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

Sponsor

Seoul National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02180334

Collaborator

Daewoong Pharmaceutical Co. LTD. (Industry)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Mosapride citrate Drug: Linagliptin Drug: Acetaminophen (paracetamol)	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

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®

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

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®

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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