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

Primary Purpose

Chronic Renal Insufficiency, Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Omarigliptin

About this trial

This is an interventional treatment trial for Chronic Renal Insufficiency

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Part 1: Mild Renal Impairment (Panel A)

Part 1: Control to Match Panel A (Panel B)

Part 1: Moderate Renal Impairment (Panel C)

Part 1: Control to Match Panel C (Panel D)

Part 1: Severe Renal Impairment (Panel E)

Part 1: Control to Match Panel E (Panel F)

Part 2: End-stage Renal Disease needing hemodialysis (Panel G)

Part 2: Control to Match Panel G (Panel H)

Arm Description

Outcomes

Primary Outcome Measures

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin

AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.

Maximum Concentration (Cmax) of Omarigliptin

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

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.

Concentration at 168 Hours Post-dose (C168h) of Omarigliptin

C168h is a measure of the plasma drug concentration 168 hours post-dose.

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.

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).

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.

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.

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.

Time to Maximum Concentration (Tmax) of Omarigliptin

Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose.

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%.

Secondary Outcome Measures

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.

Number of Participants Withdrawn From Study

Full Information

NCT ID

NCT01407276

First Posted

July 29, 2011

Last Updated

August 8, 2018

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01407276

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

August 8, 2011 (Actual)

Primary Completion Date

March 23, 2012 (Actual)

Study Completion Date

March 23, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Renal Insufficiency, Type 2 Diabetes Mellitus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

49 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Mild Renal Impairment (Panel A)

Arm Type

Experimental

Arm Title

Part 1: Control to Match Panel A (Panel B)

Arm Type

Experimental

Arm Title

Part 1: Moderate Renal Impairment (Panel C)

Arm Type

Experimental

Arm Title

Part 1: Control to Match Panel C (Panel D)

Arm Type

Experimental

Arm Title

Part 1: Severe Renal Impairment (Panel E)

Arm Type

Experimental

Arm Title

Part 1: Control to Match Panel E (Panel F)

Arm Type

Experimental

Arm Title

Part 2: End-stage Renal Disease needing hemodialysis (Panel G)

Arm Type

Experimental

Arm Title

Part 2: Control to Match Panel G (Panel H)

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Omarigliptin

Other Intervention Name(s)

MK-3102

Intervention Description

Single oral dose of 3 mg (3 x 1-mg capsules)

Primary Outcome Measure Information:

Title

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin

Description

AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.

Time Frame

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

Title

Maximum Concentration (Cmax) of Omarigliptin

Description

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

Time Frame

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

Title

Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin

Description

AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose.

Time Frame

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose

Title

Concentration at 168 Hours Post-dose (C168h) of Omarigliptin

Description

C168h is a measure of the plasma drug concentration 168 hours post-dose.

Time Frame

168 hours post-dose

Title

Apparent Volume of Distribution (Vd/F) of Omarigliptin

Description

Time Frame

Up to 336 hours post-dose

Title

Apparent Total Body Clearance (CL/F) of Omarigliptin

Description

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).

Time Frame

Up to 336 hours post-dose

Title

Renal Clearance (CLr) of Omarigliptin

Description

Time Frame

Up to 336 hours post-dose

Title

Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin

Description

fe48h is expressed as percentage of omarigliptin not metabolized and excreted in urine. fe48h was only determined for Panels A-F.

Time Frame

Up to 48 hours post-dose

Title

Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin

Description

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.

Time Frame

Up to 48 hours post-dose

Title

Time to Maximum Concentration (Tmax) of Omarigliptin

Description

Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose.

Time Frame

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

Title

Apparent Terminal Half-life (t1/2) of Omarigliptin

Description

T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%.

Time Frame

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 Outcome Measure Information:

Title

Number of Participants Experiencing an Adverse Event (AE)

Description

Time Frame

From pre-dose to 14 days post-dose (Up to Day 15)

Title

Number of Participants Withdrawn From Study

Time Frame

Up to Day 15

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Available IPD and Supporting Information:

Available IPD/Information Type

CSR Synopsis Links

Available IPD/Information URL

http://www.merck.com/clinical-trials/study.html?id=3102-009&kw=3102-009&tab=access

Learn more about this trial

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

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