Subjects with Type 2 Diabetes Mellitus and Essential Hypertension Type 2 Diabetes Mellitus and Essential Hypertension
Conditions
Interventions
The participant will receive the investigational drugs THP-00101 (Dapagliflozin 10 mg), THP-00102 (Telmisartan 80 mg), and a placebo for THP-00103 once a day by per oral over 12 weeks
,The participan
Experimental Drug,Placebo Comparator Drug,Placebo Comparator Drug,Experimental Drug
Study group,Control group 1,Control group 2,Exploratory group
Sponsors
THPharm Corp.
Eligibility
Sex/Gender
All
Age
19 Years to No maximum
Inclusion criteria
Inclusion criteria: Screening (V1) 1) Adult males and females aged 19 (the legal adult age of each country) and above on the date of written informed consent 2) Subjects with type 2 diabetes mellitus accompanied by essential hypertension 3) Subjects with the following hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels at screening (V1)* - hemoglobin A1c less than or equal to 9.5% and more than 6.5% - fasting plasma glucose less than or equal to 270 mg/dL *Including subjects who did not use oral hypoglycemic agents within 8 weeks from screening and subjects who took metformin monotherapy or dual combination therapy that included metformin for 8 weeks or longer from screening 4) Subjects with the following mean sitting systolic blood pressure (MSSBP) measured in the reference arm** at screening (V1)*** - If not taking antihypertensive agents : MSSBP less than 160 mmHg and more than 140 mmHg - If taking antihypertensive agents : MSSBP less than 160 mmHg and more than 130 mmHg **Reference arm: The arm with the higher MSSBP after measuring it 3 times in each arm at screening (V1) (If the MSSBP is the same between both arms, then the arm with the higher mean sitting diastolic blood pressure (MSDBP) is selected as the reference arm.) ***Classified based on whether antihypertensive agents were administered within 4 weeks from screening (V1) 5) Subjects considered by the investigator appropriate to discontinue the use of oral hypoglycemic agents and antihypertensive agents, other than the existing metformin, during the study (with metformin maintained at a minimum of 1,000 mg/day) 6) Subjects who received a sufficient explanation of the objectives and content of the study and voluntarily provided written informed consent [Baseline (V2)] 1) Subjects with the following HbA1c and FPG levels at baseline (V2) - HbA1c less than or equal to 9.5% and more than 6.5% - FPG less than or equal to 270 mg/dL 2) Subjects with the following MSSBP measured in the reference arm at baseline (V2) - MSSBP less than 160 mmHg and more than 140 mmHg 3) Subjects who did not take oral hypoglycemic agents other than the same dose of metformin (More than 1,000 mg/day) for at least 8 weeks before baseline (V2) 4) Subjects who did not take antihypertensive agents for at least 2 weeks before baseline (V2) 5) Subjects with no disqualifying inclusion/exclusion criteria of screening (V1) when evaluating eligibility again at baseline (V2) 6) Subjects with compliance of 70% or higher with the investigational product during the run-in period [Extension Period] 1) Subjects who have completed all procedures of the treatment period. Subjects who are unsuitable to participate in the study of the extension period, considering safety, etc., can be excluded. 2) Subjects who received a sufficient explanation of the objectives and content of the extension period study and voluntarily provided written informed consent
Exclusion criteria
Exclusion criteria: 1) Subjects with the following blood pressures measured at screening, V1 and randomization, V2 1.1) Subjects with the following mean sitting diastolic blood pressure (MSDBP) measured in the reference arm - MSDBP less than or equal to 110 mmHg 1.2) Subjects with the following difference in mean blood pressure measured three times consecutively in each arm at least 2 minutes apart at screening, V1: mean sitting systolic blood pressure (MSSBP) less than or equal to 20 mmHg and MSDBP less than or equal to 10 mmHg 2) Subjects with a body mass index (BMI) of greater than 35 kg/m2 3) Subjects with the following comorbidities or conditions 3.1) Mild to severe hepatic impairment (3.2) Biliary obstruction or cholestasis 3.3) AST or ALT more than 2 times ULN 3.4) Total bilirubin greater than 2 times upper limit normal (ULN) 3.5) Patients with moderate, stage 3b, or severe renal impairment (eGFR by IDMS-MDRD greater than 45 mL/min/1.73 m2) 3.6) Acute conditions that may affect renal function, such as dehydration, severe infection, cardiovascular collapse (shock), and sepsis 3.7) Diabetic precoma and coma 3.8) Severe infection or severe traumatism 3.9) Malnutrition, starvation, debilitation, pituitary insufficiency, or adrenal dysfunction 3.10) Acute or chronic diseases that may cause tissue hypoxia such as respiratory failure (pulmonary infarction and severe pulmonary dysfunction) and shock, and gastrointestinal disorders including dehydration, diarrhea, and vomiting 3.11) Orthostatic hypotension with symptoms 3.12) Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter, or other arrhythmia considered clinically significant as judged by the investigator 3.13) Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve or mitral valve stenosis 3.14) Wasting diseases, autoimmune diseases, and connective tissue diseases 3.15) Dysuria, anuria, oliguria, and ischuria that cannot be controlled by drugs 3.16) Gastrointestinal diseases that may affect the absorption of the investigational product (gastrointestinal ulcer, gastritis, gastric spasm, gastroesophageal reflux disease, Crohn's disease, etc.) 3.17) Subjects who are HBsAg positive**** or HCV antibody positive***** ****Subjects who are taking antiviral products stably may participate *****Subjects with negative HCV RNA test results may participate 3.18) Subjects who are positive for HIV Ag/Ab combo test 4) Subjects with the following past medical history 4.1) Hereditary angioedema or angioedema caused by ACE inhibitor or angiotensin II antagonist treatment. 4.2) Hereditary problems such as galactose intolerance, Lapp lactose deficiency, glucose-galactose malabsorption, etc. 4.3) Type 1 diabetes mellitus, secondary diabetes mellitus, lactic acidosis, acute or chronic metabolic acidosis, and ketoacidosis including diabetic ketoacidosis accompanied or not accompanied by coma 4.4) Drug abuse or alcohol abuse 4.5) Past medical history of secondary hypertension or all medical history suspected of secondary hypertension (not limited to the following: coarctation of aorta, primary hyperaldosteronism, renal artery stenosis, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, etc.) 4.6) Severe cardiac failure (NYHA class III and IV), ischemic heart disease (unstable angina and myocardial infarction), and peripheral vascular diseases that oc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in Hemoglobin A1c (HbA1c) 12 weeks The Hemoglobin A1c will be measured using the high performance liquid chromatography (HPLC) method. ,Changes in Mean Sitting Systolic Blood Pressure (MSSBP) 12 Weeks When using a digital blood pressure monitor, the subject should sit on a chair with their back supported, relax for at least 5 minutes, and keep their arm at heart level during the measurement | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in glycemic parameter: hemoglobin A1c,fasting plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function (HOMA-beta) 4, 8, and 12 weeks from baseline HbA1c, FPG, HOMA-IR, and HOMA-beta will be measured using high-performance liquid chromatography and the hexokinase method, with HOMA-IR and HOMA-beta calculated, respectively.,Changes in blood pressure: mean sitting systolic blood pressure, mean sitting diastolic blood pressure, pulse pressure, percentage of normalized blood pressure, and response rate of blood pressure 4, 8, and 12 weeks from baseline When using a digital blood pressure monitor, the subject should sit on a chair with their back supported, relax for at least 5 minutes, and keep their arm at heart level during the measurement | — |
Countries
Thailand
Contacts
Public ContactJaewoo Park
THPharm Corp.
Outcome results
None listed