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Completed

NCT Number: NCT05138653

A Single and Multiple Ascending Dose Trial 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.

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Key information

Conditions

Healthy Participants

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Labcorp Drug Development

Dallas, Texas, 75247, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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, Electrocardiogram (ECG), vital sign measurements, and laboratory test results, as evaluated by the investigator.
  • 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.
  • 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 informed consent form (ICF).
  • Any condition that could possibly affect drug absorption
  • 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.
  • 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.
  • 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 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
  • 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 millilitre/minute/1.73m^2 (mL/min/1.73 m^2), 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.

Treatment and study plan

CVL-354

Drug

Oral solution/suspension

Placebo

Drug

Placebo matched to CVL-354

Primary outcomes

  1. Part A: Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame: 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.

  2. Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters

    Time frame: 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.

  3. Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Vital Sign Measurements

    Time frame: 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.

  4. Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

    Time frame: 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.

  5. Part A: Cohorts 1 and 2: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations

    Time frame: 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.

  6. 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)

    Time frame: 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.

  7. Part A: Cohort 3: Number of Participants With TEAEs

    Time frame: 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.

  8. Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in ECG Parameters

    Time frame: 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.

  9. Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Vital Sign Measurements

    Time frame: 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.

  10. Part A: Cohorts 3: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

    Time frame: 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.

  11. Part A: Cohort 3: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations

    Time frame: 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.

  12. Part A: Cohort 3: Number of Participants With Changes in C-SSRS

    Time frame: 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.

  13. Part B: Number of Participants With TEAEs

    Time frame: 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.

  14. Part B: Number of Participants With Clinically Significant Changes in ECG Parameters

    Time frame: 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.

  15. Part B: Number of Participants With Clinically Significant Changes in Vital Sign Measurements

    Time frame: 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.

  16. Part B: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

    Time frame: 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.

  17. Part B: Number of Participants With Clinically Significant Changes in Physical and Neurological Examinations

    Time frame: 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.

  18. Part B: Number of Participants With Changes in C-SSRS

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Cerevel Therapeutics, LLC

Industry

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Dec 1, 2021
Registry last updated
Nov 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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