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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01537757
First received: February 17, 2012
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: MK-8931
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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])

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of MK-8931 [ Time Frame: Predose through 120 hours post single dose of MK-8931 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Renal clearance (CLr) of MK-8931 [ Time Frame: Predose through 120 hours post single dose of MK-8931 ] [ Designated as safety issue: No ]
  • Fraction of MK-8931 dose excreted in urine (fe) [ Time Frame: Predose through 120 hours post single dose of MK-8931 ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: March 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01537757     History of Changes
Other Study ID Numbers: P08535, MK-8931-009
Study First Received: February 17, 2012
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alzheimer Disease
Renal Insufficiency
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on April 20, 2014