E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
People with hyperglycaemia related diabetes. |
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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 |
Treatment with Dapagliflozin will result in a statistically significant difference in palmitate production when compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
Treatment with Dapagliflozin will result in a statistically significant difference in glucose production, ketone body formation and flux when compared with placebo.
Treatment with Dapagliflozin will result in a statistically significant difference action in the sympathetic nervous system and cardiac function when compared with placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Able in the opinion of the investigator, and willing to give informed consent obtained before any study-related activities. • Diagnosis of type 2 diabetes greater than 12 months. • Single, dual or triple therapy glucose lowering agents comprising of sulphonylureas, biguanides and DDP-IV. • No previous exposure to SGLT2 inhibitors. • Aged 18 – 75 years. • BMI of less than 40. • HbA1c of greater or equal to 6.5% and less than 9% within 1 month of screening. • Able to comply with the study and the study procedures. • Patients who are or who have previously been involved in research are eligible provided they have not received an investigational drug within one month of entry into the study.
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E.4 | Principal exclusion criteria |
• Participants over 75. • Participants under 18. • Participants who cannot adequately understand verbal and / or written explanations given in English. • Clinical suspicion of Hypoglycaemic unawareness. • LADA –latent autoimmune diabetes in adults due to differing nature of the illness/Type 1. • Confirmed excessive and compulsive drinking of alcohol i.e. alcohol abuse as determined from GP medical notes by the Fast Alcohol Screening Test (FAST) or history of previous alcohol abuse. • Has a history of chronic pancreatitis • Restricted food intake - Determined by history. • Diagnosis of osteoporosis confirmed by DEXA scan. • Participants on insulin, insulin analogs or GLP-1 in the preceding 6 months. • Proliferative retinopathy that has required acute treatment within last three months. • Moderate to severe renal impairment (creatinine clearance [CrCl] < 60 ml/min or estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2. • History of unstable or rapidly progressing renal disease. • Severe hepatic insufficiency / and or significant abnormal liver function defines as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and / or alanine aminotransferase (ALT) > 3ULN. • Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody. • Congestive heart failure defined as New York Heart Association (NYHA) class III and IV, unstable or acute congestive heart failure. • Uncontrolled cardiac arrhythmias. • Uncontrolled hypertension. (BP greater than 160/90). • Mental incapacity. • Pregnancy or breast feeding women. • Those of child-bearing potential not taking adequate contraception precautions.
Adequate protection is defined as barrier protection, oral contraceptive pill or intrauterine device. • Volume depleted patients, patients at risk of volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status. • History of unstable angina. • Acute Coronary Syndrome (ACS) within 2 months prior to enrolment • Hospitalisation for unstable angina or acute myocardial infarction within 2 months prior to enrolment. • Acute Stroke or TIA within two months prior to enrolment. • Less than two months post coronary artery revascularisation. • History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalisation) within 1 month prior to the screening visit. • Known or suspected allergy to study products.
• Known Lactose-intolerant. • Have severe and enduring mental health problems • Are not primarily responsible for their own care
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint outcome measure: Plasma palmitate production rate.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Treatment with Dapagliflozin will result in a statistically significant difference in glucose production, ketone body formation and flux with Dapagliflozin when compared with placebo.
Treatment with Dapagliflozin will result in a statistically significant difference action on the sympathetic nervous system and cardiac function with chronic administration of SGLT2 inhibitors in people with Type 2 diabetes.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Metabolic assessment: 480 minutes.
Exercise test. At end of individual exercise test. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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Date when all samples have been processed for the primary and secondary endpoints. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 29 |