Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to evaluate the safety and tolerability of multiple ascending doses of elpipodect in participants with Alzheimer's Disease (AD) with or without symptoms of agitation-aggression and/or psychosis.
Interventions
DRUGElpipodect
MK-8189 administered orally once a day (QD) at a titration via tablet in 4 mg and 12 mg dose strengths
DRUGPlacebo
MK-8189 matching placebo administered orally QD
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Has a documented diagnosis of probable Alzheimer Disease based on National Institute on Aging-Alzheimer Association criteria for AD, with a history of cognitive and functional decline with gradual onset and slow progression for at least 1 year before screening, that is either corroborated by an informant who knows the participant well or is documented in medical records * Lives in the community setting with a reliable trial partner/caregiver or lives alone in an assisted living facility, with supervision and has a reliable trial partner/caregiver * Has a reliable and competent trial partner/caregiver who must have a close relationship with the participant and is knowledgeable of the participant's condition and progress and able to read, understand and speak the designated language at the study site * Can read at the 6th grade level/equivalent as determined by the investigator * Has an academic and/or employment history sufficient to exclude intellectual disability and is able, in the opinion of the investigator, to fully participate in the study * Participants receiving treatment with a cholinesterase inhibitor or other treatment for AD, must have been on a stable regimen for 3 months prior to screening and there are no expected changes in co-medication during the study * Is able to discontinue any antipsychotic medication they are taking at the time of Screening * Has a body mass index (BMI) \> 18 and ≤ 35kg/m2, inclusive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 42 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose. |
| Number of Participants Discontinuing From Study Therapy Due to AE | Up to approximately 42 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
This study was conducted at 8 sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Titration 1: MK-8189 Participants received MK-8189 8 mg on Days 1 to 3 and MK-8189 16 mg on Days 4 to 28 during Titration 1. | 6 |
| Titration 1: Placebo Participants received placebo matched to MK-8189 during Titration 1. | 2 |
| Titration 2: MK-8189 Participants received MK-8189 8 mg on Days 1 to 3, 16 mg on Days 4 to 6, and 24 mg on Days 7 to 28 during Titration 2. | 16 |
| Titration 2: Placebo Participants received placebo matched to MK-8189 during Titration 2. | 5 |
| Total | 29 |
Baseline characteristics
| Characteristic | Titration 1: MK-8189 | Titration 1: Placebo | Titration 2: MK-8189 | Titration 2: Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 73.0 years STANDARD_DEVIATION 4 | 71.5 years STANDARD_DEVIATION 0.7 | 71.6 years STANDARD_DEVIATION 7.6 | 71.2 years STANDARD_DEVIATION 4.5 | 71.7 years STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 11 Participants | 5 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 5 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 0 Participants | 11 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 7 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 9 Participants | 2 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 | 0 / 14 | 0 / 7 |
| other Total, other adverse events | 3 / 22 | 8 / 22 | 5 / 14 | 1 / 7 |
| serious Total, serious adverse events | 0 / 22 | 1 / 22 | 0 / 14 | 0 / 7 |
Outcome results
Primary
Number of Participants Discontinuing From Study Therapy Due to AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose.
Time frame: Up to approximately 42 days
Population: All treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8189 8 mg | Number of Participants Discontinuing From Study Therapy Due to AE | 1 Participants |
| MK-8189 16 mg | Number of Participants Discontinuing From Study Therapy Due to AE | 0 Participants |
| MK-8189 24 mg | Number of Participants Discontinuing From Study Therapy Due to AE | 0 Participants |
| Placebo | Number of Participants Discontinuing From Study Therapy Due to AE | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose.
Time frame: Up to approximately 42 days
Population: All treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8189 8 mg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| MK-8189 16 mg | Number of Participants Who Experienced an Adverse Event (AE) | 8 Participants |
| MK-8189 24 mg | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |