Study to Assess Efficacy and Safety of Combination of Dapagliflozin, Glimepiride and Metformin Hydrochloride Tablets in Comparison to Glimepiride and Metformin Hydrochloride as Separate Tablets in Patients With Diabetes Mellitus

Phase 3

Completed

• Conditions: Type 2 diabetes mellitus without complications,

• Registration Number: CTRI/2022/06/043249
• Lead Sponsor: Sun Pharma Laboratories Limited

Brief Summary

rT

This was a phase III, randomized, open-label, four-arm, multicenter, parallel-group, active-controlled comparative study. In this study, the total treatment period was 28 weeks (maximum). The 28-week of treatment period was divided into treatment period 1(16 weeks) and treatment period 2 (12 weeks).

The study was conducted at approximately 21 number of centers in India, having qualified Investigators. The study will be initiated only after the receipt of Regulatory and EC approval. A total of 536 patients were randomized from 21 geographically distributed centers in India.

\*Screening period was maximum up to 1 week, however, patients who were eligible at screening visit immediately entered run-in period. After confirming the eligibility, patients were randomized by allotting the randomization number. Of 536 patients, 134 each in test arm 1 and test arm 2 of FDC of Dapagliflozin, Glimepiride and Metformin Hydrochloride Tablets BID, 134 each in Comparator arm 1 and comparator arm 2.

Of 536 patients, 134 each in test arm 1 and test arm 2 of FDC of Dapagliflozin, Glimepiride and Metformin Hydrochloride Tablets BID, 134 each in Comparator arm 1 and comparator arm 2.

The study treatment period was 28 weeks, which consisted of treatment period 1 (16 weeks) and treatment period 2 (12 weeks).

During the study, assessments were performed as mentioned in Schedule of Assessment. At the end of Week 16, based on HbA1c level, patients entered treatment period 2. For patients who were not eligible had EOS visit at Week 18

in comparison to co-administration of dual therapies (Metformin Hydrochloride and Glimepiride tablets

Mean change in HbA1c from baseline to end of Week 16was statistically significant in FDC of Dapagliflozin, Glimepiride and Metformin Hydrochloride tablets BID (test arm 1 and test arm 2)compared to co-administration of Metformin Hydrochloride and Glimepiride tablets IP BID (comparator arm 1 and comparator arm 2). The proportion of patients achieving HbA1c <7.0% were higher and statistically significant in FDC of Dapagliflozin, Glimepiride and Metformin Hydrochloride tablets arm as compared to co-administration of Metformin Hydrochloride and Glimepiride tablets arm at the end of Week 16 demonstrating better glycaemic control. The results of safety analysis showed that the incidence of TEAEs were comparable in all arms. Apart from the safety that is already known for the study products, no new safety concerns were observed in the study. Overall, the study products were safe and well tolerated.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-20
• Study Completion: 2023-06-15
• Last Update Posted: 2023-07-17

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 536

Inclusion Criteria

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 2 mg and Metformin 1000 mg to 2000 mg (both inclusive) for at least 8 weeks prior to screening 4) Patients with HbA1c ≥ 8.0% and ≤ 11% at screening and randomization 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.

Exclusion Criteria

• 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) and randomization 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 screening 6) Patients planning to take any anti-diabetic drugs (other than study drugs or rescue medication) or weight loss drugs 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 screening; topical, nasal or inhaled corticosteroids are allowed 8) Patients with history of HIV, HBV, and HCV 9) Patients having significant renal impairment eGFR below 45 mL/min/1.73 m2 or end-stage renal disease or on dialysis) or hepatic impairment (AST and ALT ˃ 3 x ULN) at screening.
• 10. Patients taking loop diuretics within one week prior to screening or planning to take during the study.
• 11. Any condition (e.g. infection, trauma, and surgery) which requires insulin therapy at the time of screening or during the study period.
• Short term use i.e. ≤ 7 days will be allowed.
• 12. History of bariatric surgery (i.e. any surgery to treat obesity; e.g. gastric banding or procedures that involve bypassing or transposing sections of the small intestine).
• History of liposuction will be allowed.
• 13. Patients having history of acute or chronic metabolic acidosis, including diabetic ketoacidosis and lactic acidosis, pancreatitis or hyperosmolar state (including coma) 14) Patients who are lactose intolerant 15) 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 16) 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 17) Patients with history of unstable angina prior to 3 months from screening 18) Patients with history of sustained and clinically relevant ventricular arrhythmia 19) Any of the following ECG abnormalities at screening: Second or third degree AV block without a pacemaker, Long QT syndrome or QTc greater than 500 ms, 20) 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 21) Patients with symptomatic diarrhoea or any other medical condition which the Investigators may judge to be a risk for dehydration and hypovolemia 22) Patients with known alcohol or other substance abuse within last one year as per DSM-5 criteria 23) Patients with NYHA class III or IV heart failure 24) Patients with uncontrolled hypertension ≥160/100 mmHg at screening and randomization 25) Patients with inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption 26) 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 patient or the conduct of the study, or prevent the patient from meeting or performing study requirements.
• 27. 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.
• 28. Pre-planned surgery or medical procedure that would interfere with the conduct of the study 29) 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.
• 30. Pregnant or lactating woman 31) Patients who have participated in another investigational study within 30 days prior to screening in this study or planning to participate during the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mean change in HbA1c from Baseline at the end of Week 16	Baseline, at the end of Week 16

Secondary Outcome Measures

Name	Time	Method
Mean change in HbA1c from Baseline at the end of Weeks 12 and 28	Baseline, at the end of Weeks 12 and 28
Mean change in PPBG from Baseline at the end of Weeks 12, 16 and 28	Baseline, at the end of Weeks 12 and 28
Mean change in FBG from Baseline at the end of Weeks 12, 16 and 28	Baseline, at the end of Weeks 12 and 28
Safety assessment includes TEAEs reported during the study	till end of study
Proportion of Participants Achieving HbA1c 7.0% at the end of Weeks 12, 16 and 28	Weeks 12, 16 and 28
Number of patients requiring hypoglycemia management by Weeks 16 and 28	Weeks 16 and 28
Mean change in bodyweight from Baseline at the end of Weeks 12, 16 and 28	Baseline, at the end of Weeks 12 and 28
Number of patients requiring rescue medications by Weeks 16 and 28	Weeks 16 and 28

Trial Locations

Locations (21)

BGS Global Institute of Medical Sciences; 🇮🇳 Bangalore, KARNATAKA, India

Citizen Hospital; 🇮🇳 Bangalore, KARNATAKA, India

District Civil Hospital; 🇮🇳 Aurangabad, MAHARASHTRA, India

Global Hospital and Research Institute; 🇮🇳 Pune, MAHARASHTRA, India

GSVM Medical College; 🇮🇳 Nagar, UTTAR PRADESH, India

Hormone Care; 🇮🇳 Aurangabad, MAHARASHTRA, India

Janta Hospital; 🇮🇳 Varanasi, UTTAR PRADESH, India

M.V. Hospitals; 🇮🇳 Lucknow, UTTAR PRADESH, India

Maharaja Agrasen Superspeciality Hospital; 🇮🇳 Jaipur, RAJASTHAN, India

Maya Hospital & Maternity Centre; 🇮🇳 Nagar, UTTAR PRADESH, India

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BGS Global Institute of Medical Sciences

🇮🇳Bangalore, KARNATAKA, India

Dr G Balachandra

Principal investigator

9845111559

drgbalachandra@gmail.com