Patients with T2DM and hypertension aged 40 to 70 years (including)
Conditions
Interventions
Trade Name: Forxiga
Product Name: Forxiga
Pharmaceutical Form: Film-coated tablet
CAS Number: 461432-26-8
Other descriptive name: DAPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
University Hospital Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female patients aged between 40 and 70 years (including) • Diagnosis of type 2 diabetes mellitus (T2DM) with HbA1c between 7.5-10% (including) • Stable treatment with insulin with or without oral antidiabetic drugs (OADs) over the last 4 weeks • Body mass index (BMI) between 25 kg/m2 and 35 kg/m2 (including) • Blood pressure > 140/85 mmHg • Ability to perform at least 75 W in spiroergometry • Ability to understand and follow study-related instructions • Negative pregnancy test • Patients who are receiving the following medications must be on a stable treatment regimen for at least 2 months prior to the Screening visit (V1): antihypertensive agents, thyroid replacement therapy, antidepressant agents Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 37 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: Diagnosis of Type 1 diabetes • History of diabetic ketoacidosis, hyperosmolar coma or corticosteroid-induced T2DM • Patients with significant thyroid disease • Clinically significant cardiovascular disease (CVD) or procedure within 3 months prior to enrolment or expected to require coronary revascularization procedure • Presence of history of severe congestive heart failure (NYHA III and IV), pace maker or aortic stenosis (AS) > II • Creatinine clearance (CrCl) of 3 x upper limit of normal (ULN) and/or total bilirubin (TB) > 2 mg/dL (> 34.2 µmol/L) (patients with TB allowed to participate) • Known or suspected human immunodeficiency virus (HIV) infection • History of organ transplantation • Malignancy (with the exception of basal and squamous cell carcinoma of the skin) within 5 years prior to the Screening visit (V1) • Hemoglobinopathy, hemolytic anemia, or chronic anemia or any other condition known to interfere with the HbA1c methodology • Has donated blood or had a significant blood loss within 2 months of first dose of study medication or is planning to donate blood during the study • Has donated plasma within 7 days prior to first dose of study medication • Any previous exposure to dapagliflozin or any other SGLT2 inhibitor, or HCT • Systemic corticosteroids within 3 months prior to the Screening visit (V1) known to have a high rate of systemic absorption • History of chronic obstructive pulmonary disease (COPD) or asthma • Disabilities contraindicating spiroergometry • Uncontrolled hypertension with blood pressure > 180/100 mmHg • Alcohol consumption > 20 g/day for women or > 30 g/day for men • History of hypersensitivity to any of the study drugs or their ingredients • Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study • Pregnant or breastfeeding women • Women of childbearing potential unless women who meet the following criteria: o Post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum follicle-stimulating hormone [FSH] > 40 U/mL) o Postoperatively (six weeks after bilateral ovariectomy with or without hysterectomy) o Regular and correct use of a contraceptive method with error rate < 1% per year such as implants, depot injections, oral contraceptives or intrauterine devices. As applicable, all methods must be in effect prior to receiving the first dose of study medication and must be practiced during the study and for 10 weeks after the last dose of study medication. o Sexual abstinence o Vasectomy of the partner
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate the change in erythropoietin (EPO) levels after 2 weeks of treatment with dapagliflozin in comparison to treatment with placebo;Secondary Objective: to evaluate the change in physical fitness as assessed by spiroergometry and lactate threshold • to evaluate the impact of hydrochlorothiazide (HCT) on EPO levels • to measure the change in reticulocyte concentration, hematocrit and red blood cells • to measure the change in hypoxia-inducible factor (HIF) regulated hepcidin concentrations • to measure the change in iron status • to measure the change in catecholamine and steroid hormone concentrations Other objective(s) • to monitor glucose control • to monitor the safety and tolerability of the treatments as determined by the occurrence of adverse events and changes in vital signs and laboratory parameters • to evaluate the change in blood EPO levels between baseline and end of treatment (EoT);Primary end point(s): Change in blood EPO levels between baseline and after 2 weeks of treatment;Timepoint(s) of evaluation of this end point: Change in blood EPO levels between baseline and after 2 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Change in physical fitness between baseline and EoT as assessed by spiroergometry (VO2max, heart rate and lactate threshold) • Change in reticulocyte concentration, hematocrit and red blood cells between baseline and after 2 and 4 weeks of treatment • Change in hepcidin between baseline and after 2 and 4 weeks of treatment • Change in iron status between baseline and after 2 and 4 weeks of treatment as measured by Fe, ferritin, transferrin • Change in catecholamine (adrenalin, noradrenalin, and metabolites metanephrine and normetanephrine) and steroid hormone concentrations between baseline and after 2 and 4 weeks of treatment ;Secondary end point(s): Change in physical fitness between baseline and EoT as assessed by spiroergometry (VO2max, heart rate and lactate threshold) • Change in reticulocyte concentration, hematocrit and red blood cells between baseline and after 2 and 4 weeks of treatment • Change in hepcidin between baseline and after 2 and 4 weeks of treatment • Change in iron status between baseline and after 2 and 4 weeks of treatment as measured by Fe, ferritin, transferrin • Change in catecholamine (adrenalin, noradrenalin, and metabolites metanephrine and normetanephrine) and steroid hormone concentrations between baseline and after 2 and 4 weeks of treatment Other variable(s) • Fasting blood glucose (FBC) and HbA1c • Parameters derived from Flash Glucose Monitoring between screening and baseline (V1 to V2) and between V3 and EoT (V3 to V4) • Adverse events, vital signs (pulse, blood pressure), safety laboratory parameters • Change in blood EPO levels between baseline and EoT | — |
Countries
Germany
Contacts
Public ContactManola Zago
University Hospital Tuebingen
Outcome results
None listed