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 (SMART)

• ClinicalTrials.gov Identifier: NCT02243176
• Recruitment Status: Completed
• First Posted: September 17, 2014
• Results First Posted: April 14, 2017
• Last Update Posted: April 14, 2017
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

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

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Saxagliptin; Drug: Acarbose	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 689 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2014
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Saxagliptin; The dose of saxaglitpin will be 5mg oral qd.; Other Name: Onglyza
Active Comparator: 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.	Drug: 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.; Other Name: Glucobay

Outcome Measures

Primary Outcome Measures :

1. Absolute Change From Baseline in HbA1c at Week 24 (DAO) [ Time Frame: From baseline to 24 week ]
   Primary Objective: Efficacy of saxagliptin plus metformin on glycemic control compared with acarbose plus metformin in patients with T2D inadequately controlled with metformin. By Measure absolute change from baseline in HbA1c at Week 24
2. Absolute Change From Baseline in HbA1c at Week 24 (DAO) [ Time Frame: From baseline to 24 week ]
   The primary endpoint was analyzed based on Per protocol analysis set as the supportive analysis.

Secondary Outcome Measures :

1. Proportion (%) of Patients With Any GI Adverse Events [ Time Frame: 24 weeks ]
   Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients with any gastrointestinal adverse events.
2. Proportion (%) of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c<7.0% [ Time Frame: 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%
3. Proportion (%) of Patients Achieving HbA1c<7.0% Without GI Adverse Events [ Time Frame: 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.
4. Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: 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
5. Change From Baseline in 2H Postprandial Glucose (2HPPG) [ Time Frame: 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
6. Change From Baseline in HOMA-β [ Time Frame: 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
7. Change From Baseline in Body Weight [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 150 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Diagnosed with type 2 diabetes mellitus
2. Men and women (non-pregnant and using a medically approved birth-control method) aged at least 18 years at screening.
3. 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
4. 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)
5. FPG ≤ 13.3 mmol/L (≤ 240 mg/dL) at pre-randomization visit (by central laboratory)
6. Able and willing to provide written informed consent and to comply with the study protocol

Exclusion Criteria:

1. 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.

2. 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.
3. Previous treatment with any dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past one year.
4. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to dipeptidyl peptidase-4 inhibitor (DPP4) or Acarbose.
5. Treatment with any anti-diabetic medication for more than 7 consecutive days other than metformin in the last 8 weeks prior to screening

Contacts and Locations

Locations

China

Research Site

Shanghai, China

Sponsors and Collaborators

AstraZeneca

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Du J, Liang L, Fang H, Xu F, Li W, Shen L, Wang X, Xu C, Bian F, Mu Y. Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: Results of a Phase IV open-label randomized controlled study (the SMART study). Diabetes Obes Metab. 2017 Nov;19(11):1513-1520. doi: 10.1111/dom.12942. Epub 2017 Jul 6.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02243176
• Other Study ID Numbers: D1680L00018
• First Posted: September 17, 2014
• Results First Posted: April 14, 2017
• Last Update Posted: April 14, 2017
• Last Verified: March 2017

Keywords provided by AstraZeneca:

Saxagliptin; Acarbose; Type 2 Diabetes; Metformin

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Saxagliptin; Acarbose; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Glycoside Hydrolase Inhibitors