A Study of the Effects of Co-Administration of Sitagliptin (MK-0431) and Metformin on Incretin Hormone Concentrations (MK-0431-110)

A Study to Assess the Effects of Co-Administration of Sitagliptin and Metformin on Incretin Hormone Concentrations

This study will assess the effects of sitagliptin and metformin alone and after co-administration on incretin hormone concentrations in patients with Type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: sitagliptin phosphate; Drug: Comparator: placebo metformin; Drug: metformin hydrochloride; Drug: Comparator: placebo sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female subjects must have a negative pregnancy test
• Subject has type 2 diabetes and is not currently receiving treatment with an oral AHA agent, has not received such treatment for 3 months prior to study, and/or has not received more than 4 total weeks treatment with an oral AHA agent for 12 to 18 months prior to the study
• Subject is a nonsmoker or has not smoked and/or used nicotine for at least 6 months

Exclusion Criteria:

• Subject has a history of stroke, seizures, or major neurological disorders
• Female subject is breastfeeding
• Subject cannot refrain from use of any prescription or non-prescription drugs beginning 2 weeks prior to first dose of study drug
• Subject consumes more than 3 alcoholic beverages per day
• Subject consumes more than 6 caffeinated beverages per day
• Subject has had major surgery, or has donated or lost 1 unit of blood within 4 weeks of screening
• Subject has a history of cancer, except certain skin or cervical cancer or other cancers treated more than 10 years prior to screening
• Subject has a history of multiple and/or severe allergies or intolerance to drugs or food

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin + placebo metformin	Drug: sitagliptin phosphate; Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.; Other Names: Januvia; Drug: Comparator: placebo metformin; Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods.
Experimental: Metformin + placebo sitagliptin	Drug: metformin hydrochloride; Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods.; Other Names: Glucophage; Drug: Comparator: placebo sitagliptin; Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.
Experimental: Sitagliptin + metformin; Co-administration of sitagliptin and metformin	Drug: sitagliptin phosphate; Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.; Other Names: Januvia; Drug: metformin hydrochloride; Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods.; Other Names: Glucophage
Placebo Comparator: Placebo sitagliptin + placebo metformin; Co-administration of placebo to sitagliptin and placebo to metformin	Drug: Comparator: placebo metformin; Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods.; Drug: Comparator: placebo sitagliptin; Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations	Meal was given 2 hours postdose. Blood samples for determination of active GLP-1 concentration were collected (4 hours postmeal) on Day 2 in each treatment period.	6 hours postdose (4 hours postmeal) on Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
β-cell Sensitivity	β-cell sensitivity was defined as the incremental post-prandial 4-hour area under the curve (AUC) for insulin secretion rate (ISR) normalized by the incremental post-prandial 4-hour plasma glucose AUC.	6 hour post-dose (4 hour postmeal) on Day 2
Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations	Meal was given 2 hours postdose. Blood samples for determination of glucose concentration were collected (4 hours postmeal) on Day 2 in each treatment period.	6 hours postdose (4 hours postmeal) on Day 2

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2008
• Primary Completion (Actual): April 30, 2009
• Study Completion (Actual): May 14, 2009

Study Registration Dates

• First Submitted: January 26, 2009
• First Submitted That Met QC Criteria: January 26, 2009
• First Posted (Estimate): January 27, 2009

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-110; 2009_521

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

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