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 |
Type 1 diabetes is a metabolic disease characterized by deficient 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 | 21.1 |
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 |
The primary objective of the study is to evaluate the efficacy, safety and feasibility of outpatient-utilization of low-dose (80 μg) dasiglucagon administered via an investigational trial device (a multi-dose reusable pen injector) in preventing and treating mild hypoglycemia in insulin pump-treated people type 1 diabetes |
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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 • Use of insulin pump therapy (without sensor-augmented insulin suspension/adjustment functionality) ≥ 6 months • Use of CGM (real-time or intermittently scanned) ≥ 3 months and ≥ 70% during the previous 14 days • HbA1c ≤ 70 mmol/l (8.5%) • Performs aerobic exercise on a regular basis (≥ 2 times per week; self-reported) and desires to exercise per American Diabetes Association guidelines (150 minutes per week) during the study. • Use of carbohydrate counting and bolus calculator (self-reported) • Sensor glucose level (SGL) < 3.9 mmol/l on ≥ 4/14 previous days assessed by CGM data
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E.4 | Principal exclusion criteria |
• Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period and within 30 days prior to study start • Know or suspected allergies to glucagon or related products • History of hypersensitivity or allergic reaction to dasiglucagon or any of the excipients (refer to Table 1 in the Investigators brochure) • Patients with pheochromocytoma or insulinoma • Hypoglycemia unawareness • Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (methods are considered adequate for study enrollment for females: an intrauterine device, hormonal contraception (birth control pills, implant, patch, vaginal ring or injection), a single partner who is sterile or infertile, or sexual abstinence. Contraception is required throughout the study duration. Sterilized or postmenopausal women (>12 months since last period) are not required to use contraception) • Inability to understand the individual information and to give informed consent • Current participation in another clinical trial that, in the judgment of the investigator, will compromise the results of the study or the safety of the subject • Concomitant medical or psychological conditions identified through review of medical history, physical examination and clinical laboratory analysis that, according to the investigator's assessment, makes the individual unsuitable for study participation
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percentage of time in target glucose range [SGL ≥ 3.9 mmol/l and ≤ 10.0 mmol/l] |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From start (day 1) to end (day 14) of each intervention period. |
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E.5.2 | Secondary end point(s) |
• Percentage of time in hypoglycemia [SGL < 3.9 mmol/l] • Percentage of time in hyperglycemia [SGL > 10 mmol/l] • Coefficient of variation (%) • Successful cases (%) of hypoglycemia treatment* [initial SGL ≥ 2.2 mmol/l and ≤ 3.9 mmol/l AND SGL > 3.9 mmol/l 30 minutes post-treatment] • Successful cases (%) of hypoglycemia treatment* [initial SGL ≥ 2.2 mmol/l and ≤ 3.9 mmol/l AND SGL > 3.9 mmol/l 30 minutes post-treatment] without subsequent hyperglycemia [SGL > 10 mmol/l during the first two hours post-treatment] • Successful cases (%) of hypoglycemia prevention* [initial SGL > 3.9 mmol/l AND SGL < 3.9 for ≤ 15 consecutive minutes during the first two hours post-treatment] • Time (min) from hypoglycemia treatment [initial SGL ≥ 2.2 mmol/l and ≤ 3.9 mmol/l] to euglycemia [SGL ≥ 3.9 mmol/l] • Incidence rate of supplement carbohydrate administration during the first hour following dasiglucagon administration • Average daily carbohydrate intake registered on the insulin pump • Average total daily insulin dose (basal and bolus) • Number and intensity (mild/moderate/severe) of episodes with nausea, headache, stomach-ache, palpitations and injection site pain [assessed by questionnaire each day during the two intervention periods (appendix 3)] • Percentage of participants scoring a favorable outcome [likely OR very likely] on the patient-reported outcome questionnaire [measured on a four-point Likert scale**] *Cases where the assigned intervention (carbohydrate consumption or dasiglucagon) was used to treat/prevent the hypoglycemic event **How likely is it that you, given the option, would use dasiglucagon as part of your diabetes management? (Very unlikely, unlikely, likely, very likely)
Safety evaluation endpoints: • Percentage of participants with treatment-induced or treatment-boosted anti-dasiglucagon antibodies
Device endpoint: • Device failures/malfunctions occurring during the trial.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From start (day 1) to end (day 14) of each intervention period. |
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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) | 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 | 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 |
Usual care, i.e. use of carbohydrates (food/drinks) to prevent or treat mild hypoglycemia |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |