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CTRI Number  CTRI/2021/03/032103 [Registered on: 18/03/2021] Trial Registered Prospectively
Last Modified On: 29/04/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   A clinical trial to study the efficacy and safety of fixed dose combination of Glimepiride plus Voglibose plus Metformin Tablets in the treatment of type 2 diabetes mellitus. 
Scientific Title of Study   "An Open Label, Prospective, Randomized, Comparative, Multicenter and Phase IV Clinical Study to Evaluate the Efficacy and Safety of Fixed Dose Combination of Glimepiride plus Voglibose plus Metformin Tablets in Patients with Type 2 Diabetes Mellitus". 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CRPL/CT/20/006  Protocol Number 
Version No.: 00 and Dated Nov 12, 2020  Other 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr A Gopal Rao 
Designation  Associate Professor 
Affiliation  Government Medical College & Government General Hospital (Old RIMSGGH) 
Address  Department of Medicine, Government Medical College & Government General Hospital (Old RIMSGGH), Srikakulam-532001.

Srikakulam
ANDHRA PRADESH
532001
India 
Phone  8942279033  
Fax    
Email  drgopalraoa@gmail.com  
 
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.I.G: 19, H. No. 1-9-25/19, 4th Floor, Above Karur Vysya Bank, Dr. A.S. Rao Nagar, Hyderabad-500062.

Hyderabad
TELANGANA
500062
India 
Phone  7989233379  
Fax    
Email  dr.sekhar@clinwave.co.in  
 
Details of Contact Person
Public Query
 
Name  Dr Rajasekhara Reddy Tamma 
Designation  Managing Director 
Affiliation  Clinwave Research Pvt. Ltd. 
Address  Clinwave Research Pvt. Ltd., H.I.G: 19, H. No. 1-9-25/19, 4th Floor, Above Karur Vysya Bank, Dr. A.S. Rao Nagar, Hyderabad- 500062.

Hyderabad
TELANGANA
500062
India 
Phone  7989233379  
Fax    
Email  dr.sekhar@clinwave.co.in  
 
Source of Monetary or Material Support  
Inventia Healthcare Ltd., A-214, Road No. 30, Wagle Industrial Estate, Thane-400604, Mumbai, Maharashtra, India. 
 
Primary Sponsor  
Name  Inventia Healthcare Ltd 
Address  A-214, Road No. 30, Wagle Industrial Estate, Thane-400604, Mumbai, Maharashtra, India. 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 16  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr S Poorna Gopal Azad  Anu Hospitals  Department of Clinical Research, Kovelamudivari Street, Suryaraopet, Vijayawada-520002.
Krishna
ANDHRA PRADESH 
7794022370

drcresearch@gmail.com 
Dr Vipul Khandelwal  Apex Hospitals Private Limited  Department of Clinical Research, SP-4 & 6, Malviya Industrial Area, Near Apex Circle, Malviya Nagar, Jaipur-302017.
Jaipur
RAJASTHAN 
9829193517

dr.vipul@yahoo.co.in 
Dr Swapnav Borthakur  Down Town Hospital  Department of Clinical Research, Down Town Hospital, Dispur, G.S. Road, Guwahati-781006.
Kamrup
ASSAM 
9864038704

swapnav.borthakur@gmail.com 
Dr Solanki Dipakkumar Becharlal  Dr. M. K. Shah Medical College & Research Centre & SMT S.M.S Multispecialty Hospital  Department of Medicine, Near Tapovan Circle, Visat - Gandhinagar Highway, Chandkheda, Ahmedabad-382424.
Ahmadabad
GUJARAT 
9909961231

drdeepaksolanki3@gmail.com 
Dr J Naganna  Gandhi Medical College / Hospital  In Patient Block, 5th Floor, Department of General Medicine, Gandhi Medical College / Hospital, Musheerabad, Secunderabad-500003.
Hyderabad
TELANGANA 
9666345120

nagan99@gmail.com 
Dr A Gopal Rao  Government Medical College & Government General Hospital (Old RIMSGGH)  Department of Clinical Research, Government Medical College & Government General Hospital (Old RIMSGGH), Srikakulam-532001.
Srikakulam
ANDHRA PRADESH 
8942279033

drgopalraoa@gmail.com 
Dr Vinayak Maruti Sawardekar  Grant Government Medical College  Department of Clinical Research, J J Marg, Byculla, Mumbai-400008.
Mumbai
MAHARASHTRA 
9820747703

vinayaks1812@gmail.com 
Dr Mahendra Pal Singh  GSVM Medical College  Post Graduate Department of Medicine, Swaroop Nagar, Kanpur-208002.
Kanpur Nagar
UTTAR PRADESH 
8765379671

drmahendrapalsingh@gmail.com 
Dr Ved Prakash  Indira Gandhi Institute of Medical Sciences (IGIMS)  Department of Endocrinology, Sheikhpura, Patna-800014.
Patna
BIHAR 
9472008685

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

doctor.sanjiv@gmail.com 
Dr Prabhat Kumar Sharma  Maharaja Agrasen Superspeciality Hospital  Department of Clinical Research, Central Spine, Agrasen Aspatal Marg, Sector 7, Vidyadhar Nagar, Jaipur-302039.
Jaipur
RAJASTHAN 
9983995050

agrasenhospital2003@gmail.com 
Dr Raja Bhattacharya  Medical College and Hospital  Department of Medicine, Medical College and Hospital, Kolkata, 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))  Department of Clinical Research, 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  Department of Clinical Research, Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital, Dasara Chowk, Town Hall, Bhausingji Road, Kolhapur-416002.
Kolhapur
MAHARASHTRA 
8080328480

rscmgmc.research@gmail.com 
Dr Sagar Vivek Redkar  Redkar Hospital and Research Centre  Department of Clinical Research, Mumbai-Goa Highway, Oxelbag, Dhargal, Tal-Pernem, Goa-403513.
North Goa
GOA 
9158592177

cromgoa@gmail.com 
Dr Mohan Kumar Singh  W Pratiksha Hospital  Department of Clinical Research, Golf Course Ext. Road, Sushant Lok II, Sector 56, Gurugram-122011.
Gurgaon
HARYANA 
9910431665

drmksingh2012@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 16  
Name of Committee  Approval Status 
Ethics Committee, Down Town Hospital  Submittted/Under Review 
Ethics Committee, GSVM Medical College  Approved 
Institutional Ethics Committee for Human Research Medical College  Approved 
Institutional Ethics Committee, Anu Hospitals  Approved 
Institutional Ethics Committee, Apex Hospitals Private Limited  Approved 
Institutional Ethics Committee, Dr. M. K. Shah Medical College & Research Centre & SMT S.M.S Multispecialty Hospital  Approved 
Institutional Ethics Committee, Gandhi Medical College/Gandhi Hospital  Approved 
Institutional Ethics Committee, Government Medical College & Government General Hospital (Old RIMSGGH)  Approved 
Institutional Ethics Committee, Grant Government Medical College  Approved 
Institutional Ethics Committee, Indira Gandhi Institute of Medical Sciences (IGIMS)  Approved 
Institutional Ethics Committee, Jawahar Lal Nehru Medical College  Approved 
Institutional Ethics Committee, Maharaja Agrasen Superspeciality Hospital  Approved 
North East Healthcare Private Limited, W Pratiksha Hospital  Approved 
Prakash Medical College Institutional Ethics Committee  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 
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 Glimepiride 1 mg plus Voglibose 0.2 mg plus Metformin Hydrochloride ER 500 mg Tablets; FDC of Glimepiride 2 mg plus Voglibose 0.2 mg plus Metformin Hydrochloride ER 500 mg Tablets  Patients will be advised to take one tablet two times daily just before the meal (or with the first bite of each main meal), for 24 weeks. 
Comparator Agent  FDC of Voglibose 0.2 mg plus Metformin 500 mg Tablets; FDC of Voglibose 0.3 mg plus Metformin 500 mg Tablets; FDC of Glimepiride 1 mg plus Metformin 500 mg Tablets; FDC of Glimepiride 2 mg plus Metformin 500 mg Tablets  Patients will be advised to take one tablet two times daily just before the meal (or with the first bite of each main meal), for 24 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).
2. Patients with confirmed documented diagnosis of type 2 diabetes mellitus.
3. Patients, along with diet and exercise control, additionally on treatment with stable daily dose of Metformin 1000 mg for at least 3 months prior to screening and having inadequate glycemic control at screening defined as HbA1c levels between ≥ 8.0 to ≤ 10.0%.
4. Patients with fasting blood glucose ≤ 270 mg/dL at screening visit.
5. Patients with postprandial blood glucose (2 hours post meal) concentration > 200 mg/dL at screening visit.
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 / baseline visit.
7. Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
8. Patients willing to comply with the protocol requirements. 
 
