SchizophreniaPhase 1NCT04136873
A Multiple Ascending Dose Trial of CVL-231 in Subjects With Schizophrenia
A Phase 1 study testing CVL-231 in people with Schizophrenia, run by Cerevel Therapeutics, LLC at 5 sites in United States.
Trial summary
The aim of this trial is to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CVL-231 following multiple-dose oral administration in subjects with schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- CVL-231
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 5 sitesUnited States
- Study dates
- 15 Oct 2019to 3 Jun 2021
- 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
- No healthy volunteers
- Adult
Who may be able to join
- Subjects with a primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI.
- Subjects with the following scores on the PANSS at time of signing ICF and at Day -1: • Positive Subscale 7 (hostility) ≤3 (normal to moderate) • General Psychopathology Subscale 8 (uncooperativeness) ≤3 (normal to moderate)
- Subjects with the following scores (normal to mild symptoms) at time of signing ICF and at Day -1: • All individual items of the Modified SAS (M-SAS) <2 • All individual items (Items 1-7) of the Abnormal Involuntary Movement Scale (AIMS) <2 • Clinical global assessment item of the Barnes Akathisia Rating Scale (BARS) <3
- Body mass index of 17.5 to 38.0 kg/m2 and a total body weight >50 kg (110 lbs).
- Cohorts 1 Through 5 (Part A):
- Subjects are eligible to be included in trial (Cohorts 1 through 5) only if all of the following additional criteria apply:
Show all 20Show fewer
- Male and female subjects, ages 18 to 50 years, inclusive.
- Subjects with a score on the CGI-S ≤4 (normal to moderately ill) at time of signing ICF and at Day -1.
- Subjects with a PANSS total score of ≤80 at the time of signing ICF and at Day -1.
- Cohort 6 (Part B):
- Subjects are eligible to be included in trial (Cohort 6) only if all of the following additional criteria apply:
- Male and female subjects, ages 18 to 55 years, inclusive.
- Subjects with a score on the CGI-S ≥4 (moderately to severely ill) at time of signing ICF and at Day -1.
- Subjects with a PANSS total score of ≥80 at the time of signing ICF and at Day -1. Additionally, subjects must meet a score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale items at the time of signing ICF and at Day -1:
- Positive Scale 1 (delusions)
- Positive Scale 2 (conceptual disorganization)
- Positive Scale 3 (hallucinatory behavior)
- Positive Scale 6 (suspiciousness/persecution)
- Subjects with a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding the current episode.
- Subjects must be experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months prior to signing ICF.
Who cannot join
- Subjects with a current DSM-5 diagnosis other than schizophrenia including, but not limited to, mental retardation; schizoaffective disorder; schizophreniform disorder; psychotic depression; major depressive disorder; bipolar disorder; post-traumatic stress disorder; generalized anxiety disorder, obsessive compulsive disorder, eating disorders (bulimia, anorexia), or other anxiety disorders as a primary diagnosis (subjects with anxiety symptoms secondary to schizophrenia are allowed); delirium, dementia, amnestic, or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
- Subjects with schizophrenia who were considered resistant/refractory to antipsychotic treatment by history or who had a history of failure to respond to clozapine or response to clozapine treatment only.
- Subjects with EPS being treated with a medication that required dose modification and/or new treatment within 6 months prior to signing ICF.
- Subjects with a current history of significant pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine (including newly diagnosed diabetes mellitus or subjects with known diabetes mellitus with glycosylated hemoglobin (HbA1c)>7.5%), hematological, immunological, psychiatric (excluding schizophrenia), or neurological disease.
- Subjects with a current or past history of significant cardiovascular disease.
- Subjects who experienced acute depressive symptoms within the past 30 days.
Show all 38Show fewer
- Subjects with epilepsy or a history of seizures, except for a single seizure episode, eg, a childhood febrile seizure, or a seizure related to trauma or alcohol withdrawal.
- An active central nervous system infection, demyelinating disease, degenerative neurological disease, mental retardation, or any central nervous system disease deemed to be progressive.
- History of moderate to severe substance or alcohol-use disorder (excluding nicotine or caffeine) as per DSM-5 criteria within 12 months prior to signing ICF.
- Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent).
- Human immunodeficiency virus seropositive status or acquired immunodeficiency syndrome, chronic hepatitis B or C.
