Alzheimer's Disease, Healthy Elderly
Conditions
Keywords
Alzheimer's Disease, Agitation Associated Dementia, NMRA-323511
Brief summary
This study consists of 2 parts, Part A and Part B. Part A is a single center, randomized, double-blind, placebo-controlled cohort designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of NMRA-323511 among healthy elderly. Part B is a multicenter, randomized, double-blinded, placebo-controlled, parallel-group cohort to evaluate the safety, tolerability, and efficacy of NMRA-323511 among adults with Agitation Associated with Dementia due to Alzheimer's Disease. Part A consists of a Screening Period (up to 28 days), a 10-day Treatment Period, and a 10- day Follow-up clinic visit after last dose of study treatment. Part B consists of a Screening Period (up to 28 days), an 8-week Treatment Period, and a 10-day Follow-up clinic visit after last dose of study treatment.
Interventions
DRUGNMRA-323511
Participants will receive NMRA-323511 orally.
DRUGPlacebo
Participants will receive matching placebo tablets orally.
Sponsors
Neumora Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
Part A * Healthy participants * Age 65 to 80 years * Body mass index (BMI) ≥18.0 and ≤32.0 kg/m\^2 at the screening and check-in visit Part B * Participants aged 55 to 90 years * Diagnosis of probable AD or Alzheimer's clinical syndrome according to the National Institute of Aging-Alzheimer's Association criteria at least 12 months prior to screening * Agitation meets the International Psychogeriatric Association (IPA) consensus definition * Mini-Mental State Examination (MMSE) score = 5 - 24 (mild to severe dementia) at screening
Exclusion criteria
Part A * Participant is actively suicidal * Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit * Diagnosis of epilepsy taking anticonvulsants for seizure control, history of seizures Part B * Dementia or memory impairment due to a reason other than AD * Clinically significant neurologic disorder other than AD * Have any clinically significant and uncontrolled medical condition Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Safety and Tolerability Assessments Based on Treatment Emergent Adverse Events (TEAEs) and Validated Clinical Scales | Up to 53 days | An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical examinations, and Columbia Suicide Severity Rating Scale (C-SSRS) scores will be reported as TEAEs. |
| Part B: Safety and Tolerability Assessments Based on Treatment Emergent Adverse Events and Validated Clinical Scales | Up to Week 10 | An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as a TEAE. Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical examinations, and C-SSRS scores will be reported as TEAEs. |
| Part B: Change from Baseline to Week 8 on the Cohen-Mansfield Agitation Inventory (CMAI) Total Score | Baseline to Week 8 | The CMAI is a 29-item scale to assess the frequency of agitated behaviors. The 29 agitated behaviors are categorized into agitation factors, including aggressive behavior, physically non-aggressive behavior, and verbally agitated behavior. Each item is rated over the past 2 weeks on a 7-point scale ranging from "Never" (score of 1) to "Several times per hour" (score of 7). The CMAI total score is calculated as the sum of all 29 items and range from 29 (no agitation) to 203 (most severe agitation). A score \>45 is commonly regarded as clinically significant agitation. |
Countries
United States
Outcome results
None listed