A Phase 3 interventional study of Faster-acting insulin aspart and Insulin aspart in Diabetes and Diabetes Mellitus, Type 2, sponsored by Novo Nordisk A/S. Completed at 167 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-01-11.
Sponsored by Novo Nordisk A/S · Phase 3, Interventional, and Treatment
The study compares 2 medicines for type 2 diabetes: fast-acting insulin aspart (a new medicine) and NovoRapid®/NovoLog® (a medicine doctors can already prescribe). Fast-acting insulin aspart will be tested to see how well it works and if it is safe. Participants will get either fast-acting insulin aspart or NovoRapid®/ NovoLog® - which treatment you get is decided by chance. Both medicines will be taken together with insulin degludec. Participants will need to take 1 injection 4 times every day (all insulins will be provided in pens). The study will last for about 8 months (34 weeks).
Inclusion Criteria: - Male or female, age equal to or above 18 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus for 10 years or longer prior to screening (Visit 1). - Treated with a basal-bolus insulin regimen for 1 year or longer prior to the day of screening (Visit 1). A basal-bolus insulin regimen is defined as basal insulin once or twice daily and bolus insulin analogue taken with meals at least 3 times daily. Treatment with premixed insulin or soluble insulin combination is not considered a basal-bolus regimen. - Treated with or without oral antidiabetic drugs including extended release formulations. - HbA1c 7.0-10.0% (both inclusive) as assessed by central laboratory at screening (Visit 1). Exclusion Criteria: - Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening (Visit 1). - Subjects presently classified as being in New York Heart Association (NYHA) Class IV. - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening (Visit 1). - Treatment with injectable GLP-1 receptor agonists in a period of 90 days prior to screening (Visit 1). - Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
Drug: Faster-acting insulin aspart · Drug: Insulin degludec · Drug: Metformin
Drug: Insulin aspart · Drug: Insulin degludec · Drug: Metformin
Faster aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.
Insulin aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.
Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.
Only participants who took metformin before the study should take metformin tablets, same dose as before the study
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Change From Baseline in 1-hour PPG Increment
Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Change From Baseline in 1,5-anhydroglucitol
Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) in fasting plasma glucose was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No)
Number of participants reaching HbA1c \<7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: 16 weeks after randomisation
Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No)
Number of participants reaching HbA1c \<7.0% (53 mmol/L) without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: 16 weeks after randomisation
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test])
Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour postprandial glucose (PPG \[meal test\]) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.
Time frame: Week 0, week 16
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test)
Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal. PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value.
Time frame: Week 0, week 16
Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile
Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. 7-9-7 point SMPG was measured at the following mentioned time points: 1) Before breakfast, 2) 60 mins after the start of Breakfast, 3) Before lunch, 4) 60 mins after the start of lunch, 5) Before main evening meal, 6) 60 mins after the start of main evening meal, 7) At bedtime, 8) At 4 AM, 9) Before breakfast.
Time frame: Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal)
Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal)
Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. PPG increment based on the 7-9-7-point profiles were derived separately for PG measurements made at 1 hour after main meals (breakfast, lunch and main evening meal). PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile
Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-9-7 point SMPG profile from baseline (week 0) after 16 weeks of randomisation (i.e., week 16). The results are presented as ratio to baseline. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements
Change from baseline (week 0) in nocturnal SMPG measurements was assessed by considering the differences between PG values available at bedtime, at 4 AM and the before breakfast value the following day: (4 AM PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 4 AM PG value). Change from baseline in nocturnal increments in SMPG measurements of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation and presented during three different time intervals as follows: 1) 04:00 to breakfast, 2) bedtime to 04:00, and 3) bedtime to breakfast. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No)
Participants reaching overall PPG (1 hour) ≤7.8 mmol/L \[140 mg/dL\] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: 16 weeks after randomisation
Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No)
Participants reaching overall PPG (1 hour) ≤7.8 mmol/L \[140 mg/dL\] without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: 16 weeks after randomisation
