A Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Participants With Type 2 Diabetes Mellitus (MK-0893-005)

A Multi-Center, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel Panel Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Patients With Type 2 Diabetes Mellitus

This study will assess the safety, tolerability and glucose-lowering efficacy of MK-0893 in participants with type 2 diabetes mellitus. The primary hypothesis is that MK-0893 will reduce 24-hour weighted mean glucose (WMG) significantly more than placebo.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: MK-0893; Drug: Placebo; Drug: Placebo; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes
• Not currently on antihyperglycemic agent (AHA) or AHA monotherapy (not to include treatment with insulin or thiazolidinediones [i.e., peroxisome proliferator activated receptor-gamma, PPARγ agents])
• male or a female of non-childbearing potential. Women must be postmenopausal or premenopausal and documented surgically sterilized
• A body mass index (BMI) that is > 20 and ≤ 40 kg/m2

Exclusion Criteria:

• History of type 1 diabetes or assessed by the investigator as possibly having type 1 diabetes
• History of ketoacidosis; clinically unstable or rapidly progressive diabetic retinopathy, nephropathy, neuropathy
• Treatment for diabetes within 3 months of study participation with combination anti-hyperglycemic therapy, insulin or thiazolidinediones (e.g., rosiglitazone or pioglitazone)
• oral corticosteroid medications within 2 weeks prior to study participation, or requires digoxin, warfarin, warfarin-like anticoagulants, theophylline, anti-dysrhythmic or anti-seizure medications, immunosuppressants, or anti-neoplastic agents, or herbal remedies
• History of acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)
• History of gastrointestinal problems or disorders or extensive bowel or gastric surgery
• History of significant or unstable cardiovascular disease
• History of neoplastic disease
• History of hepatic disease
• History of seizures, epilepsy or other neurologic disease
• History of myelodysplastic or pre-leukemic disorders or other severe hematological disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MK-0893 (40 mg); MK-0893 40-mg q.d. (quaque die, once daily) group will receive MK-0893 40-mg tablets (after loading dose with 160 mg) and matching placebo to metformin and matching placebo to MK-0893.	Drug: MK-0893; 10 mg and 100 mg tablets; Drug: Placebo; Placebo tablets matching MK-0893; Drug: Placebo; Placebo tablets matching metformin
EXPERIMENTAL: MK-0893 (120 mg); MK-0893 at 120 mg q.d. group will receive MK-0893 120 mg q.d. tablets (after loading dose of 500 mg on Day 1) and matching placebo tablets to metformin and matching placebo to MK-0893	Drug: MK-0893; 10 mg and 100 mg tablets; Drug: Placebo; Placebo tablets matching MK-0893; Drug: Placebo; Placebo tablets matching metformin
ACTIVE_COMPARATOR: Metformin (2000 mg); Metformin taken orally, 500 mg tablets, Day 1 to Day 6: 500 mg b.i.d. (bis in die, twice daily), Day 7 to Day 13: 1000 mg in the morning and 500 mg in the evening, and Day 14 to Day 28: 1000 mg. b.i.d. and matching placebo to MK-0893.	Drug: Placebo; Placebo tablets matching MK-0893; Drug: Placebo; Placebo tablets matching metformin; Drug: Metformin; 500 mg metformin tablets; Other Names: Glucophage; Glucophage XR; Glumetza; Fortamet; Riomet
PLACEBO_COMPARATOR: Placebo; Placebo tablets matching the MK-0893 and placebo tablets matching metformin.	Drug: Placebo; Placebo tablets matching MK-0893; Drug: Placebo; Placebo tablets matching metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4	Blood samples were collected 30 minutes prior to all meals, and 15, 30, 60, 90, 120, 180 minutes post-meal, then and at midnight, 3 AM, and the next morning at 6:30 AM and 7:30 AM. A 24-hour weighted mean glucose (WMG) was determined by averaging multiple plasma glucose measurements over a 24-hour period.	Baseline and Week 4
Number of Participants Experiencing an Adverse Event (AE)	An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.	Up to 42 days
Number of Participants Discontinuing Study Treatment Due to an AE	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG)	Plasma Glucose levels were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in Fructosamine at Week 4	Fructosamine levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in Fasting C-peptide at Week 4	Fasting C-peptide levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in Fasting Insulin at Week 4	Fasting insulin levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4	2-hour post-prandial glucose excursion is the change in glucose concentration in the blood 2 hours after a meal. Change from baseline in 2-hour post-prandial glucose excursion at Week 4 is defined as Week 4 minus baseline.	Baseline and Week 4
Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4	Blood samples collected for glucose 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour AUC for Glucose was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in 3-hour AUC for C-peptide at Week 4	Blood samples were collected for C-peptide 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour AUC for C-peptide was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in 3-hour Insulin Total AUC at Week 4	Blood samples were collected for insulin 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour Insulin Total AUC was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 11, 2006
• Primary Completion (ACTUAL): February 7, 2007
• Study Completion (ACTUAL): February 7, 2007

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 3, 2013
• First Posted (ESTIMATE): December 9, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Metformin; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Pharmacologic Actions; Therapeutic Uses; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Molecular Mechanisms of Pharmacological Action
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 0893-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis