A Multicentric, Prospective, Active Controlled, Parallel Group, Randomized, Double Blind, Comparative, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Linagliptin, Glimepiride and Metformin Hydrochloride Extended Release Tablets Versus Fixed Dose Combination of Glimepiride and Metformin Hydrochloride Sustained Release Tablets in Patients with Type 2 Diabetes Mellitus.
试验速览
- 阶段
- 3 期
- 状态
- Not Applicable
- 入组人数
- 288
- 试验地点
- 8
- 主要终点
- Mean change in glycosylated haemoglobin (HbA1c) from baseline to end of the study visit (week 16).
研究概览
简要总结
This trial is a multicentric, prospective, active controlled, parallel group, randomized, double blind, comparative, phase III clinical study to evaluate the efficacy, safety and tolerability of fixed dose combination of Linagliptin, Glimepiride and Metformin Hydrochloride Extended Release Tablets versus fixed dose combination of Glimepiride and Metformin Hydrochloride Sustained Release Tablets in patients with type 2 diabetes mellitus.
Patients who are willing and able to participate in the study will sign and date the Informed Consent Form on the day of screening / baseline visit (Visit 1). During this screening period, patients who are willing to give consent will be evaluated for all the eligibility criteria. Eligible patients (male or female) aged between 18 to 65 years (both inclusive), along with diet and exercise control, additionally on stable total daily dose of Glimepiride 4 mg and Metformin Hydrochloride ≥ 1500 mg for at least 10 weeks prior to screening and glycosylated hemoglobin (HbA1c) levels of ≥ 8.0% to ≤ 11.0% will be considered for the study.
After confirming the inclusion/exclusion criteria the subject will be randomized and provided with study medication at randomization visit. Subjects will be provided with patient diary at randomization visit, which need to be brought along with in each subsequent visit till the last visit. Follow up visits will be done on week 2/day 14(±3), week 6/day 42(±3), week 12/day 84(±3) and week 16/day 112(±3) (Final Visit) of treatment to assess efficacy and safety.
Patients will be assigned to either of the three arms i.e., Arm A or Arm B or Arm C consisting of FDC of Linagliptin 2.5 mg + Glimepiride 1 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets or FDC of Linagliptin 2.5 mg + Glimepiride 2 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets or FDC of Glimepiride 2 mg + Metformin Hydrochloride Sustained Release 1000 mg Tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients aged between 18 to 65 years (both inclusive) with diagnosis of type 2 diabetes mellitus.
- •Patients, along with diet and exercise control, additionally on stable total daily dose of Glimepiride 4 mg and Metformin Hydrochloride ≥ 1500 mg for at least 10 weeks prior to screening.
- •Patients with glycosylated hemoglobin (HbA1c) levels of ≥ 8.0% to ≤ 11.0%.
- •Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study.
- •WOCBP must have a negative urine pregnancy test at screening or baseline visit.
- •Patients with no abnormality on 12-lead ECG at screening or baseline visit.
- •Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
- •Patients willing to comply with the protocol requirements.
排除标准
- •Patients with a history of type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus.
- •Patients with a history of metabolic acidosis or diabetic ketoacidosis.
- •Patients with Fasting Plasma Glucose (FPG) more than or equal to 270 mg by dL at screening.
- •Patients with the Body Mass Index (BMI) more than 45.0 kg by m2 at screening.
- •Patients with Estimated glomerular filtration rate (eGFR) less than 60 mL by min by 1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
- •Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the ULN and or Total bilirubin more than 1.5X the ULN) at screening.
- •Patients with a history of congestive heart failure defined as New York Heart Association (NYHA) class III or IV, unstable or acute congestive heart failure.
- •Patients with significant cardiovascular history defined as: myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization (coronary angioplasty or bypass grafts), or cerebrovascular accident.
- •Patients with history of sustained and clinically relevant ventricular arrhythmia.
- •Patients with history or currently suffering with bullous pemphigoid requiring hospitalization and taking DPP-4 inhibitors.
- •Patients with history of inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption.
- •Patients with any condition (e.g., infection, trauma and surgery) which require insulin therapy at the time of screening or during the study period.
- •Patients with uncontrolled hypertension with sitting systolic BP more than or equal to 160 mmHg and or diastolic BP more than or equal to 100 mmHg at screening.
- •Any abnormality on 12-lead ECG at screening that in the opinion of the investigator is clinically significant and is judged as potential risk for patient’s participation in the study.
- •Patients who are accepting treatments of arrhythmias.
- •Patients with a history of anaemia or haemoglobinopathy and or haemoglobin less than 10 g by dL for men; haemoglobin less than 9 g by dL for women at screening.
- •Patients with intolerance, contraindication or potential allergy or hypersensitivity to DPP4 inhibitors.
- •Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
- •Female patients who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (like hormonal, barrier methods or intrauterine device).
- •Patients with history of any malignancy.
- •Patients with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to screening.
- •Patients with a history of substance abuse or dependence that in the opinion of the Investigator is considered to interfere with the patient’s participation in the study.
- •Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
- •Patients currently taking any of the prohibited medications(s) and inability or unwillingness to discontinue them for the entire study period.
- •Suspected inability or unwillingness to comply with the study procedures.
- •Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient.
结局指标
主要结局
Mean change in glycosylated haemoglobin (HbA1c) from baseline to end of the study visit (week 16).
时间窗: At Screening or baseline visit (Visit 1), | Visit 5 [Week 12 or Day 84(±3)] and | Visit 6 [Week 16 or Day 112(±3)].
次要结局
- Mean change in fasting plasma glucose (FPG) from baseline to end of the study visit (week 16).(At Screening or baseline visit (Visit 1),)
- Mean change in 2-hr post prandial plasma glucose (2-hr PPG) from baseline to end of the study visit (week 16).(At Screening or baseline visit (Visit 1),)
- Proportion of patients achieving a therapeutic glycemic response, defined as HbA1c less than 7% at the end of the study visit (week 16).(At Visit 6 [Week 16 or Day 112(±3)].)
- Number of patients requiring hypoglycemia management during the study.(Throughout the study.)
- Number of patients requiring rescue medications during the study.(Throughout the study.)
- Mean change in body weight from baseline to end of the study visit (week 16).(At Screening or baseline visit (Visit 1),)
- Hypoglycemic episodes during the study.(Throughout the study.)
- Adverse events and or serious adverse events reported during the study(Throughout the study.)
- Changes in clinical laboratory parameters from baseline to end of the study visit (week 16).(At Screening or baseline visit (Visit 1) and)
研究者
Dr Aditya Kaushik
Synokem Pharmaceuticals Ltd.