Healthy ParticipantsPhase 1NCT05138653
A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants
A Phase 1 study testing CVL-354 in people with Healthy Participants, run by Cerevel Therapeutics, LLC at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- CVL-354
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Oct 2021to 23 Jan 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Double-blind (Investigator and Participant), First-in-Human Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of CVL-354 in Healthy Participants
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.
- Conditions
- Healthy Participants
- Being tested
- CVL-354, Placebo
- Keywords
- Healthy Volunteer, CVL-354
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVL-354Drug
Oral solution/suspension
PlaceboDrug
Placebo matched to CVL-354
CVL-354Drug
Capsule
| Study group | Role | What they receive |
|---|---|---|
| Part A: Cohort 1: Sequence 1 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 1: Sequence 2 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 1: Sequence 3 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 1: Sequence 4 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 2: Sequence 1 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 2: Sequence 2 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 2: Sequence 3 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 2: Sequence 4 | Experimental | 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. Receives: Drug: CVL-354; Drug: Placebo |
| Part A: Cohort 3: Sequence 1: Fed/Fasted Sequence | Experimental | 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. Receives: Drug: CVL-354 |
| Part A: Cohort 3: Sequence 2: Fasted/Fed Sequence | Experimental | 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 Receives: Drug: CVL-354 |
| Part B: Cohort 1: CVL-354 10 mg | Experimental | Participants received oral dose of CVL-354 10 mg or Placebo, once daily (QD) from Day 1 up to Day 14 in Cohort 1. Receives: Drug: CVL-354; Drug: Placebo |
| Part B: Cohort 2: CVL-354 25 mg | Experimental | Participants received oral dose of CVL-354 25 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 2. Receives: Drug: Placebo; Drug: CVL-354 |
| Part B: Cohort 3: CVL-354 50 mg | Experimental | Participants received oral dose of CVL-354 50 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 3. Receives: Drug: Placebo; Drug: CVL-354 |
| Part B: Cohort 4: CVL-354 80 mg | Experimental | Participants received oral dose of CVL-354 80 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 4. Receives: Drug: Placebo; Drug: CVL-354 |
| Part B: Cohort 5: CVL-354 85 mg | Experimental | Participants received oral dose of CVL-354 85 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 5. Receives: Drug: Placebo; Drug: CVL-354 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From the first dose of study drug up to end of treatment (Up to 31 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start18 Oct 2021
- Primary completion23 Jan 2023
- Study completion23 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerevel Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Matthew Leoni, MD, MBA, Study director, Cerevel Therapeutics, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05138653
- Sponsor's protocol ID
- CVL-354-1001
- Other IDs
- 1UG3DA052166-01A1
- Status last verified
- Nov 2024
- First submitted
- 17 Nov 2021
- Last updated
- 26 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Double-blind (Investigator and Participant), First-in-Human Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of CVL-354 in Healthy Participants
- ClinicalTrials.gov ID
- NCT05138653
- Acronym / sponsor ID
- CVL-354-1001
- Conditions
- Healthy Participants
- Keywords
- Healthy Volunteer, CVL-354
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Cerevel Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 18 Oct 2021 (actual)
- Primary completion
- 23 Jan 2023 (actual)
- Study completion
- 23 Jan 2023 (actual)
- First posted
- 1 Dec 2021 (actual)
- Results
- Posted 26 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Part A: Cohort 1: Sequence 1 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 1: Sequence 2 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 1: Sequence 3 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 1: Sequence 4 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 2: Sequence 1 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 2: Sequence 2 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 2: Sequence 3 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 2: Sequence 4 | Experimental | Drug: CVL-354, Drug: PlaceboParticipants 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. |
| Part A: Cohort 3: Sequence 1: Fed/Fasted Sequence | Experimental | Drug: CVL-354Participants 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. |
| Part A: Cohort 3: Sequence 2: Fasted/Fed Sequence | Experimental | Drug: CVL-354Participants 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 |
| Part B: Cohort 1: CVL-354 10 mg | Experimental | Drug: CVL-354, Drug: PlaceboParticipants received oral dose of CVL-354 10 mg or Placebo, once daily (QD) from Day 1 up to Day 14 in Cohort 1. |
| Part B: Cohort 2: CVL-354 25 mg | Experimental | Drug: Placebo, Drug: CVL-354Participants received oral dose of CVL-354 25 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 2. |
| Part B: Cohort 3: CVL-354 50 mg | Experimental | Drug: Placebo, Drug: CVL-354Participants received oral dose of CVL-354 50 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 3. |
| Part B: Cohort 4: CVL-354 80 mg | Experimental | Drug: Placebo, Drug: CVL-354Participants received oral dose of CVL-354 80 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 4. |
| Part B: Cohort 5: CVL-354 85 mg | Experimental | Drug: Placebo, Drug: CVL-354Participants received oral dose of CVL-354 85 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 5. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CVL-354Oral solution/suspension | Drug | Part A: Cohort 1: Sequence 1, Part A: Cohort 1: Sequence 2, Part A: Cohort 1: Sequence 3, Part A: Cohort 1: Sequence 4, 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 B: Cohort 1: CVL-354 10 mg |
| PlaceboPlacebo matched to CVL-354 | Drug | Part A: Cohort 1: Sequence 1, Part A: Cohort 1: Sequence 2, Part A: Cohort 1: Sequence 3, Part A: Cohort 1: Sequence 4, 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 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 |
| CVL-354Capsule | Drug | Part A: Cohort 3: Sequence 1: Fed/Fasted Sequence, Part A: Cohort 3: Sequence 2: Fasted/Fed Sequence, 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 |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Leoni, MD, MBA study director
Cerevel Therapeutics, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CVL-354 in people with Healthy Participants, run by Cerevel Therapeutics, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.