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

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo acarbose; Drug: Acarbose; Drug: placebo metformin

• Registration Number: NCT01490918
• Lead Sponsor: The Catholic University of Korea

Brief Summary

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.

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 Timeline

• Study First Submitted: 2011-12-09
• Study First Submitted QC: 2011-12-11
• Study First Posted: 2011-12-13
• Study Start: 2012-04
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Results First Submitted: 2019-02-07
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-31
• Last Update Submitted: 2020-07-31
• Results First Posted: 2020-08-17
• Last Update Posted: 2020-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 165

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acarbose placebo, Metformin, Sitagliptin	Placebo acarbose	The Acarbose placebo should be changed into real Acarbose from the 16th week.
Sitagliptin, Metformin, Acarbose	Acarbose	Metformin, Sitagliptin, Acarbose group
Metformin placebo, Sitagliptin, Acarbose	placebo metformin	The Metformin placebo should be changed into real Metformin from the 16th week.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

MedicalExcellence; 🇰🇷 Seoul, Korea, Republic of