Total Bolus Insulin Dose: in Units/Day
Total bolus insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: 16 weeks from randomisation
Total Bolus Insulin Dose: in Units/kg/Day
Total bolus insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: 16 weeks from randomisation
Total Basal Insulin Dose: in Units/Day
Total basal insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: 16 weeks from randomisation
Total Basal Insulin Dose: in Units/kg/Day
Total basal insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: 16 weeks from randomisation
Individual Meal Insulin Dose: in Units
Individual meal time bolus insulin dose (Units) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: 16 weeks from randomisation
Individual Meal Insulin Dose: in Units/kg
Individual meal time bolus insulin dose (Units/kg) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: 16 weeks from randomisation
Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline
Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values are given as ratio to baseline (week 0) after 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
Time frame: Week 0, week 16
Number of Treatment Emergent Adverse Events
Number of treatment emergent adverse events were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Injection Site Reactions
Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall
ADA classification of hypos: 1. Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. 2. Documented symptomatic: PG ≤3.9 mmol/L with symptoms. 3. Asymptomatic: PG ≤3.9 mmol/L without symptoms. 4. Probable symptomatic: No measurement with symptoms. 5. Pseudo: PG \>3.9 mmol/L with symptoms. 6. Unclassifiable. NN classification of hypos: 1. BG confirmed: PG \<3.1 mmol/L with/without symptoms. 2. Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG \<3.1 mmol/L with symptoms. 3. Severe or BG confirmed: Severe as per ADA and BG confirmed by PG \<3.1 mmol/L with/without symptoms. 4. Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive)
Number of treatment emergent day time hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 06:00 and 00:00 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)
Number of treatment emergent nocturnal hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 00:01 and 05:59 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 1 hour after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 2 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Weeks 0-16
Change From Baseline in Physical Examination
Participants with physical examination findings, normal, abnormal NCS (non- clinically significant) and abnormal CS (clinically significant) at baseline (week 0) and week 16 presented. Results are based on the data from the on-treatment observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system 2) Central \& Peripheral nervous system 3) Gastrointestinal system incl. mouth 4) Head, ears, eyes, nose, throat and neck 5) Musculoskeletal system 6) Respiratory system 7) Skin
Time frame: Week 0, week 16
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure
Change in vital signs - systolic and diastolic blood pressure from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Vital Signs: Pulse
Change in vital signs - pulse from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Electrocardiogram (ECG)
Changes in electrocardiogram (ECG) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Fundoscopy/Fundus Photography
Changes in fundoscopy/fundus photography from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Haematology - Haematocrit
Changes in haematology - haematocrit from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Haematology - Haemoglobin
Changes in haematology - haemoglobin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Haematology - Leukocytes
Changes in haematology - leukocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Haematology - Thrombocytes
Changes in haematology - thrombocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Haematology - Erythrocytes
Changes in haematology - erythrocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT)
Changes in biochemistry - alanine aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Alkaline Phosphatase
Changes in biochemistry - alkaline phosphatase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST)
Changes in biochemistry - aspratate aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Albumin
Changes in biochemistry - albumin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Creatinine
Changes in biochemistry - creatinine from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Potassium
Changes in biochemistry - potassium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Sodium
Changes in biochemistry - sodium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Total Bilirubin
Changes in biochemistry - total bilirubin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Biochemistry - Total Protein
Changes in biochemistry - total protein from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Body Weight
Changes in body weight from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
Change From Baseline in Body Mass Index (BMI)
Change in the body mass index (BMI) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
Time frame: Week 0, week 16
The trial was conducted at 165 sites in 17 countries as follows: Argentina-3, Bulgaria-4, Canada-10, Croatia-4, Czech Republic-4, Germany-6, Greece-8, Italy-4, Poland-10, Republic of Korea-6, Romania-6, Russia-8, Serbia-9, Slovakia-5, Spain-8, Ukraine-6 and United States (US)-62. Two sites in the US screened but didn't randomise any subject.
