Pharmacodynamics of Mitiglinide/Sitagliptin Compared to Mitiglinide and Sitagliptin

Pharmacodynamics After Concomitant Administration With Mitiglinide and Sitagliptin Compared to Mitiglinide, Sitagliptin Single Administration in Patients With Type 2 Diabetes

1. Explore pharmacodynamics

   • glucose
   • insulin
   • C-peptide
   • glucagon
   • intact GLP-1
   • DPP-4 activity
   • CGMS (continuous glucose monitoring system)

2. Assess Safety

   • adverse events
   • clinical laboratory test
   • physical examination

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin; Drug: Mitiglinide; Drug: Sitagliptin, Mitiglinide

Detailed Description

Pharmacodynamic assessment

• CGMS data is obtained from day 1 to day 3 (48 hours)

• PD is measured before (day 1) and after drug administration (day 2)

  1. AUC of glucose, insulin, C-peptide, glucagon, intact GLP-1, DPP-4 activity
  2. MAGE (mean amplitude of glycemic excursion) from CGMS data

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients with type 2 diabetes mellitus
• 6.5% ≤ HbA1c < 9.0%
• Stopped treatment of sulfonylurea and biguanide for more than 8 weeks
• Stopped treatment of other anti-diabetic agents for more than 12 weeks
• 16 kg/m2 ≤ body mass index < 30 kg/m2

Exclusion Criteria:

• Fasting glucose ≥ 200 mg/dL
• Required insulin therapy
• Patients with neuropathy, retinopathy or renopathy
• Contraindicated for mitiglinide or sitagliptin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sitagliptin	Drug: Sitagliptin; Single oral administration of sitagliptin 100 mg
Active Comparator: Mitiglinide	Drug: Mitiglinide; Single oral administration of mitiglinide 10 mg
Experimental: Sitagliptin + Mitiglinide	Drug: Sitagliptin, Mitiglinide; Concomitant administration of sitagliptin 100 mg and mitiglinide 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (area under the curve) of plasma glucose	Differences of AUC before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period
AUC of insulin	Differences of AUC before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period
AUC of intact GLP-1	Differences of AUC before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period
AUC of C-peptide	Differences of AUC before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period
AUC of glucagon	Differences of AUC before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period
MAGE	Differences of MAGE before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period
AUC of DPP-4 activity	Differences of AUC before treatment (day 1) and after treatment (day 2) is compared between treatment groups	day 1 and day 2 of each period

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: JW Pharmaceutical
• Investigators: Principal Investigator: Wooseong Hur, MD, PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Jung JA, Kaku K, Kim JH, Kim JR, Ko JW, Lee SY, Huh W. Additive postprandial glucose-lowering effects of mitiglinide and sitagliptin in patients with type 2 diabetes mellitus. Adv Ther. 2013 Nov;30(11):1018-29. doi: 10.1007/s12325-013-0072-x. Epub 2013 Nov 19. Erratum In: Adv Ther. 2014 Jan;31(1):149.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: August 10, 2011
• First Submitted That Met QC Criteria: August 23, 2011
• First Posted (Estimate): August 24, 2011

Study Record Updates

• Last Update Posted (Estimate): September 7, 2011
• Last Update Submitted That Met QC Criteria: September 6, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Safety; type 2 diabetes mellitus; Pharmacodynamics; sitagliptin; mitiglinide
• 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; Sitagliptin Phosphate; Mitiglinide
• Other Study ID Numbers: 2010-04-071