CTRI/2023/01/049222 [Registered on: 25/01/2023] Trial Registered Prospectively
Last Modified On:
12/08/2024
Post Graduate Thesis
Yes
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Clinical Trial on Type 2 diabetes Mellitus (T2DM)
Scientific Title of Study
A phase 3, multicenter, randomized, double-blind, double-dummy, parallel-group study to compare the efficacy and safety of fixed dose combination tablets of Dapagliflozin 10 mg and Linagliptin 5 mg versus Trajenta 5 mg (Linagliptin 5 mg) in patients with Type 2 Diabetes Mellitus (T2DM) inadequately controlled on Metformin
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
LCT-02/21, version no. 1.0 , date 23-Sep-22
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Mukund Zarapkar
Designation
Vice President- Clinical
Affiliation
LifeSan Clinical Research, division of Centaur Pharmaceuticals Pvt.Ltd.
Address
5th and 6th floor, B-wing, Centaur House, Near Hotel Grand Hyatt,Santacruz East, Mumbai 400055, Maharashtra, India.
Mumbai (Suburban) MAHARASHTRA 400055 India
Phone
91-22-66499154
Fax
91-22-66499108
Email
drzarapkar@lifesan.in
Details of Contact Person Scientific Query
Name
Dr Mukund Zarapkar
Designation
Vice President- Clinical
Affiliation
LifeSan Clinical Research, division of Centaur Pharmaceuticals Pvt.Ltd.
Address
5th and 6th floor, B-wing, Centaur House, Near Hotel Grand Hyatt,Santacruz East, Mumbai 400055, Maharashtra, India.
MAHARASHTRA 400055 India
Phone
91-22-66499154
Fax
91-22-66499108
Email
drzarapkar@lifesan.in
Details of Contact Person Public Query
Name
Mr Rajendra M Sawant
Designation
Executive-Clinical Trial
Affiliation
LifeSan Clinical Research, division of Centaur Pharmaceuticals Pvt.Ltd.
Address
5th and 6th floor, B-wing, Centaur House, Near Hotel Grand Hyatt,Santacruz East, Mumbai 400055, Maharashtra, India.
Mumbai (Suburban) MAHARASHTRA 400055 India
Phone
91-22-66499243
Fax
91-22-66499108
Email
rajendras@lifesan.in
Source of Monetary or Material Support
Sponsor of the study:Theon Pharma, Nalgarh, Himachal Pradesh
Contact: Tel. No.: 01725011077
Primary Sponsor
Name
Theon Pharma
Address
Village Saini Majra, Tehsil, Nalagarh, Majra, Himachal Pradesh 174101
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
CRO LifeSan Clinical Research division of Centaur Pharmaceuticals Pvt Ltd
5th and 6th floor, B-wing, Centaur House,near grand Hyatt hotel, Vakola, SantacruzEast, Mumbai-400055 Maharashtra.
Good Society Ethical Research for Dr. Shivani Bansal
Approved
Government medical college Institutional Ethics Committee, Jalgaon (GMCIEC) for Dr. Aastha Ganeriwal
Approved
Hycare Super Speciality Hospital Ethics committee for Dr. K. Padmanabhan
Approved
Independent Ethics Committee Clinisyd Research Global Solutions Private Limited for Dr. Madhusudan
Approved
Institutional Ethics Committee Charak Hospital and Research Centre for Dr. Hemali Jha
Approved
Institutional Ethics Committee Life Line Diagnostic Center cum Nursing Home for Dr. Gouranga Sarkar
Approved
Institutional Ethics Committee S. N. Medical college for Dr. Prabhat
Approved
Institutional Ethics Committee, JMF’s ACPM Medical College for Dr. Emaran Teli
Approved
Lakeview Ethics Committee for Dr. Girish Sonwalkar
Approved
Mandya Institute of Medical Sciences Institutional Ethics committee for Dr Anikethana G V
Approved
Royal Pune Independent Ethics Committee for Dr. Suhas Erande
Approved
Suyash Hospital Institutional Ethics Committee for Dr. Rudra Prasad Sahu
Approved
Vighnaharta Multi Speciality Hospital Institutional Ethics Committee for Dr. Imran Pinjari
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
Fixed dose combination tablets of Dapagliflozin 10 mg and Linagliptin 5 mg
one tablet daily after food for 16 weeks.
Comparator Agent
Linagliptin tablets 5 mg
one tablet daily after food for 16 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Age: 18 to 65 years [Both inclusive]
2. Gender: male or Female patients
3. All the patients willing to voluntarily participate in the clinical trial and signing on duly filled informed consent form
4. All patients with type 2 diabetes mellitus
5. Patients who have inadequate glycemic control to metformin monotherapy ≥1000 mg/day for at least 6 weeks.
6. Patients with HbA1c value between 7.5 % and 10.5 %
ExclusionCriteria
Details
1. Known hypersensitivity to linagliptin or dapagliflozin or to any of the excipients of the investigational products.
2. Patients with BMI ≥ 40 kg/m2.
3. Laboratory findings measured at screening:
a. eGFR < 60 mL/min/1.73 m2 by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation
b. Hemoglobin <10 g/dl
c. Neutrophils < 2000/mm3
d. Platelets <100000/mm3
e. Total bilirubin > 1.5 times more than upper normal limit [ULN]
f. ALT/ AST > 2.5 times more than ULN
g. Serum amylase and/or lipase > 3 times more than ULN
h. Any other screening laboratory value that is clinically significant in the Investigator’s opinion precluding patient’s participation in the study
