A Multi-centric, Prospective, Randomized, Double- blind Study to Evaluate the Safety and Efficacy of Saroglitazar 2 / 4 mg as Compared to Pioglitazone in Type 2 Diabetes Mellitus
Trial Acronym
PRESS XII
Secondary IDs if Any
Secondary ID
Identifier
SARO.14.002.01.1.PROT,Version 1.1 Dated 12th December 2014
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Deven Parmar
Designation
Vice president
Affiliation
Zydus Research Center
Address
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A
Moraiya, Ahmedabad 382213, India
Dayanand Medical College and Hospital,Ludhiana-141001
Ludhiana PUNJAB
9814077536
pam.endo@yahoo.co.in
Dr K Sunil Naik
Department of GeneralMedicine Rajiv Gandhi Institute of Medical Science
Department of General Medicine Rajiv Gandhi Instotute of Medical Science and RIMS Government General Hospital,Situated at Srikakulam-532001,Andhra Pradesh,India
Srikakulam ANDHRA PRADESH
9440828299
rimsrresearch@gmail.com
Dr R N Sarkar
Department of Medicine
"Department of Medicine,Medical College and Hospital,Kolkata,
88, College Street,
Chittaranjan Avenue,Kolkata-700073,West Bangal Kolkata WEST BENGAL
9433069803
drrnsarkar09@gmail.com
DrSanjeev Phatak
DHL Research Centre
DHL Research Centre,Sushri Jasumati Shantilal Surti Chartitable General Hospital ,Opp Vimanagar,Near Shivranjani Cross Road,Satellite .Ahmedabad-380015,Gujarat ,India
Ahmadabad GUJARAT
9824030932
phatak_sanjeev@yahoo.co.in
Dr R P Agarwal
Diabetes Care& Research Centre
Diabetes Care& Research Centre, S.P Medical College & A.G Hospitals HRMC Cardiovascular Sciences & Research Centre, Bikaner 334001
Bikaner RAJASTHAN
0151-2202131
drrpagarawal@yahoo.co.in
DrRoopam Das
Down Town Hospital
Down Town Hospital,G.S Road,Guwahati,Assam,India781006
Kamrup ASSAM
9864116999
rupamdas_in@yahoo.com
Dr Ajaykumar Kumar
Dr B L kapur Memorial Hospital
Room No 114,1st floor, Dr BL kapur Memorial Hospital, Pusa road, New delhi 110005
New Delhi DELHI
011-30403040
ajay_ajamani@hotmail.com
Dr Kodilkar Jitandra
Dr. Vasantrao Medical College, Hospital & Research Centre
Dr.Jivraj Mehta Smarak Health Foundation and Bakeri medical research centre
Dr.Jivraj Mehta Smarak Health Foundation and Bakeri medical research centre Ayojanagar ,Near Shreyas Crossing Road,Jivraj Mehta Marg,Jivraj Park,Ahmedabad-380007
Ahmadabad GUJARAT
9377439343
draskhatri@yahoo.com
DrSrikanth Kongara
Endocare Hospital
Endocare Hospital, A unit of Coastal Endocrine Speciality Hospitals Pvt Ltd, D.No 29-19-59, Dornakar Road, Suryaraopet, Vijaywada -520002,Andhra Pradesh, India
Krishna ANDHRA PRADESH
Institute of Post Graduate Medical Education and research
Institute of Post Graduate medical Education and research,Ronald Ross building ,4th Floor, Room No 9,9A, 244,AJC Bose Road,Kolkata-700020
Kolkata WEST BENGAL
9830027985
satinath.mukhopadhyay@gmail.com
Dr Madusudhan Babu
King George Hospital
King George Hospital,Visakhapatnam-530002
Visakhapatnam ANDHRA PRADESH
891270582
drmadhusudhan12@hotmail.com
DrBalamurugan Ramanathan
Kovai Diabetes Specialty Centre and Hospital
Kovai Diabetes Specialty Centre and Hospital, 15, Vivekanand Road, Ramnagar, Coimbatore 641009
Coimbatore TAMIL NADU
04224377732
balamurugandr@hotmail.com
DrP Vamsi Krishna
Krishna Institute of Medical Sciences
Krishna Institute of Medical Sciences situated at Dargamitta, Nellore, Andhra Pradesh-500003 India
Nellore ANDHRA PRADESH
9703133690
drvamsipr1@gmail.com
DrVinod Kumar Pavithran
KVM Hospital
KVM Hospital, PB No. 30, Cherthala, Kerala
Alappuzha KERALA
Room No.3, First Floor, Marwari Hospital and Research Centre, ECRC-HEC Research Unit, S. J. Road, Athgaon,Guwahati-781008,Assam,India
Kamrup ASSAM
2602738
drdinesh944@gmail.com
Dr Manish Agarwal
Medilink Hospital and Research Centre
First Floor,Unit head of diabetes and obesity department ,Opp Someshwara Jain Temple,
132 Ft Ring Road,
Satellite, Ahmadabad-380015
Gujarat,India. Ahmadabad GUJARAT
07926762821
medilinkhospital@yahoo.com
Dr Girish Bhatia
Medipoint Hospital Pvt. Ltd
241/1, New D. P. Road, Aundh, Pune 411007 Pune MAHARASHTRA
7387003636
Drbhatia.pentagon@gmail.com
Dr Sengupta Nilanjan
Nilratan Sircar Medical College and Hospital
"Nilratan Sircar Medical College and Hospital
138, AJC Bose Road,Kolkata 700014,West Bengal Kolkata WEST BENGAL
9231612841
drnilanjansengupta@gmail.com
DrPiyush Desai
Nirmal Hospital
Nirmal Hospital, Ring Road, Surat 395002
Surat GUJARAT
Type 2 Diabetes Mellitus, (1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Pioglitazone
Dosage:-30mg
Route:-Oral Form:-Tablet Duration :-OD for 56 weeks
mg
Intervention
Saroglitazar
Dosage:-2mg and 4mg
Route:-Oral
Form:-Tablet
Duration :-OD for 56 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Subjects age 18- 75 years, of either sex.