| Milestone | Faster Aspart | NovoRapid |
|---|---|---|
| Started | 546 | 545 |
| Full analysis set | 546 | 545 |
| Safety analysis set | 544 | 544 |
| Completed | 531 | 531 |
| Not completed | 15 | 14 |
| Withdrew: Death | 2 | 1 |
| Withdrew: Lost to follow-up | 2 | 2 |
| Withdrew: Withdrawal by subject | 11 | 11 |
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Percentage of HbA1c | Faster Aspart | NovoRapid |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | -0.15 ± 0.62 | -0.09 ± 0.60 |
Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in 1-hour PPG Increment | -0.43 ± 2.45 | 0.08 ± 2.65 |
Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in 1,5-anhydroglucitol | 1.38 ± 3.10 | 0.89 ± 3.31 |
Change from baseline (week 0) in fasting plasma glucose was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) | 0.56 ± 2.38 | 0.68 ± 2.40 |
Number of participants reaching HbA1c \<7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Yes | 271 | 282 |
| No | 275 | 263 |
Number of participants reaching HbA1c \<7.0% (53 mmol/L) without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Yes | 265 | 278 |
| No | 281 | 267 |
Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour postprandial glucose (PPG \[meal test\]) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| 30-min | 0.31 ± 2.90 | 0.55 ± 2.80 |
| 1-hour | 0.03 ± 3.30 | 0.68 ± 3.23 |
| 2-hour | 0.08 ± 3.96 | 0.61 ± 3.48 |
| 3-hour | 0.30 ± 3.85 | 0.89 ± 3.72 |
| 4-hour | 0.51 ± 3.47 | 0.75 ± 3.51 |
Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal. PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| 30-min | -0.13 ± 1.85 | -0.05 ± 1.95 |
| 1-hour | -0.43 ± 2.45 | 0.08 ± 2.65 |
| 2-hour | -0.37 ± 3.25 | 0.001 ± 3.13 |
| 3-hour | -0.15 ± 3.23 | 0.28 ± 3.54 |
| 4-hour | 0.04 ± 3.00 | 0.15 ± 3.45 |
Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. 7-9-7 point SMPG was measured at the following mentioned time points: 1) Before breakfast, 2) 60 mins after the start of Breakfast, 3) Before lunch, 4) 60 mins after the start of lunch, 5) Before main evening meal, 6) 60 mins after the start of main evening meal, 7) At bedtime, 8) At 4 AM, 9) Before breakfast.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile | -0.56 ± 1.66 | -0.50 ± 1.61 |
Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Breakfast | -0.38 ± 2.53 | -0.28 ± 2.44 |
| Lunch | -0.78 ± 2.48 | -0.58 ± 2.68 |
| Main evening meal | -1.04 ± 2.67 | -0.71 ± 2.50 |
| All meals | -0.75 ± 1.89 | -0.52 ± 1.91 |
Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. PPG increment based on the 7-9-7-point profiles were derived separately for PG measurements made at 1 hour after main meals (breakfast, lunch and main evening meal). PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Breakfast | -0.56 ± 2.23 | -0.42 ± 2.17 |
| Lunch | -0.38 ± 2.69 | -0.23 ± 2.46 |
| Main evening meal | -0.44 ± 2.61 | -0.10 ± 2.28 |
| All meals | -0.48 ± 1.55 | -0.23 ± 1.42 |
Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-9-7 point SMPG profile from baseline (week 0) after 16 weeks of randomisation (i.e., week 16). The results are presented as ratio to baseline. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Ratio | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile | 0.82 ± 48.32 | 0.85 ± 55.06 |
Change from baseline (week 0) in nocturnal SMPG measurements was assessed by considering the differences between PG values available at bedtime, at 4 AM and the before breakfast value the following day: (4 AM PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 4 AM PG value). Change from baseline in nocturnal increments in SMPG measurements of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation and presented during three different time intervals as follows: 1) 04:00 to breakfast, 2) bedtime to 04:00, and 3) bedtime to breakfast. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Bedtime to 04:00 | 0.70 ± 4.09 | 0.29 ± 4.09 |
| Bedtime to breakfast | 1.30 ± 4.25 | 0.90 ± 3.99 |
| 04:00 to breakfast | 0.66 ± 2.76 | 0.75 ± 2.87 |
