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

NCT01407276 | Completed Phase 1 Results

• 1 other identifier: 3102-009
• Study Type: interventional
• Target: 49
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Renal Insufficiency; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (11)

• 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.

  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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Number of Participants Experiencing an Adverse Event (AE)

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

• Number of Participants Withdrawn From Study

  Up to Day 15

Study Arms (8)

Part 1: Mild Renal Impairment (Panel A)

EXPERIMENTAL

Drug: Omarigliptin

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

EXPERIMENTAL

Drug: Omarigliptin

Part 1: Moderate Renal Impairment (Panel C)

EXPERIMENTAL

Drug: Omarigliptin

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

EXPERIMENTAL

Drug: Omarigliptin

Part 1: Severe Renal Impairment (Panel E)

EXPERIMENTAL

Drug: Omarigliptin

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

EXPERIMENTAL

Drug: Omarigliptin

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

EXPERIMENTAL

Drug: Omarigliptin

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

EXPERIMENTAL

Drug: Omarigliptin

Interventions

Omarigliptin DRUG

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

Also known as: MK-3102

Part 1: Control to Match Panel A (Panel B); Part 1: Control to Match Panel C (Panel D); Part 1: Control to Match Panel E (Panel F); Part 1: Mild Renal Impairment (Panel A); Part 1: Moderate Renal Impairment (Panel C); Part 1: Severe Renal Impairment (Panel E); Part 2: Control to Match Panel G (Panel H); Part 2: End-stage Renal Disease needing hemodialysis (Panel G)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2

Interventions

2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2011
• First Posted: August 2, 2011
• Study Start: August 8, 2011
• Primary Completion: March 23, 2012
• Study Completion: March 23, 2012
• Last Updated: September 10, 2018
• Results First Posted: December 3, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share