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CTRI Number  CTRI/2024/01/062128 [Registered on: 31/01/2024] Trial Registered Prospectively
Last Modified On: 02/12/2025
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 Linagliptin, Glimepiride and Metformin Tablets in diabetic patients. 
Scientific Title of Study   A Multicentric, Prospective, Active Controlled, Parallel Group, Randomized, Double Blind, Comparative, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Linagliptin, Glimepiride and Metformin Hydrochloride Extended Release Tablets Versus Fixed Dose Combination of Glimepiride and Metformin Hydrochloride Sustained Release Tablets in Patients with Type 2 Diabetes Mellitus. 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
CT/2023/20, Version No.: 01 and Dated May 12, 2023  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Aditya Kaushik 
Designation  President - Drug Regulatory Affairs 
Affiliation  Synokem Pharmaceuticals Ltd. 
Address  Synokem Pharmaceuticals Ltd., 14/486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi.

New Delhi
DELHI
110087
India 
Phone  9818637035  
Fax    
Email  aditya.kaushik@synokempharma.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Aditya Kaushik 
Designation  President - Drug Regulatory Affairs 
Affiliation  Synokem Pharmaceuticals Ltd. 
Address  Synokem Pharmaceuticals Ltd., 14/486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi.


DELHI
110087
India 
Phone  9818637035  
Fax    
Email  aditya.kaushik@synokempharma.com  
 
Details of Contact Person
Public Query  
Name  Dr Aditya Kaushik 
Designation  President - Drug Regulatory Affairs 
Affiliation  Synokem Pharmaceuticals Ltd. 
Address  Synokem Pharmaceuticals Ltd., 14/486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi.


DELHI
110087
India 
Phone  9818637035  
Fax    
Email  aditya.kaushik@synokempharma.com  
 
Source of Monetary or Material Support  
Synokem Pharmaceuticals Ltd. 
 
Primary Sponsor  
Name  Synokem Pharmaceuticals Ltd 
Address  14 by 486, Sunder Vihar, Outer Ring Road, Paschim Vihar, New Delhi-110087, India. 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 8  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Arindam Naskar  Calcutta School of Tropical Medicine  Department of Endocrinology, Government of West Bengal, 108, Chittranjan Avenue, Calcutta-700073.
Kolkata
WEST BENGAL 		 9874749626

dr.arindam83@gmail.com 
Dr Arindam Ray  College of Medicine & Sagore Dutta Hospital  Department of Medicine, 578, B.T Road, Kamarhati, Kolkata-700058.
Kolkata
WEST BENGAL 		 9477058636

rayarindam09@gmail.com 
Dr Jilla Naganna  Gandhi Medical College and Hospital  In Patient Block, 3rd Floor, Department of General Medicine, Musheerabad, Secunderabad-500003.
Hyderabad
TELANGANA 		 9666345120

nagan99@gmail.com 
Dr Sanjiv Maheshwari  Jawahar Lal Nehru (J.L.N) Medical College  Department of Medicine, Kala Bagh, Ajmer-305001.
Ajmer
RAJASTHAN 		 9460479888

doctor.sanjiv@gmail.com 
Dr Prabhat Kumar Sharma  Maharaja Agrasen Superspeciality Hospital  Room No. 109, Basement, Central Spine, Agrasen Aspatal Marg, Sector 7, Vidyadhar Nagar, Jaipur-302039.
Jaipur
RAJASTHAN 		 9983995050

pksharma.clinical@gmail.com 
Dr Raja Bhattacharya  Medical College and Hospital, Kolkata  Department of Medicine, MCH Building, 4th Floor, 88 College Street, Kolkata-700073.
Kolkata
WEST BENGAL 		 9477305539

rbrbhattacharya@gmail.com 
Dr Vijaykumar Shivajirao Patil  Prakash Institute of Medical Sciences & Research (PIMS&R)  Research Room, Urun-Islampur, Islampur-Sangali Road, Islampur, Tal-Walwa, Dist-Sangali-415409.
Sangli
MAHARASHTRA 		 9371877555

prakashmc.research@gmail.com 
Dr Vijaykumar Bhagwan Barge  Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and CPR General Hospital  Department of Medicine, Dasara Chowk, Town Hall, Bhausingji Road, Kolhapur-416002.
Kolhapur
MAHARASHTRA 		 8080328480

rcsmgmc.research@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 8  
Name of Committee  Approval Status 
Clinical Research Ethics Committee, Calcutta School of Tropical Medicine  Submittted/Under Review 
Institutional Ethics Committee for Human Research, Medical College and Hospital  Submittted/Under Review 
Institutional Ethics Committee, College of Medicine & Sagore Dutta Hospital  Submittted/Under Review 
Institutional Ethics Committee, Gandhi Medical College and Hospital  Submittted/Under Review 
Institutional Ethics Committee, Jawahar Lal Nehru Medical College  Submittted/Under Review 
Institutional Ethics Committee, Maharaja Agrasen Superspeciality Hospital  Approved 
Prakash Medical College Institutional Ethics Committee, Prakash Institute of Medical Sciences & Research (PIMS&R)  Submittted/Under Review 
Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital, Kolhapur Institutional Ethics Committee 2 (RCSMGMCIEC2)  Submittted/Under Review 
 
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 
Comparator Agent  FDC of Glimepiride 2 mg + Metformin Hydrochloride Sustained Release 1000 mg Tablets  One Tablet of FDC of Glimepiride 2 mg + Metformin Hydrochloride Sustained Release 1000 mg Tablets twice daily 15-30 minutes before meal orally, swallowed with water in the morning and evening preferably same time every day for 16 weeks. 
Intervention  FDC of Linagliptin 2.5 mg + Glimepiride 1 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets  One Tablet of FDC of Linagliptin 2.5 mg + Glimepiride 1 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets twice daily 15-30 minutes before meal orally, swallowed with water in the morning and evening preferably same time every day for 16 weeks. 
Intervention  FDC of Linagliptin 2.5 mg + Glimepiride 2 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets  One Tablet of FDC of Linagliptin 2.5 mg + Glimepiride 2 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets twice daily 15-30 minutes before meal orally, swallowed with water in the morning and evening preferably same time every day for 16 weeks. 
 