4. Patients with Type 1 Diabetes Mellitus.
5. Patients with fasting plasma glucose of > 270 mg/dL
6. Patients with hypothyroidism or hyperthyroidism
7. Patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease
8. Patients who are on dialysis
9. Patients with any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis etc.)
10. Patients with acute conditions with the potential to alter renal function such as dehydration, severe infection, shock, or intravascular administration of iodinated contrast agents
11. Patients with history of pancreatitis
12. Patients with pancreatic insulin deficiency from any cause, caloric restriction, or alcohol abuse
13. Patients with genital mycotic infections or urinary tract infections
14. Patients with hypotension requiring intervention
15. Patients who have used corticosteroids for one week or more within 3 months prior to screening
16. Patients with a prior history of heart failure
17. Positive testing for HIV, hepatitis B (hepatitis B virus surface antigen [HBsAg]) or hepatitis C (hepatitis C virus antibody [HCV Ab]) virology
18. Patients who had suffered from COVID-19 within 8 weeks prior to study drug administration or patients with suspected signs and symptoms of COVID-19/ confirmed novel coronavirus infection (COVID-19)
19. Women of child bearing potential not practicing any acceptable methods of contraception during study. For this study, acceptable and effective methods of contraception for females include at least one of the following:
a. Intrauterine device placed at least 6 months prior to the first study dose and agree to follow throughout the study
b. Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide plus a male or female condom)
c. Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner)
d. Females who are surgically sterile
e. Females who are post-menopausal for at least one year
f. Pregnant or lactating women
20. Patients with clinically significant medical history, vital signs, physical examination requiring exclusion of the patient as deemed by the investigator or designee.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
The primary objective of this study is to evaluate the efficacy of fixed-dose combination dapagliflozin 10 mg and linagliptin 5 mg vis-Ã -vis active control medication, i.e. linagliptin 5 mg on the basis of primary and secondary endpoints.
Change in HbA1c levels from baseline to Week 16.
Change in body weight from baseline to Week 16.
Change in fasting plasma glucose (FPG) from baseline to Week 16.
Change in post-prandial blood glucose (PPG) levels from baseline to Week 16.
Visit 0 is the baseline visit for screening, followed by:
Visit 1: Week 4
Visit 2: Week 8
Visit 3: Week 12
Visit 4: Week 16
Secondary Outcome
Outcome
TimePoints
The secondary objective of this study is to evaluate the safety of fixed-dose combination dapagliflozin 10 mg and linagliptin 5 mg vis-Ã -vis active control medication, i.e. linagliptin 5 mg by comparing treatment-emergent adverse events or serious adverse events as well as comparison of baseline and end-of-study assessment by virtue of physical examination and clinical laboratory investigations.
Visit 0 is the baseline visit for screening, followed by:
Visit 1: Week 4
Visit 2: Week 8
Visit 3: Week 12
Visit 4: Week 16
Target Sample Size
Total Sample Size="232" Sample Size from India="232" Final Enrollment numbers achieved (Total)= "268" Final Enrollment numbers achieved (India)="268"
Study Title is A phase 3, multicenter, randomized, double-blind, double-dummy, parallel-group study to compare the efficacy and safety of fixed dose combination tablets of Dapagliflozin 10 mg and Linagliptin 5 mg versus Trajenta 5 mg (Linagliptin 5 mg) in patients with Type 2 Diabetes Mellitus (T2DM) inadequately controlled on Metformin.
It will be a phase III, multicenter, randomized, double blind, double-dummy, parallel-group, active-controlled study clinical trial to test the safety and efficacy of fixed dose combination tablets of Dapagliflozin 10 mg and Linagliptin 5 mg in T2DM.
The study will be conducted in the hospital setup, with number of patients not less than 232, i.e. at least 116 in the Test arm and 116 in the Reference arm for a period of 16 weeks. The patients could be treated on outpatient [OP] basis or may be in need of in-patient admission [IP].
Total maximum duration of the clinical trial will be of 16 weeks for any patient who is enrolled. The trial could end prior to week 16 for an individual patient, in case patient voluntarily drops out.
In case of adverse event/ serious adverse event irrespective of whether it is due to study procedure or study drug and anytime within 16 weeks from the enrolment, the investigator could withdraw the patient and switch to appropriate medical management of the said AE/ SAE.
On day 0, patient/ patient’s legally acceptable representative [LAR] will be informed by the delegated staff of clinical trial site under supervision of investigator about the objectives and procedure and duration of this trial along with entire information about the study drugs along with possible adverse events as well as responsibilities of the patient throughout the trial. Sufficient time would be given to the patient for understanding the procedures of the trial and following his/ her voluntary informed consent, the Subject would be screened for participation in the trial.
There will be a screening period of 4 weeks including 2 weeks of run-in period, i.e. screening would be conducted within 4 weeks prior to actual enrolment in the trial.
During the run-in period, the patient would be advised to continue the anti-diabetic diet, which is part of standard care.
After completion of run-in period, the patient would be randomized to Test or Active-control treatment for the treatment period of 16 weeks.
Since the study is blinded, the patient, investigator or any study staff would not know the nature of the treatment [Test or Active-control] until end of the study or until after the code is broken in case of AE or SAE.
End-of-study [EOS] assessment would be performed at Week 16 or at the time of early discontinuation or withdrawal of the patient