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Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes

Primary Purpose

Diabetes Mellitus, Type II

Status

Unknown status

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

triple combination therapy

Stepwise add-on therapy

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type II

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Drug-naïve patients with type 2 diabetes by American Diabetes Association criteria
HbA1c ≥ 8%, < 10.5% at screening
Age ≥ 18 years, < 65 years
Body mass index (BMI) ≥ 23 kg/m2, < 35 kg/m2
Estimated GFR (eGFR) ≥ 60 ml/min/1.73m2

Exclusion Criteria:

Uncontrolled hyperglycemia > 270 mg/dl after an overnight fast
Diabetic ketoacidosis
Type 1 diabetes
Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening
Congestive heart failure (New York Heart Association functional class IV)
severe hepatic dysfunction (serum levels of either AST, ALT, or alkaline phosphatase above 3 x upper limit of normal (ULN))
alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women
use of systemic glucocorticoid

Sites / Locations

Korea University Anam Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Triple combination therapy group

Stepwise add-on therapy group

Arm Description

Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks

Participants were started on metformin 1000mg once daily after screening & assignment At each visits, FPG and HbA1c are measured. Sequential add-on therapy regimen is described

Outcomes

Primary Outcome Measures

Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks

Secondary Outcome Measures

∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks

Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks

Change in body HbA1c from baseline to week 104

Change in body weight from baseline to week 104

Change in systolic blood pressure from baseline to week 104

Changes in fat and lean mass from baseline to at 104 weeks

Full Information

NCT ID

NCT02946632

First Posted

October 25, 2016

Last Updated

October 26, 2016

Sponsor

Korea University Anam Hospital

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT02946632

Brief Title

Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes

Official Title

Effectiveness and Tolerability of Novel, Initial Triple Combination Therapy With Xigduo (Dapagliflozin Plus Metformin) and Saxagliptin vs. Conventional Stepwise add-on Therapy in Drug-naïve Patients With Type 2 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Unknown status

Study Start Date

December 2016 (undefined)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Korea University Anam Hospital

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In this study, the investigators will assess the efficacy and tolerability of a novel, initial triple combination therapy with metformin, saxaglipitin, and dapagliflozin, compared to conventional stepwise add-on therapy in drug-naïve patients with recently onset type 2 diabetes.

Detailed Description

ADA/EASD guideline recommends sequential treatment approach starting with metformin, and adding other classes of anti-diabetic medications if target HbA1c is not achieved. However, several clinical studies clearly showed that initial dual or triple combination therapy was more favorable in terms of glycemic control. A DPP-4 inhibitor saxagliptin increases serum level of GLP-1, and potentiates its action of increasing glucose-dependent insulin secretion and lowering glucagon secretion. A SGLT-2 inhibitor dapagliflozin lowers hyperglycemia via blocking SGLT-2 to increase glucosuria, that is, in an insulin-independent manner. Therefore, the mechanism of action of these drugs are complimentary to that of metformin, and all of these have a low risk of hypoglycemia and weight gain.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type II

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Triple combination therapy group

Arm Type

Experimental

Arm Description

Xigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks

Arm Title

Stepwise add-on therapy group

Arm Type

Active Comparator

Arm Description

Participants were started on metformin 1000mg once daily after screening & assignment At each visits, FPG and HbA1c are measured. Sequential add-on therapy regimen is described

Intervention Type

Drug

Intervention Name(s)

triple combination therapy

Other Intervention Name(s)

metformin 1000mg, dapagliflozin 10mg, saxagliptin 5mg

Intervention Description

Xigduo (metformin 1000mg + dapagliflozin 10mg) saxagliptin 5mg

Intervention Type

Drug

Intervention Name(s)

Stepwise add-on therapy

Other Intervention Name(s)

Metformin, Glimepiride, Sitagliptin

Intervention Description

metformin -> glimepirde -> sitagliptin

Primary Outcome Measure Information:

Title

Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks

Time Frame

104 weeks

Secondary Outcome Measure Information:

Title

∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks

Time Frame

52 weeks

Title

Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks

Time Frame

104 weeks

Title

Change in body HbA1c from baseline to week 104

Time Frame

104 weeks

Title

Change in body weight from baseline to week 104

Time Frame

104 weeks

Title

Change in systolic blood pressure from baseline to week 104

Time Frame

104 weeks

Title

Changes in fat and lean mass from baseline to at 104 weeks

Time Frame

104 weeks

Other Pre-specified Outcome Measures:

Title

AEs/SAEs

Description

hypoglycemia, GI trouble, urinary tract infection, genital infection, volume depletion, panreatitis, severe cutaneous events, hypersensitivity reactions) Vital signs Collection of clinical chemistry/haematology parameters

Time Frame

104 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Drug-naïve patients with type 2 diabetes by American Diabetes Association criteria HbA1c ≥ 8%, < 10.5% at screening Age ≥ 18 years, < 65 years Body mass index (BMI) ≥ 23 kg/m2, < 35 kg/m2 Estimated GFR (eGFR) ≥ 60 ml/min/1.73m2 Exclusion Criteria: Uncontrolled hyperglycemia > 270 mg/dl after an overnight fast Diabetic ketoacidosis Type 1 diabetes Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening Congestive heart failure (New York Heart Association functional class IV) severe hepatic dysfunction (serum levels of either AST, ALT, or alkaline phosphatase above 3 x upper limit of normal (ULN)) alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women use of systemic glucocorticoid

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

SinGon Kim, MD

Phone

010-4191-0958

k50367@korea.ac.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

SinGon Kim, MD

Organizational Affiliation

'Korea University Anam Hospital' in Seoul, Korea

Official's Role

Principal Investigator

Facility Information:

Facility Name

Korea University Anam Hospital

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

8554220

Citation

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Results Reference

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Citation

Moss SE, Klein R, Klein BE, Meuer SM. The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med. 1994 Nov 14;154(21):2473-9.

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PubMed Identifier

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Citation

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum In: Lancet 1999 Aug 14;354(9178):602.

Results Reference

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PubMed Identifier

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Citation

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Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes

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