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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01490918
• Other study ID #: ACADEMIC
• Status: Completed
• Phase: Phase 4
• Start date: April 2012
• Est. completion date: September 2014

Study information

• Verified date: July 2020
• Source: The Catholic University of Korea
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Acarbose
Acarbose 50mg b.i.d at first, at the 2nd week 50mg t.i.d and the 4th week, 100mg tid.
• Placebo acarbose
acarbose placebo
• placebo metformin
metformin placebo

Locations

Country	Name	City	State
Korea, Republic of	MedicalExcellence	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
The Catholic University of Korea	Bayer

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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