Clinical trial NCT01537757: A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535])
Official title: 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])
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-02-23
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of MK-8931
timeFrame: Predose through 120 hours post single dose of MK-8931
Secondary outcomes:
measure: Renal clearance (CLr) of MK-8931
timeFrame: Predose through 120 hours post single dose of MK-8931
measure: Fraction of MK-8931 dose excreted in urine (fe)
timeFrame: Predose through 120 hours post single dose of MK-8931
Other outcomes:
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