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

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])

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: MK-8931

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: February 17, 2012
• First Submitted That Met QC Criteria: February 17, 2012
• First Posted (Estimate): February 23, 2012

Study Record Updates

• Last Update Posted (Estimate): January 26, 2015
• Last Update Submitted That Met QC Criteria: January 23, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Renal Insufficiency; Alzheimer Disease
• Other Study ID Numbers: P08535; MK-8931-009 (Other Identifier: Schering -Plough)