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
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type II
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
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
No
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
Email
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:
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Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes
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