E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 and Type 3c diabetes |
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E.1.1.1 | Medical condition in easily understood language |
People with hyperglycaemia related to a pancreatic condition secondary to pancreatic surgery or immune condition |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
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 |
To determine the difference in glucose concentration of Dapagliflozin when compared with placebo treatment following insulin withdrawal.
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E.2.2 | Secondary objectives of the trial |
To determine the difference in glucose and lipid flux of Dapagliflozin when compared to placebo following insulin withdrawal. |
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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 trial-related activities. • Type 1 diabetes or type 3c (chronic pancreatitis or undergone pancreatic surgery) according to clinical judgment. • Duration of type 1 or type 3c diabetes (chronic pancreatitis or undergone pancreatic surgery) greater than 12 months. • Current treatment basal bolus or insulin pump therapy • Aged 18 years or over • BMI of less than 35. • HbA1c of greater or equal to 6.5% and less than 9%. • Able and willing to complete the trial. • 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 65 • Participants who cannot adequately understand verbal and / or written explanations given in English • Proliferative retinopathy that has required acute treatment within last three months. • 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 • Restricted food intake (e.g. on VLC diets) - as this depletes the person of calories and may affect your data. Consider excluding Individuals on a severe calorie restricted diet <800cals/day. Determined by history • Diagnosis of osteoporosis confimed by DEXA scan. • 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. Note: eligible patients with congestive heart failure, especially • 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 depleting due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status • History of unstable angina. • Recent Cardiovascular Events in a patient: • 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 revascularization • History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. Accident and Emergency and/or hospitalisation) within 1 month prior to the Screening visit. • Known or suspected allergy to trial products. • Known lactose-intolerant individuals. • Any other medical or psychological conditions that would interfere with the trial participation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Plasma glucose concentration at 600 minutes following insulin cessation or at the time of glycaemic rescue, whichever occurs first. |
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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) |
1. Endogenous glucose production 2. Peripheral glucose uptake 3. Urinary glucose excretion 4. Glycerol rate of appearance 5. Non-esterified fatty acid production 6. Ketone body production
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 31 |
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 | 28 |