Study to Evaluate the Efficacy of Acarbose,Metformin,Sitagliptin Combination Treatment in DM Patients

A Multicenter, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy of Acarbose Added on Top of Metformin and Sitagliptin Combination Treatment in Type 2 Diabetes Mellitus Patients

Primary objective To evaluate the efficacy of Acarbose add-on therapy on glucose control in subjects with type 2 diabetes inadequately controlled with Metformin and Sitagliptin combination therapy.

The effect of acarbose, an alpha glucosidase inhibitor as a third-line therapeutic medication in subject who are inadequately controlled with metformin and DPP4 inhibitor will be evaluated with multicenter, randomized, 24-week, double blinded, placebo-controlled study in Korea.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo acarbose; Drug: Acarbose; Drug: placebo metformin

Detailed Description

Eligible subjects will be assigned among 3 groups randomly at a ration of 2:2:1 to the following groups and primary efficacy variable analyzed at week 16.

group 1 : acarbose placebo + metformin + sitagliptin (with switching placebo to acarbose qt week 16) group 2 : acarbose + metformin + sitagliptin group 3 : acarbose + metformin placebo + sitagliptin (with switching placebo to metformin at week 16)

After 16 week of treatment, all subjects in 3 groups will be treated as triple combination of acarbose + metformin + sitagliptin, and diabetes related variables be collected and analyzed.

1. Primary Endpoint Changes in HbA1c (hemoglobin A1c) at 16 week from baseline between group1 vs grou2
2. Secondary Endpoints (1) Changes of HbA1c at 24 week between 3 groups (2) Changed of post-prandial blood glucose at 2 hour (ppg2h) at 16, 24 week

for exploratory purpose, following data will be collected and analyzed

1. continuous glucose monitoring system (CGMS) data among selected subjects in 3 groups
2. mixed meal tolerance test in only available institution. (glucose, insulin, GLP-1, GIP, glucagon ) among selected subjects in group 1 and group 2
3. oxidative stress markers (8-OHdG, nitrotyrosin, CML)
4. self monitoring of blood glucose

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
    • MedicalExcellence

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with type-II diabetes mellitus;
2. Subjects aged between 20 and 80;
3. Subjects whose HbA1c ratio is between 7.0% and 10.0%;
4. Subjects who took Metformin and Sitagliptin for at least 12 weeks;
5. Subjects who were given the explanation about this clinical study and signed the consent form.

Exclusion Criteria:

1. Subjects who have taken drugs that are likely to affect blood glucose or who need to take such drugs, e.g., glucocorticoid;
2. Subjects with severe renal diseases (men: Scr>1.5 / women: Scr>1.4);
3. Subjects with severe liver diseases or whose AST and ALT are at least 2.5 times higher than the upper limits of normal (ULN);
4. Subjects having the case history of lactic acidosis;
5. Subjects who have the case history of myocardial infarction or unstable angina or who underwent the coronary artery bypass graft 6 months before the screening test or who have arrhythmia to be treated;
6. Subjects with congestive heart failures to be treated;
7. Subjects who fall into New York Heart Association (NYHA) class III or IV;
8. Subjects having the case history of acute or chronic metabolic acidosis including ketoacidosis;
9. Subjects who have been pregnant or who are in the period of lactation;
10. Subjects diagnosed with malignant tumors within 5 years;
11. Subjects who are hypersensitive to Metformin, Sitagliptin and Acarbose or their ingredients;
12. Subjects with inflammatory bowel diseases or intestinal ulcers or enterostenosis (includes Subjects who are vulnerable to enterostenosis) or chronic enteric diseases related to digestion and absorption or whose symptoms are likely to worsen due to intestinal gas;
13. Subjects who participated in other clinical studies as Subjects within 60 days before this study (or before taking the investigational drugs);
14. Subjects judged unfit for this study by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Acarbose placebo, Metformin, Sitagliptin; The Acarbose placebo should be changed into real Acarbose from the 16th week.	Drug: Placebo acarbose; acarbose placebo; Other Names: dual combination (metformin+sitagliptin)
Experimental: Sitagliptin, Metformin, Acarbose; Metformin, Sitagliptin, Acarbose group	Drug: Acarbose; Acarbose 50mg b.i.d at first, at the 2nd week 50mg t.i.d and the 4th week, 100mg tid.; Other Names: triple combination
Other: Metformin placebo, Sitagliptin, Acarbose; The Metformin placebo should be changed into real Metformin from the 16th week.	Drug: placebo metformin; metformin placebo; Other Names: dual combination (acarbose + sitagliptin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change of Glycated Hemoglogin(HbA1c) From Baseline to 16 Weeks of Treatment	The change of glycated hemoglogin(HbA1c) from baseline to 16 weeks of treatment between Placebo + Metformin+Sitagliptin and Metformin + Sitagliptin + Acarbose group	baseline, 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change of HbA1c From Baseline to 24 Weeks of Treatment	The change of glycated hemoglogin(HbA1c) from baseline to 24 weeks of treatment between 3 groups	baseline, 24 weeks
The Change of PPG2hr From Baseline to 24 Weeks of Treatment	The change of PPG2hr (post prandia blood glucose 2hr from baseline to 24 weeks of treatment between 3 groups	baseline, 24 weeks
Changes in Glucose During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),	Change of AUC(area under the curve) of glucose at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)	Visit 2(baseline) and Visit 5(16W)
Changes in Insulin During Mixed Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),	Change of AUC(area under the curve) of insulin at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)	Visit 2(baseline) and Visit 5(16W)
Change in Active GLP-1 at 0 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2)	Change of active GLP-1 at 0 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2)	baseline, 16 week
Change in Active GLP-1 at 120 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2)	Change of active GLP-1 at 120 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2)	baseline, 16 week
Changes in Glucagon During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),	Change of AUC(area under the curve) of glucagon at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)	Visit 2(baseline) and Visit 5(16W)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Mean Glucose During CGMS Between 3 Group	Change of mean glucose of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 3 groups	Visit 2(baseline) and Visit 5(16W)
Changes in Variation of Glucose During CGMS Between 3 Group	Change of standard deviation of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 3 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin vs placebo + acarbose + sitagliptin)	Visit 2(baseline) and Visit 5(16W)
Changes in MAGE of Glucose During CGMS Between 2 Group(Group 1 vs Group 2),	Change of mean amplitude of glycemic excursion of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)	Visit 2(baseline) and Visit 5(16W)

Collaborators and Investigators

• Sponsor: The Catholic University of Korea
• Collaborators: Bayer
• Investigators: Principal Investigator: kun-ho YOON, professor, Seoul st. mary's hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: December 9, 2011
• First Submitted That Met QC Criteria: December 11, 2011
• First Posted (Estimate): December 13, 2011

Study Record Updates

• Last Update Posted (Actual): August 17, 2020
• Last Update Submitted That Met QC Criteria: July 31, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Acarbose; ACADEMIC
• 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; Glycoside Hydrolase Inhibitors; Metformin; Sitagliptin Phosphate; Acarbose
• Other Study ID Numbers: ACADEMIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO