Type 1 Diabetes MedDRA version: 21.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Fast-acting insulin aspart (Fiasp® 100 U/mL) in 3 mL FlexTouch®
Product Name: Fiasp
Product Code: A10AB05
Pharmaceutical Form: Injection
INN or Proposed INN: INSULIN ASPART
CAS Number: 116
Sponsors
Medical University of Graz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults with type 1 diabetes mellitus (as diagnosed clinically) = 12 months • Treated with multiple daily insulin injections = 12 months • Body mass index 18.0-29.4 kg/m2 (both inclusive) • Mass-specific peak oxygen consumption (VO2peak) >20 ml/kg/min • HbA1c = 9.5 % (80 mmol/mol) • C-peptide = 0.3 nmol/L Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity to trial product(s) or related products 2. Known haemoglobin < 8.0 mmol/l (<12.8 g/dl) (male) or < 6.4 mmol/l (10.3 g/dl) (female) 3. 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. 4. 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 who 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. 5. Participant with a heart rate < 40 beats per minute (bpm) at screening (after resting for 5 min in supine position) 6. 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 7. Supine blood pressure at screening (after resting for 5 min in supine position) outside the range of 90-140 mmHg for systolic or 50-90 mmHg for diastolic (excluding white-coat hypertension; If white coat hypertension is observed then participants will be measured over 15 - 30 min every 5 min in a separate room and mean blood pressure will be used for eligibility assessment.). This exclusion criterion also pertains to participants being on anti-hypertensives 8. Clinically significant abnormal ECG at screening, as judged by the Investigator 9. Severe retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator 10. Any chronic disorder or severe disease which, in the opinion of the Investigator might jeopardise participant’s safety or compliance with the protocol 11. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction (except celiac disease – patient must exclude foods that contain gluten from the diet) 12. Surgery or trauma with significant blood loss (more than 500 mL) within the last 3 months prior to screening 13. Participant known to be positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies (or diagnosed with active hepatitis), for HIV-1 antibodies, HIV-2 antibodies or HIV-1 antigen 14. Significant history of alcoholism or drug/chemical abuse as per Investigator’s judgement. 15. Smoker (defined as a participant who is smoking more than 5 cigarettes or the equivalent per day) 16. Not able or willing to refrain from smoking, or use of nicotine substitute products during the inpatient period 17. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the past 12 months) 18. Hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months 19. Participant with mental incapacity or language barriers precluding adequate unders
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To compare changes in BG concentrations of Fiasp® and NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) during exercise in 44 patients with type 1 diabetes (T1D) in a randomised, multi-centre, double blind, four-period cross-over, twice dose trial.;Secondary Objective: To compare: •the pharmacodynamic effect of Fiasp® and NovoRapid® for the same pre- and post-exercise dose reduction (for both 2x50% and 2x75% reduced short-acting insulin dose) during exercise •the pharmacodynamic effect of Fiasp® and NovoRapid® for the same pre- and post-exercise dose reduction (for both 2x50% and 2x75% reduced short-acting insulin dose) on BG excursions before and after exercise, around pre-exercise and post-exercise dosing •the pharmacokinetic effect of Fiasp® and NovoRapid® for the same pre- and post-exercise dose reduction (for both 2x50% and 2x75% reduced short-acting insulin dose) on insulin excursions before, during and after exercise, around a pre-exercise and post-exercise dosing •the counter-regulatory hormone, the inflammatory response, metabolic response, cardio-respiratory responses and CGM accuracy around exercise & 24h after 2nd dosing •the interstitial glucose response of Fiasp® and NovoRapid® from 4h after 1st- to 28 hours after 2nd dosing ;Primary end point(s): •BG +60 to +105 exercise: Changes in BG concentrations of Fiasp® compared with NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) during exercise, as measured by changes over time in the corrected (to time 0min) BG concentrations between 60 and 105 min after first dosing (during exercise);Timepoint(s) of evaluation of this end point: The timepoint for the primary endpoint will be from minute 60 to minute 105 after the first dosing (injection) during exercise. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Timepoints for the evaluation of all secondary outcomes will range from -5 minutes before the first dosing, up to 28 hours afterthe first dosing.;Secondary end point(s): • BGAUC +60 to +105 exercise: Pharmacodynamic effect of Fiasp® compared with NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) on BG excursions during exercise, as measured by the corrected (to time 0min) area under the glucose concentration–time curve (AUC) between 60 and 105 min after first dosing (during exercise) • BGAUC pre-exercise/first dosing: Pharmacodynamic effect of Fiasp® compared with NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) on BG for corrected (to time 0min) incremental AUC from 0min to +30min and from +30min to +60min after first dosing • BGAUC +105 to +240post-exercise/first dosing: Pharmacodynamic effect of Fiasp® compared with NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) on BG for corrected (to time 0min) incremental AUC from +105 min to +150 min, from +150min to +195min and from +195min to +240min. • BGAUC a0 to ++240post-exercise/second dosing: Pharmacodynamic effect of Fiasp® compared with NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) on BG for corrected (to time a0min) incremental AUC from a0min (second dosing) to ++60min, from ++60min to ++120min, from ++120min to ++180min and from ++180min to ++240min after second dosing • ?BGmax first dosing: Pharmacodynamic effect of Fiasp® compared with NovoRapid® for the same pre- and post-exercise dose reduction (for both 2 x 50% and 2 x 75% reduced short-acting insulin dose) on maximum BG excursion after first dosing from 0min to +240min • ?BGmax second dosing: Pharmacod | — |
Countries
Austria
Contacts
Public ContactDepartment of Internal Medicine
Medical University of Graz
Outcome results
None listed