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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 whether dapagliflozin (either taken regularly or as a single dose) can delay/prevent the onset of hypoglycaemia during moderate intensity exercise. |
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E.2.2 | Secondary objectives of the trial |
1. Whether dapagliflozin can prevent late-onset exercise-induced hypoglycaemia (overnight or the following day).
2. Measure the release of glucagon and somatostatin during and after exercise, on and off dapagliflozin.
3. Determine the changes in plasma electrolytes during exercise. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age >18 2. Type 1 diabetes diagnosed at least 12months prior to screening test 3. On insulin pump or multiple daily injections 4. HbA1c <10% (86mmol/mol) 5. Engage in some form of regular exercise 6. Have experienced at least one episode of exercise-induced hypoglycaemia 7. Adequate treatment of celiac disease if it exists. 8. Willing and able to give informed consent for participation in the trial 9. In the Investigator’s opinion is able and willing to comply with all trial requirements 10. Willing to allow their General Practitioner and/or consultant, if appropriate, to be notified of participation in the trial.
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E.4 | Principal exclusion criteria |
1. History of seizure or coma associated with hypoglycaemia in the past 2 years 2. Active diabetic retinopathy (including proliferative diabetic retinopathy or vitreous haemorrhage in the past 6 months) 3. Pregnant or planning to become pregnant during the course of the study 4. History of ischemic heart disease (unless has had successful reperfusion), stroke/TIA, ventricular rhythm disturbances or thromboembolic disease 5. Renal impairment (eGFR <60ml/min/1.73m2) 6. Untreated Graves disease 7. ECG or stress test findings indicating active ischemia or a condition that would compromise the participant’s safety 8. Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse 9. Known or suspected allergy to trial medication 10. Oral or injectable steroid treatment 30 days prior to the start or at any time during the trial period 11. On beta-blocker medication 12. Known malignancy or any other condition or circumstance which, in the opinion of the investigator, would affect the patient’s ability to participate in the protocol 13. Receipt of any investigational trial drug within 3 month prior to participation in the current trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to hypoglycemia during exercise challenge (before and after dapagliflozin treatment), and between treatment groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Exercise challenge in part A and part B. |
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E.5.2 | Secondary end point(s) |
1. Duration of time in hypoglycaemia (categorised as <4mmol/L or <3mmol/L) from CGM recordings before and after dapagliflozin treatment, and between treatment groups.
2. Concentration of plasma glucose, glucagon and somatostatin-14 (pancreatic-specific) at each 10min interval during exercise challenge.
3. Concentration of plasma potassium, sodium, calcium and pH at each 10min interval during exercise challenge.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 24-hour period after each exercise challenge.
2. 10 minute intervals during each exercise challenge.
3. 10 minute intervals during each exercise challenge.
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | No |
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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The end of the trial is defined as the date of the last telephone follow up of with the last participant. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 19 |