Back to resultsPharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations in Fasted and Fed Healthy Participants
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
10 mg CVL-231 as IR formulation
30 mg CVL-231 as slow-release MR formulation
30 mg CVL-231 as medium release MR formulation
30 mg CVL-231 as fast release MR formulation
30 mg CVL-231 Target Release, Fasted
30 mg CVL-231 Target Release, Fed
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Healthy Volunteer, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders
Eligibility Criteria
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.
Sites / Locations
- Celerion Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions
Arm Description
Oral Dose
Oral Dose
Outcomes
Primary Outcome Measures
Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
Primary Part A & B: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (CV-0000364)
Primary Part A & B: Time prior to the first measurable (non-zero) concentration (Tlag) for CVL-231 and Metabolite (CV-0000364)
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)
Primary Part A & B: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-231 and Metabolite (CV-0000364)
Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)
Primary Part A only: Dose normalized Cmax, derived by Cmax divided by the dose administered (Cmax/D) for CVL-231 and Metabolite (CV-0000364)
Primary Part A only: Dose normalized AUClast, derived by AUClast divided by the dose administered (AUClast/D) for CVL-231 and Metabolite (CV-0000364)
Primary Part A only: Dose normalized AUCinf, derived by AUCinf divided by the dose administered (AUCinf/D) for CVL-231 and Metabolite (CV-0000364)
Secondary Outcome Measures
Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Secondary: Incidence of clinically significant changes in electrocardiogram (ECG) results
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.
Secondary: Incidence of clinically significant changes in clinical laboratory results
Secondary: Incidence of clinically significant changes in vital sign measurements
Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.
Secondary: Incidence of clinically significant changes in physical and neurological examination results
Secondary: Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)
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).
Full Information
NCT ID
NCT05106309
First Posted
November 1, 2021
Last Updated
April 25, 2022
Sponsor
Cerevel Therapeutics, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05106309
Brief Title
Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations in Fasted and Fed Healthy Participants
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
December 29, 2021 (Actual)
Primary Completion Date
February 24, 2022 (Actual)
Study Completion Date
February 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerevel Therapeutics, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Healthy Volunteer, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Arm Type
Experimental
Arm Description
Oral Dose
Arm Title
Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions
Arm Type
Experimental
Arm Description
Oral Dose
Intervention Type
Drug
Intervention Name(s)
10 mg CVL-231 as IR formulation
Intervention Description
Tablets
Intervention Type
Drug
Intervention Name(s)
30 mg CVL-231 as slow-release MR formulation
Intervention Description
Capsules
Intervention Type
Drug
Intervention Name(s)
30 mg CVL-231 as medium release MR formulation
Intervention Description
Capsules
Intervention Type
Drug
Intervention Name(s)
30 mg CVL-231 as fast release MR formulation
Intervention Description
Capsules
Intervention Type
Drug
Intervention Name(s)
30 mg CVL-231 Target Release, Fasted
Intervention Description
Capsules
Intervention Type
Drug
Intervention Name(s)
30 mg CVL-231 Target Release, Fed
Intervention Description
Capsules
Primary Outcome Measure Information:
Title
Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
Time Frame
Up to 72 Hours in each period
Title
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
Title
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
Title
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
Title
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
Title
Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)
Time Frame
Up to 72 Hours in each period
Title
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
Title
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
Title
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 Outcome Measure Information:
Title
Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Time Frame
Up to Day 14
Title
Secondary: Incidence of clinically significant changes in electrocardiogram (ECG) results
Description
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.
Time Frame
Up to 72 Hours in each period
Title
Secondary: Incidence of clinically significant changes in clinical laboratory results
Time Frame
Up to 72 Hours in each period
Title
Secondary: Incidence of clinically significant changes in vital sign measurements
Description
Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate.
Time Frame
Up to 72 Hours in each period
Title
Secondary: Incidence of clinically significant changes in physical and neurological examination results
Time Frame
Up to 72 Hours in each period
Title
Secondary: Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)
Description
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).
Time Frame
Up to 72 Hours in each period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Leoni, MD, MBA
Organizational Affiliation
Cerevel Therapeutics, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Celerion Inc.
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85283
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations in Fasted and Fed Healthy Participants
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