Study to evaluate Efficacy and Safety of Fixed Dose Combination of Sitagliptin Phosphate, Metformin Hydrochloride and Glimepiride Tablets as Compared to administration of both Metformin Hydrochloride Tablets and Glimepiride Tablets in Patients with Type 2 Diabetes Mellitus

Phase 3

Completed

• Conditions: Type 2 diabetes mellitus without complications,

• Registration Number: CTRI/2021/11/038169
• Lead Sponsor: Sun Pharma Laboratories Limited

Brief Summary

This is a phase 3, randomized, double-blind,double-dummy, multicenter, active-controlled study followed by an open-label,single-arm study. The study will be initiated only after the receipt ofRegulatory and Ethics committee (EC) approval.

Approximately392 patients are planned to be randomized in the study.

Efficacy and safety data of initial 120 patients from 16 weekstreatment will be shared with Drugs Controller General of India (DCGI) forreview by Subject Expert Committee (SEC). Enrolment of remaining 265 patientswill commence only after receiving a go-ahead recommendation from Central DrugsStandard Control Organisation (CDSCO) based on SEC recommendations.

During screening period, after obtaining thewritten informed consent, patients were screened by undergoing variousassessments as mentioned in the Schedule of Assessments.

After confirming eligibility, these 127 patients will be randomizedin 1:1 ratio in double-blind manner into either Test arm of FDC of SitagliptinPhosphate, Metformin Hydrochloride and Glimepiride tablets (50 mg/1000 mg/1 mg)BID or Comparator arm of co-administration of Metformin Hydrochloride 500 mg (2tablets BID) and Glimepiride 2 mg tablets (BID).

Patients with receive either 1 tablet of FDC of SitagliptinPhosphate, Metformin Hydrochloride and Glimepiride (50 mg/1000 mg/1 mg), 2tablets of matching placebo of Metformin Hydrochloride 500 mg and 1 tablet ofmatching placebo of Glimepiride 2 mg, BID 15-30 minutes before meal in Test armOR 2 tablets of Metformin Hydrochloride 500 mg, and 1 tablet of Glimepiride 2mg and 1 tablet of matching placebo of FDC of Sitagliptin Phosphate, MetforminHydrochloride and Glimepiride (50 mg/1000 mg/1 mg), BID 15-30 minutes beforemeal in Comparator arm. Total double-blinded treatment period was of 16 weeks.

After 16 weeks of double-blinded double-dummy treatment period,the study will be continued in single-arm and open-label manner for 12 weeks(Week 28). For each patient, at the end of Week 16, unblinding will be done todetermine the further course of therapy. Based on HbA1c level, patients in Testarm will continue to receive the same dose of FDC of Sitagliptin Phosphate,Metformin Hydrochloride and Glimepiride tablets (50 mg/1000 mg/1 mg) or there willbe up titration in dose and patients will receive FDC of Sitagliptin Phosphate,Metformin Hydrochloride and Glimepiride tablets (50 mg/1000 mg/2 mg) BID tillWeek 28. For patients in Comparator arm, Week 16 will be EOS visit and they willbe provided alternative treatments as per Investigator’s discretion.

All the patients in this study will be provided with diary at thetime of enrollment along with glucometer to record details about study drugadministration, adverse events (AEs) and self-monitoring of blood glucoselevels. Patients will be required to bring completed diary at each visit.

Duringthe study, assessments will be performed as mentioned in Schedule ofAssessments. Patients terminating early from thestudy completed the EOT assessments.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-24
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 392

Inclusion Criteria

• Patients of either sex, aged 18 to 65 years (both inclusive) and ready to give written informed consent to participate in the study.
• Patients with diagnosis of type 2 diabetes.
• Patients, along with diet and exercise control, additionally on stable total daily dose of Glimepiride 4 mg & Metformin Hydrochloride ≥ 1500 mg for at least 10 weeks prior to screening 4.
• Patients with HbA1c ≥ 8% and ≤ 11 % 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 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 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.
• Postmenopausal 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].