- Subject with a positive urine drug screen for illicit drugs or a positive breathalyzer test for alcohol.
- Subjects with medically significant abnormal laboratory test results, vital sign results, or ECG findings.
- Subjects who received transcranial magnetic stimulation or electroconvulsive therapy within 60 days of screening.
- Any condition possibly affecting drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding).
- Subjects with difficulty swallowing.
- Subjects with a history of neuroleptic malignant syndrome.
- Subject who refuses to abstain from grapefruit-containing foods or beverages, or Seville orange-containing foods or beverages.
- Cohorts 1 Through 5 (Part A) Subjects are excluded from the trial (Cohorts 1 through 5) if any of the following additional criteria apply:
- Subjects who have experienced psychosis requiring hospitalization within the 6 months prior to signing ICF.
- Subjects who experienced psychosis requiring a change in their antipsychotic medication (either drug type or dose) within the 3 months prior to signing ICF.
- Subjects who fulfill any of the following dietary restrictions: • History of chronic consumption of >400 mg/day of caffeine-containing drinks or food • Refuses to abstain from caffeine-containing foods or caffeinated beverages for 48 hours prior to Day -1 through Follow up Visit • Refuses to abstain from alcohol from 7 days prior to Day -1 through Follow-up Visit
- Subjects who have participated in any clinical trial within 60 days prior to signing ICF.
- Subjects with a 12-lead ECG demonstrating any of the following:
- Abnormal ST-T-wave morphologies that may interfere with QT analysis, such as flat or poorly defined end of the T wave or prominent U waves
- Left ventricular hypertrophy
- QT interval corrected for heart rate QTcF >450 msec
- QRS interval >110 msec
- Left or right bundle branch block
- PR interval >240 msec
- Heart rate <50 bpm or >90 bpm
- Second- or third-degree atrioventricular block
- Systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg at Screening or Day -1, will be taken with subjects in the supine/semi-recumbent position, or symptomatic hypotension, or orthostatic hypotension, which is defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the immediately previous supine blood pressure. Subjects who are receiving chronic treatment with antihypertensive medications at Screening are also excluded.
- Cohort 6 (Part B) Only Subjects are excluded from trial (Cohort 6 only) if any of the following additional criteria apply:
- Subjects who have been hospitalized >14 days for the current episode of schizophrenia at the time of signing the ICF, excluding hospitalization for psychosocial reasons.
- Subjects presenting with a first episode of schizophrenia, based on clinical judgment of the investigator.
- Subjects with a 12-lead ECG exclusion as in Part A but will allow right bundle branch block in Part B.
- Systolic blood pressure >130 mmHg and/or diastolic blood pressure >80 mmHg at Screening or Day -1 and subjects with orthostatic hypotension, defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the average resting supine/semi-recumbent blood pressure at Screening or Day -1, will be excluded. Subjects with a heart rate <50 bpm or >90 bpm. Subjects who are receiving chronic treatment with antihypertensive medications at Screening are also excluded.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Pillar Clinical Research
Bentonville, Arkansas, 72712
Synergy San Diego
Lemon Grove, California, 91945
Woodlands International Research Group
Little Rock, Arkansas, 72211
Collaborative Neuroscience Network, LLC
Long Beach, California, 90806
Hassman Research Institute
Marlton, New Jersey, 08053
About this study
Official title: A Phase 1B Trial To Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of CVL-231 in Subjects With Schizophrenia
The aim of this trial is to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CVL-231 following multiple-dose oral administration in subjects with schizophrenia.
