CTRI/2020/04/024841 [Registered on: 24/04/2020] Trial Registered Prospectively
Last Modified On:
03/05/2021
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 trial to study the efficacy and safety of fixed dose combination of remogliflozin etabonate and teneligliptin in the treatment of type 2 diabetes mellitus.
Scientific Title of Study
A randomised, double-blind, double-dummy, parallel-group, multicentre, active-controlled study to evaluate efficacy and safety of fixed dose combination of remogliflozin etabonate and teneligliptin in subjects with type-2 diabetes mellitus.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
GPL/CT/2019/007/III, version no. 2.0, dated: 04.02.2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Rahul Kodgule
Designation
GM-Clinical Development Branded Generics
Affiliation
Glenmark Pharmaceuticals Ltd
Address
Glenmark Pharmaceuticals Ltd Glenmark House, B D Sawant Marg Chakala, Andheri(East)District: Mumbai State: Maharashtra
Institutional Human Ethics Committee Hindusthan Hospital
Approved
Life care Hospital Institutional Review Board
Approved
Lifepoint Research Ethics Committee
Approved
Medisys Clinisearch Ethical Review Board
Approved
Medstar Speciality Hospital Ethics Committee
Approved
Nirmal Hospital Ethics Committee
Approved
Shivam Ethics Committee
Approved
Shree Siddhivinayak Hospital Ethics Committee
Approved
Supe Hospital Ethics Committee
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 remogliflozin etabonate 100 mg and Teneligliptin 10 mg (or Matching Placebo) tablet, orally twice daily
Dosage Form: Tablet
Dosage Frequency: Twice daily
Dose: Remogliflozin etabonate 100 mg and Teneligliptin 10 mg
Mode of Administration: Twice daily with food preferably at similar time of the day.
Total Duration of treatment: 16 weeks
Comparator Agent
Teneligliptin 20 mg (or Matching Placebo) tablet
Name of Comparator: Teneligliptin 20 mg (or Matching Placebo)
Dosage Form: Tablet
Dosage Frequency: Once daily
Dose: 20 mg
Mode of Administration: Once daily in the morning with food preferably at similar time of the day.
Total Duration of treatment: 16 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Male and female subjects ≥18 and ≤ 65 years of age, diagnosed with T2DM.
Subjects who have received stable dose of metformin ≥1500 mg/day as monotherapy for at least 10 weeks prior to screening and having inadequate glycemic control at screening defined as HbA1c levels of ≥8% to ≤11%.
Subjects must be willing and able to provide written informed consent.
Willing and able to comply with all aspects of the protocol.
Must be willing to use a highly effective form of contraception (with pearl index < 1%) e.g. double barrier method, for the duration of the study. Methods like periodic abstinence, post ovulation procedures and withdrawal are not considered adequate. Oral contraceptive pills are not allowed due to potential of drug interaction with investigational product. If the subject is a female of childbearing potential, the result of a urine pregnancy test at screening must be negative. Each female will be considered to have childbearing potential unless surgically sterilized by hysterectomy or has been post-menopausal for at least 2 years.
ExclusionCriteria
Details
History of Type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus
History of metabolic acidosis or diabetic ketoacidosis
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, subject will be excluded from the study.
BMI ≥45.0 kg/m2 at screening
Subjects with elevated thyroid stimulating hormone (TSH) level at screening with or without thyroid hormone replacement therapy
Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation or serum creatinine level of > 1.5 mg/dL for male subjects and > 1.4 mg/dL for female subjects, at screening
Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3X ULN or total serum bilirubin >2.0 mg/dL at screening
Congestive heart failure defined as New York Heart Association (NYHA) class III/IV, unstable or acute congestive heart failure.
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.