Exclusion Criteria

• Patients with FBG ≥ 270 mg/dL at screening 2.
• Patients with history of hypersensitivity to any of the study drug or to drugs of similar chemical classes (e.g. sulfonamide).
• Patients taking anti-diabetic drugs other than study drug at the time of screening or planning to take during the study.
• Patients with history of HIV, HBV, and HCV.
• Patients diagnosed with type 1 diabetes.
• Monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing syndrome or acromegaly- associated diabetes) 6.
• Patients having significant renal (eGFR below 45 mL/min/1.73 m2) or hepatic impairment (aspartate AST] and ALT ˃ 3 x ULN).
• Patients having history of acute or chronic metabolic acidosis, including diabetic ketoacidosis and lactic acidosis or hyperosmolar state (including coma) within the past 6 months.
• Any condition (e.g. infection, trauma, and surgery) which require insulin therapy at the time of screening or during the study period.
• Any weight loss medications within 3 months prior to randomization 10.
• Patients with NYHA class III or IV 11.
• Patients with history of myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, stroke or transient ischemic attack within past 6 months 12.
• Patients with history of unstable angina within the past 3 months.
• Patients with history of sustained and clinically relevant ventricular arrhythmia.
• Patients having history or currently suffering with severe and disabling arthralgia 15.Patients having history or currently suffering with bullous pemphigoid requiring hospitalization and taking DPP-4 inhibitors 16.
• Patients with inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption.
• Any of the following ECG abnormalities: Second or third degree AV block without a pacemaker Long QT syndrome or QTc > 500 ms 18.
• Patients with any clinically significant laboratory abnormalities/condition 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.
• Pre-planned surgery or medical procedure that would interfere with the conduct of the study 20.
• Patients with known alcohol or other substance abuse within last one year as per DSM-5 criteria.
• 21.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.
• Pregnant, lactating women or women of childbearing age who are not willing to use an acceptable method of birth control during the study period.

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	At the end of Week 16

Secondary Outcome Measures

Name	Time	Method
1. Mean Change in HbA1c from baseline at the end of Week 28
Mean Change in Postprandial Blood Glucose (PPBG) from baseline at the end of Weeks 12, 16, 24 and 28	at the end of Weeks 12, 16, 24 and 28
Mean Change in FBG from baseline at the end of Weeks 12, 16, 24 and 28	at the end of Weeks 12, 16, 24 and 28
Proportion of Participants Achieving HbA1c 7.0% at Weeks 12, 16 and 28	at Weeks 12, 16 and 28
Number of patients requiring hypoglycemia management	till end of treatment
Number of patients requiring rescue medications	Till End of treatment
Safety assessment includes Treatment Emergent Adverse Events (TEAEs) assessment during the study	during the study

Trial Locations

Locations (16)

Citizen hospital; 🇮🇳 Bangalore, KARNATAKA, India

District Civil Hospital; 🇮🇳 Aurangabad, MAHARASHTRA, India

Government Medical College & Government General Hospital; 🇮🇳 Srikakulam, ANDHRA PRADESH, India

Grant Govt. Medical College & Sir J.J. Group of Hospitals; 🇮🇳 Mumbai, MAHARASHTRA, India

IMS and SUM Hospital; 🇮🇳 Khordha, ORISSA, India

Kovai diabetes speciality hospital; 🇮🇳 Coimbatore, TAMIL NADU, India

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

Medstar Speciality Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Motilal Nehru Medical College; 🇮🇳 Allahabad, UTTAR PRADESH, India

Opal Hospital Private Limited; 🇮🇳 Varanasi, UTTAR PRADESH, India

Scroll for more (6 remaining)

Citizen hospital

🇮🇳Bangalore, KARNATAKA, India

Dr Ambana Gowda

Principal investigator

9845270377

dr.ambanagowda@gmail.com