2. Documented history of type 2 diabetes mellitus defined by ADA criteria.
3. History of stable metformin dose atleast since last 6 weeks (total daily dose should not exceed 2 gm)
in conjunction with diet and exercise.
4. Fasting plasma glucose ≤270 mg/dL (14.98 mmol/L).
5. HbA1c should be ≥7.5%.
6. Subject has given informed consent for participation in this trial.
ExclusionCriteria
Details
Type 1 diabetes mellitus or a history of ketoacidosis or secondary forms of diabetes.
2. Subjects who have been treated with insulin for ≥7 days within 3 months prior to the screening visit.
3. History of recurrent or severe hypoglycemia within in last 3 months.
4. History of acute or chronic metabolic acidosis, including diabetic ketoacidosis.
5. Subjects on glitazone / glitazar therapy in the past 1 month.
6. History of unstable or rapidly progressive diabetic retinopathy, nephropathy (serum
creatinine 1.5 mg/dL).
7. History of uncontrolled thyroid disorder, not controlled by thyroid modulating drugs.
8. History of clinically significant peripheral edema in past 3 months.
9. Subjects with coronary insufficiency (e.g., a myocardial infarction, a coronary angioplasty or bypass
graft, unstable angina, transient ischemic attacks, or a documented cerebrovascular accident within 6
months prior to the screening visit).
10. Subjects with cardiac failure or history of cardiac failure (New York Heart Association [NYHA] Stages 3
to 4).
11. Uncontrolled hypertension (BP160/100 mmHg).
12. History of cancer (except non-melanoma skin cancer) or unexplained haematuria.
13. Subjects with an alanine transaminase (ALT) level ≥2.5 times the upper normal limit (UNL), active liver
disease, or jaundice.
14. Subject with systemic corticosteroid therapy for 2 week within past 3 months or history of chronic or
recurrent use.
15. History of any hemoglobinopathy (such as hemolytic anemia or sickle cell disease) that may affect
determination of HbA1c.
16. Subjects with microscopic hematuria.
17. History of AIDS / HIV infection.
18. History of viral hepatitis B or C.
19. Pregnant or breastfeeding female.
20. Subjects with any medical condition that may complicate participation in the trial.
21. Subjects who is unsuitable for the study according to the investigator. Subjects who have participated
in any trial in past 3 months.
22. Subjects who are unable to understand and give informed consent.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Change from baseline in glycosylated hemoglobin (HbA1c) for
Saroglitazar 4 mg, 2 mg and Pioglitazone 30 mg
Week 24
Secondary Outcome
Outcome
TimePoints
Comparision of Change from baseline in glycosylated hemoglobin
(HbA1c) between Saroglitazar 4 mg, 2 mg and Pioglitazone 30 mg
Week 12, Week 24, and Week 56]
Change from baseline in glycosylated hemoglobin (HbA1c) for
Saroglitazar 4 mg, 2 mg and Pioglitazone 30 mg
Week 12,and Week 56
Comparision of Change from baseline in fasting plasma glucose between
Saroglitazar 4 mg, 2 mg and Pioglitazone 30 mg
Week 12,
Week 24, and Week 56
Change from baseline in fasting plasma glucose for Saroglitazar 4 mg, 2
mg and Pioglitazone 30 mg
Week 12, Week 24, and Week
56]
Change from baseline in 2 hour postprandial plasma glucose for
Saroglitazar 4 mg, 2 mg and Pioglitazone 30 mg
Week 12,
Week 24, and Week 56
Change from baseline in lipid profile and lipoprotein.
Triglyceride (TG) cholesterol
Low density lipoprotein (LDL) cholesterol
Very low density lipoprotein (VLDL) cholesterol
High density lipoprotein (LDL) cholesterol
Total cholesterol (TC) cholesterol,Non HDL cholesterol
Apolipoprotein (Apo) A1
Apo B.
Week
12, Week 24, and Week 56
Target Sample Size
Total Sample Size="1140" Sample Size from India="1140" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
A Phase III of 12 week duration to evaluate the efficacy and safety of Saroglitazar in diabetic dyslipidemic patients not controlled with atorvastatin 10 mg revealed statistically significant reduction in the TG levels as compared to placebo. Statistically significant reduction in the LDL cholesterol, total cholesterol and apolipoprotein B levels with Saroglitazar 4 mg was observed as compared to baseline. Thus far,Saroglitazar clinical studies have included mild to moderate dyslipidemic patients and showed favorable effects .
The preclinical and clinical experience of Saroglitazar showed favourable effects not only on lipid profile but also glycemic control. . Thus based on the result of above studies the present study is proposed to assess the effects of 2 mg and 4 mg of Saroglitazar as compared to Pioglitazone 30 mg in patients with T2DM.