A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants

Sponsor

Cerevel Therapeutics, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05138653

Collaborator

(none)

Enrollment

Location

Arms

16.4

Anticipated Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Drug: CVL-354 Drug: Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Part A of the trial is a double-blind, randomized, placebo-controlled 4-period, 4-sequence, crossover design to evaluate the PK, safety, and tolerability of single doses of CVL-354 in healthy participants. Except for a potential food effect period, all treatments will be administered under fasted conditions. Part B of the trial is a double-blind, randomized, placebo-controlled trial to evaluate PK, safety, and tolerability of CVL-354 in multiple ascending doses.Part A of the trial is a double-blind, randomized, placebo-controlled 4-period, 4-sequence, crossover design to evaluate the PK, safety, and tolerability of single doses of CVL-354 in healthy participants. Except for a potential food effect period, all treatments will be administered under fasted conditions. Part B of the trial is a double-blind, randomized, placebo-controlled trial to evaluate PK, safety, and tolerability of CVL-354 in multiple ascending doses.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 18, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Ascending Dose (SAD) Cohorts 1-3 In Cohorts 1 and 2, all participants will receive treatment with up to 3 single oral doses of CVL-354 and/or 1 single oral dose of placebo in a 4-period crossover design. The starting dose of CVL-354 will be 0.5 mg. Participants will be randomized to 1 of 4 treatment sequences. Cohort 3 may be used to evaluate additional doses or evaluate food effect, depending on the results from Cohorts 1 and 2.	Drug: Drug: CVL-354 Oral solution/suspension Drug: Drug: Placebo Oral solution/suspension
Experimental: Multiple Ascending Dose (MAD) Cohorts 1-5 All participants will receive treatment with multiple oral doses of CVL-354 (dose and regimen to be determined) or matching placebo for 14 days.	Drug: Drug: CVL-354 Oral solution/suspension Drug: Drug: Placebo Oral solution/suspension

Arm

Intervention/Treatment

Experimental: Single Ascending Dose (SAD) Cohorts 1-3

In Cohorts 1 and 2, all participants will receive treatment with up to 3 single oral doses of CVL-354 and/or 1 single oral dose of placebo in a 4-period crossover design. The starting dose of CVL-354 will be 0.5 mg. Participants will be randomized to 1 of 4 treatment sequences. Cohort 3 may be used to evaluate additional doses or evaluate food effect, depending on the results from Cohorts 1 and 2.

Drug: Drug: CVL-354

Oral solution/suspension

Drug: Drug: Placebo

Oral solution/suspension

Experimental: Multiple Ascending Dose (MAD) Cohorts 1-5

All participants will receive treatment with multiple oral doses of CVL-354 (dose and regimen to be determined) or matching placebo for 14 days.

Drug: Drug: CVL-354

Oral solution/suspension

Drug: Drug: Placebo

Oral solution/suspension

Outcome Measures

Primary Outcome Measures

Primary Part A&B: Incidence and severity of Treatment -Emergent Adverse Events (TEAEs) [Up to 29 days following last dose with IMP]
Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward will be counted as treatment-emergent AE (TEAE).
Primary Part A&B: Incidence of clinically significant changes in electrocardiogram (ECG) results [Up to 17 days following last dose with IMP]
Primary Part A&B: Incidence of clinically significant changes in vital sign measurements [Up to 17 days following last dose with IMP]
Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.
Primary Part A&B: Incidence of clinically significant changes in clinical laboratory results [Up to 17 days following last dose with IMP]
Primary Part A&B: Incidence of clinically significant changes in physical and neurological examination results [Up to 17 days following last dose with IMP]
Primary Part A&B: Changes in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS) [Up to 17 days following last dose with IMP]
The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the Behavior subscale) indicates increased risk.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Women of nonchildbearing potential and men 18 to 55 years, inclusive.
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 30.0 kg/m2, inclusive, and total body weight >50 kg (110 lb) at Screening.
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.
Capable of giving signed informed consent
Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements.

Exclusion Criteria:

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.
Serious risk of suicide in the opinion of the Investigator
History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the ICF.
Any condition that could possibly affect drug absorption
Receipt of SARS-CoV2 vaccination or booster as follows:

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 IMP will be excluded.

Have recently been diagnosed with symptomatic COVID-19 or test positive 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 (eg, prescription and over-the-counter medications, herbal medications, vitamins, and supplements) during the trial
Either of the following:

History of HIV, hepatitis B, or hepatitis C infection
Positive result for HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

Positive drug screen (including nicotine) or a positive test for alcohol
Abnormal clinical laboratory test results or vital measurements at Screening and Check-in
Estimated glomerular filtration rate at Screening <90 mL/min/1.73 m2, as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
Abnormal 12-lead ECG at Screening or initial Check-In (Day -1).
Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.
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.
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.