Healthy Participants
Conditions
Keywords
Healthy Volunteer, CVL-354
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.
Interventions
DRUGCVL-354
Oral solution/suspension
DRUGPlacebo
Placebo matched to CVL-354
Sponsors
National Institute on Drug Abuse (NIDA)
Cerevel Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study drug up to end of follow-up period (Up to 72 days) | 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. |
| Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | From the first dose of study drug up to end of treatment (Up to 72 days) | 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. |
| Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | From the first dose of study drug up to end of treatment (Up to 72 days) | 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. |
| Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | From the first dose of study drug up to end of treatment (Up to 72 days) | 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. |
| Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | From the first dose of study drug up to end of treatment (Up to 72 days) | 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. |
| 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) | From the first dose of study drug up to end of treatment (Up to 72 days) | 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. |
| Part A: Cohort 3: Number of Participants With TEAEs | From the first dose of study drug up to end of follow up period (Up to 22 days) | 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. |
| Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in ECG Parameters | From the first dose of study drug up to end of treatment (Up to 22 days) | 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. |
| Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | From the first dose of study drug up to end of treatment (Up to 22 days) | 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. |
| Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | From the first dose of study drug up to end of treatment (Up to 22 days) | 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. |
| Part A: Cohort 3: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | From the first dose of study drug up to end of treatment (Up to 22 days) | 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. |
| Part A: Cohort 3: Number of Participants With Changes in C-SSRS | From the first dose of study drug up to end of treatment (Up to 22 days) | 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. |
| Part B: Number of Participants With TEAEs | From the first dose of study drug up to end of follow up period (Up to 31 days) | 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. |
| Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | From the first dose of study drug up to end of treatment (Up to 31 days) | 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. |
| Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | From the first dose of study drug up to end of treatment (Up to 31 days) | 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. |
| Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | From the first dose of study drug up to end of treatment (Up to 31 days) | 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. |
| Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | From the first dose of study drug up to end of treatment (Up to 31 days) | 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. |
| Part B: Number of Participants With Changes in C-SSRS | From the first dose of study drug up to end of treatment (Up to 31 days) | 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. |
Countries
United States
Participant flow
Recruitment details
73 participants took part in the study at 1 investigative site in the United States of America from 18 October 2021 to 23 January 2023.
Pre-assignment details
Healthy participants were enrolled in single ascending dose (Part A: Cohorts 1 & 2), food effect (Part A: Cohorts 3) & multiple ascending dose (Part B: Cohorts 1-5) of the study. The data for the 4 sequences in Cohorts 1 and 2 was collected and presented in a pooled manner in the participant flow.
Participants by arm
| Arm | Count |
|---|---|
| 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 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. | 2 |
| 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. | 4 |
| 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. | 2 |
| 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. | 2 |
| 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. | 3 |
| 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. | 2 |
| 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. | 3 |
| 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. | 2 |
| Part A: Cohort 3: 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. | 4 |
| Part A: Cohort 3: 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. | 3 |
| Part B: Pooled Placebo Participants received oral dose of placebo matching CVL-354, QD from Day 1 up to Day 14 of Cohort 1 to 5 in Part B. | 9 |
| Part B: Cohort 1: CVL-354 10 mg Participants received oral dose of CVL-354 10 mg, QD from Day 1 up to Day 14 in Cohort 1. | 8 |
| Part B: Cohort 2: CVL-354 25 mg Participants received oral dose of CVL-354 25 mg, QD from Day 1 up to Day 14 in Cohort 2. | 6 |
| Part B: Cohort 3: CVL-354 50 mg Participants received oral dose of CVL-354 50 mg, QD from Day 1 up to Day 14 in Cohort 3. | 7 |
| Part B: Cohort 4: CVL-354 80 mg Participants received oral dose of CVL-354 80 mg, QD from Day 1 up to Day 14 in Cohort 4. | 8 |
| Part B: Cohort 5: CVL-354 85 mg Participants received oral dose of CVL-354 85 mg, QD from Day 1 up to Day 14 in Cohort 5. | 8 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Multiple Ascending Dose (Up to 12 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