- Conditions
- Schizophrenia
- Being tested
- CVL-231, Matching Placebo
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVL-231Drug
CVL-231
Matching PlaceboDrug
Placebo matching CVL-231
| Study group | Role | What they receive |
|---|---|---|
| Part A: 5 mg QD CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part A: 5 mg QD Placebo | Placebo comparator | Matching Placebo; Oral Dose Receives: Drug: Matching Placebo |
| Part A: 10 mg QD CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part A: 10 mg QD Placebo | Placebo comparator | Matching Placebo; Oral Dose Receives: Drug: Matching Placebo |
| Part A: 20 mg QD CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part A: 20 mg QD Placebo | Placebo comparator | Matching Placebo; Oral Dose Receives: Drug: Matching Placebo |
| Part A: 5-10-20 mg BID CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part A: 5-10-20 mg BID Placebo | Placebo comparator | Matching Placebo; Oral Dose Receives: Drug: Matching Placebo |
| Part A: 30 mg QD CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part A: 30 mg QD Placebo | Placebo comparator | Matching Placebo; Oral Dose Receives: Drug: Matching Placebo |
| Part B 30 mg QD CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part B 30 mg QD Placebo | Placebo comparator | Matching Placebo; Oral Dose Receives: Drug: Matching Placebo |
| Part B 20 mg BID CVL-231 | Active comparator | Oral Dose Receives: Drug: CVL-231 |
| Part B 20 mg BID Placebo | Placebo comparator | Not described Receives: Drug: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment Emergent Adverse Events (TEAEs)
Includes Incidence of Significant ECG Abnormalities Occurring Post-Baseline, significant changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature), and changes in laboratory measures (hematology, serum chemistry and urinalysis)
Measured: Up to Day 72
Incidence of suicidality as assessed by 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 Day 72
Change from Baseline of Simpson-Angus Scale (SAS) Results
Evaluating Extrapyramidal symptoms using the SAS. The SAS consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms and a score of 4 representing a severe condition. The SAS total score is the sum of the scores for all 10 items.
Measured: Up to Day 72
Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) Results
The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the subject is at rest, and the investigator also makes global judgments on the subject's dyskinesias (items 8 through 10). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness, severe distress). In addition, the AIMS includes 2 yes/no questions that address the subject's dental status.
The AIMS Movement Rating Score is defined as the sum of items 1 through 7 (ie, items 1 through 4, facial and oral movements; items 5 and 6, extremity movements; and item 7, trunk movements).
Measured: Up to Day 72
Change from Baseline of Barnes Akathisia Rating Scale (BARS) Results
Evaluating Extrapyramidal symptoms using the BARS. The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the subject, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation is made on a 6-point scale, with a score of 0 representing absence of symptom and a score of 5 representing severe akathisia.
Measured: Up to Day 72
Secondary outcomes (22)
Single-dose: Area under the plasma concentration vs. time curve (AUC) for CVL-231 and Metabolite (PF-06892787)
Measured: Day 1
Single-dose: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (PF-06892787)
Measured: Day 1
Single-dose: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (PF-06892787)
Measured: Day 1
Single-dose: Metabolite to parent ratio for Cmax for CVL-231 and Metabolite (PF-06892787)
Measured: Day 1
Single-dose: Metabolite to parent ratio for AUC tau for CVL-231 and Metabolite (PF-06892787)
Measured: Day 1
Multiple-dose: Steady state CVL-231 Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Trough plasma concentration (Ctrough) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Minimum blood plasma concentration (Cmin) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Area under the plasma concentration-time curve (AUCτ) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Apparent Total Clearance of Drug from plasma: CL/F for CVL-231
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Steady-state average plasma drug concentration: Css for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Peak Trough Ratio (PTR) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Accumulation ratio calculated from Cmax,ss and Cmax after single dosing (Rac, Cmax) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Accumulation ratio calculated from AUCτ,ss and AUCτ after single dosing (Rac, AUC) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28 and/or 36
Multiple-dose: Elimination half-life (t½) for CVL-231 and Metabolite (PF-06892787)
Measured: Day 14-17 and/or Day 28-31
Multiple-dose: Elimination rate constant (kel) for CVL-231 and Metabolite (PF-06892787)
Measured: Day 14-17 and/or Day 28-31
Multiple-dose: Ae (amount eliminated unchanged in urine) for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28
Multiple-dose: Renal clearance for parent only for CVL-231
Measured: Days 14 and/or 28
Multiple-dose: Metabolite to parent ratio for Cmax for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28
Multiple-dose: Metabolite to parent ratio for AUCtau for CVL-231 and Metabolite (PF-06892787)
Measured: Days 14 and/or 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2019
- Study start15 Oct 2019
- Primary completion7 May 2021
- Study completion3 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerevel Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Matthew Leoni, MD, Study director, Cerevel Therapeutics, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04136873
- Sponsor's protocol ID
- CVL-231-SCH-001
- Status last verified
- Jul 2021
- First submitted
- 16 Oct 2019
- Last updated
- 2 Jul 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Krystal JH, Kane JM, Correll CU, Walling DP, Leoni M, Duvvuri S, Patel S, Chang I, Iredale P, Frohlich L, Versavel S, Perry P, Sanchez R, Renger J. Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. Lancet. 2022 Dec 17;400(10369):2210-2220. doi: 10.1016/S0140-6736(22)01990-0.
