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

NCT01537757 | Completed Phase 1

• 2 other identifiers: P08535MK-8931-009
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (6)

Part 1, Panel A - Severe Renal Impairment Group

EXPERIMENTAL

Drug: MK-8931

Part 1, Panel B - Healthy Control Group to Match Panel A

EXPERIMENTAL

Drug: MK-8931

Part 2, Panel C - Moderate Renal Impairment Group

EXPERIMENTAL

Drug: MK-8931

Part 2, Panel D - Healthy Control Group to Match Panel C

EXPERIMENTAL

Drug: MK-8931

Part 2, Panel E - Mild Renal Impairment Group

EXPERIMENTAL

Drug: MK-8931

Part 2, Panel F - Healthy Control Group to Match Panel E

EXPERIMENTAL

Drug: MK-8931

Interventions

MK-8931 DRUG

Single dose, administered as oral capsules

Part 1, Panel A - Severe Renal Impairment Group; Part 1, Panel B - Healthy Control Group to Match Panel A; Part 2, Panel C - Moderate Renal Impairment Group; Part 2, Panel D - Healthy Control Group to Match Panel C; Part 2, Panel E - Mild Renal Impairment Group; Part 2, Panel F - Healthy Control Group to Match Panel E

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• eGFR ≥80 mL/min/1.73m\^2

You may not qualify if:

• 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
• Rapidly fluctuating renal function as determined by historical measurements
• Suspected renal artery stenosis

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Alzheimer Disease

Interventions

verubecestat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2012
• First Posted: February 23, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: January 26, 2015

Record last verified: 2015-01