Participants reaching overall PPG (1 hour) ≤7.8 mmol/L \[140 mg/dL\] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Yes | 186 | 192 |
| No | 360 | 353 |
Participants reaching overall PPG (1 hour) ≤7.8 mmol/L \[140 mg/dL\] without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Yes | 182 | 190 |
| No | 364 | 355 |
Total bolus insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Units/day | Faster Aspart | NovoRapid |
|---|---|---|
| Total Bolus Insulin Dose: in Units/Day | 54.72 ± 35.82 | 53.38 ± 35.35 |
Total bolus insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Units/kg/day | Faster Aspart | NovoRapid |
|---|---|---|
| Total Bolus Insulin Dose: in Units/kg/Day | 0.57 ± 0.33 | 0.55 ± 0.34 |
Total basal insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Units/day | Faster Aspart | NovoRapid |
|---|---|---|
| Total Basal Insulin Dose: in Units/Day | 63.76 ± 35.21 | 62.25 ± 36.03 |
Total basal insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Units/kg/day | Faster Aspart | NovoRapid |
|---|---|---|
| Total Basal Insulin Dose: in Units/kg/Day | 0.66 ± 0.32 | 0.64 ± 0.32 |
Individual meal time bolus insulin dose (Units) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Units | Faster Aspart | NovoRapid |
|---|---|---|
| Breakfast | 16.27 ± 12.04 | 15.52 ± 11.38 |
| Lunch | 18.51 ± 12.09 | 17.96 ± 11.73 |
| Daily main evening meal | 19.88 ± 13.46 | 19.85 ± 14.47 |
Individual meal time bolus insulin dose (Units/kg) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Units/kg | Faster Aspart | NovoRapid |
|---|---|---|
| Breakfast | 0.17 ± 0.12 | 0.16 ± 0.11 |
| Lunch | 0.19 ± 0.11 | 0.19 ± 0.12 |
| Daily main evening meal | 0.21 ± 0.13 | 0.20 ± 0.14 |
Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values are given as ratio to baseline (week 0) after 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
| Ratio | Faster Aspart | NovoRapid |
|---|---|---|
| Total cholesterol | 1.01 ± 15.98 | 1.00 ± 17.09 |
| High density lipoproteins | 0.97 ± 14.47 | 0.98 ± 17.57 |
| Low density lipoproteins | 0.99 ± 25.36 | 0.99 ± 40.51 |
Number of treatment emergent adverse events were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Events | Faster Aspart | NovoRapid |
|---|---|---|
| Number of Treatment Emergent Adverse Events | 667 | 643 |
Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of injection site reactions | Faster Aspart | NovoRapid |
|---|---|---|
| Number of Treatment Emergent Injection Site Reactions | 3 | 1 |
ADA classification of hypos: 1. Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level. 2. Documented symptomatic: PG ≤3.9 mmol/L with symptoms. 3. Asymptomatic: PG ≤3.9 mmol/L without symptoms. 4. Probable symptomatic: No measurement with symptoms. 5. Pseudo: PG \>3.9 mmol/L with symptoms. 6. Unclassifiable. NN classification of hypos: 1. BG confirmed: PG \<3.1 mmol/L with/without symptoms. 2. Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG \<3.1 mmol/L with symptoms. 3. Severe or BG confirmed: Severe as per ADA and BG confirmed by PG \<3.1 mmol/L with/without symptoms. 4. Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 18 | 14 |
| ADA: Documented symptomatic | 5038 | 6165 |
| ADA: Asymptomatic | 3761 | 3681 |
| ADA: Probable symptomatic | 68 | 68 |
| ADA: Pseudo | 145 | 75 |
| ADA: Unclassifiable | 3 | 3 |
| NN: BG confirmed | 2209 | 2735 |
| NN: Severe or BG confirmed symptomatic | 1490 | 2055 |
| NN: Severe or BG confirmed | 2227 | 2749 |
| NN: Unclassifiable | 6806 | 7257 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Number of treatment emergent day time hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 06:00 and 00:00 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 16 | 12 |
| ADA: Documented symptomatic | 4703 | 5700 |
| ADA: Asymptomatic | 3617 | 3484 |
| ADA: Probable symptomatic | 62 | 64 |
| ADA: Pseudo | 141 | 66 |
| ADA: Unclassifiable | 3 | 3 |
| NN: BG confirmed | 2016 | 2442 |
| NN: Severe or BG confirmed symptomatic | 1333 | 1814 |
