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The primary purpose of the study is to evaluate the safety and tolerability of emraclidine administered orally to healthy elderly participants in Part A (multiple ascending doses) and participants with dementia due to Alzheimer's disease (AD) in Part B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Cohort 1: Emraclidine Dose 1 | Experimental | Participants will receive emraclidine dose 1 or emraclidine-matching placebo tablets, orally, once daily (QD) up to Day 14. |
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| Part A: Cohort 2: Emraclidine Dose 2 | Experimental | Participants will receive emraclidine dose 2 or emraclidine-matching placebo tablets, orally, QD up to Day 14. |
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| Part A: Cohort 3: Emraclidine Dose 3 | Experimental | Participants will receive emraclidine dose 3 or emraclidine-matching placebo tablets, orally, QD up to Day 14. |
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| Part A: Cohort 4: Emraclidine Dose 4 | Experimental | Participants will receive emraclidine dose 4 or emraclidine-matching placebo tablets, orally, QD up to Day 14. |
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| Part A: Cohort 5: Emraclidine Dose 5 | Experimental | Participants will receive emraclidine dose 5 or emraclidine-matching placebo tablets, orally, QD up to Day 14. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emraclidine | Drug | Oral tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 28 | |
| Part A: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Up to Day 17 | |
| Part A: Number of Participants With Clinically Significant Changes in Laboratory Assessments | Up to Day 17 | |
| Part A: Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Up to Day 17 | |
| Part A: Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Up to Day 17 | |
| Part A: Changes in Suicidality Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS) | The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk. | Up to Day 17 |
| Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Simpson Angus Scale (SAS) | The SAS consists of a list of 10 symptoms of parkinsonism. 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. | Up to Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Maximum Observed Plasma Concentration (Cmax) of Emraclidine and its Metabolite CV-0000364 | Days 1 and 14 | |
| Part A: Time to Maximum Plasma Concentration (Tmax) of Emraclidine and its Metabolite CV-0000364 | Days 1 and 14 |
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Inclusion Criteria:
Cohorts 1 to 5 (Part A)
Male participants and female participants of nonchildbearing potential, ages 65 to 85 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 17.5 to 32.0 kilograms per square meter (kg/m^2), inclusive, and total body weight >45 kg (100 pounds [lb]) at Screening.
Female participants will be of nonchildbearing potential, defined as follows:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, and confirmed with a serum follicle-stimulating hormone level >40 international units per milliliter (IU/mL).
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the full protocol.
Cohort 6 (Part B)
Exclusion Criteria:
All Cohorts
"Yes" responses for any of the following items on the C-SSRS (within the past 6 months):
Diagnosis of moderate to severe substance or alcohol-use disorder (excluding nicotine or caffeine) as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria within 12 months prior to signing the ICF.
Positive drug screen or a positive test for alcohol at Screening or Baseline Visits.
Any of the following clinical laboratory test results at the Screening Visit (as assessed by the central laboratory) and at Check-in (Day -1; as assessed by the local laboratory), and confirmed by a single repeat measurement, if deemed necessary:
Cohorts 1 to 5 (Part A)
Cohort 6 (Part B)
Has either of the following:
Has evidence of a clinically relevant neurological disorder other than possible or probable Alzheimer's disease such as, but not limited to, the following:
Estimated glomerular filtration rate <60 mL/min/1.73 m2, as calculated using the CKD-EPI 2021 equation the Screening Visit.
NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cypress, California | Cypress | California | 90630 | United States | ||
| San Diego, California |
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| Part B: Cohort 6: Emraclidine Dose 6 | Experimental | Participants with dementia due to AD will receive emraclidine dose 6 or emraclidine-matching placebo tablets, orally, QD up to Day 28. |
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| Placebo | Drug | Oral tablets |
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| Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Abnormal Involuntary Movement Scale (AIMS) | The AIMS assessment consists of 10 items describing symptoms of dyskinesia. 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 participant's dental status. | Up to Day 14 |
| Part A: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms Evaluated Using the Barnes Akathisia Rating Scale (BARS) | The BARS consists of 4 items related to 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. | Up to Day 14 |
| Part B: Number of Participants With TEAEs, Clinically Significant Changes in ECG Parameters, Laboratory Assessments, Vital Sign Measurements, and Physical and Neurological Examination Results | Up to Day 28 |
| Part B: Changes in Suicidality Assessed Using the C-SSRS | Up to Day 28 |
| Part B: Number of Participants With Clinically Significant Findings in Extrapyramidal Symptoms | Extrapyramidal symptoms will be evaluated using SAS, AIMS, and BARS scales. | Up to Day 28 |
| Part A: Area Under the Plasma Concentration-time Curve (AUC) of Emraclidine and its Metabolite CV-0000364 | Days 1 and 14 |
| Part A: Trough Plasma Concentration (Ctrough) of Emraclidine and its Metabolite CV-0000364 | Days 1 and 14 |
| Part A: Peak to Trough Ratio (PTR) of Emraclidine and its Metabolite CV-0000364 | Day 14 |
| Part A: Apparent Clearance of Drug From Plasma (CL/F) of Emraclidine | Days 1 and 14 |
| Part A: Apparent Volume of Distribution During Terminal Phase (Vz/F) of Emraclidine | Days 1 and 14 |
| Part A: Apparent Terminal Half-life (t1/2) of Emraclidine and its Metabolite CV-0000364 | Days 1 and 14 |
| Part A: Accumulation Ratio (Rac) of Emraclidine and its Metabolite CV-0000364 | Rac would be calculated from AUC and Cmax of emraclidine and its metabolite. | Day 14 |
| Part A: Metabolite to Parent Ratio of Emraclidine and its Metabolite CV-0000364 | Days 1 and 14 |
| Part B: Plasma Concentrations of Emraclidine and its Metabolite CV-0000364 | Days 1 to 28 |
| San Diego |
| California |
| 92103 |
| United States |
| Hialeah, Florida | Hialeah | Florida | 33014 | United States |
| Decatur, Georgia | Decatur | Georgia | 30030 | United States |
| Honolulu, Hawaii | Honolulu | Hawaii | 96817 | United States |
| Overland Park, Kansas | Overland Park | Kansas | 66212 | United States |
| Farmington Hills, Michigan | Farmington Hills | Michigan | 48334 | United States |
| Marlton, New Jersey | Marlton | New Jersey | 08053 | United States |
| Princeton, New Jersey | Princeton | New Jersey | 08540 | United States |
| Staten Island, New York | Staten Island | New York | 10314 | United States |
| North Canton, Ohio | North Canton | Ohio | 44720 | United States |