Fast-acting insulin aspart (faster aspart) will be tested to see how well it works and if it is safe. The study compares 2 medicines for type 1 and type 2 diabetes - faster aspart (a new medicine) and insulin aspart (a medicine doctors can already prescribe). Participants will either get faster aspart or insulin aspart (NovoRapid®) - which treatment is decided by chance. Both medicines will be taken together with insulin degludec. Participants will need to take 1 injection 4 times every day: 3 injections 0-2 minutes before breakfast, lunch and dinner and 1 injection at the same time every day. All study medicines are provided in pens. A pen is a tool to inject insulin under the skin.The study will last for about 7 months (30 weeks). Participants will have 11 clinic visits and 17 phone contacts with the study doctor. At 8 clinic visits participants will have blood samples taken. At 3 clinic visits participants cannot eat or drink (water is allowed) 8 hours before the visits - at 2 of these visits participants will be asked to drink a liquid meal and to stay at the clinic for about 5 hours. Participants will fill in a diary the last 3 days before the visits/phone contacts. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
331
Administered s.c. (subcutaneously, under the skin) for 16 weeks
Administered s.c. (subcutaneously, under the skin) for 16 weeks
Administered s.c. (subcutaneously, under the skin) for 16 weeks
Anhui Provincial Hospital-Endocrinology
Hefei, Anhui, China
The First Affiliated Hospital of Anhui Medical University-Endocrinology
Hefei, Anhui, China
Beijing Chao-Yang Hospital, Capital Medical University-Endocrinology
Beijing, Beijing Municipality, China
The Fifth Medical Center of PLA General Hospital-Endocrinology
Beijing, Beijing Municipality, China
The General Hospital of the PLA Rocket Force-Endocrinology
Beijing, Beijing Municipality, China
Change From Baseline in Glycosylated Haemoglobin (HbA1c) (Percentage [%])
Change from baseline (week 0) in HbA1c (%) as 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.
Time frame: Baseline (week 0), week 16
Change From Baseline in HbA1c (Millimoles Per Mole [mmol/Mol])
Change from baseline (week 0) in HbA1c (mmol/mol) 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.
Time frame: Baseline (week 0), week 16
Change From Baseline in 30-minutes, 1-hour, 2-hour and 3-hour Post Prandial Glucose (PPG) Increment (Meal Test)
Change from baseline (week 0) in 30-minute, 1-hour, 2-hour and 3-hour PPG increment (meal test) was evaluated at 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. Meal test: The participants were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The participants were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2 and 3 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: Baseline (week 0), week 16 (30 minutes, 1 hour, 2 hour and 3 hour)
Change From Baseline in 30-minutes, 1-hour, 2-hour and 3-hour PPG (Meal Test)
Change from baseline (week 0) in 30-minute, 1-hour, 2-hour and 3-hour PPG (meal test) was evaluated at 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. Meal test: The participants were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The participants were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2 and 3 hours from the start of the meal.
Time frame: Baseline (week 0), week 16 (30 minutes, 1 hour, 2 hour and 3 hour)
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) in fasting plasma glucose (FPG) 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.
Time frame: Baseline (week 0), week 16
Change From Baseline in 7-9-7-point Self-measured Plasma Glucose (SMPG) for Mean of the 7-9-7-point Profile
Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. 7-9-7 SMPG point profile was performed on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. The mean of the 7-9-7-point profile was defined as the area under the curve profile divided by the measurement time, and was calculated using the linear trapezoidal technique. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: Baseline (week 0), week 16
Change From Baseline in 7-9-7-point SMPG for 1-hour PPG (Mean, Breakfast, Lunch, Main Evening Meal)
Change from baseline (week 0) in 1-hour 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. 7-9-7 SMPG point profile was performed on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. Results were derived from the three profiles: post-breakfast, post-lunch, post-main evening meal. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: Baseline (week 0), week 16
Change From Baseline in 7-9-7-point SMPG for PPG Increment (Mean, Breakfast, Lunch, Main Evening Meal)
Change from baseline (week 0) in PPG increment of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. 7-9-7 SMPG point profile was performed on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. PPG increment for each meal was derived from the 7-point and 9-point profile as the difference between PPG values and the PG value before the meal in each separate profile. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: Baseline (week 0), week 16
Change From Baseline in 7-9-7-point SMPG for Fluctuation in 7-9-7-point Profile: Ratio to Baseline
Fluctuation in SMPG profile was the average absolute difference from the mean of the SMPG profile. Change from baseline is represented as ratio to baseline value. 7-9-7 SMPG point profile was performed on the 3 consecutive days just before selected visit. 7-point profile (day 3 and day 1 before selected visit): before breakfast, 60 minutes after the start of breakfast, before lunch, 60 minutes after the start of lunch, before main evening meal, 60 minutes after the start of main evening meal, and at bedtime. 9-point profile (day 2 before selected visit) included all timepoints of 7-points profile with addition of SMPG measurement at 4 a.m. and before breakfast on the following day. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: Baseline (week 0), week 16
Number of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Yes/No)
Number of participants who achieved HbA1c \< 7% measured as 53 mmol/mol at week 16 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values \< 7% and "No" infers the number of participants who have not achieved HbA1c values \< 7%. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: At week 16
