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 characterised 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 compare the efficacy of single-administration low-dose (150 µg) s.c. glucagon and split-administration low-dose (2 x 75 µg) s.c. glucagon to placebo for prevention of exercise-induced hypoglycemia in people with type 1 diabetes using insulin pumps and multiple daily injections (MDI).
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to compare the accuracy of three continuous glucose monitors - Dexcom G6, FreeStyle Libre 2 and Guardian 4 during and after exercise in inpatient and outpatient settings. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 • T1D ≥ 2 years • Use of insulin pump or MDI therapy for ≥ 6 months • Current use of insulin aspart • HbA1c ≤ 70mmol/mol (8.5%) • Body mass index (BMI) ≤ 30 kg/m2 • Performs exercise ≥ 1 time per week
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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 Professional athletes or highly active individuals (≥ 5 hours of exercise per week) Known or suspected allergies to glucagon or related products History of hypersensitivity or allergic reaction to glucagon or lactose Allergy to the patch of the CGM devices Patients with pheochromocytoma, insulinoma or gastroparesis 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) |
The primary endpoint is: Incidence rate of hypoglycemia (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 180 minutes post-intervention |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: • Percentage of time below range (PG < 3.9) from 0-180 minutes post-intervention • Percentage of time in range (PG ≥ 3.9 mmol/l and ≤ 10.0 mmol/l) from 0-180 minutes post-intervention • Time (min) to hypoglycemia (PG < 3.9 mmol/l) • Change in plasma glucose levels • Incidence rate of 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 • Plasma glucose Area Under the Curve (AUC) from 0 to 180 min post-intervention • Percentage of time in hyperglycemia (PG > 10 mmol/l) from 0-180 minutes post-intervention • Change in visual analogue scale (VAS) for nausea, headache, stomach ache, injection site pain and palpitations from intervention (tintervention = 0) to 180 min post-intervention (tintervention = 180)
1A sub-analysis looking at the 60-minutes exercise session and 2-hour observation period separately will also be conducted.
The secondary CGM endpoints are the difference between the Dexcom G6, FreeStyle Libre 2 and Guardian 4 sensors in: • Mean absolute relative difference (MARD) during the 60-minutes exercise session (using SMBG as the reference value) • MARD during the three-day outpatient period (using the 5 daily SMBG as the reference value) • MARD during the three-hour inpatient study visit (using YSI as reference value) • Rate-of change (ROC) accuracy (using SMBG and YSI as the reference value) • Point accuracy with the Clarke Error Grid Analysis (CEGA) (using SMBG and YSI as the reference value)
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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 endpoints" 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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
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 | |