The Effect of Combination of Mosapride and DPP-4 Inhibitor on Plasma Concentration of Incretin Hormones

The Effect of Combination of Mosapride and Dipeptidyl Peptidase-4 (DPP-4) Inhibitor on Plasma Concentration of Incretin Hormones

The aim of this study is to investigate the effects of combined administration of mosapride as modulator of gastrointestinal motility and DPP-4 inhibitor on secretion of gut hormone such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), and oral glucose tolerance. Additionally, change in lipid profile and insulin secretion will be also assessed.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Mosapride citrate; Drug: Linagliptin; Drug: Acetaminophen (paracetamol)

Detailed Description

This is randomized, double-blind, placebo-controlled, cross-over study. After screening and enrollment, participants will take 5 mg of linagliptin once a day for one week of run-in period (Day 1 to Day 7). Randomization will be done on Day 8 to assign the participants to either mosapride arm or placebo arm. If a subject is assigned to mosapride arm, mixed meal tolerance test (MMTT) will be performed after taking mosapride with linagliptin. If a subject is assigned to placebo arm, he/she will take placebo instead of mosapride before MMTT. On Day 9, all subjects will be crossed over to the other arm and MMTT will proceed with medication depending on their arms. Gastric emptying time measurement with paracetamol will be done along with MMTT. Plasma incretin hormone levels in two arms will be compared.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• type 2 diabetes mellitus
• BMI < 35 kg/m2
• HbA1c 6.5~8.0% for whom is on lifestyle modification only, 6.0~8.0% for whom is taking oral antidiabetic drug(s).
• on lifestyle modification or oral antidiabetic therapy (sulfonylurea, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and DPP-4 inhibitors)
• Who read and signed the informed consent agreement

Exclusion Criteria:

• chronic disease(s) requiring medication other than diabetes mellitus
• type 1 diabetes mellitus or history of diabetic ketoacidosis
• on insulin therapy or requiring insulin therapy
• history of gastrointestinal surgery excluding appendectomy, hernia repair and hemorrhoid surgery
• serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) to be more than 2.5 times above the upper limit of normal
• estimated glomerular filtration rate to be less than 50 mL/min/1.73m2
• genetic disorders associated with digestion and absorption such as galactose intolerance, Lapp lactase deficiency, and glucose-galactose malabsorption
• history of hypersensitivity including anaphylaxis and angioedema to mosapride citrate, linagliptin, or paracetamol (acetaminophen)
• history of asthma associated with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
• currently taking drugs that can prolong QT interval, including procainamide, quinidine, flecainide, sotalol, tricyclic antidepressants
• currently taking anticholinergics such as atropine sulfate, scopolamine butylbromide
• child-bearing or lactating women
• women in reproductive age who disagree with contraception with proper method or urine pregnancy test during the study period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mosapride; Mosapride citrate 5 mg (Gasmotin®): 1 tablet (5 mg) will be administered 1 hour before MMTT.; Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT.; Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.	Drug: Mosapride citrate; On the day of MMTT, 1 tablet (5 mg) of mosapride will be administered orally to participants of 'mosapride' arm. After 1 hour, MMTT will be performed.; Other Names: Gasmotin®; Drug: Linagliptin; During run-in period, 1 tablet (5mg) per day will provided for 7 days. On the day of MMTT, 1 tablet (5 mg) of linagliptin will be administered orally to participants of both arms. After 1 hour, MMTT will be performed.; Other Names: Trajenta®; Drug: Acetaminophen (paracetamol); On the day of MMTT, 3 tablets (1500 mg) of acetaminophen (paracetamol) will be administered orally to participants of both arms at the start of MMTT with manufactured mixed meal (0 min).; Other Names: Tylenol®
Placebo Comparator: Control; Placebo drug: 1 tablet will be administered 1 hour before MMTT.; Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT.; Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.	Drug: Linagliptin; During run-in period, 1 tablet (5mg) per day will provided for 7 days. On the day of MMTT, 1 tablet (5 mg) of linagliptin will be administered orally to participants of both arms. After 1 hour, MMTT will be performed.; Other Names: Trajenta®; Drug: Acetaminophen (paracetamol); On the day of MMTT, 3 tablets (1500 mg) of acetaminophen (paracetamol) will be administered orally to participants of both arms at the start of MMTT with manufactured mixed meal (0 min).; Other Names: Tylenol®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of plasma total GLP-1 levels	AUC of plasma total GLP-1 levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of plasma total GIP levels	AUC of plasma total GIP levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Area under the curve (AUC) of plasma glucose levels	AUC of plasma glucose levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Area under the curve (AUC) of plasma insulin levels	AUC of plasma insulin levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Area under the curve (AUC) of plasma C-peptide levels	AUC of plasma C-peptide levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Area under the curve (AUC) of serum triglyceride levels	AUC of serum triglyceride levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Area under the curve (AUC) of serum nonesterified fatty acid (NEFA) levels	AUC of serum NEFA levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Area under the curve (AUC) of plasma active GLP-1 levels	AUC of plasma active GLP-1 levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of plasma paracetamol levels	AUC of plasma paracetamol levels during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
The peak concentration of plasma paracetamol	The peak concentration of plasma paracetamol during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
The time to peak concentration of plasma paracetamol	The time to peak concentration of plasma paracetamol during MMTT	0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Daewoong Pharmaceutical Co. LTD.
• Investigators: Study Chair: Young Min Cho, MD, PHD, Seoul National University College of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: June 30, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: November 27, 2017
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Gastric Emptying; Incretins; Glucagon-Like Peptide 1; Gastrointestinal Motility
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Serotonin Agents; Serotonin Receptor Agonists; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Acetaminophen; Linagliptin; Mosapride
• Other Study ID Numbers: H-1311-104-537; 2013-2641 (Other Identifier: SNUH Institutional Review Board)