24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy, Safety and Tolerability of Saxagliptin Compared With Acarbose When in Combination With Metformin in Patients With T2D Inadequately Controlled With Metformin Monotherapy

Phase 4

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Saxagliptin
Drug: Acarbose

Registration Number: NCT02243176

Lead Sponsor: AstraZeneca

Brief Summary: SMART Study - A 24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy, Safety and Tolerability of Saxagliptin Compared with Acarbose when in Combination with Metformin in Patients with Type 2 Diabetes Mellitus (T2D) Inadequately Controlled with Metformin Monotherapy

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 689

Inclusion Criteria

Diagnosed with type 2 diabetes mellitus
Men and women (non-pregnant and using a medically approved birth-control method) aged at least 18 years at screening.
T2D patients treated with stable metformin monotherapy for at least 8 weeks prior to screening. Metformin dose should be ≥ 1500 mg/day (or individual maximally tolerated dose), but not more than the maximum dose specified in the label
HbA1c ≥ 7.5% and ≤ 11.0% at screening or within 4 weeks prior to screening (by local laboratory) and HbA1c ≥ 7.0% and ≤ 11.0% at pre-randomization visit (by central laboratory)
FPG ≤ 13.3 mmol/L (≤ 240 mg/dL) at pre-randomization visit (by central laboratory)
Able and willing to provide written informed consent and to comply with the study protocol

Exclusion Criteria

Women who are pregnant, intending to become pregnant during the study period, lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.
Diagnosis or history of:
1. Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome.
2. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.
Previous treatment with any dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past one year.
History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to dipeptidyl peptidase-4 inhibitor (DPP4) or Acarbose.
Treatment with any anti-diabetic medication for more than 7 consecutive days other than metformin in the last 8 weeks prior to screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saxagliptin	Saxagliptin	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.
Acarbose	Acarbose	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.

Primary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in HbA1c at Week 24 (DAO)	From baseline to 24 week	The primary endpoint was analyzed based on Per protocol analysis set as the supportive analysis.

Secondary Outcome Measures

Name	Time	Method
Proportion (%) of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c<7.0%	24 weeks	Secondary Objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c\<7.0%
Change From Baseline in Body Weight	From baseline to 24 week	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24
Change From Baseline in 2H Postprandial Glucose (2HPPG)	From baseline to 24 week	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24
Change From Baseline in HOMA-β	From baseline to 24 week	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function was estimated by the Homeostasis model assessment-β (HOMA-β), which was defined as fasting insulin (mU/mL) x 20 / (fasting glucose (mmol/mL) - 3.5, body weight at week 24
Proportion (%) of Patients With Any GI Adverse Events	24 weeks	Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients with any gastrointestinal adverse events.
Proportion (%) of Patients Achieving HbA1c<7.0% Without GI Adverse Events	Whole study duration	Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients achieving HbA1c\<7.0% without GI adverse events.
Change From Baseline in Fasting Plasma Glucose (FPG)	From baseline to 24 week	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24