Dapagliflozin Effect on Erythropoiesis and Physical Fitness

• Status: Unknown status
• Trial end date: 2021-03-31
• Target enrollment: 0
• Participant gender: All

Summary

Dapagliflozin effect on erythropoiesis and physical fitness in patients with type 2 diabetes

• a randomized, double-blind, controlled, parallel group, exploratory study

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GWT-TUD GmbH
• Treatments: Dapagliflozin; Hydrochlorothiazide

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

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 < 60 ml/min, unstable or rapidly progressing renal disease or anuria

• Concomitant medication with loop diuretics

• Triglyceride concentrations ≥ 700 mg/dL (≥ 7.98 mmol/L) at the Screening visit (V1)

• History or presence of inflammatory bowel disease or other severe gastrointestinal diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis

• History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded

• Significant hepatic disease, including, but not limited to, acute hepatitis, chronic active hepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) and/or total bilirubin (TB) > 2 mg/dL (> 34.2 μmol/L) (patients with TB > 2 mg/dL [> 34.2 μmol/L] and documented Gilbert's syndrome will be 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:

• Post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum follicle-stimulating hormone [FSH] > 40 U/mL)

• Postoperatively (six weeks after bilateral ovariectomy with or without hysterectomy)

• 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.

• Sexual abstinence

• Vasectomy of the partner