CTRI/2024/01/061927 [Registered on: 29/01/2024] Trial Registered Prospectively
Last Modified On:
10/09/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to assess the efficacy and safety of Dapagliflozin plus Telmisartan Tablets in kidney patients.
Scientific Title of Study
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.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CT/2023/67, Version No.: 00 and Dated Oct 18, 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
Clinwave Research Pvt. Ltd.,
LIG: B/466, H. No.: 1-16-10/466, Dr. A.S. Rao Nagar, Kapra, Medchal-Malkajgiri (Dist.).
Hyderabad TELANGANA 500062 India
Phone
7989233379
Fax
Email
dr.sekhar@clinwave.co.in
Details of Contact Person Scientific Query
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
Clinwave Research Pvt. Ltd.,
LIG: B/466, H. No.: 1-16-10/466, Dr. A.S. Rao Nagar, Kapra, Medchal-Malkajgiri (Dist.).
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.
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.
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.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients aged 18 to 65 years (both inclusive).
2. 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.
3. 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.
4. Patients with serum potassium levels less than or equal to 5 mmol per L at screening visit.
5. Patients who were on the highest dose of Telmisartan Tablets 80 mg for more than 4 weeks.
6. 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.
7. Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to screening.
8. Patients willing to comply with all the protocol requirements.
ExclusionCriteria
Details
1. Patients with a history of Type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus.
2. Patients with a history of metabolic acidosis or diabetic ketoacidosis.
3. Patients with autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis.
4. Patients who are receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment.
5. Patients with a history of organ transplantation.
6. Patients with MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to screening.
7. 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.
8. 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.
9. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
10. 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).
11. 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%.
12. 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.
13. 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.
14. Patients with a history of autonomic dysfunction (e.g., history of fainting or clinically significant orthostatic hypotension).
15. Patients with a history of amputations.
16. Patients with eGFR change more than 30% in the last six months before screening.
17. 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.
18. Patients with history of inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption.
19. 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.
20. 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.
21. Patients with intolerance, contraindication or potential allergy or hypersensitivity to any of the ingredients of study medication.
22. Patients with known immunocompromised status.
23. Patients with a history of any malignancy.
24. Patients with known case of infection with hepatitis B, hepatitis C or HIV.
25. Patients with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to screening.
26. 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.
27. Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
28. Patients currently taking any of the prohibited medications(s) and inability or unwillingness to discontinue them for the entire study period.
29. Patients with suspected inability or unwillingness to comply with the study procedures.
30. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Percentage change in urine albumin-to-creatinine ratio (UACR) from baseline to end of the study visit (Week 12).
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).
Secondary Outcome
Outcome
TimePoints
Mean change in estimated glomerular filtration rate (eGFR) from baseline to end of the study visit (Week 12).
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).
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,
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).
Mean change in serum potassium levels from baseline to end of the study visit (Week 12).
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).
Mean change in systolic blood pressure from baseline to end of the study visit (Week 12).
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).
Percentage change in estimated glomerular filtration rate (eGFR) from baseline to end of the study visit (Week 12).
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).
Adverse events 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 12).
Visit 1 - Screening or Baseline visit and
Visit 6 - End of the study visit or Week 12 (Day 84±2).
Target Sample Size
Total Sample Size="273" Sample Size from India="273" Final Enrollment numbers achieved (Total)= "276" Final Enrollment numbers achieved (India)="276"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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).
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.
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.