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

Cerevel Therapeutics

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: CVL-354; Drug: Placebo

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT05138653

CVL-354-1001

1UG3DA052166-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 73 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Women of nonchildbearing potential and men 18 to 55 years, inclusive.
2. Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, Electrocardiogram (ECG), vital sign measurements, and laboratory test results, as evaluated by the investigator.
3. Body mass index of 18.5 to 30.0 Kilograms per square meter (kg/m^2), inclusive, and total body weight >50 Kilogram (kg) [110 Pound (lb)] at Screening.
4. A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use contraception during the trial and 14 days following the last dose of study drug.
5. Capable of giving signed informed consent
6. Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements.

Exclusion criteria

1. Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine, hematological, immunological, or neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.

2. Serious risk of suicide in the opinion of the Investigator

3. History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the informed consent form (ICF).

4. Any condition that could possibly affect drug absorption

5. Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination or booster as follows:

   • messenger ribonucleic acid (mRNA): within 14 days prior to dosing
   • Non-mRNA: within 28 days prior to dosing In addition, participants who plan to receive SARS-CoV2 vaccination or booster while participating in the trial or for at least 14 days after the last dose of investigational medicinal product (IMP) will be excluded.

6. Have recently been diagnosed with symptomatic corona virus disease-2019 (COVID-19) or test positive for COVID-19 within 30 days prior to signing the ICF.

7. Use of prohibited medication prior to randomization or likely to require prohibited concomitant therapy (eg, prescription and over-the-counter medications, herbal medications, vitamins, and supplements) during the trial

8. Either of the following:

   • History of human immunodeficiency viruses (HIV), hepatitis B, or hepatitis C infection
   • Positive result for HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

9. Positive drug screen (including nicotine) or a positive test for alcohol

10. Abnormal clinical laboratory test results or vital measurements at Screening and Check-in

11. Estimated glomerular filtration rate at Screening <90 millilitre/minute/1.73m^2 (mL/min/1.73 m^2), as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

12. Abnormal 12-lead ECG at Screening or initial Check-In (Day -1).

13. Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.

14. Current enrollment or past participation within 30 days or 5 half-lives (whichever is longer) prior to signing the ICF in any other clinical trial involving an IMP.

15. Any other abnormal safety findings unless, based on the investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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73 participants in 15 patient groups

Part A: Cohort 1: Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 1: Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 1: Sequence 3

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 1: Sequence 4

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 2: Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 2: Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 2: Sequence 3

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 2: Sequence 4

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 3: Sequence 1: Fed/Fasted Sequence

Experimental group

Description:

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.

Treatment:

Drug: CVL-354

Drug: CVL-354

Part A: Cohort 3: Sequence 2: Fasted/Fed Sequence

Experimental group

Description:

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

Treatment:

Drug: CVL-354

Drug: CVL-354

Part B: Cohort 1: CVL-354 10 mg

Experimental group

Description:

Participants received oral dose of CVL-354 10 mg or Placebo, once daily (QD) from Day 1 up to Day 14 in Cohort 1.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part B: Cohort 2: CVL-354 25 mg

Experimental group

Description:

Participants received oral dose of CVL-354 25 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 2.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part B: Cohort 3: CVL-354 50 mg

Experimental group

Description:

Participants received oral dose of CVL-354 50 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 3.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part B: Cohort 4: CVL-354 80 mg

Experimental group

Description:

Participants received oral dose of CVL-354 80 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 4.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354

Part B: Cohort 5: CVL-354 85 mg

Experimental group

Description:

Participants received oral dose of CVL-354 85 mg or Placebo, QD from Day 1 up to Day 14 in Cohort 5.

Treatment:

Drug: Placebo

Drug: CVL-354

Drug: CVL-354