ExclusionCriteria 
Details  1. Patients with intolerance, contraindication or potential allergy/hypersensitivity to any of the ingredients of study medication or drugs of similar class.
2. Patients with a history of Type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus.
3. Patients with a history of metabolic acidosis or diabetic ketoacidosis.
4. Patients with the Body Mass Index (BMI) < 18.5 and / or > 29.9 kg/m2 at screening visit.
5. 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.
6. Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the UNL and/or Total bilirubin more than 1.5X the UNL) at screening.
7. Patients receiving Miconazole.
8. Patients with a history of congestive heart failure defined as New York Heart Association (NYHA) class III/IV, unstable or acute congestive heart failure.
9. 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.
10. Patients with uncontrolled hypertension with sitting systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg at screening.
11. 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.
12. Patients with a history of anaemia or haemoglobinopathy and/or haemoglobin < 10 g/dL for men; haemoglobin < 9 g/dL for women at screening.
13. Pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.
14. 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).
15. Patients with known case of infection with hepatitis B, hepatitis C or HIV.
16. Patients with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to screening.
17. 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.
18. Patients with concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
19. Patients currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
20. 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   Permuted block randomization, fixed 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Mean change in glycosylated hemoglobin (HbA1c) from baseline to end of the study visit (24 weeks).  Visit 1 (Baseline / Day -7), Visit 4 (Week 12 / Day 84) and Visit 6 (Week 24 / Day 168). 
 
Secondary Outcome  
Outcome  TimePoints 
Mean change in fasting blood glucose (FBG) and 2-hr post prandial blood glucose (2-hr PPBG) from baseline to end of the study visit (24 weeks).  Visit 1 (Baseline / Day -7), Visit 3 (Week 6 / Day 42), Visit 4 (Week 12 / Day 84), Visit 5 (Week 18 / Day 126) and Visit 6 (Week 24 / Day 168). 
Proportion of patients achieving HbA1c 7.0% at week 12 and week 24.  Visit 4 (Week 12 / Day 84) and Visit 6 (Week 24 / Day 168). 
Proportion of patients reporting incidences of AE and/or SAE during the study and their assessment in respect to intensity, duration, pattern and causal relationship to the study medication.  Visit 3 (Week 6 / Day 42), Visit 4 (Week 12 / Day 84), Visit 5 (Week 18 / Day 126) and Visit 6 (Week 24 / Day 168). 
Changes in clinical laboratory parameters from baseline to end of the study visit (24 weeks).  Visit 1 (Baseline / Day -7) and Visit 6 (Week 24 / Day 168). 
 
Target Sample Size   Total Sample Size="339"
Sample Size from India="339" 
Final Enrollment numbers achieved (Total)= "355"
Final Enrollment numbers achieved (India)="355" 
Phase of Trial   Phase 4 
Date of First Enrollment (India)   22/03/2021 
Date of Study Completion (India) 25/03/2022 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

This trial is an open label, prospective, randomized, three arm, comparative, multicenter and phase IV clinical study.

 

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 were on diet and exercise control, additionally on treatment with stable daily dose of Metformin 1000 mg for at least 3 months, fasting blood glucose levels ≤ 270 mg/dL, postprandial blood glucose levels > 200 mg/dL and having inadequate glycemic control defined as HbA1c levels between ≥ 8.0 to ≤ 10.0% at screening visit 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 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 6/day 42(±2), week 12/day 84(±2), week 18/day 126(±2) and week 24/day 168(±2) (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 Glimepiride 1 mg + Voglibose 0.2 mg + Metformin Hydrochloride ER 500 mg Tablets or FDC of Voglibose 0.2 mg + Metformin 500 mg Tablets or FDC of Glimepiride 1 mg + Metformin 500 mg Tablets. At Week 12/Day 84, If the fasting blood glucose (FBG) assessment report is > 200 mg/dL, patients should be up titrated to further dose. Patients will be given the study medication twice daily for 24 weeks. 
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