E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 1 diabetes |
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E.1.1.1 | Medical condition in easily understood language |
Metabolic disease in which a person has high blood glucose values due to insufficient insulin production |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012608 |
E.1.2 | Term | Diabetes mellitus insulin-dependent |
E.1.2 | System Organ Class | 100000004861 |
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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 |
The aims of this two-phase project are to 1) demonstrate proof-of-concept and 2) to compare dual-hormone with single-hormone closed-loop glucose control. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years - T1D ≥ 2 years - Insulin pump therapy with rapid-acting analog insulin ≥ 1 year - HbA1c ≤ 8.5% (69 mmol/mol) - Ability and willingness to comply with all protocol procedures |
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E.4 | Principal exclusion criteria |
- Pregnancy or nursing - Plan to become pregnant or sexually active and not using adequate contraceptive methods (sterilization, intrauterine device, contraceptive pill, patch or injection) - Hypoglycemia unawareness (self-reported lack of hypoglycemia symptoms when blood glucose is < 3.0 mmol/l) - Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during or within 30 days prior to study participation - History of coronary artery disease or congestive heart failure - Abnormal ECG suggestive of coronary artery disease and increased risk of malignant arrhythmia - Allergy to glucagon or lactose - Pheochromocytoma - Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of time with glucose values < 3.9 mmol/l as measured by CGM and YSI* Number of CHO interventions to treat hypoglycemia*
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation is performed after completion of the second study session, i.e. after two times 33-hours |
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E.5.2 | Secondary end point(s) |
Number of hypoglycemic episodes overnight and during daytime* Nadir blood glucose value for each hypoglycemic episode as measured by CGM and YSI Duration of each hypoglycemic event as measured by YSI and CGM Low Blood Glucose Index (LBGI) overnight and during daytime (YSI and CGM)* Percentage of time with glucose values < 3.3 mmol/l as measured by CGM and YSI* Percentage of time with glucose values in the range 3.9-8.0 mmol/l measured by CGM and YSI* Percentage of time with glucose values in the range 3.9-10.0 mmol/l measured by CGM and YSI* Mean blood glucose value measured by CGM and YSI* Percentage of patients with a mean blood glucose value (YSI and CGM) ≤ 8.6 mmol/l (corresponding to an estimated HbA1c of 7.0% / 53 mmol/mol) Percentage of patients with a mean blood glucose value (YSI and CGM) ≤ their standard therapy mean glucose value (calculated based on HbA1c measurement) Difference in percentage of time with glucose values <3.3, < 3.9 mmol/l, 3.9-8.0 mmol/l, 3.9-10.0 mmol/l (pairwise comparison between previous two weeks and single-hormone and dual-hormone studies, respectively) Mean Absolute Relative Difference (MARD) between CGM and YSI glucose* Blood pressure Pulse rate Steps per 33 hours (pedometer) Nausea level (VAS) Mean insulin dose Mean bolus insulin dose Mean basal insulin dose Mean glucagon dose CHO counting ability (pictures vs. actual meals) Self-assessment of glucose levels (Clarke Error Grid) Accuracy of Navigator Flash (mean absolute relative difference)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation is performed after completion of the second study session, i.e. after two times 33-hours |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Automated glucose control with insulin only, i.e. without glucagon |
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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.8.5 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |