CTRI/2022/03/041424 [Registered on: 28/03/2022] Trial Registered Prospectively
Last Modified On:
31/05/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Study to Assess Efficacy and Safety of Combination drug of Dapagliflozin, Glimepiride and Metformin Hydrochloride Tablets having extended release compared to Combination of Metformin Hydrochloride having prolonged release and Glimepiride Tablets in patients with Type 2 Diabetes Mellitus
Scientific Title of Study
A Multicenter, Randomized, Active-Controlled, Open-Label, Parallel-Group, Two-Arm, Phase III Study to Assess Efficacy and Safety of Fixed Dose Combination of Dapagliflozin, Glimepiride and Extended Release Metformin Hydrochloride Tablets in Comparison to Fixed Dose Combination of Metformin Hydrochloride Prolonged Release and Glimepiride Tablets in Patients with Type 2 Diabetes Mellitus
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ICR/21/006 V2.0 Dated 20 Sep 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Lalit Lakhwani
Designation
AVP and Head-India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
lalit.lakhwani@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Piyush Patel
Designation
Deputy General Manager – India Clinical Research
Affiliation
Sun Pharma Laboratories Ltd
Address
Sun House, Plot No. 201 B/1,Western Express Highway, Goregaon (E),Mumbai - 400 063, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400 063 India
Phone
02243244324
Fax
02243244343
Email
piyush.patel5@sunpharma.com
Details of Contact Person Public Query
Name
Rajesh Gaikwad
Designation
Deputy General Manager – India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063
Mumbai (Suburban) MAHARASHTRA 400 063 India
Phone
02243244324
Fax
02243244343
Email
Rajesh.Gaikwad@sunpharma.com
Source of Monetary or Material Support
Sun Pharma Laboratories Limited, Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Diabetes Thyroid & Endocrine Centre, A-1, Madrampur, Near 4 No ESI Hospital Jaipur - 302006 (India) Jaipur RAJASTHAN
9929959070
sksharma.cr@gmail.com
Dr Sandip Gofne
District Civil Hospital
Department of Medicine, District Civil Hospital, Chikalthana, Aurangabad, Near Airport, Jalna Road, Aurangabad, 431007, Maharashtra. Aurangabad MAHARASHTRA
9579268780
drsandipgofne@gmail.com
Dr Saurabh Agarwal
GSVM Medical College
Room No 05, Department of Medicine, GSVM Medical College, Swaroop Nagar, Kanpur 208002 Kanpur Nagar UTTAR PRADESH
9415039582
drsaurabh.agarwal@gmail.com
Dr Lomte Nilesh Keshavrao
Hormone Care
Room No.02, 2nd Floor, Oberoi Chambers, Besides Hotel Amarpreet, Jalna Road, Aurangabad 431005, Maharashtra, India Aurangabad MAHARASHTRA
8652225827
enileshlomte@gmail.com
Dr Gupta Hemant Ramsharan
J.J. Group of Hospitals
OPD No. 20, Department of Medicine, OPD Building, Grant Govt. Medical College & Sir J.J. Group of Hospitals, Byculla, Mumbai-400008. Mumbai (Suburban) MAHARASHTRA
9870456888
drhemantgupta@hotmail.com
Dr Sreenivasa Murthy L
Life Care Hospital & Research Centre
Life Care Hospital & Research Centre
Door no. #2748/2152, M.L.N Enclave, 16th ‘E’ Cross Road, 8th main, ‘D’ Block, Next to Corporation Bank, Sahakarnagar, Bangalore-560092, Karnataka. India
Bangalore KARNATAKA
9448051046
drlsm@lcrc.in
Dr Priyanka Kashid
Lifepoint Multispecialty Hospital
Lifepoint Multispecialty Hospital,145/1,Mumbai Bangalore Highway, Near Hotel Sayaji, Wakad, Pune-411057, Maharashtra, India Pune MAHARASHTRA
9028628647
kashiddrpriyanka@gmail.com
Dr Sandeep Kumar Gupta
M.V. Hospital and reserch centre
M.V. Hospital and reaserch centre , 314/30, Mirza Mandi Chowk, lucknow,226003, Uttar Pradesh, India Lucknow UTTAR PRADESH
9336077839
sandeepkumar.gupta@rediffmail.com
Dr Pujara Gauravkumar Navinchandra
Maruti Multispecialty Hospital
Shop No. 32/233/234/235, second floor, vithal plaza, Naroda, G.E.C, New Naroda, Ahmedabad – 382330
Ahmadabad GUJARAT
8866851485
Shivam_cr@theshivamhospital.com
Dr Manish Kumar Singh
Maya Hospital & Maternity Centre
Maya Hospital & Maternity Centre 343 E block Panki, Kanpur-208020 Kanpur Nagar UTTAR PRADESH
7007592197
drmanishkumar820@gmail.com
Dr Manoj Kumar Srivastava
Om Surgical Center & Maternity Home
