E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
type 1 diabetes mellitus |
type 1 diabetes mellitus |
|
E.1.1.1 | Medical condition in easily understood language |
type 1 diabetes mellitus |
type 1 suikerziekte |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
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 |
To investigate the effect of three degludec dosing regimens on the risk of post-exercise nocturnal hypoglycaemia (time spent in glucose range ≤3.8 mmol/l, 00:00 to 05:59h) in type 1 diabetes mellitus patients at elevated risk of hypoglycaemia. |
Onderzoek naar het effect van drie degludec doseringsschema's op het risico op nachtelijke hypoglykemieën (tijd in glucose range ≤3.8 mmol/l, 00:00 tot 05:59h) bij patiënten met type 1 diabetes mellitus met verhoogd risico op hypoglycemie. |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of three post-exercise degludec dosing regimens on:
- Time spent in nocturnal hyperglycaemia
- Number of nocturnal hypoglycaemic events
- Number of serious hypoglycaemic events (in the 6 days following exercise)
- Number of severe hypoglycaemic events (in the 14 days following exercise)
- Total number of hypoglycaemic events (in the 6 days following exercise)
|
Onderzoek naar het effect van drie degludec doseringsschema's op:
- Tijd in nachtelijke hypoglykemie
- Aantal nachtelijke hypoglykemieën
- Aantal ernstige (serious) hypoglykemieën (in de 6 dagen na de inspanning)
- Aantal ernstige (severe) hypoglykemieën (in de 14 dagen na de inspanning)
- Totaal aantal hypoglykemieën (in de 6 dagen na de inspanning) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adults with type 1 diabetes mellitus, 18-60 years
• Diabetes duration at least two years
• Treatment with long-acting insulin in combination with short-acting insulin analogue, according to basal-bolus regimen for at least one year
• Stable glycaemic control with HbA1c ≤75 mmol/mol (9%)
• At least one severe hypoglycaemia in the past year and/or ≥2 points on Dutch modified version of Clarke score or ≥3 points on Gold score
• Regularly engaging in exercise of moderate intensity or more (at least one hour per week)
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• Volwassenen met type 1 diabetes mellitus, 18-60 jaar
• Diabetesduur minimaal twee jaar
• Behandeling met langwerkende insuline in combinatie met kortwerkende insuline volgens basaal-bolus schema gedurende minimaal één jaar
• Stabiele glucosecontrole met HbA1c ≤75 mmol/mol (9%)
• Minimaal één ernstige hypoglykemie in het afgelopen jaar en/of ≥2 punten in de Nederlandse gemodificeerde versie van de Clarke score of ≥3 punten op de Gold score
• Regelmatig minimaal matige inspanning (minimaal één uur per week)
|
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E.4 | Principal exclusion criteria |
• Microvascular complications, except background retinopathy or microalbuminuria
• History of cardiovascular disease, including heart failure, symptomatic cardiac valve disease and treatment-requiring arrhythmia
• Use of drugs affecting glucose metabolism other than insulin or metformin
• BMI >30 kg/m2
• Blood pressure >160/90 mmHg or use of blood pressure lowering drugs
• Pregnancy or the wish to become pregnant
• MDRD-GFR <60 ml/min/1.73 m2
|
• Microvasculaire complicaties, behalve achtergrond retinopathie of microalbuminurie
• Voorgeschiedenis van hart-vaatziekten, inclusief hartfalen, symptomatische hartklepaandoening en arrhythmie die behandeling behoeft
• Gebruik van geneesmiddelen die het glucosemetabolisme beïnvloeden anders dan insuline of metformine
• BMI >30 kg/m2
• Bloeddruk >160/90 mmHg of gebruik van antihypertensiva
• Zwangerschap of de wens zwanger te worden
• MDRD-GFR <60 ml/min/1.73 m2 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time spent in hypoglycaemic range (i.e. glucose ≤3.8 mmol/l) during the night (00:00 to 05:59h) following the exercise day measured by continuous glucose monitoring. |
Tijd in hypoglykemische range (i.e. glucose ≤3.8 mmol/l) gedurende de nacht (00:00 tot 05:59h) volgend op de inspanning gemeten met continue glucose monitoring |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of each treatment period |
Aan het eind van elke behandelingsperiode |
|
E.5.2 | Secondary end point(s) |
• Time spent in hyperglycaemic range during the night (00:00 to 05:59h) following the exercise day measured by CGM
• Number of nocturnal hypoglycaemic events during the night (00:00 to 05:59h) following the exercise day measured by CGM
• Number of serious hypoglycaemic events during the 6 days following the exercise day measured by CGM
• Number of severe hypoglycaemic events during the 14 days following the exercise day
• Total number of hypoglycaemic events during the 6 days following the exercise day measured by CGM
|
• Tijd in hyperglykemische range gedurende de nacht (00:00 tot 05:59h) volgend op de inspanning gemeten met CGM
• Aantal nachtelijke hypoglykemieën gedurende de nacht (00:00 tot 05:59h) volgend op de inspanning gemeten met CGM
• Aantal ernstige (serious) hypoglycemieën in de 6 dagen volgend op de inspanning gemeten met CGM
• Aantal ernstige (severe) hypoglycemieën in de 14 dagen volgend op de inspanning
• Totaal aantal hypoglykemieën in de 6 dagen volgend op de inspanning gemeten met CGM |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of each treatment period |
Aan het eind van elke behandelingsperiode |
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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 | No |
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 | 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 |
Same medicinal product in other dosing regimen |
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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 | |