Clinical trial NCT05138653: A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants
Official title: A Phase 1, Double-blind (Investigator and Participant), First-in-Human Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of CVL-354 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Healthy Volunteer
CVL-354
Lead sponsor: Cerevel Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2021-12-01
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a 2-part, double-blind, randomized, placebo-controlled, first-in-human trial evaluating a single ascending dose (4-way crossover, Part A) and multiple ascending doses (Part B) of CVL-354.


Eligibility criteria: Inclusion Criteria:

1. Women of nonchildbearing potential and men 18 to 55 years, inclusive.
2. Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, Electrocardiogram (ECG), vital sign measurements, and laboratory test results, as evaluated by the investigator.
3. Body mass index of 18.5 to 30.0 Kilograms per square meter (kg/m\^2), inclusive, and total body weight \>50 Kilogram (kg) \[110 Pound (lb)\] at Screening.
4. A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use contraception during the trial and 14 days following the last dose of study drug.
5. Capable of giving signed informed consent
6. Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements.

Exclusion Criteria:

1. Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine, hematological, immunological, or 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.
2. Serious risk of suicide in the opinion of the Investigator
3. History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the informed consent form (ICF).
4. Any condition that could possibly affect drug absorption
5. Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination or booster as follows:

   * messenger ribonucleic acid (mRNA): within 14 days prior to dosing
   * Non-mRNA: within 28 days prior to dosing In addition, participants who plan to receive SARS-CoV2 vaccination or booster while participating in the trial or for at least 14 days after the last dose of investigational medicinal product (IMP) will be excluded.
6. Have recently been diagnosed with symptomatic corona virus disease-2019 (COVID-19) or test positive for COVID-19 within 30 days prior to signing the ICF.
7. Use of prohibited medication prior to randomization or likely to require prohibited concomitant therapy (eg, prescription and over-the-counter medications, herbal medications, vitamins, and supplements) during the trial
8. Either of the following:

   * History of human immunodeficiency viruses (HIV), hepatitis B, or hepatitis C infection
   * Positive result for HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody
9. Positive drug screen (including nicotine) or a positive test for alcohol
10. Abnormal clinical laboratory test results or vital measurements at Screening and Check-in
11. Estimated glomerular filtration rate at Screening \<90 millilitre/minute/1.73m\^2 (mL/min/1.73 m\^2), as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
12. Abnormal 12-lead ECG at Screening or initial Check-In (Day -1).
13. Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.
14. Current enrollment or past participation within 30 days or 5 half-lives (whichever is longer) prior to signing the ICF in any other clinical trial involving an IMP.
15. Any other abnormal safety findings unless, based on the investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results.

Primary outcomes:
measure: Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the first dose of study drug up to end of follow-up period (Up to 72 days)
measure: Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
timeFrame: From the first dose of study drug up to end of treatment (Up to 72 days)
measure: Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements
timeFrame: From the first dose of study drug up to end of treatment (Up to 72 days)
measure: Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: From the first dose of study drug up to end of treatment (Up to 72 days)
measure: Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations
timeFrame: From the first dose of study drug up to end of treatment (Up to 72 days)
measure: Part A: Cohorts 1 and 2: Number of Participants With Changes in Suicidal Ideation or Suicidal Behavior Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS)
timeFrame: From the first dose of study drug up to end of treatment (Up to 72 days)
measure: Part A: Cohort 3: Number of Participants With TEAEs
timeFrame: From the first dose of study drug up to end of follow up period (Up to 22 days)
measure: Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in ECG Parameters
timeFrame: From the first dose of study drug up to end of treatment (Up to 22 days)
measure: Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Vital Sign Measurements
timeFrame: From the first dose of study drug up to end of treatment (Up to 22 days)
measure: Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: From the first dose of study drug up to end of treatment (Up to 22 days)
measure: Part A: Cohort 3: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations
timeFrame: From the first dose of study drug up to end of treatment (Up to 22 days)
measure: Part A: Cohort 3: Number of Participants With Changes in C-SSRS
timeFrame: From the first dose of study drug up to end of treatment (Up to 22 days)
measure: Part B: Number of Participants With TEAEs
timeFrame: From the first dose of study drug up to end of follow up period (Up to 31 days)
measure: Part B: Number of Participants With Clinically Significant Changes in ECG Parameters
timeFrame: From the first dose of study drug up to end of treatment (Up to 31 days)
measure: Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements
timeFrame: From the first dose of study drug up to end of treatment (Up to 31 days)
measure: Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: From the first dose of study drug up to end of treatment (Up to 31 days)
measure: Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations
timeFrame: From the first dose of study drug up to end of treatment (Up to 31 days)
measure: Part B: Number of Participants With Changes in C-SSRS
timeFrame: From the first dose of study drug up to end of treatment (Up to 31 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Labcorp Drug Development
state: Texas
Study officials:
affiliation: Cerevel Therapeutics, LLC
name: Matthew Leoni, MD, MBA
role: STUDY_DIRECTOR
References: