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

Alzheimer's Disease Clinical Trial

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])

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01537757
• Other study ID #: P08535
• Secondary ID: MK-8931-009
• Status: Completed
• Phase: Phase 1
• First received: February 17, 2012
• Last updated: January 23, 2015
• Start date: March 2012
• Est. completion date: May 2012

Study information

• Verified date: January 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Renal Insufficiency

Intervention

Drug:
• MK-8931
Single dose, administered as oral capsules

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Renal clearance (CLr) of MK-8931		Predose through 120 hours post single dose of MK-8931	No
Secondary	Fraction of MK-8931 dose excreted in urine (fe)		Predose through 120 hours post single dose of MK-8931	No