| Multiple Ascending Dose (Up to 12 Weeks) | Disciplinary Reason | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Multiple Ascending Dose (Up to 12 Weeks) | Withdrawal of Consent | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Single Ascending Dose (Up to 13 Weeks) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single Ascending Dose (Up to 13 Weeks) | Investigator's Discretion | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single Ascending Dose (Up to 13 Weeks) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single Ascending Dose (Up to 13 Weeks) | Withdrawal of Consent | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: Cohort 1: Sequence 2 | Part A: Cohort 1: Sequence 3 | Part A: Cohort 1: Sequence 4 | Part A: Cohort 1: Sequence 1 | Part A: Cohort 2: Sequence 1 | Part A: Cohort 2: Sequence 2 | Part A: Cohort 2: Sequence 3 | Part A: Cohort 2: Sequence 4 | Part A: Cohort 3: Fed/Fasted Sequence | Part A: Cohort 3: Fasted/Fed Sequence | Part B: Pooled Placebo | Part B: Cohort 1: CVL-354 10 mg | Part B: Cohort 2: CVL-354 25 mg | Part B: Cohort 3: CVL-354 50 mg | Part B: Cohort 4: CVL-354 80 mg | Part B: Cohort 5: CVL-354 85 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 9 Participants | 8 Participants | 6 Participants | 7 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 8 Participants | 5 Participants | 6 Participants | 4 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 7 Participants | 4 Participants | 5 Participants | 2 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 67 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 8 Participants | 8 Participants | 6 Participants | 7 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 9 | 0 / 8 | 0 / 6 | 0 / 7 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 16 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 5 | 1 / 5 | 0 / 4 | 2 / 6 | 2 / 6 | 0 / 7 | 2 / 7 | 2 / 9 | 0 / 8 | 1 / 6 | 2 / 7 | 2 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 9 | 0 / 8 | 0 / 6 | 0 / 7 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 22 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohort 3: Number of Participants With Changes in C-SSRS | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohort 3: Number of Participants With Changes in C-SSRS | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 22 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohort 3: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohort 3: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of follow up period (Up to 22 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohort 3: Number of Participants With TEAEs | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohort 3: Number of Participants With TEAEs | 2 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 72 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | 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) | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | 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) | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | 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) | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | 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) | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | 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) | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | 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) | 0 Participants |
| Part A: Cohort 2: CVL-354 90 mg | 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) | 0 Participants |
| Part A: Cohort 2: CVL-354 150 mg | 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) | 0 Participants |
| Part A: Cohort 2: CVL-354 200 mg | 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) | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 72 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 90 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 150 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 200 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 72 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 90 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 150 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 200 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 72 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 2: CVL-354 90 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 2: CVL-354 150 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 2: CVL-354 200 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 72 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 2: CVL-354 90 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 2: CVL-354 150 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 2: CVL-354 200 mg | Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of follow-up period (Up to 72 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Part A: Cohort 2: CVL-354 90 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Part A: Cohort 2: CVL-354 150 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| Part A: Cohort 2: CVL-354 200 mg | Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 22 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 22 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 22 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 31 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part B: Number of Participants With Changes in C-SSRS | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part B: Number of Participants With Changes in C-SSRS | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part B: Number of Participants With Changes in C-SSRS | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part B: Number of Participants With Changes in C-SSRS | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part B: Number of Participants With Changes in C-SSRS | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part B: Number of Participants With Changes in C-SSRS | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 31 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 31 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part B: Number of Participants With Clinically Significant Changes in ECG Parameters | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 31 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of treatment (Up to 31 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 Participants |
Primary
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.
Time frame: From the first dose of study drug up to end of follow up period (Up to 31 days)
Population: Safety Analysis Set included all randomized participants who had received at least 1 dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 and 2: Pooled Placebo | Part B: Number of Participants With TEAEs | 2 Participants |
| Part A: Cohort 1: CVL-354 0.5 mg | Part B: Number of Participants With TEAEs | 0 Participants |
| Part A: Cohort 1: CVL-354 1.5 mg | Part B: Number of Participants With TEAEs | 1 Participants |
| Part A: Cohort 1: CVL-354 5 mg | Part B: Number of Participants With TEAEs | 2 Participants |
| Part A: Cohort 1: CVL-354 15 mg | Part B: Number of Participants With TEAEs | 2 Participants |
| Part A: Cohort 2: CVL-354 45 mg | Part B: Number of Participants With TEAEs | 3 Participants |