E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with T2DM aged 40 to 70 years (including) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Diabetes type 2 aged 40 to 70 years (including) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to investigate the change in H2O2 concentration as a read out of reactive oxygen species (ROS) production in skeletal muscle biopsies from T2DM patients before and after treatment with empagliflozin or insulin glargine. |
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E.2.2 | Secondary objectives of the trial |
• to evaluate the change in skeletal muscle respiration rates (O2 consumption) as a read-out for skeletal muscle mitochondrial function • to measure the change in skeletal muscle lipid peroxidation as a functional consequence of increased ROS production • to analyze the 24-hour urinary excretion rate of 8-iso prostaglandin F2α (PGF2α) as a marker for oxidative stress • to evaluate the difference in genome wide DNA methylation pattern at single-nucleotide resolution in skeletal muscle • to evaluate contribution of circulating free fatty acid (FFA) levels to skeletal muscle ROS production
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patients aged between 40 and 70 years (including) at the first screening visit • T2DM patients with HbA1c between 7-9% (including), receiving metformin and/or DPP IV-inhibitor • Accepted background medication: Metformin and/or DPP-IV inhibitors • Stable treatment with antidiabetic drugs over the last 4 weeks • Body mass index (BMI) between 25 kg/m2 and 40 kg/m2 (including) • Ability to understand and follow study-related instructions
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E.4 | Principal exclusion criteria |
• Unstable Angina pectoris, myocardial infarction or stroke within 1 year before inclusion in the study • History of atrial fibrillation • Uncontrolled arterial hypertension (> 160/100 mmHg in three subsequent measurements – mean value) • eGFR < 60 ml/min/1.73 m2 • Marcoalbuminuria defined as albumin > 200 mg/l in spontaneous urine • Triglyceride > 250mg/dl • Genetic muscle disease • Known coagulation disorder • Treatment with anti-platelet therapy and anticoagulation which cannot be paused for medical reasons • Treatment with anticoagulants within 7 days prior to the muscle biopsy • Occurrence of ketoacidosis with the requirement for emergency care • Contraindications according to the local SmPC of Lantus® or Jardiance® (see Appendix 1) • History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure or to the local anesthetic scandicaine or lidocaine • 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 breast-feeding women
• Women of childbearing potential unless women who meet the following criteria: • Post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum 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 • Sexual abstinence • Vasectomy of the partner Males must agree not to father a child and to refrain from donating semen or sperm while participating in the study and for 90 days following discontinuation from this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change in skeletal muscle H2O2 concentration between baseline and end of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline and end of treatment |
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E.5.2 | Secondary end point(s) |
• Change in skeletal muscle mitochondrial function (O2 consumption) between baseline and EoT • Change in skeletal muscle lipid peroxidation between baseline and EoT • Change in 24-hour urinary excretion rate of 8-iso PGF2α between baseline and EoT • Changes in DNA methylation pattern in skeletal muscle between baseline and EoT as well as difference in DNA methylation pattern in skeletal muscle between the treatment groups at EoT • Change in plasma FFA levels between baseline and EoT
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at baseline and end of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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As for this study, the primary outcome will be analyzed after LPLV; the end of the study as a whole will be the date of clean database. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |