CTRI Number |
CTRI/2022/09/045148 [Registered on: 01/09/2022] Trial Registered Prospectively |
Last Modified On: |
10/04/2023 |
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 Vildagliptin plus Pioglitazone Tablets in patients with diabetes. |
Scientific Title of Study
|
“A Phase III, Prospective, Randomized, Double Blind, Comparative, Parallel Group, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Tolerability of FDC of Vildagliptin SR 100 mg plus Pioglitazone 15 mg Tablets Versus FDC of Teneligliptin 20 mg plus Pioglitazone 15 mg Tablets in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Monotherapy.†|
Trial Acronym |
|
Secondary IDs if Any
|
Secondary ID |
Identifier |
CRPL/CT/20/004, Version No.: 01 and Dated Apr 11, 2022 |
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.,
Plot No.: 38,
Kamala Prasanna Nagar,
Near Ramalayam Temple,
Kukatpally.
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.,
Plot No.: 38,
Kamala Prasanna Nagar,
Near Ramalayam Temple,
Kukatpally.
Hyderabad TELANGANA 500072 India |
Phone |
7989233379 |
Fax |
|
Email |
dr.sekhar@clinwave.co.in |
|
Details of Contact Person Public Query
|
Name |
Mr Surender Kumar Arora |
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 |
9811015684 |
Fax |
|
Email |
ska@synokempharma.com |
|
Source of Monetary or Material Support
|
Synokem Pharmaceuticals Ltd. |
|
Primary Sponsor
|
Name |
Synokem Pharmaceuticals Ltd |
Address |
14/486, Sunder Vihar,
Outer Ring Road, Paschim Vihar,
New Delhi-110087, India. |
Type of Sponsor |
Pharmaceutical industry-Indian |
|
Details of Secondary Sponsor
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
No of Sites = 10 |
Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
Dr Chintan B Patel |
Aatman Hospital |
Clinical Research Room, 5, Anveshan Row House, Bopal Gam BRTS, Bopal-Ghuma Road, Bopal, Ahmedabad-380058. Ahmadabad GUJARAT |
9825182251
cr.aatman@gmail.com |
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 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 Lalit Kumar |
GSVM Medical College |
Post Graduate Department of Medicine, LLR Hospital, Swaroop Nagar, Kanpur-208002. Kanpur Nagar UTTAR PRADESH |
9889264230
lalit85gsvm@gmail.com |
Dr Sanjiv Maheshwari |
Jawahar Lal Nehru (J.L.N) Medical College |
Department of Medicine, KalaBagh, 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 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 |
Dr Sagar Vivek Redkar |
Redkar Hospital and Research Centre |
Research Room,
Mumbai-Goa Highway, Oshalbag, Village-Dhargal, Tal-Pernem,
Goa-403513. North Goa GOA |
9158592177
redkar.research@gmail.com |
Dr Mohan Kumar Singh |
W Pratiksha Hospital |
Research Room, Basement-2, 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= 10 |
Name of Committee |
Approval Status |
Clinical Research Ethics Committee, Calcutta School of Tropical Medicine |
Approved |
Ethics Committee, GSVM Medical College |
Approved |
Institutional Ethics Committee for Human Research, Medical College and Hospital |
Approved |
Institutional Ethics Committee, Aatman Hospital |
Approved |
Institutional Ethics Committee, Gandhi Medical College/Gandhi Hospital |
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 |
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
|
|
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 Teneligliptin 20 mg plus Pioglitazone 15 mg Tablets |
Patients will be advised to take one tablet orally, swallowed as a whole with water in the morning after breakfast around same time every day for 16 weeks. |
Intervention |
FDC of Vildagliptin SR 100 mg plus Pioglitazone 15 mg Tablets |
Patients will be advised to take one tablet orally, swallowed as a whole with water in the morning after breakfast around 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 (both inclusive) years with diagnosis of Type 2 diabetes mellitus.
2. Patients who have received stable dose of Metformin ≥ 1500 mg/day 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 1.5X the UNL) at screening.
