E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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 |
To compare the effects of insulin degludec once daily and insulin glargine 300 units/mL once daily
on hypoglycaemia in subjects with type 2 diabetes mellitus, inadequately treated with basal insulin
with or without oral anti-diabetic drugs. |
|
E.2.2 | Secondary objectives of the trial |
To compare insulin degludec and insulin glargine 300 units/mL in terms of basal insulin
requirement.
To compare insulin degludec and insulin glargine 300 units/mL in terms of safety and parameters of
glycaemic control. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age above or equal to 18 years at the time of signing informed consent.
- Subjects fulfilling at least one of the below criteria *:
a. Experienced at least one severe hypoglycaemic episode within the last year
(according to the ADA definition, April 2013**).
b. Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59
mL/min/1.73 m^2 per CKD-EPI by central laboratory analysis.
c. Hypoglycaemic symptom unawareness***.
d. Treated with insulin for more than 5 years.
e. Episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode
with low glucose measurement (below or equal to 70 mg/dL [below or equal to 3.9 mmol/L])) within the last 12 weeks prior to Visit 1(screening).
- Subjects diagnosed (clinically) with type 2 diabetes mellitus.
- Treated with basal only insulin (once daily or twice-daily insulin (insulin detemir; insulin
glargine 100 U/mL, biosimilar of insulin glargine 100 U/mL or insulin Neutral Protamine
Hagedorn)) at least 90 days prior to the day of screening with or without any of the following
anti-diabetic drugs with stable doses for at least 90 days prior to screening:
a Metformin
b Dipeptidyl peptidase -4 inhibitor
c Sodium-glucose co-transporter 2 inhibitor
d Alpha-glucosidase-inhibitors (acarbose)
e Thiazolidinediones
f Marketed oral combination products only including the products listed in criteria 5a-
5e
- HbA1c below or equal to 9.5% (80 mmol/mol) at screening by central laboratory analysis.
- BMI below or equal to 45 kg/m^2.
* For this inclusion criterion the aim is to include minimum 80% of individuals with a previous
episode of hypoglycaemia (criterion e). The remaining subjects will have to fulfil at least one of
criteria a-d.
** An episode requiring assistance of another person to actively administer carbohydrate, glucagon,
or take other corrective actions. Plasma glucose concentrations may not be available during an
event, but neurological recovery following the return of plasma glucose to normal is considered
sufficient evidence that the event was induced by a low plasma glucose concentration.
*** History of impaired autonomic responses (tremulousness, sweating, palpitations, and hunger)
during hypoglycaemia. |
|
E.4 | Principal exclusion criteria |
- Treatment with any medication for the indication of diabetes or obesity other than stated in
the inclusion criteria in a period of 90 days before the day of screening. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Number of severe or blood glucose confirmed symptomatic hypoglycaemic episodes |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. During maintenance 2 (36 weeks) |
|
E.5.2 | Secondary end point(s) |
1. Basal insulin dose (units)
2. Number of nocturnal, severe or blood glucose confirmed symptomatic
hypoglycaemic episodes
3. Number of severe hypoglycaemic episodes
4. Change in HbA1c
5. Hypoglycaemia: Number of severe or blood glucose confirmed symptomatic hypoglycaemic episodes
6. Hypoglycaemia: Number of nocturnal, severe or blood glucose confirmed symptomatic hypoglycaemic episodes
7. Hypoglycaemia: Number of severe hypoglycaemic episodes
8. Number of adverse events
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At end of treatment (up to 88 weeks)
2. During maintenance 2 (36 weeks)
3. During maintenance 2 (36 weeks)
4. From baseline to end of treatment (up to 88 weeks)
5. During treatment (up to 88 weeks)
6. During treatment (up to 88 weeks)
7. During treatment (up to 88 weeks)
8. During treatment (up to 88 weeks) |
|
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 | No |
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) | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
European Union |
Norway |
Serbia |
United States |
|
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
|
|
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 | 27 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 27 |