| NN: Severe or BG confirmed | 2032 | 2454 |
| NN: Unclassifiable | 6510 | 6875 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Number of treatment emergent nocturnal hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 00:01 and 05:59 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 2 | 2 |
| ADA: Documented symptomatic | 335 | 465 |
| ADA: Asymptomatic | 144 | 197 |
| ADA: Probable symptomatic | 6 | 4 |
| ADA: Pseudo | 4 | 9 |
| ADA: Unclassifiable | 0 | 0 |
| NN: BG confirmed | 193 | 293 |
| NN: Severe or BG confirmed symptomatic | 157 | 241 |
| NN: Severe or BG confirmed | 195 | 295 |
| NN: Unclassifiable | 296 | 382 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 1 hour after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 2 | 0 |
| ADA: Documented symptomatic | 149 | 148 |
| ADA: Asymptomatic | 87 | 80 |
| ADA: Probable symptomatic | 11 | 8 |
| ADA: Pseudo | 2 | 4 |
| ADA: Unclassifiable | 0 | 0 |
| NN: BG confirmed | 72 | 65 |
| NN: Severe or BG confirmed symptomatic | 48 | 50 |
| NN: Severe or BG confirmed | 74 | 65 |
| NN: Unclassifiable | 177 | 175 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 2 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 2 | 1 |
| ADA: Documented symptomatic | 465 | 446 |
| ADA: Asymptomatic | 201 | 159 |
| ADA: Probable symptomatic | 16 | 11 |
| ADA: Pseudo | 10 | 7 |
| ADA: Unclassifiable | 0 | 0 |
| NN: BG confirmed | 233 | 246 |
| NN: Severe or BG confirmed symptomatic | 181 | 212 |
| NN: Severe or BG confirmed | 235 | 247 |
| NN: Unclassifiable | 459 | 377 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 6 | 9 |
| ADA: Documented symptomatic | 1627 | 1882 |
| ADA: Asymptomatic | 852 | 744 |
| ADA: Probable symptomatic | 37 | 27 |
| ADA: Pseudo | 55 | 26 |
| ADA: Unclassifiable | 0 | 0 |
| NN: BG confirmed | 762 | 965 |
| NN: Severe or BG confirmed symptomatic | 557 | 820 |
| NN: Severe or BG confirmed | 768 | 974 |
| NN: Unclassifiable | 1809 | 1714 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Number of hypoglycaemic episodes | Faster Aspart | NovoRapid |
|---|---|---|
| ADA: Severe | 4 | 8 |
| ADA: Documented symptomatic | 1162 | 1436 |
| ADA: Asymptomatic | 651 | 585 |
| ADA: Probable symptomatic | 21 | 16 |
| ADA: Pseudo | 45 | 19 |
| ADA: Unclassifiable | 0 | 0 |
| NN: BG confirmed | 529 | 719 |
| NN: Severe or BG confirmed symptomatic | 376 | 608 |
| NN: Severe or BG confirmed | 533 | 727 |
| NN: Unclassifiable | 1350 | 1337 |
| Not able to selftreat - unclassifiable | 0 | 0 |
Participants with physical examination findings, normal, abnormal NCS (non- clinically significant) and abnormal CS (clinically significant) at baseline (week 0) and week 16 presented. Results are based on the data from the on-treatment observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system 2) Central \& Peripheral nervous system 3) Gastrointestinal system incl. mouth 4) Head, ears, eyes, nose, throat and neck 5) Musculoskeletal system 6) Respiratory system 7) Skin
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Cardiovascular system (week 0) — Normal | 459 | 460 |
| Cardiovascular system (week 0) — Abnormal NCS | 79 | 79 |
| Cardiovascular system (week 0) — Abnormal CS | 6 | 5 |
| Cardiovascular system (week 16) — Normal | 448 | 457 |
| Cardiovascular system (week 16) — Abnormal NCS | 71 | 72 |
| Cardiovascular system (week 16) — Abnormal CS | 6 | 4 |
| Central and Peripheral nervous sys. (week 0) — Normal | 398 | 404 |
| Central and Peripheral nervous sys. (week 0) — Abnormal NCS | 133 | 127 |
| Central and Peripheral nervous sys. (week 0) — Abnormal CS | 13 | 13 |
| Central and Peripheral nervous sys. (week 16) — Normal | 383 | 400 |
| Central and Peripheral nervous sys. (week 16) — Abnormal NCS | 128 | 122 |
| Central and Peripheral nervous sys. (week 16) — Abnormal CS | 14 | 11 |
| Gastrointestinal sys. including mouth (Week 0) — Normal | 491 | 485 |
| Gastrointestinal sys. including mouth (Week 0) — Abnormal NCS | 53 | 59 |
| Gastrointestinal sys. including mouth (Week 0) — Abnormal CS | 0 | 0 |
| Gastrointestinal sys. including mouth (week 16) — Normal | 480 | 476 |
| Gastrointestinal sys. including mouth (week 16) — Abnormal NCS | 45 | 57 |
| Gastrointestinal sys. including mouth (week 16) — Abnormal CS | 0 | 0 |
| Head, ears, eyes, nose, throat, neck (week 0) — Normal | 498 | 492 |
| Head, ears, eyes, nose, throat, neck (week 0) — Abnormal NCS | 43 | 48 |
| Head, ears, eyes, nose, throat, neck (week 0) — Abnormal CS | 3 | 4 |
| Head, ears, eyes, nose, throat, neck (week 16) — Normal | 485 | 483 |
| Head, ears, eyes, nose, throat, neck (week 16) — Abnormal NCS | 40 | 49 |
| Head, ears, eyes, nose, throat, neck (week 16) — Abnormal CS | 0 | 1 |
| Musculoskeletal system (week 0) — Normal | 504 | 496 |
| Musculoskeletal system (week 0) — Abnormal NCS | 36 | 42 |
| Musculoskeletal system (week 0) — Abnormal CS | 4 | 6 |
| Musculoskeletal system (week 16) — Normal | 489 | 494 |
| Musculoskeletal system (week 16) — Abnormal NCS | 32 | 33 |
| Musculoskeletal system (week 16) — Abnormal CS | 4 | 6 |
| Respiratory system (week 0) — Normal | 535 | 534 |
| Respiratory system (week 0) — Abnormal NCS | 9 | 9 |
| Respiratory system (week 0) — Abnormal CS | 0 | 1 |
| Respiratory system (week 16) — Normal | 520 | 517 |
| Respiratory system (week 16) — Abnormal NCS | 5 | 14 |
| Respiratory system (week 16) — Abnormal CS | 0 | 2 |
| Skin (week 0) — Normal | 438 | 429 |
| Skin (week 0) — Abnormal NCS | 96 | 108 |
| Skin (week 0) — Abnormal CS | 10 | 7 |
| Skin (week 16) — Normal | 418 | 430 |
| Skin (week 16) — Abnormal NCS | 98 | 98 |
| Skin (week 16) — Abnormal CS | 9 | 5 |
Change in vital signs - systolic and diastolic blood pressure from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| mmHg | Faster Aspart | NovoRapid |
|---|---|---|
| Systolic blood pressure | 0.4 ± 14.0 | -1.2 ± 14.8 |
| Diastolic blood pressure | -0.4 ± 8.9 | -0.7 ± 8.9 |
Change in vital signs - pulse from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Beats per min | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Vital Signs: Pulse | 0.5 ± 9.0 | 0.03 ± 8.9 |
Changes in electrocardiogram (ECG) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Week 0 — Normal | 287 | 270 |
| Week 0 — Abnormal NCS | 252 | 264 |
| Week 0 — Abnormal CS | 5 | 10 |
| Week 16 — Normal | 274 | 272 |
| Week 16 — Abnormal NCS | 245 | 253 |
| Week 16 — Abnormal CS | 6 | 8 |
Changes in fundoscopy/fundus photography from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Participants | Faster Aspart | NovoRapid |
|---|---|---|
| Left eye (week 0) — Normal | 225 | 219 |
| Left eye (week 0) — Abnormal NCS | 287 | 297 |
| Left eye (week 0) — Abnormal CS | 32 | 27 |
| Left eye (week 16) — Normal | 205 | 198 |
| Left eye (week 16) — Abnormal NCS | 278 | 288 |
| Left eye (week 16) — Abnormal CS | 31 | 30 |
| Right eye (week 0) — Normal | 224 | 217 |
| Right eye (week 0) — Abnormal NCS | 288 | 300 |
| Right eye (week 0) — Abnormal CS | 32 | 27 |
| Right eye (week 16) — Normal | 208 | 194 |
| Right eye (week 16) — Abnormal NCS | 276 | 297 |
| Right eye (week 16) — Abnormal CS | 30 | 26 |
Changes in haematology - haematocrit from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| Percentage | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Haematology - Haematocrit | 0.48 ± 2.47 | 0.35 ± 2.47 |
Changes in haematology - haemoglobin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Haematology - Haemoglobin | -0.02 ± 0.47 | -0.04 ± 0.43 |
Changes in haematology - leukocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| 10^9 leukocytes/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Haematology - Leukocytes | 0.01 ± 1.60 | -0.01 ± 1.35 |
Changes in haematology - thrombocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| 10^9 thrombocytes/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Haematology - Thrombocytes | -0.9 ± 37.1 | -1.3 ± 38.7 |
