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Completed

NCT Number: NCT05106309

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

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.

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Key information

Conditions

Schizophrenia Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Celerion Inc.

Tempe, Arizona, 85283, United States

About this study

CVL-231 is a muscarinic acetylcholine receptor (mAChR) activator that selectively binds to the M4 muscarinic receptor subtype (M4 mAChR) and is being developed for treatment of psychosis in schizophrenia. Part A of this 2-part trial will investigate the PK of CVL-231 in healthy participants following a single oral dose of CVL-231 as 3 modified-release (MR) formulations with different release rates and an immediate-release (IR) formulation under fasted conditions. Upon selection of an MR formulation with appropriate PK characteristics, the effect of food on the PK of CVL-231 and its metabolite following single oral doses of the selected MR formulation may be evaluated in Part B.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Women of nonchildbearing potential and men 18 to 55 years, inclusive.
  • Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, 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.

Exclusion criteria

  • 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
  • 12-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.

Treatment and study plan

10 mg CVL-231 as IR formulation

Drug

Tablets

30 mg CVL-231 as slow-release MR formulation

Drug

Capsules

30 mg CVL-231 as medium release MR formulation

Drug

Capsules

30 mg CVL-231 as fast release MR formulation

Drug

Capsules

30 mg CVL-231 Target Release, Fasted

Drug

Capsules

30 mg CVL-231 Target Release, Fed

Drug

Capsules

Primary outcomes

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

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

  4. 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)

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

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

    Time frame: Up to 72 Hours in each period

Secondary outcomes

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

    Time frame: Up to Day 14

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

    Time frame: Up to 72 Hours in each period

    Assessment of clinically significant changes in QT intervals measured by 12-lead ECG recording after the participant has been supine and at rest for at least 3 minutes.

  3. Secondary: Incidence of clinically significant changes in clinical laboratory results

    Time frame: Up to 72 Hours in each period

  4. Secondary: Incidence of clinically significant changes in vital sign measurements

    Time frame: Up to 72 Hours in each period

    Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.

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

    Time frame: Up to 72 Hours in each period

  6. Secondary: Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)

    Time frame: Up to 72 Hours in each period

    The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).

Sponsors and collaborators

Lead sponsor

Cerevel Therapeutics, LLC

Industry

Registry information

Official study title

A Phase 1, Open-label Trial to Evaluate the Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations Under Fasted and Fed Conditions in Healthy Participants

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Nov 3, 2021
Registry last updated
Apr 27, 2022

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

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

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

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