A Study of Omarigliptin (MK-3102) in Participants With Impaired Renal Function (MK-3102-009)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

An Open-Label, Two-Part, Single-Dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of MK-3102 in Patients With Impaired Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01407276
• Other study ID #: 3102-009
• Status: Completed
• Phase: Phase 1
• Start date: August 8, 2011
• Est. completion date: March 23, 2012

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 2-part study in participants with renal impairment and matched healthy participants to investigate the effect of impaired renal function on the plasma and urine levels of omarigliptin (MK-3102) after taking a single 3 mg dose by mouth.

Description:

In Part I, three panels of 6 participants each will be enrolled with varying degrees of renal disease (mild, moderate, or severe renal impairment) based on their estimated glomerular filtration rate (eGFR). Each of these panels will be matched with a corresponding panel of equal number of healthy, age-, race-, BMI- and gender-matched control participants. All panels will receive a single oral dose of 3-mg omarigliptin, followed by plasma sampling and urine collection. In Part II, 6 participants with end stage renal disease (ESRD) requiring hemodialysis will receive a single 3-mg oral dose of omarigliptin immediately following hemodialysis (HD) (Period 1) and 2 hours prior to HD (Period 2).There will be approximately 1 month between Period 1 and Period 2. A corresponding panel of equal number, healthy matched control subjects (age, race, BMI, gender) will also receive a single 3 mg dose by mouth. Omarigliptin dose administration will be followed by plasma sampling for both panels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 23, 2012
• Est. primary completion date: March 23, 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Impaired Renal Function Subjects:

• Females of reproductive potential must have a negative pregnancy test and agree to use 2 methods of birth control

• Diagnosis of renal insufficiency based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation

Healthy Subjects:

• Females of reproductive potential must have a negative pregnancy test and agree to use 2 methods of birth control;

• In general good health

Exclusion Criteria:

Impaired Renal Function Subjects:

• Is mentally or legally incapacitated

• Has rapidly fluctuating renal function or has demonstrated or suspected renal artery stenosis

• History of significant endocrine (other than Type 2 diabetes), gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases

• History of stroke, chronic seizures or major neurological disease

• Uncontrolled Type 2 diabetes or history of Type 1 diabetes or ketoacidosis

• History of cancer (Some exceptions apply)

• Regular user of barbiturates or sleep aides

• Consumes excessive amounts of alcohol (more than 2 drinks/day)

• Consumes excessive amounts of caffeinated beverages (more than 6/day)

• Has had major surgery or has lost or donated 1 unit of blood within 4 weeks

• Has a history of significant multiple and/or severe allergies

• Current or history of illicit drug abuse

• Nursing mothers

Healthy Subjects:

• Is mentally or legally incapacitated;

• Has a history of stroke, chronic seizures, or major neurological disorder

• Renal impairment

• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases

• Hypoglycemia, glucose intolerance, Type 1 or Type 2 diabetes, or ketoacidosis

• History of cancer (Some exceptions apply)

• Regular user of barbiturates or sleep aides

• Consumes excessive amounts of alcohol (more than 2 drinks/day)

• Consumes excessive amounts of caffeinated beverages (more than 6/day)

• Has had major surgery or has lost or donated 1 unit of blood within 4 weeks

• Has a history of significant multiple and/or severe allergies

• Current or history of illicit drug abuse

• Nursing mothers

Related Conditions & MeSH terms

• Chronic Renal Insufficiency
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Renal Insufficiency
• Renal Insufficiency, Chronic
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Omarigliptin
Single oral dose of 3 mg (3 x 1-mg 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 Concentration-time Curve From Time 0 to Infinity (AUC0-8) of Omarigliptin	AUC0-8 is a measure of the mean concentration levels of drug in the plasma after the dose.	Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Primary	Maximum Concentration (Cmax) of Omarigliptin	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.	Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Primary	Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin	AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose.	Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose
Primary	Concentration at 168 Hours Post-dose (C168h) of Omarigliptin	C168h is a measure of the plasma drug concentration 168 hours post-dose.	168 hours post-dose
Primary	Apparent Volume of Distribution (Vd/F) of Omarigliptin	Vd/F is defined as the distribution of a medication between the plasma and the rest of the body after the dose. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug.	Up to 336 hours post-dose
Primary	Apparent Total Body Clearance (CL/F) of Omarigliptin	CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic, and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes).	Up to 336 hours post-dose
Primary	Renal Clearance (CLr) of Omarigliptin	CLr is a calculation of the rate at which a drug is removed from the body via renal clearance pathways, expressed as volume (milliliters) per unit of time (minutes). CLr was only determined for Panels A-F.	Up to 336 hours post-dose
Primary	Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin	fe48h is expressed as percentage of omarigliptin not metabolized and excreted in urine. fe48h was only determined for Panels A-F.	Up to 48 hours post-dose
Primary	Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin	Ae0-48h is a measure of the cumulative amount of drug excreted in the urine for 48 hours post-dose. Ae0-48h was only determined for Panels A-F.	Up to 48 hours post-dose
Primary	Time to Maximum Concentration (Tmax) of Omarigliptin	Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose.	Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Primary	Apparent Terminal Half-life (t1/2) of Omarigliptin	T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%.	Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Secondary	Number of Participants Experiencing an Adverse Event (AE)	An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product.	From pre-dose to 14 days post-dose (Up to Day 15)
Secondary	Number of Participants Withdrawn From Study		Up to Day 15