A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535])

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Two-Part, Single-Dose Study to Investigate the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (Protocol No. MK-8931-009 [P08535])

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: MK-8931


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria Specific to Renally Impaired Participants: Rapidly fluctuating renal function as determined by historical measurements Suspected renal artery stenosis

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1, Panel A - Severe Renal Impairment Group<br> | Drug: MK-8931<br>* Single dose, administered as oral capsules<br>|
| Experimental: Part 1, Panel B - Healthy Control Group to Match Panel A<br> | Drug: MK-8931<br>* Single dose, administered as oral capsules<br>|
| Experimental: Part 2, Panel C - Moderate Renal Impairment Group<br> | Drug: MK-8931<br>* Single dose, administered as oral capsules<br>|
| Experimental: Part 2, Panel D - Healthy Control Group to Match Panel C<br> | Drug: MK-8931<br>* Single dose, administered as oral capsules<br>|
| Experimental: Part 2, Panel E - Mild Renal Impairment Group<br> | Drug: MK-8931<br>* Single dose, administered as oral capsules<br>|
| Experimental: Part 2, Panel F - Healthy Control Group to Match Panel E<br> | Drug: MK-8931<br>* Single dose, administered as oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 |