Clinical trial NCT02280486: Efficacy and Safety of Saxagliptin VS. Glimepiride in Chinese T2DM Patients Controlled Inadequately With Metformin
Official title: Efficacy and Safety of Saxagliptin and Glimepiride in Chinese Patients With Type 2 Diabetes Controlled Inadequately With Metformin Monotherapy (SPECIFY Study) : a 48-week, Multi-center, Randomized, Open-label Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: saxagliptin
glimepiride
metformin monotherapy
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital with Nanjing Medical University
name: Zhongda Hospital
name: Nanjing PLA General Hospital
name: Changzhou No.2 People's Hospital
name: The First Affiliated Hospital of Soochow University
name: Wuxi People's Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: Huai'an First People's Hospital
First posted: 2014-10-31
Enrollment: 388
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-centre, open-label, randomized, parallel trial to investigate the efficacy and safety profile of saxagliptin and glimepiride treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy.

Detailed description: This is a multi-centre, open-label, randomized, parallel trial to investigate the efficacy and safety profile of saxagliptin and glimepiride treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy.

Screening will be made to select eligible participants before intervention. The trial will include 1-week run-in period of stable doses of metformin (1500mg) and 48-week treatment period. After the run-in period, patients were randomly assigned to one of two groups for antihyperglycaemic therapies for a total of 48-weeks: saxagliptin and glimepiride. The treatment of saxagliptin will be initiated and maintained at 5mg every morning until the completion of the study. Glimepiride will be initially treated with 1 mg every morning, and further titrated up at 4-week intervals until to reach the target fasting blood glucose (FPG).As to Glimepiride groups, if the fasting blood glucose dose not achieved the target after the maximal doses, maintain the maximal doses(6mg per day) until the completion of the study.Meanwhile, participants in both groups should take metformin 1500mg per day throughout the whole 48 weeks. At the end of the study, data will be collected and analyzed.

Eligibility criteria: Inclusion Criteria:

* For inclusion in the study subjects should fulfill the following criteria:
* Provision of informed consent prior to any study specific procedures
* Type2 diabetic patients had been on stable, maximum tolerated doses of metformin (≧1500mg/d, ≧8 weeks)
* Male or female age ≧ 25 years and ≦75 years old
* HbA1c ≧7.0 and ≦9.5%
* BMI ≧ 20 and ≦ 30 kg/m2

Exclusion Criteria:

* Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
* Known or suspected allergy to trial products or related products.
* Impaired renal function defined as serum-creatinine ≥ 1.5 mg/dL (≥ 132.6 μmol/l).
* Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, shock.
* Hepatic insufficiency, acute alcohol intoxication, alcoholism.
* Subjects has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association-class Ⅲ and Ⅳ).
* Proliferative retinopathy or muscular oedema requiring acute treatment.
* Lactation.
* Pregnant or positive pregnancy test at screening, nursing mother, or unwillingness to use adequate contraception (adequate contraceptive measures are sterilization, intrauterine device, oral contraceptives or barrier methods).
* Treatment with systemic corticosteroids within the past two months prior to screening.
* Tested positive for glutamic acid decarboxylase antibody.
* Receipt of any investigational drug within 1 month prior to this trial.

Primary outcomes:
measure: Proportion of subjects achieving glycemic response defined as Glycosylated hemoglobin (HbA1c) < 7.0%
timeFrame: Change from Baseline after 48 weeks treatment
Secondary outcomes:
measure: The change in blood glucose fluctuations of subjects.
timeFrame: Change from Baseline after 48 weeks treatment
measure: The improvement in beta-cell function of subjects
timeFrame: Change from Baseline after 48 weeks treatment
measure: The change in body composition of subjects.
timeFrame: Change from Baseline after 48 weeks treatment
measure: Safety and tolerability of saxagliptin vs. glimepiride measured by adverse events, serious adverse events (SAEs); laboratory assessments (biochemistry, lipids, blood and urine routine tests
timeFrame: Change from Baseline after 48 weeks treatment
Other outcomes:
Locations:
city: Nanjing
country: China
facility: at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
state: Jiangsu
Study officials:
affiliation: the Affiliated Drum Tower Hospital of Nanjing University
name: Dalong Zhu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gu T, Ma J, Zhang Q, Zhu L, Zhang H, Xu L, Cheng J, Shi B, Li D, Shao J, Sun Z, Zhong S, Bi Y, Zhu D. Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centre, randomized, controlled trial. Diabetes Obes Metab. 2019 Apr;21(4):939-948. doi: 10.1111/dom.13605. Epub 2019 Jan 4.