Changes in haematology - erythrocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| 10^12 erythrocytes/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Haematology - Erythrocytes | -0.02 ± 0.28 | -0.04 ± 0.27 |
Changes in biochemistry - alanine aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| U/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT) | -0.1 ± 9.4 | 3.1 ± 65.4 |
Changes in biochemistry - alkaline phosphatase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| U/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Alkaline Phosphatase | 2.9 ± 22.6 | 2.2 ± 18.3 |
Changes in biochemistry - aspratate aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| U/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST) | -0.2 ± 7.9 | 2.2 ± 45.7 |
Changes in biochemistry - albumin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| g/dL | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Albumin | 0.02 ± 0.25 | 0.01 ± 0.26 |
Changes in biochemistry - creatinine from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| umol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Creatinine | 0.1 ± 11.1 | 1.5 ± 13.2 |
Changes in biochemistry - potassium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Potassium | -0.001 ± 0.50 | 0.02 ± 0.43 |
Changes in biochemistry - sodium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| mmol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Sodium | -0.6 ± 2.6 | -0.7 ± 2.8 |
Changes in biochemistry - total bilirubin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| umol/L | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Total Bilirubin | 0.1 ± 2.7 | 0.1 ± 3.0 |
Changes in biochemistry - total protein from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| g/dL | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Biochemistry - Total Protein | -0.01 ± 0.35 | -0.02 ± 0.36 |
Changes in body weight from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| kg | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Body Weight | 1.19 ± 2.95 | 1.12 ± 4.01 |
Change in the body mass index (BMI) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
| kg/m^2 | Faster Aspart | NovoRapid |
|---|---|---|
| Change From Baseline in Body Mass Index (BMI) | 0.43 ± 1.04 | 0.40 ± 1.40 |
Collected over Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Faster Aspart | 2/544 (0.4%) | 38/544 (7%) | 32/544 (5.9%) |
| NovoRapid | 1/544 (0.2%) | 40/544 (7.4%) | 33/544 (6.1%) |
| Event | Faster Aspart | NovoRapid |
|---|---|---|
| HypoglycaemiaMetabolism and nutrition disorders | 4/544 | 3/544 |
| Hypoglycaemic unconsciousnessNervous system disorders | 3/544 | 0/544 |
| Accidental overdoseInjury, poisoning and procedural complications | 2/544 | 0/544 |
| Acute coronary syndromeCardiac disorders | 2/544 | 0/544 |
| Angina pectorisCardiac disorders | 0/544 | 2/544 |
| Cardiac failureCardiac disorders | 2/544 | 1/544 |
| Cardiac failure congestiveCardiac disorders | 0/544 | 2/544 |
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 0/544 | 2/544 |
| Coronary artery diseaseCardiac disorders | 0/544 | 2/544 |
| DizzinessNervous system disorders | 0/544 | 2/544 |
| Event | Faster Aspart | NovoRapid |
|---|---|---|
| NasopharyngitisInfections and infestations | 32/544 | 33/544 |
| Age, Continuous(Years) | Faster Aspart | NovoRapid | Total |
|---|---|---|---|
| Mean | 62.6 ± 8.6 | 62.1 ± 8.8 | 62.3 ± 8.7 |
| Sex: Female, Male(Participants) | Faster Aspart | NovoRapid | Total |
|---|---|---|---|
| Female | 281 | 256 | 537 |
| Male | 265 | 289 | 554 |
| Race/Ethnicity, Customized(Participants) | Faster Aspart | NovoRapid | Total |
|---|---|---|---|
| White | 487 | 487 | 974 |
| Asian | 43 | 31 | 74 |
| Black or African American | 14 | 19 | 33 |
| Native Hawaiian or Other Pacific Islander | 2 | 5 | 7 |
| Other | 0 | 3 | 3 |
| Race/Ethnicity, Customized(Participants) | Faster Aspart | NovoRapid | Total |
|---|---|---|---|
| Not Hispanic or Latino | 485 | 488 | 973 |
| Hispanic Latino | 61 | 57 | 118 |
Showing the first 100 of 167 sites across 18 countries.
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