A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535])
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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]) |
- 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 ]
- 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 |
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
More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT01537757 History of Changes |
| Other Study ID Numbers: | P08535, MK-8931-009 |
| Study First Received: | February 17, 2012 |
| Last Updated: | December 12, 2012 |
| 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 June 18, 2013