SchizophreniaPhase 1NCT05106309

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

A Phase 1 study testing 10 mg CVL-231 as IR formulation, 30 mg CVL-231 as slow-release MR formulation and 30 mg CVL-231 as medium release MR formulation in people with Schizophrenia, run by Cerevel Therapeutics, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Schizophrenia
What is being tested?: 10 mg CVL-231 as IR formulation, 30 mg CVL-231 as slow-release MR formulation and 30 mg CVL-231 as medium release MR formulation
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: 29 Dec 2021to 24 Feb 2022
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

Show all 15Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Celerion Inc.
Tempe, Arizona, 85283

Other trials in United States

About this study

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

Read the 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.

Conditions: Schizophrenia
Being tested: 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
Keywords: Schizophrenia, Healthy Volunteer, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders
Medical subject headings: Schizophrenia, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

10 mg CVL-231 as IR formulationDrug
Tablets
30 mg CVL-231 as slow-release MR formulationDrug
Capsules
30 mg CVL-231 as medium release MR formulationDrug
Capsules
30 mg CVL-231 as fast release MR formulationDrug
Capsules
30 mg CVL-231 Target Release, FastedDrug
Capsules
30 mg CVL-231 Target Release, FedDrug
Capsules

Study groups in NCT05106309
Study group	Role	What they receive
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions	Experimental	Oral Dose Receives: 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 Receives: Drug: 30 mg CVL-231 Target Release, Fasted; Drug: 30 mg CVL-231 Target Release, Fed

What is being measured

The primary outcome is the main question the study is designed to answer.

Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
Measured: Up to 72 Hours in each period
Primary Part A & B: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (CV-0000364)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Up to 72 Hours in each period
Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Up to 72 Hours in each period

Secondary outcomes (6)

Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Measured: Up to Day 14
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.
Measured: Up to 72 Hours in each period
Secondary: Incidence of clinically significant changes in clinical laboratory results
Measured: Up to 72 Hours in each period
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.
Measured: Up to 72 Hours in each period
Secondary: Incidence of clinically significant changes in physical and neurological examination results
Measured: Up to 72 Hours in each period
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).
Measured: Up to 72 Hours in each period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Dec 202124 Feb 2022

First posted3 Nov 2021
Study start29 Dec 2021
Primary completion24 Feb 2022
Study completion24 Feb 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for SchizophreniaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
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)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05106309
Sponsor's protocol ID: CVL-231-1004
Status last verified: Apr 2022
First submitted: 1 Nov 2021
Last updated: 27 Apr 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 27 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05106309
Acronym / sponsor ID: CVL-231-1004
Conditions: Schizophrenia
Keywords: Schizophrenia, Healthy Volunteer, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Cerevel Therapeutics, LLCIndustry (pharma, biotech, devices)
Study start: 29 Dec 2021 (actual)
Primary completion: 24 Feb 2022 (actual)
Study completion: 24 Feb 2022 (actual)
First posted: 3 Nov 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2
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.

Arm	Type	Receives
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions	Experimental	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 formulationOral Dose
Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions	Experimental	Drug: 30 mg CVL-231 Target Release, Fasted, Drug: 30 mg CVL-231 Target Release, FedOral Dose

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (15 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
10 mg CVL-231 as IR formulationTablets	Drug	Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
30 mg CVL-231 as slow-release MR formulationCapsules	Drug	Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
30 mg CVL-231 as medium release MR formulationCapsules	Drug	Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
30 mg CVL-231 as fast release MR formulationCapsules	Drug	Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
30 mg CVL-231 Target Release, FastedCapsules	Drug	Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions
30 mg CVL-231 Target Release, FedCapsules	Drug	Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions

Primary outcome

Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
Time frame: Up to 72 Hours in each period
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
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
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
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
Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Up to 72 Hours in each period

6 secondary outcomes

Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to Day 14
Secondary: Incidence of clinically significant changes in electrocardiogram (ECG) results
Time frame: Up to 72 Hours in each period
Secondary: Incidence of clinically significant changes in clinical laboratory results
Time frame: Up to 72 Hours in each period
Secondary: Incidence of clinically significant changes in vital sign measurements
Time frame: Up to 72 Hours in each period
Secondary: Incidence of clinically significant changes in physical and neurological examination results
Time frame: Up to 72 Hours in each period
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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2022.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Matthew Leoni, MD, MBA study director

Cerevel Therapeutics, LLC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364) (time frame: Up to 72 Hours in each period). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05106309.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.