Alzheimer's Disease
Conditions
Brief summary
This study will assess the pharmacokinetics of MK-8931, a ß-secretase inhibitor, in participants with renal insufficiency. In Part 1 of the study, pharmacokinetics of MK-8931 in participants with severe renal disease and in healthy matched control participants will be studied. If data from Part 1 confirms that severe renal impairment does not alter the pharmacokinetics of MK-8931 to the extent requiring dosage adjustment, then no further study will be required and Part 2 will be optional. If the data does not support this conclusion, then Part 2 will be conducted to study the pharmacokinetics of MK-8931 in participants with moderate and mild renal impairment compared to healthy matched controls.
Interventions
DRUGMK-8931
Single dose, administered as oral capsules
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index ≤39 kg/m\^2 * No clinically significant abnormality on electrocardiogram * Female participant must be postmenopausal or surgically sterilized * Non-vasectomized men must agree to use a condom with spermicide or abstain from sexual intercourse, during the trial and for 3 months after stopping the medication Inclusion Criteria Specific to Renally Impaired Participants: * Clinical diagnosis of renal insufficiency based on Estimated Glomerular Filtration rate (eGFR): severely decreased eGFR, defined as \<30 mL/min/1.73m\^2 and participant is not on dialysis; moderately decreased eGFR, defined as ≥30 to \<60 mL/min/1.73m\^2; mildly decreased eGFR, defined as ≥60 to \<80 mL/min/1.73m\^2 * Stable baseline health based on medical history, physical examination, vital signs, and laboratory tests Inclusion Criterion Specific to Healthy Participants: * eGFR ≥80 mL/min/1.73m\^2
Exclusion criteria
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug, including history or presence of inflammatory bowel disease, gastrointestinal or rectal bleeding; presence of active ulcer; history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; history of pancreatic injury or pancreatitis; history or presence of liver disease or liver injury; history of urinary obstruction or difficulty in voiding * History of any infectious disease within 4 weeks prior to drug administration * Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies (HCV) or human immunodeficiency virus (HIV) * History of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of Long QT Syndrome) * Participant has had a kidney removed or has a functioning renal transplant * History of alcohol or drug abuse in the past 2 years * Blood donation or loss of significant volume of blood in the past 60 days prior to dosing * Previously received MK-8931 * History of significant multiple and/or severe allergies (including latex allergy), or anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food * History of malignancy occurring within the 5 years immediately before screening, except for a participant who has been adequately treated for basal cell or squamous cell skin cancer; or in situ cervical cancer; or localized prostate carcinoma; or has undergone potentially curative therapy with no evidence of recurrence ≥1 year post-therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of MK-8931 | Predose through 120 hours post single dose of MK-8931 |
Secondary
| Measure | Time frame |
|---|---|
| Renal clearance (CLr) of MK-8931 | Predose through 120 hours post single dose of MK-8931 |
| Fraction of MK-8931 dose excreted in urine (fe) | Predose through 120 hours post single dose of MK-8931 |
Outcome results
None listed