PubMed 36528376
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B Trial To Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of CVL-231 in Subjects With Schizophrenia
- ClinicalTrials.gov ID
- NCT04136873
- Acronym / sponsor ID
- CVL-231-SCH-001
- Conditions
- Schizophrenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Cerevel Therapeutics, LLCIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2019 (actual)
- Primary completion
- 7 May 2021 (actual)
- Study completion
- 3 Jun 2021 (actual)
- First posted
- 23 Oct 2019 (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.
The aim of this trial is to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CVL-231 following multiple-dose oral administration in subjects with schizophrenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Part A: 5 mg QD CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part A: 5 mg QD Placebo | Placebo comparator | Drug: Matching PlaceboMatching Placebo; Oral Dose |
| Part A: 10 mg QD CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part A: 10 mg QD Placebo | Placebo comparator | Drug: Matching PlaceboMatching Placebo; Oral Dose |
| Part A: 20 mg QD CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part A: 20 mg QD Placebo | Placebo comparator | Drug: Matching PlaceboMatching Placebo; Oral Dose |
| Part A: 5-10-20 mg BID CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part A: 5-10-20 mg BID Placebo | Placebo comparator | Drug: Matching PlaceboMatching Placebo; Oral Dose |
| Part A: 30 mg QD CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part A: 30 mg QD Placebo | Placebo comparator | Drug: Matching PlaceboMatching Placebo; Oral Dose |
| Part B 30 mg QD CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part B 30 mg QD Placebo | Placebo comparator | Drug: Matching PlaceboMatching Placebo; Oral Dose |
| Part B 20 mg BID CVL-231 | Active comparator | Drug: CVL-231Oral Dose |
| Part B 20 mg BID Placebo | Placebo comparator | Drug: Matching Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- Subjects with a primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI.
- Subjects with the following scores on the PANSS at time of signing ICF and at Day -1: • Positive Subscale 7 (hostility) ≤3 (normal to moderate) • General Psychopathology Subscale 8 (uncooperativeness) ≤3 (normal to moderate)
- Subjects with the following scores (normal to mild symptoms) at time of signing ICF and at Day -1: • All individual items of the Modified SAS (M-SAS) <2 • All individual items (Items 1-7) of the Abnormal Involuntary Movement Scale (AIMS) <2 • Clinical global assessment item of the Barnes Akathisia Rating Scale (BARS) <3
- Body mass index of 17.5 to 38.0 kg/m2 and a total body weight >50 kg (110 lbs).
- Subjects are eligible to be included in trial (Cohorts 1 through 5) only if all of the following additional criteria apply:
Key exclusion criteria (38 listed)
- Subjects with a current DSM-5 diagnosis other than schizophrenia including, but not limited to, mental retardation; schizoaffective disorder; schizophreniform disorder; psychotic depression; major depressive disorder; bipolar disorder; post-traumatic stress disorder; generalized anxiety disorder, obsessive compulsive disorder, eating disorders (bulimia, anorexia), or other anxiety disorders as a primary diagnosis (subjects with anxiety symptoms secondary to schizophrenia are allowed); delirium, dementia, amnestic, or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
- Subjects with schizophrenia who were considered resistant/refractory to antipsychotic treatment by history or who had a history of failure to respond to clozapine or response to clozapine treatment only.
- Subjects with EPS being treated with a medication that required dose modification and/or new treatment within 6 months prior to signing ICF.
- Subjects with a current history of significant pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine (including newly diagnosed diabetes mellitus or subjects with known diabetes mellitus with glycosylated hemoglobin (HbA1c)>7.5%), hematological, immunological, psychiatric (excluding schizophrenia), or neurological disease.
- Subjects with a current or past history of significant cardiovascular disease.
