| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Participants in this study have type 1 diabetes which is defined as the lack of an own insulin production. |
|
| 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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045228 |
| E.1.2 | Term | Type I diabetes mellitus |
| E.1.2 | System Organ Class | 100000004861 |
|
| 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 |
Primary objective
• To compare time spent in hypoglycaemia (< 3.9 mmol/L [<70 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose |
|
| E.2.2 | Secondary objectives of the trial |
Exploratory objectives
• To compare numbers of hypoglycaemic event (< 3.9 mmol/L [< 70 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• To compare time spent in hypoglycaemia (< 3.9 mmol/L [< 70 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose stratified for day- (06.00 AM – 11.59 PM) and night-time (12.00 AM – 05.59 AM)
• and others
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Informed consent obtained
2. Male or female aged 18-65 years (both inclusive)
3. Type 1 diabetes (as diagnosed clinically) ≥ 12 months
4. Treated with multiple daily insulin injections ≥ 12 months
5. Body mass index 18.0-29.9 kg/m2 (both inclusive)
6. Participants performing regular physical cardio-respiratory activity during the last 3 months prior to screening
7. HbA1c ≤ 10% (86 mmol/mol)
8. Mass-specific peak oxygen consumption (VO2peak) >20 ml/kg/min |
|
| E.4 | Principal exclusion criteria |
1. Known or suspected hypersensitivity to trial product(s) or related products
2. Receipt of any investigational medicinal product within 1 week prior to screening in this trial
3. Haemoglobin <13.0 g/dl (male) or <12 g/dl (female)
4. Systemic (oral or i.v.) corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers, growth hormone and non-routine vitamins and herbal products. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months.
5. Suffer from or history of a life-threatening disease (i.e. cancer judged not to be in full remission except basal cell skin cancer or squamous cell skin cancer), or clinically severe diseases that directly influence the study results, as judged by the Investigator. This does not prohibit the participation of patients taking medications that influences the metabolism (e.g. statin) or cardio-respiratory system (e.g. asthma spray) as long as the therapy is stable and is not adapted throughout the run of the trial. Furthermore, it does not excluded patients how have celiac disease (or similar diseases or allergies), as long as the disease is stable, and patients are able to stay on their specific (e.g.) gluten-free diet.
6. Participant with a heart rate < 35 beats per minute (bpm) at screening (after resting for 5 min in supine position)
7. Cardiac problems defined as decompensated heart failure (New York Heart Association (NYHA) class III and IV) 10 at any time and/or angina pectoris within the last 12 months and/or acute myocardial infarction at any time
8. Supine blood pressure at screening (after resting for 5 min in supine position) outside the range of 90-150 mmHg for systolic or 50-95 mmHg for diastolic (excluding white-coat hypertension; therefore, if a repeated measurement on a second screening Visit shows values within the range, the participant can be included in the trial). This exclusion criterion also pertains to participants being on anti-hypertensives
9. Clinically significant abnormal ECG at screening, as judged by the Investigator
10. Severe retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
11. Any chronic disorder or severe disease which, in the opinion of the Investigator might jeopardise participant’s safety or compliance with the protocol
12. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction
13. Significant history of alcoholism or drug/chemical abuse as per Investigator’s judgement or a positive result in the urine drug/alcohol screen at the screening Visit.
14. Smoker (defined as a participant who is smoking more than 5 cigarettes or the equivalent per day)
15. Not able or willing to refrain from smoking, or use of nicotine substitute products during the inpatient period
16. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the past 12 months)
17. Hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 12 months
18. Participant with mental incapacity or language barriers precluding adequate understanding or cooperation or who, in the opinion of their general practitioner or the Investigator, should not participate in the trial
19. Potentially non-compliant or uncooperative during the trial, as judged by the Investigator
20. Any condition that would interfere with trial participation or evaluation of results, as judged by the Investigator
21. Female of childbearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods (adequate contraceptive measures include sterilisation, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner).