Number of Participants Who Achieved HbA1c <7.0% Without Severe Hypoglycaemia Episodes (Yes/No)
Number of participants who achieved HbA1c \< 7% (measured as 53 mmol/mol) without severe hypoglycaemia episodes at week 16 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values \< 7% without severe hypoglycaemia episodes and "No" infers the number of participants who have not achieved HbA1c values less than the 7%. without severe hypoglycaemia episodes The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: At week 16
Number of Participants Who Achieved PPG Target (Overall Mean of Daily PPG Measurements in SMPG) for Overall PPG (1-hour) Less Than or Equal (≤) to 7.8 mmol/L (Yes/No)
Number of participants who achieved overall PPG (1-hour) ≤ 7.8 mmol/L measured as 140 milligrams per deciliter (mg/dL) at week 16 is presented. In the reported data, "Yes" infers the number of participants who have achieved overall PPG (1-hour) values ≤ 7.8 mmol/L and "No" infers the number of participants who have not achieved overall PPG (1-hour) values ≤ 7.8 mmol/L. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: At week 16
Number of Participants Who Achieved PPG Target (Overall Mean of Daily PPG Measurements in SMPG) for Overall PPG (1-hour) Less Than or Equal (≤) to 7.8 mmol/L Without Severe Hypoglycaemia (Yes/No)
Number of participants who achieved overall PPG (1-hour) ≤ 7.8 mmol/L (measured as 140 mg/dL) without severe hypoglycaemia at week 16 is presented. In the reported data, "Yes" infers the number of participants who have achieved overall PPG (1-hour) values ≤ 7.8 mmol/L without severe hypoglycaemia and "No" infers the number of participants who have not achieved overall PPG (1-hour) values ≤ 7.8 mmol/L without severe hypoglycaemia. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Time frame: At week 16
Insulin Dose (Units/Day): Total Basal
Total basal insulin dose 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.
Time frame: At week 16
Insulin Dose (Units/Day): Total Bolus
Total bolus insulin dose 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.
Time frame: At week 16
Insulin Dose (Units/Day): Individual Meal Insulin Dose
Individual meal time bolus insulin dose 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.
Time frame: At week 16
Insulin Dose (Units/kg/Day): Total Basal
Total basal insulin dose 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
Time frame: At week 16
Insulin Dose (Units/kg/Day): Total Bolus
Total bolus insulin dose 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.
Time frame: At week 16
Insulin Dose (Units/kg/Day): Individual Meal Insulin Dose
Individual meal time bolus insulin dose 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.
Time frame: At week 16
Number of Treatment Emergent Adverse Events (TEAEs)
Number of treatment emergent adverse events were recorded from week 0 to week 16. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. TEAE was defined as an event that had an onset date on or after the first day of exposure to randomised treatment, and no later than seven days after the last day of exposure to randomised treatment.
Time frame: From baseline (week 0) to 16 weeks after randomisation
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 last on-treatment value, which included the last available measurement in the on-treatment period.
Time frame: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the American Diabetes Association (ADA) Definition and Novo Nordisk (NN) Definition: Overall
ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Day Time Hypoglycaemic Episodes (00:01-05:59 - Both Inclusive)
Number of treatment emergent day time hypoglycaemic episodes as per ADA and NN definitions were evaluated. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Both Inclusive)
Number of treatment emergent nocturnal hypoglycaemic episodes as per ADA and NN definitions were evaluated. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Hypoglycaemic Episodes From Start of Meal Until 30 Minutes
Number of treatment emergent hypoglycaemic episodes as per ADA and NN definitions were evaluated during first 30-mins after start of meal. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Hypoglycaemic Episodes From Start of Meal Until 1 Hour
Number of treatment emergent hypoglycaemic episodes as per ADA and NN definitions were evaluated during first 1 hour after start of meal. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Hypoglycaemic Episodes From Start of Meal Until 2 Hours
Number of treatment emergent hypoglycaemic episodes as per ADA and NN definitions were evaluated during first 2 hours after start of meal. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Hypoglycaemic Episodes From Start of Meal Until 4 Hours
Number of treatment emergent hypoglycaemic episodes as per ADA and NN definitions were evaluated during first 4 hours after start of meal. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
Number of Treatment Emergent Hypoglycaemic Episodes Classified Both According to the ADA Definition and NN Definition: Hypoglycaemic Episodes From 2 Hours (Exclusive) to 4 Hours (Inclusive) After Start of Meal
Number of treatment emergent hypoglycaemic episodes as per ADA and NN definitions were evaluated from 2 hours to 4 hours after start of meal. ADA classification of hypoglycaemia as follows: 1) Severe: Requiring assistance to actively administer carbohydrate/glucagon/take other corrective actions. 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-hypoglycaemia: PG \>3.9 mmol/L with symptoms. 6) Unclassifiable. NN classification of hypoglycaemia as follows: 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: From baseline (week 0) to 16 weeks after randomisation
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Chinese People's Liberation Army General Hospital-Endocrinology
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Beijing, Beijing Municipality, China
Chongqing University Three Gorges Hospital
Chongqing, Chongqing Municipality, China
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