Health Condition 1: E119- Type 2 diabetes mellitus without complications
Conditions
Interventions
Intervention1: Lobeglitazone Sulfate: Dosage Form: Oral Tablet
Dose: Lobeglitazone Sulfate 0.5 mg (or Matching Placebo)
Dosage Frequency: Once daily
Mode of Administration: Once daily in the morning w
Sponsors
Glenmark Pharmaceuticals Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Subjects must be willing and able to provide written informed consent. 2. Male and female subjects = 18 and = 65 years of age, diagnosed with T2DM. 3. Subjects who have received stable dose of metformin = 1500 mg/day as monotherapy for at least 10 weeks prior to screening and having inadequate glycemic control at screening defined as HbA1c levels of =7.5% to =10.5%. For FDC Lobeglitazone/glimepiride arm inclusion criteria for HbA1c will be =8% to =11%. 4. Willing and able to comply with all aspects of the protocol. 5. Subjects with left ventricular ejection fraction of =50% as measured using 2D echocardiography at screening. 6. Must agree to the following requirements during the study: a. If male with a partner of childbearing potential, he must be willing to use condoms in combination with a second effective method of contraception, i.e., spermicide. Each man will be considered as potent unless surgically sterilized (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate). b. Male subjects should agree not to donate sperm for 180 days following administration of the study drug. c. Females subjects of childbearing potential, including pre-menopausal women defined as all females physiologically capable of becoming pregnant, are eligible if they are using highly effective methods of contraception during dosing of study treatment; must have a negative serum pregnancy test result at screening. She must be willing to use a highly effective form of contraception for the duration of the study and for at least 3 months after the last dose of study medication. Highly effective contraception methods include: - Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception, or other form of hormonal contraception that have comparable efficacy (failure rate less than 1%) - In case of use of oral contraception, woman should have been stable on the same pill for a minimum of 3 months before taking study treatment - Intrauterine device (IUD) - Intrauterine hormone-releasing system or other forms of hormonal contraception. - Female subjects are eligible to participate if they are of non-childbearing potential defined as premenopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 month of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 MIU/mL and estradiol >141 pmol/L is confirmatory). Female subjects who have undergone female sterilization (e.g., surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking investigational drug are eligible. In case of oophorectomy alone, female subjects are eligible only when the reproductive status of the woman has been confirmed by follow up hormone level assessment)
Exclusion criteria
Exclusion criteria: .History of Type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus 2. History of metabolic acidosis or diabetic ketoacidosis 3. 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, subject will be excluded from the study 4. History of more than one episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit 5. BMI = 45.0 kg/m2 at screening 6. Subjects with elevated thyroid stimulating hormone (TSH) level at screening requiring initiation of intervention (subjects with elevated TSH and no intervention is initiated will be included in the study). 7. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 × ULN or total serum bilirubin >2.0 mg/dL at screening 8. Congestive heart failure defined as New York Heart Association (NYHA) class III/IV, unstable or acute congestive heart failure. 9. 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. Subjects with edema at screening during run-in period or at randomization visit 11. History of osteoporosis or history of bone fracture any time before screening or subjects receiving treatment for osteoporosis. 12. Subjects with uncontrolled hypertension with sitting systolic BP = 160 mmHg and/or diastolic BP = 100 mmHg at screening. Note: Subjects with SBP = 160mmHg and 13. 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 subject’s participation in the study. 14. For male subjects with mean QTcF =450 msec or female subjects with mean QTcF =470 msec, triplicate ECG will be performed. If mean QTcF is =450 msec in males or mean QTcF is =470 msec in females on triplicate ECG, subject will be excluded from the study. 15. Patients with history of hereditary QT prolongation syndrome or patients having history of Torsades de pointes. 16. Patients with history of abdominal surgery or intestinal obstruction. 17. Patients with history of acute pancreatitis. 18. Uninvestigated macroscopic haematuria at screening, during the run-in period or within 1 month before screening 19. History of haemoglobinopathy and/or haemoglobin at screening 20. Donation or transfusion of blood, plasma, or platelets within the past 3 months prior to enrolment 21. History of malignancy within the last 5 years prior to enrolment, excluding non-melanoma skin cancer (e.g. basal or squamous cell skin carcinoma) or treated car
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mean change in HbA1c levels in Lobeglitazone sulfate group compared to Pioglitazone group. 2. Mean change in HbA1c levels in FDC of Lobeglitazone sulfate and Glimepiride group compared to Lobeglitazone sulfate groupTimepoint: 1. From baseline to Week-16 2. From baseline to Week-12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in fasting insulin, HOMA-IR and HOMA-ß at week 16 in Lobeglitazone sulfate arm compared to Pioglitazone armTimepoint: From baseline to Week 16;Change from baseline in fasting insulin, HOMA-IR and HOMA-ß at week-12 in FDC of Lobeglitazone sulfate and Glimepiride arm compared to Lobeglitazone sulfate armTimepoint: From baseline to Week-12;Mean change from baseline in fasting plasma glucose (FPG) levels at week 12 FDC of Lobeglitazone sulfate and Glimepiride arm compared to Lobeglitazone sulfate armTimepoint: From Baseline to Week 12;Mean change from baseline in fasting plasma glucose (FPG) levels in Lobeglitazone sulfate arm compared to Pioglitazone armTimepoint: From baseline to week-16;Mean change from baseline in post-prandial plasma glucose (PPG) at week 16 in Lobeglitazone sulfate arm compared to Pioglitazone armTimepoint: From baseline to Week-16;Mean change from baseline in postprandial plasma glucose (PPG) at week 12 in FDC of Lobeglitazone sulfate and Glimepiride arm compared to Lobeglitazone sulfate armTimepoint: From Baseline to Week 12;Mean change in HbA1c levels in Lobeglitazone sulfate arm compared to Pioglitazone armTimepoint: From baseline to week 12;Proportion of subjects achieving a therapeutic glycaemic response, at week 12 in FDC of Lobeglitazone sulfate and Glimepiride arm compared to Lobeglitazone sulfate arm defined as: - HbA1c responders: =0.7% reduction from baseline in HbA1c or a target HbA1c of less than 7% - FPG responders: = 30 mg/dL reduction from baseline in FPG or a target FPG of less than 126 mg/dL Timepoint: At Week-12;Proportion of subjects achieving a therapeutic glycaemic response, at Week-16 in Lobeglitazone sulfate arm compared to Pioglitazone arm, defined as: - HbA1c responders: =0.7% reduction from baseline in HbA1c or a target HbA1c of less than less than 7 % - FPG responders: =30 mg/dL reduction from baseline in FPG or a target FPG of less than 126 mg/dL Timepoint: At Week-16;Proportion of subje | — |
Countries
India
Contacts
Public ContactAmol Pendse
Glenmark Pharmaceuticals Ltd
Outcome results
None listed