22. Using a real-time CGM device, which allow to individually setting glycaemic thresholds (e.g. Dexcom G4/5/6, Medtronic Guardian or FreeStyle Libre 2 systems). That does not exclude using Freestyle Libre 1
23. Renal function eGFR (CKD-EPI) < 50 mL/min/1.73 m2 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary endpoint
• Time Hypoglycaemia (6x24 hrs post-exercise period): Time spent in hypoglycaemia (minutes, percentage of total time) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Exploratory endpoints
• Time Hypoglycaemia (14 day-exercise period): Time spent in hypoglycaemia (minutes, percentage of total time) for the total 14-day-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• Time Hypoglycaemia (6x24 hrs post-exercise period): Time spent in hypoglycaemia (minutes, percentage of total time) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose stratified for day- (06.00 AM – 11.59 PM) and night-time (12.00 AM – 05.59 AM)
• and others
|
|
| E.5.2 | Secondary end point(s) |
• Time Hypoglycaemia (14 day-exercise period): Time spent in hypoglycaemia (minutes, percentage of total time) for the total 14-day-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• Time Hypoglycaemia (6x24 hrs post-exercise period): Time spent in hypoglycaemia (minutes, percentage of total time) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose stratified for day- (06.00 AM – 11.59 PM) and night-time (12.00 AM – 05.59 AM)
• Time Hypoglycaemia (14 day-exercise period): Time spent in hypoglycaemia (minutes, percentage of total time) for the total 14-day-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose stratified for day- (06.00 AM – 11.59 PM) and night-time (12.00 AM – 05.59 AM)
• Numbers Hypoglycaemia (6x24 hrs post-exercise period): Numbers of hypoglycaemia (≤ 3.9 mmol/L [≤ 70 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• Numbers Hypoglycaemia (14 day-exercise period): Numbers of hypoglycaemia (≤ 3.9 mmol/L [≤ 70 mg/dL]) for the total 14-day-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• Time Glycaemic ranges (6x24 hrs post-exercise period): Time spent (minutes, percentage of total time) in prespecified glycaemic ranges (euglycaemia (4.0 ‐ 9.9 mmol/L [71 ‐ 179 mg/dL]), serious hypoglycaemia (≤ 2.9 mmol/L [≤ 53 mg/dL]), hyperglycaemia (≥ 10 mmol/L, [≥ 180 mg/dL]) and serious hyperglycaemia (≥ 16.7 mmol/L [≥ 300 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• Time Glycaemic ranges (6x24 hrs post-exercise period): Time spent (minutes, percentage of total time) in prespecified glycaemic ranges (euglycaemia (4.0 ‐ 9.9 mmol/L [71 ‐ 179 mg/dL]), serious hypoglycaemia (≤ 2.9 mmol/L [≤ 53 mg/dL]), hyperglycaemia (≥ 10 mmol/L, [≥ 180 mg/dL]) and serious hyperglycaemia (≥ 16.7 mmol/L [≥ 300 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose stratified for day- (06.00 AM – 11.59 PM) and night-time (12.00 AM – 05.59 AM)
• Time Glycaemic ranges (14 day-exercise period): Time spent (minutes, percentage of total time) in prespecified glycaemic ranges (euglycaemia (4.0 ‐ 9.9 mmol/L [71 ‐ 179 mg/dL]), serious hypoglycaemia (≤ 2.9 mmol/L [≤ 53 mg/dL]), hyperglycaemia (≥ 10 mmol/L, [≥ 180 mg/dL]) and serious hyperglycaemia (≥ 16.7 mmol/L [≥ 300 mg/dL]) for the total 14-day-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
• Time Glycaemic ranges (14 day-exercise period): Time spent (minutes, percentage of total time) in prespecified glycaemic ranges (euglycaemia (4.0 ‐ 9.9 mmol/L [71 ‐ 179 mg/dL]), serious hypoglycaemia (≤ 2.9 mmol/L [≤ 53 mg/dL]), hyperglycaemia (≥ 10 mmol/L, [≥ 180 mg/dL]) and serious hyperglycaemia (≥ 16.7 mmol/L [≥ 300 mg/dL]) for the total 14-day-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose stratified for day- (06.00 AM – 11.59 PM) and night-time (12.00 AM – 05.59 AM)
• AUC Glycaemic ranges (6x24 hrs post-exercise period): AUC following the trapezoidal rule for time spent in prespecified glycaemic ranges (euglycaemia (4.0 ‐ 9.9 mmol/L [71 ‐ 179 mg/dL]), hypoglycaemia (≤ 3.9 mmol/L [≤ 70 mg/dL]), serious hypoglycaemia (≤ 2.9 mmol/L [≤ 53 mg/dL]), hyperglycaemia (≥ 10 mmol/L, [≥ 180 mg/dL]) and serious hyperglycaemia (≥ 16.7 mmol/L [≥ 300 mg/dL]) for the 6 x 24-hour post-exercise period around multiple spontaneous exercise sessions (3 times per week spread over 2 weeks for each trial arm) on either a regular (100%) or 75% IGlar-U300 and IDeg-U100 dose
and others
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Timepoints for the evaluation of all secondary outcomes will range from acute responses to cardio-pulmonary exercise testing to 14 days following multiple spontaneous exercise sessions |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | Yes |
| 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 | 8 |
| E.8.9.1 | In the Member State concerned days | |
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