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, along with diet and exercise control, additionally on stable total daily dose of Glimepiride 4 mg and Metformin Hydrochloride ≥ 1500 mg for at least 10 weeks prior to screening.
3. Patients with glycosylated hemoglobin (HbA1c) levels of ≥ 8.0% to ≤ 11.0%.
4. 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.
5. Patients with no abnormality on 12-lead ECG at screening or baseline visit.
6. Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
7. 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 Fasting Plasma Glucose (FPG) more than or equal to 270 mg by dL at screening.
4. Patients with the Body Mass Index (BMI) more than 45.0 kg by m2 at screening.
5. Patients with Estimated glomerular filtration rate (eGFR) less than 60 mL by min by 1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
6. Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the ULN and or Total bilirubin more than 1.5X the ULN) at screening.
7. Patients with a history of congestive heart failure defined as New York Heart Association (NYHA) class III or IV, unstable or acute congestive heart failure.
8. 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.
9. Patients with history of sustained and clinically relevant ventricular arrhythmia.
10. Patients with history or currently suffering with severe and disabling arthralgia.
11. Patients with history or currently suffering with bullous pemphigoid requiring hospitalization and taking DPP-4 inhibitors.
12. Patients with history of inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption.
13. Patients with any condition (e.g., infection, trauma and surgery) which require insulin therapy at the time of screening or during the study period.
14. 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.
15. 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.
16. Patients who are accepting treatments of arrhythmias.
17. Patients with a history of anaemia or haemoglobinopathy and or haemoglobin less than 10 g by dL for men; haemoglobin less than 9 g by dL for women at screening.
18. Patients with intolerance, contraindication or potential allergy or hypersensitivity to DPP4 inhibitors.
19. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
20. 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).
21. Patients with history of any malignancy.
22. Patients with history of infection with hepatitis B, hepatitis C or HIV.
23. Patients with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to screening.
24. 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.
25. Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
26. Patients currently taking any of the prohibited medications(s) and inability or unwillingness to discontinue them for the entire study period.
27. Suspected inability or unwillingness to comply with the study procedures.
28. 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 or baseline visit (Visit 1),
Visit 5 [Week 12 or Day 84(±3)] and
Visit 6 [Week 16 or Day 112(±3)]. 
 
Secondary Outcome  
Outcome  TimePoints 
Mean change in fasting plasma glucose (FPG) from baseline to end of the study visit (week 16).  At Screening or baseline visit (Visit 1),
Visit 3 [Week 2 or Day 14(±3)],
Visit 4 [Week 6 or Day 42(±3)],
Visit 5 [Week 12 or Day 84(±3)] and
Visit 6 [Week 16 or Day 112(±3)]. 
Mean change in 2-hr post prandial plasma glucose (2-hr PPG) from baseline to end of the study visit (week 16).  At Screening or baseline visit (Visit 1),
Visit 3 [Week 2 or Day 14(±3)],
Visit 4 [Week 6 or Day 42(±3)],
Visit 5 [Week 12 or Day 84(±3)] and
Visit 6 [Week 16 or Day 112(±3)]. 
Proportion of patients achieving a therapeutic glycemic response, defined as HbA1c less than 7% at the end of the study visit (week 16).  At Visit 6 [Week 16 or Day 112(±3)]. 
Number of patients requiring hypoglycemia management during the study.  Throughout the study. 
Number of patients requiring rescue medications during the study.  Throughout the study. 
Mean change in body weight from baseline to end of the study visit (week 16).  At Screening or baseline visit (Visit 1),
Visit 3 [Week 2 or Day 14(±3)],
Visit 4 [Week 6 or Day 42(±3)],
Visit 5 [Week 12 or Day 84(±3)] and
Visit 6 [Week 16 or Day 112(±3)]. 
Hypoglycemic episodes during the study.  Throughout the study. 
Adverse events and 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 16).  At Screening or baseline visit (Visit 1) and
Visit 6 [Week 16 or Day 112(±3)]. 
 
Target Sample Size   Total Sample Size="288"
Sample Size from India="288" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   12/02/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Not Applicable 
Publication Details   N/A 
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 multicentric, prospective, active controlled, parallel group, randomized, double blind, comparative, phase III clinical study to evaluate the efficacy, safety and tolerability of fixed dose combination of Linagliptin, Glimepiride and Metformin Hydrochloride Extended Release Tablets versus fixed dose combination of Glimepiride and Metformin Hydrochloride Sustained Release Tablets in patients with type 2 diabetes mellitus.

 

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), along with diet and exercise control, additionally on stable total daily dose of Glimepiride 4 mg and Metformin Hydrochloride ≥ 1500 mg for at least 10 weeks prior to screening and glycosylated hemoglobin (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(±3), week 6/day 42(±3), week 12/day 84(±3) and week 16/day 112(±3) (Final Visit) of treatment to assess efficacy and safety.

 

Patients will be assigned to either of the three arms i.e., Arm A or Arm B or Arm C consisting of FDC of Linagliptin 2.5 mg + Glimepiride 1 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets or FDC of Linagliptin 2.5 mg + Glimepiride 2 mg + Metformin Hydrochloride Extended Release 1000 mg Tablets or FDC of Glimepiride 2 mg + Metformin Hydrochloride Sustained Release 1000 mg Tablets. 
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