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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02180334
• Other study ID #: H-1311-104-537
• Secondary ID: 2013-2641
• Status: Completed
• Phase: Phase 4
• First received: June 30, 2014
• Last updated: November 27, 2017
• Start date: July 2014
• Est. completion date: April 2015

Study information

• Verified date: June 2014
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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.
• 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.
• 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).

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Daewoong Pharmaceutical Co. LTD.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Other	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)