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 main objective of the study is to compare the efficacy of low-dose (80 and 120 μg) dasiglucagon to oral carbohydrate (15 g) consumption for prevention of s.c. insulin-induced hypoglycemia in people with 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 18-64 years
• Type 1 diabetes ≥ 3 years
• Use of continuous subcutaneous insulin infusion or multiple daily injection therapy for ≥ 6 months
• HbA1c ≤ 8.0%
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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 or within 30 days prior to study start
• History of allergy or intolerance to glucagon or glucagon-like products
• Patients with pheochromocytoma
• Clinically significant ECG abnormalities
• Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (sterilization, intrauterine device, contraceptive pill, patch or injection)
• Inability to understand the individual information and to give informed consent
• Current participation in another clinical trial that, in the judgment of the principle investigator, will compromise the results of the study or the safety of the subject
• Other concomitant medical or psychological condition 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) |
• Time (min) in hypoglycemia (P-glucose (PG) < 3.9 mmol/l) from 0-180 minutes post-intervention |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From 0-180 minutes post-intervention |
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E.5.2 | Secondary end point(s) |
• Incidence rate of hypoglycemia (PG < 3.9 mmol/l) from 0-180 minutes post-intervention
• Incidence rate of level 2 hypoglycemia (PG < 3.0 mmol/l) from 0-180 minutes post-intervention
• Incidence rate of rebound hyperglycemia (PG > 10 mmol/l) from 0-180 minutes post-intervention
• Nadir plasma glucose concentration from 0-180 minutes post-intervention
• Peak plasma glucose concentration from 0-180 minutes post-intervention
• Incremental peak in plasma glucose concentration from 0-180 minutes post-intervention
• Mean plasma glucose concentration from 0-180 minutes post-intervention
• Time (min) from intervention to first increase in plasma glucose concentration of 1.1 mmol/l
• Plasma glucose Area Under the Curve (AUC) from 0 to 180 min post-intervention
• Time to peak plasma glucose concentration from 0-180 minutes post-intervention
• Time (min) in range (PG ≥ 3.9 mmol/l and 10.0 mmol/l) from 0-180 minutes post-intervention
• Time (min) in hyperglycemia (PG > 10 mmol/l) from 0-180 minutes post-intervention
• Time (%) in hypoglycemia (PG < 3.9 mmol/l) from 0-180 minutes post-intervention (per protocol)
• Incidence rate of rescue carbohydrate administration from 0-180 minutes post-intervention
• Time (min) to rescue carbohydrate administration from 0-180 minutes post-intervention
• Plasma dasiglucagon Area Under the Curve (AUC) from 0-180 minutes post-intervention
• Peak plasma dasiglucagon concentration from 0-180 minutes post-intervention
• Time to peak plasma dasiglucagon concentration from 0-180 minutes post-intervention
• Serum insulin concentration at t = 0 and tintervention = 0
• Serum insulin AUC from 0-180 minutes post-intervention
• Dose (units) of insulin bolus at t = 0
• Change in Edinburgh Hypoglycemia Symptoms Scale (EHSS) from intervention (t-intervention = 0) to 180 min post-intervention (tintervention = 180)
• Change in visual analogue scale (VAS) for nausea, headache, stomach ache, injection site pain, palpitations and hunger from intervention (t-intervention = 0) to 180 min post-intervention (t-intervention = 180)
• Incidence rate of vomiting 0-180 minutes post-intervention
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From 0-180 minutes post-intervention (unless specified otherwise in the "Secondary end points" section |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Partially single-blinded (only dasiglucagon-dose is blinded) |
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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 |
15 g of carbohydrate (glucose tabs) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |