A Phase 2a/2b Randomized, Placebo-Controlled Clinical Study To Evaluate The Safety And Efficacy Of MK-1942 As Adjunctive Therapy In Participants With Mild To Moderate Alzheimer's Disease Dementia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 99
- 试验地点
- 74
- 主要终点
- Change From Baseline in the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) Score at Week 12
研究概览
简要总结
The main purpose of this study was to assess the safety and efficacy of MK-1942 as adjunctive therapy in participants with mild to moderate Alzheimer's Disease (AD) dementia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has mild to moderate AD dementia based on the national institute of neurological and communicative diseases and stroke/Alzheimer's Disease and related disorders association (NINCDS-ADRDA) criteria.
- •Has mini-mental state examination (MMSE) score between 12-22 (inclusive) at screening.
- •Is using acetylcholinesterase inhibitors (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.
- •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.
排除标准
- •Has a known history of stroke or cerebrovascular disease that is clinically important in the investigator's opinion.
- •Has diagnosis of a clinically relevant central nervous system (CNS) disease other than AD dementia (with protocol-specified exceptions).
- •Has a history of seizures or epilepsy within the 10 years preceding Screening.
- •Has any other major CNS trauma, or infections that affect brain function.
- •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.
- •Has a severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or administration intervention.
- •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: basal cell or squamous cell skin cancer; in situ cervical cancer; localized prostate carcinoma; 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.
- •Has a risk factor for QTc prolongation.
- •Has a history of alcoholism or drug dependency/abuse within the 5 years preceding screening.
- •Has a known allergy or intolerance to the active or inert ingredients in MK-
- •Has received any anti-amyloid agents or antibodies, or any of the following medications: CNS-penetrant anticholinergics, neuroleptics, anticonvulsants, narcotics, glutamatergic agents, agents with possible psychotropic effects, and experimental acute respiratory syndrome coronavirus 2 (COVID-19) therapies.
- •Has liver disease, including but not limited to chronic viral hepatitis, non viral hepatitis, cirrhosis, malignancies, autoimmune liver diseases.
- •Has an abnormal thyroid-stimulating hormone (TSH) value if confirmed by abnormal T4 value.
- •Resides in a nursing home or assisted care facility with need for direct continuous medical care and nursing supervision. Participant may reside in such facilities provided continuous direct medical care is not required and a qualified study partner is available for coparticipation and the participant is physically able to attend all required study visits.
- •Had major surgical procedure or donated or lost >1 unit of blood (approximately 500 mL) within the 4 weeks before screening.
研究组 & 干预措施
MK-1942 5 mg
Participants will receive a single 5 mg MK-1942 capsule twice daily (BID), taken orally for 12 weeks. A mock titration will be done to maintain the study blind despite no changes in dose.
干预措施: MK-1942 (Drug)
MK-1942 15 mg
Participants will receive a single 8 mg MK-1942 capsule twice daily (BID), taken orally for one week. Then the dose is titrated up to 15 mg MK-1942 capsule twice daily (BID), taken orally for up to 11 weeks.
干预措施: MK-1942 (Drug)
Placebo
Participants will receive a placebo capsule twice daily (BID), taken orally for 12 weeks. A mock titration will be done to maintain the study blind despite no changes in dose.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) Score at Week 12
时间窗: Baseline and Week 12
The change from baseline in ADAS-Cog11 score is presented. ADAS-Cog11 is a structured scale that evaluates memory, orientation, attention, reasoning, language, and constructional praxis. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in AD: word recall; commands; constructional praxis; naming objects and fingers; ideational praxis; orientation; word recognition; remembering test instructions; spoken language ability; word-finding difficulty; and comprehension of spoken language. The total possible score ranges from 0 to 70, with higher scores indicating greater cognitive impairment. Negative values indicate improvement relative to baseline, and vice versa.
Number of Participants Experiencing an Adverse Event (AE)
时间窗: Up to ~ 14 Weeks
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.
Number of Participants Discontinuing Study Medication Due to an Adverse Event
时间窗: Up to ~ 12 Weeks
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.
次要结局
- Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall Score at Week 12(Week 12)
- Mean Change From Baseline in The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total Score at Week 12(Baseline and Week 12)