CTRI/2022/01/039152 [Registered on: 05/01/2022] Trial Registered Prospectively
Last Modified On:
08/06/2022
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 combination of Dapagliflozin plus Sitagliptin Tablets in patients with diabetes.
Scientific Title of Study
“A Phase III, Prospective, Randomized, Double Blind, Double Dummy, Active-Controlled, Comparative, Parallel Group, Multicentric Clinical Study to Evaluate the Efficacy and Safety of Fixed Dose Combination of Dapagliflozin plus Sitagliptin Tablets in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Monotherapy.â€
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CT/2021/04, Version No.: 00 & Dated Oct 11, 2021
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.,
# H. No.: 4-32-41/13, Plot No.: 38,
Kamala Prasanna Nagar,
Near Ramalayam Temple,
Kukatpally, Hyderabad-500072.
Hyderabad TELANGANA 500072 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.,
# H. No.: 4-32-41/13, Plot No.: 38,
Kamala Prasanna Nagar,
Near Ramalayam Temple,
Kukatpally, Hyderabad-500072.
Institutional Ethics Committee, Osmania Medical College and General Hospital
Submittted/Under Review
Institutional Ethics Committee, Ruby General Hospital
Approved
North East Healthcare Private Limited, W Pratiksha Hospital
Approved
Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital, Kolhapur Institutional Ethics Committee 2 (RCSMGMCIEC2)
Approved
Redkar Hospital Institutional Ethics Committee (RHIEC), Redkar Hospital and Research Centre
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications,
Intervention / Comparator Agent
Type
Name
Details
Intervention
FDC of Dapagliflozin 10 mg plus Sitagliptin 100 mg Tablets & Matching Placebo of Reference Product
Patients will be advised to take one tablet once a day orally, swallowed with water in the morning around same time every day for 16 weeks.
Study drug should be taken along with matching placebo of reference product preferably at the same time.
Comparator Agent
Sitagliptin Tablets 100 mg & Matching Placebo of Test Product
Patients will be advised to take one tablet once a day orally, swallowed with water in the morning around same time every day for 16 weeks.
Study drug should be taken along with matching placebo of test product preferably at the same time.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or Female Patients aged between 18 to 65 years (both inclusive) with diagnosis of Type 2 diabetes mellitus.
2. Patients who are on stable dose of Metformin ≥ 1500 mg/day or maximum tolerated dose of Metformin as monotherapy for at least 3 months prior to screening and having inadequate glycemic control at screening defined as HbA1c levels of ≥ 8.0% to ≤ 11.0%.
3. 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 / baseline visit.
4. Patients with no abnormality on 12-lead ECG at screening / baseline visit.
5. Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
6. Patients willing to comply with 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 a history of bariatric surgery or lap-band procedure within 12 months prior to screening.
4. Patients with Fasting Plasma Glucose (FPG) > 270 mg/dL at screening (If FPG is > 270 mg/dL at screening, FPG will be repeated within 1 week. If repeat FPG is > 270 mg/dL, patient will be excluded from the study).
5. Patients with the Body Mass Index (BMI) ≥ 45.0 kg/m2 at screening.
6. Patients with Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
7. 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.
8. Patients taking loop diuretics within one week prior to screening or planning to take during the study.
9. Patients with a history of congestive heart failure defined as New York Heart Association (NYHA) class III/IV, unstable or acute congestive heart failure.
10. 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.
11. Patients with uncontrolled hypertension with sitting systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg at screening.
12. 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.
13. Patients with history of hereditary QT prolongation syndrome or patients having history of Torsades de pointes.
14. Patients who are accepting treatments of arrhythmias.
15. Patients with a history of anaemia or haemoglobinopathy and/or haemoglobin < 10 g/dL for men; haemoglobin < 9 g/dL for women at screening.
16. Patients with known history of acute pancreatitis.
17. Patients with intolerance, contraindication or potential allergy/hypersensitivity to any of the ingredients of study medication or any other DPP4 inhibitors or SGLT-2 inhibitors.
18. Patients with a history of severe hepatobiliary disease or hepatotoxicity with any medication.
19. Patients with known case of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.
20. Patients with a history of urinary tract infections including urosepsis and pyelonephritis.
21. Patients with a history of genital mycotic infections.
22. Patients with a history or currently suffering with bullous pemphigoid requiring hospitalization.
23. Patients with known immunocompromised status.
24. Patients receiving treatment with systemic corticosteroids.
25. Pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.
26. 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).
27. Patients with history of any malignancy.
28. Patients with known case of infection with hepatitis B, hepatitis C or HIV.
29. Patients with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to screening.
30. 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.
31. Patients with concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
32. Patients currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
33. Suspected inability or unwillingness to comply with the study procedures.
34. 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
Mean change in glycosylated haemoglobin (HbA1c) from baseline to end of the study visit (week 16).
At Screening/baseline visit,
Visit 5 [Week 12 /Day 84 (±2)] and
Visit 6 [Week 16 /Day 112 (±2)].
Secondary Outcome
Outcome
TimePoints
Mean change in fasting plasma glucose (FPG) from baseline to end of the study visit (week 16).
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, prospective, randomized, double blind, double dummy, active-controlled,
comparative, parallel group, multicentric clinical study to evaluate the efficacy
and safety of fixed dose combination of Dapagliflozin plus Sitagliptin Tablets
in patients with type 2 diabetes mellitus inadequately controlled on Metformin monotherapy.
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), who are on the treatment with Metformin Tablets ≥1500 mg/day or maximum tolerated dose of Metformin for at least 3
months weeks prior to screening and having inadequate glycaemic control
[Glycosylated Haemoglobin (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(±2), week 6/day 42(±2), week
12/day 84(±2) and week 16/day 112(±2) (Final Visit) of treatment to assess efficacy,
safety and tolerability.
Patients
will be assigned to either of the two arms i.e., Arm A or Arm B consisting of FDC
of Dapagliflozin 10 mg + Sitagliptin 100 mg Tablets or Sitagliptin Tablets 100
mg. Patients will be given the study medication once a day for 16 weeks.
Metformin Tablets ≥ 1500
mg/day will be continued throughout the study period (16 weeks).