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 | 20.0 |
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 ≥ 1 - Currently using FiAsp® - insulin - HbA1c ≤ 8.5% (69 mmol/mol)
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E.4 | Principal exclusion criteria |
- Pregnancy or nursing - Inability and willingness to comply with all protocol procedures, e.g. exercise, sleeping, blood sampling, and meal consumption - 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
Withdrawal criteria - In case of pregnancy (or desire for pregnancy), female subjects are withdrawn - Lack of compliance to any of the important study procedures in the discretion of the investigator - Unacceptable adverse effects in the discretion of the investigator - Withdrawal on participants request will be accepted at any time without further justification
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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* 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) |
Secondary outcomes between single- and dual-hormone closed-loop system: - Percentage of time with glucose values < 3.9 mmol/l as measured by YSI* - Composite outcome: Percentage of participants achieving (1) time in range (3.9-10) > 70 %, (2) time in alert hypoglycemia (<3.9 mmol/l) < 4 %, and (3) time in clinical hypoglycemia (<3.0 mmol) < 1% as measured by CGM and YSI* - Mean blood glucose value 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* - Percentage of time with glucose values in the range > 10.0 mmol/l measured by CGM and YSI* - Percentage of time with glucose values < 3.0 mmol/l as measured by CGM and YSI* - 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 - CGM glycemic variability measured as SD and CV during overnight and during daytime* - Low Blood Glucose Index (LBGI) overnight and during daytime CGM* - Percentage of participants 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) - Mean Absolute Relative Difference (MARD) between CGM and YSI glucose* - Mean blood pressure over the study period - Mean pulse rate over the study period - Mean 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) - Raw acceleration measured by ActiGraph GT9X Link - Energy expenditure measured by ActiGraph GT9X Link - Steps taken measured by ActiGraph GT9X Link - Physical activity intensity measured by ActiGraph GT9X Link - Heart rate R-R intervals measured by ActiGraph GT9X Link - Sleep latency measured by ActiGraph GT9X Link - Total sleep time measured by ActiGraph GT9X Link - Sleep efficiency measured by ActiGraph GT9X Link - Mean Borg scale level during exercise - Diabetes Treatment Satisfaction Questionnaires, DTSQ - Diabetes Technology Questionnaire, DTQ - Hypoglycemia fear survey, HFS |
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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 | Yes |
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 | |