Om Research Center, Om Surgical Center & Maternity Home, General medicine, Room No. 202, SA 17/3, P-4, Sri Krishna Nagar, Paharia, Ghazipur road, Varanasi – 221007, UP, India Varanasi UTTAR PRADESH
9415256272
omreserachcentre@gmail.com
Dr Pradeep Kumar Rai
Opal Hospital Private Limited
Opal Hospital Private Limited, N 10/60-2 kakarmatta DL W road, Varanasi, Uttar Pradesh – 221002 Varanasi UTTAR PRADESH
9336913486
pradeeppk.rai@gmail.com
Dr Rakesh Kumar Sahay
Osmania Medical College & Osmania General Hospital
Department of Endocrinology, Room No 306, 2nd Floor,
Golden Jubilee Block, Osmania Medical College and Osmania
General Hospital 500012, Telangana, India Hyderabad TELANGANA
9849597507
sahayrk@gmail.com
Dr Jayesh Arjanbhai Ambaliya
Pagarav Hospital and ICU
Room No. 03, basement, Pagarav Hospital and ICU, Plot no. 512/1, Nr. G6 Circle, Opp. SBI, Sector 23, Gandhinagar,382023, Gujarat, India Gandhinagar GUJARAT
C-4, Satyanarayan Society, Gor no Kuvo, Jasodanagar Char Rasta, Maninagar, Ahmedabad - 380008, Gujarat, India Ahmadabad GUJARAT
9825047692
dr_prakashkurmi@yahoo.co.in
Dr Vikas Agarwal
Surya Super Speciality Hospital
Department of Cardiology, Room No. 02, Surya Super Speciality Hospital a unit of G.V. Meditech (P) Ltd; B 38/46 H Raman Niwas Mahmoorganj, Varanasi 221010 U.P. INDIA Varanasi UTTAR PRADESH
9621975232
drvikasmed@gmail.com
Dr Kale Narendra Chindhu
Yashwantrao Chavan Memorial Hospital
2nd Floor, Department of General Medicine, PCMC’S PGI Yashwantrao Chavan Memorial Hospital, Sant Tukaram Nagar, Pimpri, Pune 411018 Pune MAHARASHTRA
1) Patients of either gender, aged 18 to 65 years (both inclusive) and ready to give written informed consent to participate in the study at the time of screening
2) Patients with diagnosis of type 2 diabetes mellitus
3) Patients along with diet and exercise control, additionally on stable total daily dose of Glimepiride 1 mg and Metformin Sustained Release/Prolonged Release/Extended Release 1000 mg for at least 8 weeks prior to screening
4) Patients with HbA1c ≥8.0% and ≤ 11% at screening
5) Patients with BMI ≤ 45.0 kg/m2 at screening
6) Women of childbearing potential must have a negative urine pregnancy test prior to study entry and agree to use highly effective methods of contraception to prevent pregnancy from study entry till at least two weeks after the last dose of the study medication (such contraception may include hormonal birth control e.g. combined estrogen and progestogen containing [oral, intravaginal, or transdermal] or progesterone only [oral, injectable, or implantable] hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone releasing system OR bilateral tubal occlusion, vasectomized partner, or total sexual abstinence)
[Note: Women with childbearing potential are defined as: those who are not (1) surgically sterile (bilateral oophorectomy, hysterectomy, or bilateral tubal ligation) or (2) post-menopausal. Post-menopausal woman will be defined as: Woman not using hormonal replacement therapy and have had at least 12 continuous months of natural (spontaneous) amenorrhea and be greater than 45 years of age.]
ExclusionCriteria
Details
1) Patients diagnosed with type 1 diabetes, diabetes insipidus, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing syndrome or acromegaly-associated diabetes)
2) Patients with FBG ≥ 270 mg/dL at screening (if required, measurement can be repeated and confirmed within 7 days)
3) Patients with history of hypersensitivity to any of the study drug or to drugs of similar chemical classes (e.g. sulfonamide) or to any of its excipients
4) Patients with administration of any therapy for diabetes, other than Metformin and glimepiride during 8 weeks prior to screening
5) Patients with history of taking any weight loss medications within 3 months prior to randomization
6) Patients planning to take any anti-diabetic drugs or weight loss drugs other than study drugs or rescue medication during the study
7) Treatment with glucocorticoids equivalent to oral prednisolone ≥ 10 mg (betamethasone ≥ 1.2 mg, dexamethasone ≥ 1.5 mg, hydrocortisone ≥ 40 mg) per day within 30 days prior to randomization; topical, nasal or inhaled corticosteroids are allowed
8) Patients with history of HIV, HBV, and HCV.
9) Patients having significant renal (eGFR below 45 mL/min/1.73 m2) or hepatic impairment (AST and ALT ˃ 3 x ULN).
10) Patients taking loop diuretics within one week prior to screening or planning to take during the study
11) Patients suffering with end-stage renal disease or on dialysis
12) Any condition (e.g. infection, trauma, and surgery) which require insulin therapy at the time of screening or during the study period. Short term use i.e. ≤ 7 days will be allowed
13) History of bariatric surgery (i.e. any surgery to treat obesity; for e.g. gastric banding or procedures that involve bypassing or transposing sections of the small intestine). History of liposuction is allowed.
14) Patients having history of acute or chronic metabolic acidosis, including diabetic ketoacidosis and lactic acidosis, pancreatitis or hyperosmolar state (including coma)
15) Patients who are lactose intolerant
16) Patients suffering from severe urinary tract infections (e.g. urosepsis, pyelonephritis), necrotizing fasciitis of the Perineum (Fournier’s Gangrene), intravascular volume contraction and/ or female genital mycotic infections prior to 6 months from screening
17) Patients with history of myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, stroke or transient ischemic attack prior to 6 months from screening
18) Patients with history of unstable angina prior to 3 months from screening
19) Patients with history of sustained and clinically relevant ventricular arrhythmia
20) Any of the following ECG abnormalities:
Second or third degree AV block without a pacemaker, Long QT syndrome or QTc > 500 ms
21) Patients having history or currently suffering with serious allergic and hypersensitivity reactions such as anaphylaxis, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome and urticaria.
22) Patients with symptomatic diarrhoea or any other medical condition which the Investigators may judge to be a risk for dehydration and hypovolemia
23) Patients with known alcohol or other substance abuse within last one year as per DSM-5 criteria.
24) Patients with NYHA class III or IV
25) Patients with uncontrolled hypertension ≥160/100 mmHg
26) Patients with inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption
27) Patients with any clinically significant laboratory abnormalities/condition (e.g. immunocompromised status, malignancy, hyperthyroidism etc.) which in the opinion of Investigator would compromise the well-being of the patients or the conduct of the study, or prevent the patient from meeting or performing study requirements
28) Patients are on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks prior to screening
Note: Patients who meet this criterion may be re-screened after being on a stable dose of thyroid replacement therapy for at least 6 weeks.
29) Pre-planned surgery or medical procedure that would interfere with the conduct of the study
30) Employee of the Sponsor, Investigator, or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees of Sponsor or the Investigator.
31) Pregnant or lactating woman
32) Patients who has participated in another investigational study within 30 days prior to screening in this study or planning to participate during the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Mean change in HbA1c from Baseline at the end of Week 16
This was a phase III, randomized, open-label, two-arm, multicenter,
parallel-group, active-controlled comparative study. The study is being
conducted at total 18 geographically distributed centers in India. The study
was initiated only after the receipt of Regulatory and Ethics Committee (EC)
approvals. Total 440 patients were screened to randomize 395 patients from 18
geographically distributed centers in India.
The screening period was of 2 weeks. During screening period, after
obtaining the written informed consent, patients were screened by undergoing
various assessments as mentioned in Schedule of Assessments (Appendix I).
Treatment Period
After confirming eligibility, patients were randomized into treatment
period. In this study, total treatment period was of 28 weeks. This 28 week of
treatment period was divided into 16 weeks of treatment period 1 and 12 weeks
of treatment period 2.
Total duration was
maximum 30 weeks
The study was
conducted as per below planned visits:
Visit 6*: EOS Visit (Post-Treatment Safety Follow-up visit: Day 126± 4,
(Week 18)
Visit 6**: ET/EOT Visit: Day 196 ± 4 (Week 28)
Visit 7**: EOS Visit (Post-Treatment Safety Follow-up visit: Day 210± 4,
(Week 30)
Note: * is applicable for patients under treatment period 1 and ** is
applicable for treatment period 2.
Patients were
provided with diary to record details about study drug administration, rescue
medication, and adverse events (AEs). Patients were required to bring completed
diary at each visit.
Patients who
discontinued early from the study completed ET and post-treatment safety
follow-up visit both considered as end of study visit.
Patients who discontinued early from the study completed ET and
Post-Treatment Safety Follow-up visit. Telephonic follow-up of Visit 6 (Week
18) and Visit 7 (Week 30) were also permitted if patients were unable to visit
study center. Patients who discontinued early from the study also completed
procedure of Visit 6 (Week 18) for treatment period 1 and Visit 7 (Week 30) for
treatment period 2, two weeks after discontinuation of study medication.