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 |
|---|---|---|
| CVL-231CVL-231 | Drug | Part A: 10 mg QD CVL-231, Part A: 20 mg QD CVL-231, Part A: 30 mg QD CVL-231, Part A: 5 mg QD CVL-231, Part A: 5-10-20 mg BID CVL-231, Part B 20 mg BID CVL-231, Part B 30 mg QD CVL-231 |
| Matching PlaceboPlacebo matching CVL-231 | Drug | Part A: 10 mg QD Placebo, Part A: 20 mg QD Placebo, Part A: 30 mg QD Placebo, Part A: 5 mg QD Placebo, Part A: 5-10-20 mg BID Placebo, Part B 20 mg BID Placebo, Part B 30 mg QD Placebo |
Primary outcome
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to Day 72
Includes Incidence of Significant ECG Abnormalities Occurring Post-Baseline, significant changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature), and changes in laboratory measures (hematology, serum chemistry and urinalysis)
Incidence of suicidality as assessed by Columbia-Suicide Severity Rating Scale(C-SSRS)
Time frame: Up to Day 72
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).
Change from Baseline of Simpson-Angus Scale (SAS) Results
Time frame: Up to Day 72
Evaluating Extrapyramidal symptoms using the SAS. The SAS consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms and a score of 4 representing a severe condition. The SAS total score is the sum of the scores for all 10 items.
Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) Results
Time frame: Up to Day 72
The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the subject is at rest, and the investigator also makes global judgments on the subject's dyskinesias (items 8 through 10). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness, severe distress). In addition, the AIMS includes 2 yes/no questions that address the subject's dental status. The AIMS Movement Rating Score is defined as the sum of items 1 through 7 (ie, items 1 through 4, facial and oral movements; items 5 and 6, extremity movements; and item 7, trunk movements).
Change from Baseline of Barnes Akathisia Rating Scale (BARS) Results
Time frame: Up to Day 72
Evaluating Extrapyramidal symptoms using the BARS. The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the subject, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation is made on a 6-point scale, with a score of 0 representing absence of symptom and a score of 5 representing severe akathisia.
22 secondary outcomes
Single-dose: Area under the plasma concentration vs. time curve (AUC) for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 1
Single-dose: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 1
Single-dose: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 1
Single-dose: Metabolite to parent ratio for Cmax for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 1
Single-dose: Metabolite to parent ratio for AUC tau for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 1
Multiple-dose: Steady state CVL-231 Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Trough plasma concentration (Ctrough) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Minimum blood plasma concentration (Cmin) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Area under the plasma concentration-time curve (AUCτ) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Apparent Total Clearance of Drug from plasma: CL/F for CVL-231
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Steady-state average plasma drug concentration: Css for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Peak Trough Ratio (PTR) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Accumulation ratio calculated from Cmax,ss and Cmax after single dosing (Rac, Cmax) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Accumulation ratio calculated from AUCτ,ss and AUCτ after single dosing (Rac, AUC) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28 and/or 36
Multiple-dose: Elimination half-life (t½) for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 14-17 and/or Day 28-31
Multiple-dose: Elimination rate constant (kel) for CVL-231 and Metabolite (PF-06892787)
Time frame: Day 14-17 and/or Day 28-31
Multiple-dose: Ae (amount eliminated unchanged in urine) for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28
Multiple-dose: Renal clearance for parent only for CVL-231
Time frame: Days 14 and/or 28
Multiple-dose: Metabolite to parent ratio for Cmax for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28
Multiple-dose: Metabolite to parent ratio for AUCtau for CVL-231 and Metabolite (PF-06892787)
Time frame: Days 14 and/or 28
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 2 Jul 2021.
- Derived from this study: PubMed 36528376Krystal JH, Kane JM, Correll CU, Walling DP, Leoni M, Duvvuri S, Patel S, Chang I, Iredale P, Frohlich L, Versavel S, Perry P, Sanchez R, Renger J. Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. Lancet. 2022 Dec 17;400(10369):2210-2220. doi: 10.1016/S0140-6736(22)01990-0.
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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 study director
Cerevel Therapeutics, LLC
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CVL-231 in people with Schizophrenia, run by Cerevel Therapeutics, LLC at 5 sites in United States.
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 20 inclusion and 38 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 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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. Some participants in this study may receive a placebo. 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?
Incidence of Treatment Emergent Adverse Events (TEAEs) (time frame: Up to Day 72). The study lists 5 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 NCT04136873, which also lists 1 linked publication.
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 2 Jul 2021.