) Cohort

EXPERIMENTAL

Part B will commence after Part A cohort is completed. Participants will receive single dose of CVL-354 150 mg, orally, on Day 1 along with \[11C\]-carfentanil, IV bolus injection of up to 20 mCi before the baseline and post-dose PET scans. Based on the MOR RO results from this cohort, dosing may be explored further in subsequent cohorts.

Drug: CVL-354; Drug: [11C]-carfentanil

Interventions

CVL-354 DRUG

Oral solution/capsule

Part A: Kappa Opioid Receptor (KOR) Cohort; Part B: Mu Opioid Receptor (MOR) Cohort

[11C]-LY2795050 DRUG

IV injection

Part A: Kappa Opioid Receptor (KOR) Cohort

[11C]-carfentanil DRUG

IV injection

Part B: Mu Opioid Receptor (MOR) Cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women of nonchildbearing potential and men 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF).
• Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
• Body mass index of 18.5 to 32.0 kilograms per square meter (kg/m\^2), inclusive, and total body weight \>50 kg (110 pounds \[lb\]) at Screening.
• Sexually active men with a pregnant or nonpregnant partner of childbearing potential must agree to comply with the following contraception requirements during the trial and for 7 days after the last dose of investigational medicinal product (IMP):
• Use condom or remain abstinent. In addition, male participants should not donate sperm for a minimum of 7 days following the last dose of IMP.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.

You may not qualify if:

• Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
• "Yes" responses for any of the following items on the C-SSRS (within the individual's lifetime):
• Suicidal Ideation Item 3 (Active Suicidal Ideation with Any Methods \[Not Plan\] without Intent to Act)
• Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan)
• Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent)
• Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior) "Yes" responses for any of the following items on the C-SSRS (within past 12 months):
• Suicidal Ideation Item 1 (Wish to be Dead)
• History of substance or alcohol-use disorder (excluding nicotine or caffeine) as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria within 12 months prior to signing the ICF.
• Any condition or surgery that could possibly affect drug absorption, including, but not limited to, bowel resections, bariatric weight loss surgery/procedures, gastrectomy, uncomplicated appendectomy, and cholecystectomy.
• Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or booster within 7 days of planned dosing. In addition, participants who plan to receive SARS-CoV-2 vaccination or booster while participating in the trial or for a minimum of 7 days (to cover at least 5 half-lives of IMP) after the last dose of IMP will be excluded.
• Have recently been diagnosed with symptomatic coronavirus disease-2019 (COVID-19) or test positive (i.e., using polymerase chain reaction (PCR) or rapid antigen test) for COVID-19 within 30 days prior to signing the ICF.
• Use of prohibited medication prior to randomization or likely to require prohibited concomitant therapy (e.g., prescription and over-the-counter medications, herbal medications, vitamins, and supplements) during the trial.
• Positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody with detectable viral ribonucleic acid (RNA) levels at Screening.
• Positive drug screen (including cotinine and tetrahydrocannabinol \[THC\]) or a positive test for alcohol.
• Any of the following clinical laboratory test results at the Screening Visit or Check-in (Day -1), which can be confirmed by a single repeat measurement, if deemed necessary:

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

New Haven, Connecticut

New Haven, Connecticut, 06510, United States

Location

Yale PET Center

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

3-chloro-4-(4-((2-(3-pyridyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide; carfentanil

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 21, 2022
• Study Start: March 2, 2023
• Primary Completion: July 24, 2024
• Study Completion: August 6, 2024
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)