A Phase III, Randomized, Double Blind, Active-Controlled, Prospective, Comparative, Parallel Group, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Dapagliflozin plus Telmisartan Tablets Versus Concomitant Administration of Dapagliflozin Tablets and Telmisartan Tablets in Patients with Chronic Kidney Disease.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 273
- 试验地点
- 16
- 主要终点
- Percentage change in urine albumin-to-creatinine ratio (UACR) from baseline to end of the study visit (Week 12).
研究概览
简要总结
This trial is a phase III, randomized, double blind, active-controlled, prospective, comparative, parallel group, multicentric clinical study to evaluate the efficacy, safety and tolerability of fixed dose combination of Dapagliflozin plus Telmisartan Tablets versus concomitant administration of Dapagliflozin Tablets and Telmisartan Tablets in patients with chronic kidney disease.
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 18 to 65 years (both inclusive) who are fulfilling all the inclusion and none of the exclusion criteria will be enrolled into 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(±2), week 4/day 28(±2), week 8/day 56(±2) and week 12/day 84(±2) (final visit) of treatment to assess efficacy, safety and tolerability.
Patients will be assigned to either of the three arms i.e., Arm A or Arm B or Arm C consisting of FDC of Dapagliflozin 10 mg + Telmisartan 40 mg Tablets (Arm A) or FDC of Dapagliflozin 10 mg + Telmisartan 80 mg Tablets (Arm B) or Concomitant Administration of Dapagliflozin Tablets 10 mg and Telmisartan Tablets 80 mg (Arm C).
Test Product 1 (Arm A):
FDC of Dapagliflozin 10 mg + Telmisartan 40 mg Tablets & Placebo Tablets
Patients will be advised to take one tablet of test product and one tablet of placebo once a day orally, swallowed with water in the morning around same time every day for 12 weeks.
Test Product 2 (Arm B):
FDC of Dapagliflozin 10 mg + Telmisartan 80 mg Tablets & Placebo Tablets
Patients will be advised to take one tablet of test product and one tablet of placebo once a day orally, swallowed with water in the morning around same time every day for 12 weeks.
Reference Product (Arm C):
Concomitant Administration of Dapagliflozin Tablets 10 mg and Telmisartan Tablets 80 mg
Patients will be advised to take one tablet of Dapagliflozin Tablets 10 mg and one tablet of Telmisartan Tablets 80 mg once a day orally, swallowed with water in the morning around same time every day for 12 weeks.
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 18 to 65 years (both inclusive).
- •Patients with estimated glomerular filtration rate (eGFR) more than 30 mL per min per 1.73 m2 and less than 90 mL min per 1.73 m2 (using the CKD-EPI formula) for more than 3 months and at screening visit.
- •Patients with evidence of increased albuminuria for 3 months or more before screening visit and urine albuminâ€toâ€creatinine ratio (UACR) more than or equal to 100 mg per g and less than or equal to 3500 mg per g at screening visit.
- •Patients with serum potassium levels less than or equal to 5 mmol per L at screening visit.
- •Patients who were on the highest dose of Telmisartan Tablets 80 mg for more than 4 weeks.
- •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.
- •Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
- •Patients willing to comply with all 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 autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis.
- •Patients who are receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment.
- •Patients with a history of organ transplantation.
- •Patients with MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to screening.
- •Patients with significant cardiovascular disease such as myocardial infarction, angina pectoris, percutanous transluminal coronary angioplasty, coronary artery bypass grafting, stroke, heart failure (NYHA I-IV) less than 6 months before screening.
- •Patients with Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair or replacement within 12 weeks prior to randomization or planned to undergo any of these operations after randomization.
- •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 type 2 diabetes mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value more than or equal to 8%.
- •Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the UNL and or Total bilirubin more than 2X the UNL) at screening.
- •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.
- •Patients with a history of autonomic dysfunction (e.g., history of fainting or clinically significant orthostatic hypotension).
- •Patients with a history of amputations.
- •Patients with eGFR change more than 30% in the last six months before screening.
- •Patients suffering from severe urinary tract infections (e.g., urosepsis, pyelonephritis), necrotizing fasciitis of the Perineum (Fournier’s Gangrene), intravascular volume contraction and or female genital mycotic infections prior to 6 months from screening.
- •Patients with history of inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption.
- •Patients with 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 with a history of anaemia or haemoglobinopathy and or haemoglobin less than 10 g per dL for men; haemoglobin less than 9 g per dL for women at screening.
- •Patients with intolerance, contraindication or potential allergy or hypersensitivity to any of the ingredients of study medication.
- •Patients with known immunocompromised status.
- •Patients with a history of any malignancy.
- •Patients with known case of infection with hepatitis B, hepatitis C or HIV.
- •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.
- •Patients with 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
Percentage change in urine albumin-to-creatinine ratio (UACR) from baseline to end of the study visit (Week 12).
时间窗: Visit 1 - Screening or Baseline visit, | Visit 3 - Follow up visit or Week 2 (Day 14±2), | Visit 4 - Follow up visit or Week 4 (Day 28±2), | Visit 5 - Follow up visit or Week 8 (Day 56±2) and | Visit 6 - End of the study visit or Week 12 (Day 84±2).
次要结局
- Mean change in estimated glomerular filtration rate (eGFR) from baseline to end of the study visit (Week 12).(Visit 1 - Screening or Baseline visit,)
- Mean change in urine albumin-to-creatinine ratio (UACR) from baseline to end of the study visit (Week 12).(Visit 1 - Screening or Baseline visit,)
- Mean change in serum potassium levels from baseline to end of the study visit (Week 12).(Visit 1 - Screening or Baseline visit,)
- Mean change in systolic blood pressure from baseline to end of the study visit (Week 12).(Visit 1 - Screening or Baseline visit,)
- Percentage change in estimated glomerular filtration rate (eGFR) from baseline to end of the study visit (Week 12).(Visit 1 - Screening or Baseline visit,)
- Adverse events or serious adverse events reported during the study.
- Changes in clinical laboratory parameters from baseline to end of the study visit (Week 12).(Visit 1 - Screening or Baseline visit and)
研究者
Dr Rajasekhara Reddy Tamma
Clinwave Research Pvt. Ltd.