10. Subjects with uncontrolled hypertension with sitting systolic BP ≥160 mmHg and/or diastolic BP ≥ 100 mmHg at screening. Note: Subjects with SBP ≥ 160mmHg and < 180mmHg or a DBP ≥ 100 mmHg and < 110mmHg will be able to enter the run-in period, provided their hypertension treatment is adjusted as deemed appropriate by the investigator. These subjects cannot be randomized if they meet the blood pressure exclusion criterion of SBP ≥ 160 mmHg or DBP ≥ 100 mmHg measured at randomization visit.
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 subject’s participation in the study. For male subjects with mean QTcB ≥450 msec or female subjects with mean QTcB ≥470 msec, triplicate ECG will be performed. If mean QTcB is ≥450 msec in males or mean QTcB is ≥470 msec in females on triplicate ECG, subject will be excluded from the study.
Patients with history of hereditary QT prolongation syndrome or patients having history of Torsades de pointes.
Patients with history of abdominal surgery or intestinal obstruction.
Patients with history of acute pancreatitis.
History of anaemia or haemoglobinopathy and/or haemoglobin <10 g/dL (<100 g/L) for men; haemoglobin <9 g/dL (<90 g/L) for women at screening
Donation or transfusion of blood, plasma, or platelets within the past 3 months prior to enrolment
History of malignancy within the last 5 years prior to enrolment, excluding non-melanoma skin cancer (e.g. basal or squamous cell skin carcinoma) or treated carcinoma-in-situ of cervix
Intolerance, contraindication or potential allergy/hypersensitivity to any of the ingredients of study medication or any other SGLT2 inhibitors or DPP4 inhibitors
Subjects with symptomatic diarrhoea or any other medical condition which the investigators may judge to be a risk for dehydration and hypovolemia
Subjects with symptomatic urinary tract infection or mycotic genital infection at screening or history of a recent symptomatic urogenital infection within 4 weeks prior to screening
Subject with a positive result for hepatitis B surface antigen or hepatitis C antibody at screening.
Subject is known to be seropositive for human immunodeficiency virus (HIV).
Subject not willing to comply with dietary and exercise plan provided at screening.
Subject with any condition which, in the judgment of the Investigator, may render the subject unable to complete the study or which may pose a significant risk to the subject.
Employee of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
Concurrent enrollment in another interventional clinical study.
Previous participation in another interventional clinical study within 3 months prior to screening or within 5 half-lives of the previous study drug.
Pregnant or breastfeeding women
Subjects with a history of substance abuse or dependence that in the opinion of the Investigator is considered to interfere with the subject’s participation in the study
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Mean change from baseline in HbA1c levels at week 16
16 Weeks
Secondary Outcome
Outcome
TimePoints
Mean change from baseline in HbA1c levels
12 weeks
Mean change from baseline in fasting plasma glucose (FPG) levels at week
16 weeks
Mean change from baseline in post-prandial plasma glucose (PPG)
16 weeks
Mean change from baseline in body weight
16 weeks
Proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c 7%.
16 weeks
Proportion of subjects requiring rescue medication for hyperglycaemia
During study treatment
Target Sample Size
Total Sample Size="308" Sample Size from India="308" Final Enrollment numbers achieved (Total)= "308" Final Enrollment numbers achieved (India)="308"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is a randomized, double blind, double dummy, active controlled, parallel group, multi-center trial comparing the safety and efficacy of FDC of remogliflozin etabonate (100 mg) and teneligliptin (10 mg) given twice daily with that of teneligliptin (20 mg) once daily in 308 patients who have inadequately controlled type 2 diabetes mellitus on stable dose of metformin for at least 10 weeks. The subjects will continue to receive metformin at stable doses of ≥ 1500 mg per day, throughout the study period in an open label manner. The study consists of screening period of up to 3 weeks (including 2 week run in period), 16 weeks study treatment and a safety follow up period of 2 weeks post last dose of the study drug. The primary outcome measures will be mean change from baseline in HbA1c at the end of treatment. Any adverse event (AE), either clinical/laboratory, will be recorded and assessed for severity, seriousness and causality.