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

NCT05138653 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CVL-354-10011UG3DA052166-01A1
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Keywords

Healthy Volunteer; CVL-354

Outcome Measures

Primary Outcomes (18)

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

  An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial treatment, whether or not considered related to the trial treatment. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Adverse event which was reported to have started on Day 1 with no associated onset time were defined as TEAEs. TEAEs included both serious and non-serious TEAEs.

  From the first dose of study drug up to end of follow-up period (Up to 72 days)

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

  ECG parameters were assessed using continuous ECG recordings and standard 12-lead ECGs. The parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals, PR intervals, corrected QT (QTc) intervals, corrected QT with Bazett formula (QTcB), and corrected QT with Fredericia (QTcF) parameters measurement. Clinical significance of changes in ECG parameters was based on investigator's interpretation. Number of participants with clinically significant changes in ECG were reported.

  From the first dose of study drug up to end of treatment (Up to 72 days)

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

  Vital signs include systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. Clinical significance of changes in vital signs measurements was based on investigator's interpretation. Number of participants with clinically significant changes in vital signs were reported.

  From the first dose of study drug up to end of treatment (Up to 72 days)

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

  Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinical significance of changes in laboratory parameters was based on investigator's interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.

  From the first dose of study drug up to end of treatment (Up to 72 days)

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

  The full physical examination included a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, and musculoskeletal systems. The full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength and reflexes), sensation (including Romberg sign), coordination, and gait. Clinical significance in changes of physical and neurological examination results were based on investigator's interpretation. Number of participants with clinically significant changes in physical and neurological examinations were reported.

  From the first dose of study drug up to end of treatment (Up to 72 days)

• Part A: Cohorts 1 and 2: Number of Participants With Changes in Suicidal Ideation or Suicidal Behavior Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS)

  The C-SSRS is comprised of 10 categories with binary responses. The 10 categories include: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. Categories 1-5 represent Suicidal Ideation and categories 6-10 represent Suicidal Behavior. Each category is scored as 1 if there is a positive response in the category and a 0 if there are no positive responses in the category.

  From the first dose of study drug up to end of treatment (Up to 72 days)

• Part A: Cohort 3: Number of Participants With TEAEs

  An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial treatment, whether or not considered related to the trial treatment. A SAE was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Adverse event which was reported to have started on Day 1 with no associated onset time were defined as TEAEs. TEAEs included both serious and non-serious TEAEs.

  From the first dose of study drug up to end of follow up period (Up to 22 days)

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

  ECG parameters were assessed using continuous ECG recordings and standard 12-lead ECGs. The parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals, PR intervals, corrected QT (QTc) intervals, corrected QT with Bazett formula (QTcB), and corrected QT with Fredericia (QTcF) parameters measurement. Clinical significance of changes in ECG parameters was based on investigator's interpretation. Number of participants with clinically significant changes in ECG were reported.

  From the first dose of study drug up to end of treatment (Up to 22 days)

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

  Vital signs include systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. Clinical significance of changes in vital signs measurements was based on investigator's interpretation. Number of participants with clinically significant changes in vital signs were reported.

  From the first dose of study drug up to end of treatment (Up to 22 days)

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

  Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinical significance of changes in laboratory parameters was based on investigator's interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.

  From the first dose of study drug up to end of treatment (Up to 22 days)

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

  The full physical examination included a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, and musculoskeletal systems. The full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength and reflexes), sensation (including Romberg sign), coordination, and gait. Clinical significance in changes of physical and neurological examination results were based on investigator's interpretation. Number of participants with clinically significant changes in physical and neurological examinations were reported.

  From the first dose of study drug up to end of treatment (Up to 22 days)

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

  The C-SSRS is comprised of 10 categories with binary responses. The 10 categories include: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. Categories 1-5 represent Suicidal Ideation and categories 6-10 represent Suicidal Behavior. Each category is scored as 1 if there is a positive response in the category and a 0 if there are no positive responses in the category.

  From the first dose of study drug up to end of treatment (Up to 22 days)

• Part B: Number of Participants With TEAEs

  An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial treatment, whether or not considered related to the trial treatment. A SAE was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Adverse event which was reported to have started on Day 1 with no associated onset time were defined as TEAEs. TEAEs included both serious and non-serious TEAEs.

  From the first dose of study drug up to end of follow up period (Up to 31 days)

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

  ECG parameters were assessed using continuous ECG recordings and standard 12-lead ECGs. The parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals, PR intervals, corrected QT (QTc) intervals, corrected QT with Bazett formula (QTcB), and corrected QT with Fredericia (QTcF) parameters measurement. Clinical significance of changes in ECG parameters was based on investigator's interpretation. Number of participants with clinically significant changes in ECG were reported.

  From the first dose of study drug up to end of treatment (Up to 31 days)

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

  Vital signs include systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. Clinical significance of changes in vital signs measurements was based on investigator's interpretation. Number of participants with clinically significant changes in vital signs were reported.

  From the first dose of study drug up to end of treatment (Up to 31 days)

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

  Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinical significance of changes in laboratory parameters was based on investigator's interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.

  From the first dose of study drug up to end of treatment (Up to 31 days)

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

  The full physical examination included a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, and musculoskeletal systems. The full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength and reflexes), sensation (including Romberg sign), coordination, and gait. Clinical significance in changes of physical and neurological examination results were based on investigator's interpretation. Number of participants with clinically significant changes in physical and neurological examinations were reported.

  From the first dose of study drug up to end of treatment (Up to 31 days)

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

  The C-SSRS is comprised of 10 categories with binary responses. The 10 categories include: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. Categories 1-5 represent Suicidal Ideation and categories 6-10 represent Suicidal Behavior Each category is scored as 1 if there is a positive response in the category and a 0 if there are no positive responses in the category.

  From the first dose of study drug up to end of treatment (Up to 31 days)

Study Arms (15)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

Drug: Placebo; Drug: CVL-354

Interventions

CVL-354 DRUG

Oral solution/suspension

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

Placebo DRUG

Placebo matched to CVL-354

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Labcorp Drug Development

Dallas, Texas, 75247, United States

Location

Results Point of Contact

• Title: Cerevel Central Contact
• Organization: Cerevel Therapeutics

info@cerevel.com

8572500977

Study Officials

• Matthew Leoni, MD, MBA

  Cerevel Therapeutics, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 1, 2021
• Study Start: October 18, 2021
• Primary Completion: January 23, 2023
• Study Completion: January 23, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)