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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Mosapride citrate
* Drug: Linagliptin
* Drug: Acetaminophen (paracetamol)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mosapride<br>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<br>* 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.<br>* Other names: Gasmotin®;Drug: Linagliptin<br>* 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.<br>* Other names: Trajenta®;Drug: Acetaminophen (paracetamol)<br>* 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).<br>* Other names: Tylenol®;|
| Placebo Comparator: Control<br>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<br>* 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.<br>* Other names: Trajenta®;Drug: Acetaminophen (paracetamol)<br>* 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).<br>* Other names: Tylenol®;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Emptying, Gastrointestinal Motility, Incretins, Glucagon-Like Peptide 1, Diabetes Mellitus