mk-1942/donepezil interactions in participants with alzheimer's disease (mk-1942-005)

Conditions: Alzheimer's Disease

Summary: the study investigated the effects on safety and pharmacokinetics (pk) of mk-1942 and donepezil when co-administered to participants with alzheimer's disease with mild-to-moderate cognitive impairment stably treated with donepezil. the objectives of this study were to determine if the combination of mk-1942 with donepezil increases the incidence or severity of adverse events (aes) previously reported for these agents alone, or results in unanticipated aes in the patient population targeted for mk-1942 treatment. in addition, changes in the pk parameters of either mk-1942 or donepezil as a result of co-administration were assessed.


Eligibility criteria:
inclusion criteria: * body mass index (bmi) ≥18 and ≤35 kg/m\^2, inclusive. * is in good health based on medical history, physical examination, vital sign measures and electrocardiogram performed prior to randomization. * have a negative urine drug screen prior to randomization. * have a history of cognitive and functional decline with gradual onset and slow progression for at least one year before screening that is either corroborated or well-documented. * be receiving donepezil (maximum dose: ≥10-mg, ≤15-mg) for symptomatic treatment of cognitive impairment associated with alzheimer's dementia. the dose level must be stable for at least 1 month prior to screening. * have a reliable and competent trial partner/caregiver who has a close relationship with the subject, has face-to-face contact at least three days a week for a minimum of six waking hours a week, and is willing to accompany the participant, if desired, to trial visits. the trial partner/caregiver should understand the nature of the trial and adhere to trial requirements (e.g., dosing, visit schedules, and nature and number of evaluations). * contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * male participants must refrain from donating sperm plus agree to study guidelines regarding abstinent and/or contraception during the intervention period and for at least an additional 90 days (a spermatogenesis cycle) after the last dose of study intervention: * a female participant is eligible to participate if she is a women of nonchildbearing potential by study criteria. exclusion criteria: * is positive for hepatitis b surface antigen, hepatitis c antibodies or human immunodeficiency virus (hiv). * is at imminent risk of self-harm, based on clinical interview and responses on the columbia-suicide severity rating scale (cssrs), or of harm to others in the opinion of the investigator. * had major surgery, donated or lost 1 unit of blood (approximately 500 ml) within 4 weeks prior to the pretrial (screening) visit. * has a history of uncontrolled, clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. * candidates should not have a history of asthma, chronic obstructive pulmonary disease, urinary obstructions or gastrointestinal bleeding. * has a history of cancer (malignancy) exceptions for (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or; (2) other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study. * has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food. * has evidence of a clinically relevant or unstable psychiatric disorder, based on the diagnostic and statistical manual of mental disorders (dsm-5) criteria, including schizophrenia or other psychotic disorder, bipolar disorder, or delirium at the time of the pre-study (screening) visit, or has a history of clinically significant psychiatric disorder of the last 5 years. * has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the pre-study (screening) visit.

Keywords: alzheimer's disease donepezil