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 history of hereditary QT prolongation syndrome or patients having history of Torsades de pointes.
13. Patients who are accepting treatments of arrhythmias.
14. Patients with a history of anaemia or haemoglobinopathy and/or haemoglobin < 10 g/dL for men; haemoglobin < 9 g/dL for women at screening.
15. Patients with known history of acute pancreatitis.
16. Patients with a history of treatment with estrogens and other medications known to affect bone.
17. Patients with history of clinically significant peripheral edema in past 6 months.
18. Patients with intolerance, contraindication or potential allergy/hypersensitivity to any of the ingredients of study medication or any other DPP4 inhibitors or thiazolidinediones.
19. 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 known case 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/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 hemoglobin (HbA1c) from baseline to end of the study visit (16 weeks). |
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 (16 weeks). |
At Screening / baseline visit,
Visit 3 (Week 2 / Day 14±2)
Visit 4 (Week 6 / Day 42±2)
Visit 5 (Week 12 / Day 84±2) and
Visit 6 (Week 16 / Day 112±2). |
Mean change in 2-hr post prandial plasma glucose (2-hr PPG) from baseline to end of the study visit (16 weeks). |
At Screening / baseline visit,
Visit 3 (Week 2 / Day 14±2)
Visit 4 (Week 6 / Day 42±2)
Visit 5 (Week 12 / Day 84±2) and
Visit 6 (Week 16 / Day 112±2). |
Proportion of patients achieving a therapeutic glycemic response, defined as HbA1c 7% at the end of the study visit (16 weeks). |
At Visit 6 (Week 16 / Day 112±2). |
Mean change in body weight from baseline to end of the study visit (16 weeks). |
At Screening / baseline visit,
Visit 3 (Week 2 / Day 14±2)
Visit 4 (Week 6 / Day 42±2)
Visit 5 (Week 12 / Day 84±2) and
Visit 6 (Week 16 / Day 112±2). |
Hypoglycemic episodes during the study |
During the treatment period.
From Visit 2 (Day 1) to Visit 6 (Day 112)
Visit 3 (Week 2 / Day 14±2)
Visit 4 (Week 6 / Day 42±2)
Visit 5 (Week 12 / Day 84±2) and
Visit 6 (Week 16 / Day 112±2). |
Adverse events / serious adverse events reported during the
study. |
During the treatment period.
From Visit 2 (Day 1) to Visit 6 (Day 112)
Visit 3 (Week 2 / Day 14±2)
Visit 4 (Week 6 / Day 42±2)
Visit 5 (Week 12 / Day 84±2) and
Visit 6 (Week 16 / Day 112±2). |
Changes in clinical laboratory parameters from baseline to end of the study visit (16 weeks). |
At Screening / baseline visit and
Visit 6 (Week 16 / Day 112±2). |
|
Target Sample Size
|
Total Sample Size="172" Sample Size from India="172"
Final Enrollment numbers achieved (Total)= "192"
Final Enrollment numbers achieved (India)="192" |
Phase of Trial
|
Phase 3 |
Date of First Enrollment (India)
|
12/09/2022 |
Date of Study Completion (India) |
23/03/2023 |
Date of First Enrollment (Global) |
Date Missing |
Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
|
Years="1" Months="0" 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 a phase III, prospective, randomized, double blind, comparative,
parallel group, multicenter clinical study to evaluate the efficacy, safety and
tolerability of FDC of Vildagliptin SR 100 mg + Pioglitazone 15 mg Tablets
versus FDC of Teneligliptin 20 mg + Pioglitazone 15 mg 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 for at least 3
months 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 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, safety
and tolerability.
Patients
will be assigned to either of the two arms i.e., Arm A or Arm B consisting of FDC
of Vildagliptin SR 100 mg + Pioglitazone 15 mg Tablets or FDC of Teneligliptin
20 mg + Pioglitazone 15 mg Tablets. Patients will be given the study medication
once daily for 16 weeks. In addition, subjects will continue to receive
Metformin at stable doses of ≥1500
mg/day, throughout the study period in an open label manner (16 weeks). |