Alzheimer’s Disease dementia MedDRA version: 20.0 Level: LLT Classification code 10012292 Term: Dementia of the Alzheimer's type NOS System Organ Class: 100000004852
Conditions
Interventions
Product Name: MK-1942
Product Code: [MK-1942]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MK-1942
Current Sponsor code: -
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
MERCK SHARP & DOHME LLC. UNA SUSSIDIARIA DI MERCK & CO. INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has mild to moderate AD dementia based on the NINCDS-ADRDA criteria. 2. Has MMSE score between 12-22 (inclusive) at Screening. 3. Is male or female, from 55 years to 90 years of age inclusive, at the time of providing documented informed consent. 4. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of study intervention: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 5. A female participant is eligible to participate if: - She is a WONCBP. 6. The participant (or legally acceptable representative) has provided documented informed consent for the study in accordance with local requirements. The participant (or legally acceptable representative) may also provide consent for FBR. However, the participant may participate in the study without participating in FBR. 7. Is using AChEI therapy for management of AD dementia at Screening and during the study. These medications must be at stable approved dose levels >=3 months before the first dose of study intervention and the regimens must remain constant throughout the study to the extent that is clinically appropriate. 8. Has an MRI scan at Screening that is consistent with the diagnosis of AD. MRI scans will be analyzed by a central MRI reviewer. A digital MRI performed within 18 months before the Screening Visit is acceptable provided the images are available and suitable for central review. 9. Is able to speak, read, hear, and understand the language and information provided by the study staff; and possesses the ability to respond verbally to questions, follow instructions, and complete clinical assessments, including cognitive assessments, based on the investigator’s judgment. 10. Is able and willing to adhere to dose and visit schedules in the investigator’s judgment, and is willing to have selected interviews audio recorded. 11. Has a designated study partner who can fulfill the requirements of this study. The study partner will need to spend sufficient time with the participant to be familiar with their overall function and behavior and be able to provide adequate information about the participant needed for the study including, knowledge of functional and basic activities of daily life, work/educational history, cognitive performance, emotional/psychological state, and general health status. The investigator will assess the study partner’s capabilities to reliably assess the participant. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 348
Exclusion criteria
Exclusion criteria: 1. Has a known history of stroke or cerebrovascular disease that is clinically important in the investigator’s opinion. 2. Has diagnosis of a clinically relevant central nervous system disease other than AD dementia (eg, vascular dementia, Parkinson disease, Huntington disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, neurosyphilis, posterior cortical atrophy, logopenic primary progressive aphasia, other types of dementia, cognitive developmental delay, hypoxic cerebral damage, cognitive impairment due to other disorders, or head trauma with loss of consciousness that led to persistent cognitive deficits) or other condition that negatively impacts cognition or cognitive status chronically. 3. Has structural brain disease or other features such as acute ischemic disease, hemorrhages, large infarct, lacunes in critical areas, (eg, thalamus or hippocampus) space occupying lesions, extensive white matter disease, or other brain abnormalities (eg, normal pressure hydrocephalus) as assessed by blinded independent central review of MRI/CT scans. 4. Has a history of seizures or epilepsy within the 10 years preceding Screening. 5. Has any other major CNS trauma, or infections that affect brain function (eg, HIV, syphilis, and/or neurological sequelae of COVID-19, including impact on cognition). 6. Has evidence of a clinically relevant or unstable psychiatric disorder, based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition), including schizophrenia or other psychotic disorder, bipolar disorder, major depression, or delirium. Major depression in remission is not exclusionary. 7. Has major medical illness or unstable medical condition within 3 months before Screening that, in the opinion of the investigator, may interfere with the participant’s ability to comply with study procedures and abide by study restrictions, or with the ability to interpret safety or efficacy data, including any physical disability (eg, blindness, deafness, non-AD-related speech impairment, sensory or motor dysfunction) that would prevent completion of study procedures or assessments. 8. Has a severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or administration of study intervention or may interfere with the interpretation of study results and, in the opinion of the investigator or Sponsor, would make the participant inappropriate for entry into this study. 9. Has a history of malignancy occurring within the 5 years immediately before Screening, except for a participant who has been adequately treated for 1 or more of the following: a. Basal cell or squamous cell skin cancer b. In situ cervical cancer c. Localized prostate carcinoma d. Who has undergone potentially curative therapy with no evidence of recurrence for >=3 years post-therapy, and who is deemed to be at low risk for recurrence by their treating physician. 10. Has one of the following: a. Vitamin B12 or folate deficiency confirmed by laboratory test results in the 3 months immediately before Screening, or b. Vitamin B12 or folate deficiency in addition to increased serum homocysteine or methylmalonic acid levels at Screening as determined by central laboratory normal values. 11. Has a risk factor for QTc prolongation as defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the efficacy of MK-1942 at 5 mg and 15 mg bid as adjunctive therapy on the ADAS-Cog11 score compared with placebo at Week 12. 2. To evaluate the safety and tolerability of MK-1942 as adjunctive therapy.;Secondary Objective: 1. To assess the efficacy of MK-1942 at 5 mg and 15 mg bid as adjunctive therapy on the ADCS-CGIC Overall score compared with placebo at Week 12. 2. To assess the efficacy of MK-1942 at 5 mg and 15 mg bid as adjunctive therapy on the ADCS-ADL Total score as compared with placebo at Week 12. ;Primary end point(s): 1. Change from baseline in the Alzheimer’s Disease Assessment Scale-11-item cognitive subscale (ADAS-Cog11) score at Week 12 2. Number of Participants Experiencing Adverse Events (AEs) 3. Number of Participants Discontinuing Study Intervention Due to AEs;Timepoint(s) of evaluation of this end point: 1. Baseline and Week 12 2. Up to ~ 14 Weeks 3. Up to ~ 12 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall score at Week 12 2. Change from baseline in the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total score at Week 12 ;Timepoint(s) of evaluation of this end point: 1. Week 12 2. Baseline and Week 12 | — |
Countries
Argentina, Australia, Canada, Colombia, Italy, Japan, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactDivisione Ricerca Clinica
MSD Italia Srl
Outcome results
None listed