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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: CVL-354; Drug: Placebo; Drug: CVL-354

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Labcorp Drug Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Cohort 1: Sequence 1; Participants were randomized to sequence 1 to receive placebo on Day 1 of Period 1 followed by CVL-354 1.5 milligrams (mg) on Day 1 of Period 2, followed by CVL-354 5 mg on Day 1 of Period 3 & followed by CVL-354 15 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 1: Sequence 2; Participants were randomized to sequence 2 to receive CVL-354 0.5 mg on Day 1 of Period 1 followed by placebo on Day 1 of Period 2, followed by CVL-354 5 mg on Day 1 of Period 3 & followed by CVL-354 15 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 1: Sequence 3; Participants were randomized to sequence 3 to receive CVL-354 0.5 mg on Day 1 of Period 1 followed by CVL-354 1.5 mg on Day 1 of Period 2, followed by placebo on Day 1 of Period 3 & followed by CVL-354 15 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 1: Sequence 4; Participants were randomized to sequence 4 to receive CVL-354 0.5 mg on Day 1 of Period 1 followed by CVL-354 1.5 mg on Day 1 of Period 2, followed by CVL-354 5 mg on Day 1 of Period 3 & followed by placebo on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 2: Sequence 1; Participants were randomized to sequence 1 to receive placebo on Day 1 of Period 1 followed by CVL-354 90 mg on Day 1 of Period 2, followed by CVL-354 150 mg on Day 1 of Period 3 & followed by CVL-354 200 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 2: Sequence 2; Participants were randomized to sequence 2 to receive CVL-354 45 mg on Day 1 of Period 1 followed by placebo on Day 1 of Period 2, followed by CVL-354 150 mg on Day 1 of Period 3 & followed by CVL-354 200 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 2: Sequence 3; Participants were randomized to sequence 3 to receive CVL-354 45 mg on Day 1 of Period 1 followed by CVL-354 on 90 mg Day 1 of Period 2, followed by placebo on Day 1 of Period 3 & followed by CVL-354 200 mg on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 2: Sequence 4; Participants were randomized to sequence 4 to receive CVL-354 45 mg on Day 1 of Period 1 followed by CVL-354 90 mg on Day 1 of Period 2, followed by CVL-354 150 mg on Day 1 of Period 3 & placebo on Day 1 of Period 4. Each dosing period was separated by a washout period of at least 5 days.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 3: Sequence 1: Fed/Fasted Sequence; Participants first received a single oral dose of CVL-354 50 mg, under fed state on Day 1 of Period 1 followed by a single oral dose of CVL-354 50 mg under fasted state on Day 1 of Period 2, with a washout period of 2 days between both periods.	Drug: CVL-354; Oral solution/suspension; Drug: CVL-354; Capsule
Experimental: Part A: Cohort 3: Sequence 2: Fasted/Fed Sequence; Participants first received a single oral dose of CVL-354 50 mg, under fasted state on Day 1 of Period 1 followed by a single oral dose of CVL-354 50 mg under fed state on Day 1 of Period 2, with a washout period of 2 days between both periods	Drug: CVL-354; Oral solution/suspension; Drug: CVL-354; Capsule
Experimental: Part B: Cohort 1: CVL-354 10 mg; Participants received oral dose of CVL-354 10 mg or Placebo, once daily (QD) from Day 1 up to Day 14 in Cohort 1.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part B: Cohort 2: CVL-354 25 mg; Participants received oral dose of CVL-354 25 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 2.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part B: Cohort 3: CVL-354 50 mg; Participants received oral dose of CVL-354 50 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 3.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part B: Cohort 4: CVL-354 80 mg; Participants received oral dose of CVL-354 80 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 4.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule
Experimental: Part B: Cohort 5: CVL-354 85 mg; Participants received oral dose of CVL-354 85 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 5.	Drug: CVL-354; Oral solution/suspension; Drug: Placebo; Placebo matched to CVL-354; Drug: CVL-354; Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial treatment, whether or not considered related to the trial treatment. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Adverse event which was reported to have started on Day 1 with no associated onset time were defined as TEAEs. TEAEs included both serious and non-serious TEAEs.	From the first dose of study drug up to end of follow-up period (Up to 72 days)
Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters	ECG parameters were assessed using continuous ECG recordings and standard 12-lead ECGs. The parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals, PR intervals, corrected QT (QTc) intervals, corrected QT with Bazett formula (QTcB), and corrected QT with Fredericia (QTcF) parameters measurement. Clinical significance of changes in ECG parameters was based on investigator's interpretation. Number of participants with clinically significant changes in ECG were reported.	From the first dose of study drug up to end of treatment (Up to 72 days)
Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements	Vital signs include systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. Clinical significance of changes in vital signs measurements was based on investigator's interpretation. Number of participants with clinically significant changes in vital signs were reported.	From the first dose of study drug up to end of treatment (Up to 72 days)
Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters	Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinical significance of changes in laboratory parameters was based on investigator's interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.	From the first dose of study drug up to end of treatment (Up to 72 days)
Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations	The full physical examination included a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, and musculoskeletal systems. The full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength and reflexes), sensation (including Romberg sign), coordination, and gait. Clinical significance in changes of physical and neurological examination results were based on investigator's interpretation. Number of participants with clinically significant changes in physical and neurological examinations were reported.	From the first dose of study drug up to end of treatment (Up to 72 days)
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)	The C-SSRS is comprised of 10 categories with binary responses. The 10 categories include: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. Categories 1-5 represent Suicidal Ideation and categories 6-10 represent Suicidal Behavior. Each category is scored as 1 if there is a positive response in the category and a 0 if there are no positive responses in the category.	From the first dose of study drug up to end of treatment (Up to 72 days)
Part A: Cohort 3: Number of Participants With TEAEs	An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial treatment, whether or not considered related to the trial treatment. A SAE was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Adverse event which was reported to have started on Day 1 with no associated onset time were defined as TEAEs. TEAEs included both serious and non-serious TEAEs.	From the first dose of study drug up to end of follow up period (Up to 22 days)
Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in ECG Parameters	ECG parameters were assessed using continuous ECG recordings and standard 12-lead ECGs. The parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals, PR intervals, corrected QT (QTc) intervals, corrected QT with Bazett formula (QTcB), and corrected QT with Fredericia (QTcF) parameters measurement. Clinical significance of changes in ECG parameters was based on investigator's interpretation. Number of participants with clinically significant changes in ECG were reported.	From the first dose of study drug up to end of treatment (Up to 22 days)
Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Vital Sign Measurements	Vital signs include systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. Clinical significance of changes in vital signs measurements was based on investigator's interpretation. Number of participants with clinically significant changes in vital signs were reported.	From the first dose of study drug up to end of treatment (Up to 22 days)
Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters	Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinical significance of changes in laboratory parameters was based on investigator's interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.	From the first dose of study drug up to end of treatment (Up to 22 days)
Part A: Cohort 3: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations	The full physical examination included a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, and musculoskeletal systems. The full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength and reflexes), sensation (including Romberg sign), coordination, and gait. Clinical significance in changes of physical and neurological examination results were based on investigator's interpretation. Number of participants with clinically significant changes in physical and neurological examinations were reported.	From the first dose of study drug up to end of treatment (Up to 22 days)
Part A: Cohort 3: Number of Participants With Changes in C-SSRS	The C-SSRS is comprised of 10 categories with binary responses. The 10 categories include: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. Categories 1-5 represent Suicidal Ideation and categories 6-10 represent Suicidal Behavior. Each category is scored as 1 if there is a positive response in the category and a 0 if there are no positive responses in the category.	From the first dose of study drug up to end of treatment (Up to 22 days)
Part B: Number of Participants With TEAEs	An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial treatment, whether or not considered related to the trial treatment. A SAE was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Adverse event which was reported to have started on Day 1 with no associated onset time were defined as TEAEs. TEAEs included both serious and non-serious TEAEs.	From the first dose of study drug up to end of follow up period (Up to 31 days)
Part B: Number of Participants With Clinically Significant Changes in ECG Parameters	ECG parameters were assessed using continuous ECG recordings and standard 12-lead ECGs. The parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals, PR intervals, corrected QT (QTc) intervals, corrected QT with Bazett formula (QTcB), and corrected QT with Fredericia (QTcF) parameters measurement. Clinical significance of changes in ECG parameters was based on investigator's interpretation. Number of participants with clinically significant changes in ECG were reported.	From the first dose of study drug up to end of treatment (Up to 31 days)
Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements	Vital signs include systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. Clinical significance of changes in vital signs measurements was based on investigator's interpretation. Number of participants with clinically significant changes in vital signs were reported.	From the first dose of study drug up to end of treatment (Up to 31 days)
Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters	Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinical significance of changes in laboratory parameters was based on investigator's interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.	From the first dose of study drug up to end of treatment (Up to 31 days)
Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations	The full physical examination included a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, and musculoskeletal systems. The full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength and reflexes), sensation (including Romberg sign), coordination, and gait. Clinical significance in changes of physical and neurological examination results were based on investigator's interpretation. Number of participants with clinically significant changes in physical and neurological examinations were reported.	From the first dose of study drug up to end of treatment (Up to 31 days)
Part B: Number of Participants With Changes in C-SSRS	The C-SSRS is comprised of 10 categories with binary responses. The 10 categories include: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. Categories 1-5 represent Suicidal Ideation and categories 6-10 represent Suicidal Behavior Each category is scored as 1 if there is a positive response in the category and a 0 if there are no positive responses in the category.	From the first dose of study drug up to end of treatment (Up to 31 days)

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Study Director: Matthew Leoni, MD, MBA, Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2021
• Primary Completion (Actual): January 23, 2023
• Study Completion (Actual): January 23, 2023

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Volunteer; CVL-354
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: CVL-354-1001; 1UG3DA052166-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No