Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations in Fasted and Fed Healthy Participants

NCT05106309 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-231-1004
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

A 2-part, crossover design, open-label treatment trial with 4 periods, 4 sequences (Part A) to evaluate MR formulations of CVL-231 and a 2 periods, 2 sequences (Part B) to understand effect of food on CVL-231 exposures from an MR formulation.

Conditions

Schizophrenia

Keywords

Schizophrenia; Healthy Volunteer; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Outcome Measures

Primary Outcomes (9)

• Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A & B: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A & B: Time prior to the first measurable (non-zero) concentration (Tlag) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A & B: Area under the plasma concentration-time curve from time 0 to the last measurable time point (AUClast) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A & B: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A only: Dose normalized Cmax, derived by Cmax divided by the dose administered (Cmax/D) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A only: Dose normalized AUClast, derived by AUClast divided by the dose administered (AUClast/D) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

• Primary Part A only: Dose normalized AUCinf, derived by AUCinf divided by the dose administered (AUCinf/D) for CVL-231 and Metabolite (CV-0000364)

  Up to 72 Hours in each period

Secondary Outcomes (6)

• Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)

  Up to Day 14

• Secondary: Incidence of clinically significant changes in electrocardiogram (ECG) results

  Up to 72 Hours in each period

• Secondary: Incidence of clinically significant changes in clinical laboratory results

  Up to 72 Hours in each period

• Secondary: Incidence of clinically significant changes in vital sign measurements

  Up to 72 Hours in each period

• Secondary: Incidence of clinically significant changes in physical and neurological examination results

  Up to 72 Hours in each period

Study Arms (2)

Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions

EXPERIMENTAL

Oral Dose

Drug: 10 mg CVL-231 as IR formulation; Drug: 30 mg CVL-231 as slow-release MR formulation; Drug: 30 mg CVL-231 as medium release MR formulation; Drug: 30 mg CVL-231 as fast release MR formulation

Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions

EXPERIMENTAL

Oral Dose

Drug: 30 mg CVL-231 Target Release, Fasted; Drug: 30 mg CVL-231 Target Release, Fed

Interventions

10 mg CVL-231 as IR formulation DRUG

Tablets

Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions

30 mg CVL-231 as slow-release MR formulation DRUG

Capsules

Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions

30 mg CVL-231 as medium release MR formulation DRUG

Capsules

Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions

30 mg CVL-231 as fast release MR formulation DRUG

Capsules

Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions

30 mg CVL-231 Target Release, Fasted DRUG

Capsules

Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions

30 mg CVL-231 Target Release, Fed DRUG

Capsules

Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions

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, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
• Body mass index of 18.5 to 30.0 kg/m2 and a total body weight \>50 kg (110 lbs).
• Sexually active men with a pregnant or a nonpregnant partner of childbearing potential must agree to comply with protocol contraception requirements during treatment and through 7 days post dose. In addition, male participants should not donate sperm for a minimum of 7 days following the last dose of IMP.
• 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 history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine, hematological, immunological, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
• Current or past personal or family history of any psychiatric disorder as classified by DSM-5 criteria.
• Epilepsy or a history of seizures except for a single seizure episode, eg, a childhood febrile seizure, a seizure related to trauma or alcohol withdrawal, or an unexplained loss of consciousness.
• History of moderate to severe substance or alcohol-use disorder (excluding caffeine) within 12 months prior to signing the ICF.
• Serious risk of suicide in the opinion of the investigator
• Receipt of SARS-CoV2 vaccine or booster within 28 days of dosing with CVL-231, or plan to receive SARS-CoV2 vaccination or booster from Screening through 5 days after last dose of CVL-231.
• Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF.
• Either of the following:
• History of 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 for illicit drugs or a positive test for alcohol
• lead ECG demonstrating pre-defined abnormalities at Screening and Day -1 based on local evaluation.
• Abnormal clinical laboratory tests or vital sign measurements at the Screening Visit and at Day -1 (check-in) for each period
• Known to be allergic or hypersensitive to the IMP or any of its components.
• Participation in any clinical trial within 90 days prior to signing the ICF.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Celerion Inc.

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Conditions

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Matthew Leoni, MD, MBA

  Cerevel Therapeutics, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A is an open-label, randomized, 4-period, 4-sequence, crossover design to investigate the PK, relative bioavailability, safety, and tolerability of single doses of CVL-231 IR/MR formulations in healthy participants. The following treatments, administered under fasted conditions are: 1) 10mg CVL-231 as IR formulation, 2) 30mg CVL-231 as slow release MR formulation, 3) 30mg CVL-231 as medium release MR formulation, 4) 30mg CVL-231 as fast release MR formulation. Part B is an open-label, randomized, 2-period, 2-sequence, crossover design to investigate the effect of food on CVL-231 PK following a single dose of the CVL-231 MR formulation in healthy participants. After completion of Part A, a target release formulation (MR formulation with acceptable PK characteristics) may be selected and effect of food on CVL-231 PK from the target release formulation may be evaluated. Based on Part A data, if a target release formulation cannot be selected, Part B of the trial may be canceled.

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 3, 2021
• Study Start: December 29, 2021
• Primary Completion: February 24, 2022
• Study Completion: February 24, 2022
• Last Updated: April 27, 2022

Record last verified: 2022-04

Locations

US (1)