Efficacy and Safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart Compared to NovoRapid® in Adults With Type 1 Diabetes

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 1; Diabetes
• Interventions: Drug: Faster-acting insulin aspart; Drug: insulin aspart

• Registration Number: NCT02825251
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to investigate efficacy and safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart compared to NovoRapid® in Adults with Type 1 Diabetes.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-07-04
• Study First Submitted QC: 2016-07-04
• Study Start: 2016-07-06
• Study First Posted: 2016-07-07
• Primary Completion: 2017-06-20
• Study Completion: 2017-07-21
• Results First Submitted: 2018-06-27
• Results First Submitted QC: 2018-06-27
• Results First Posted: 2018-07-24
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-12
• Last Update Posted: 2019-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 472

Inclusion Criteria

• Male or female, age at least 18 years at the time of signing the informed consent
• Diagnosed with T1DM (Type 1 Diabetes Mellitus) (based on clinical judgement and/or supported by laboratory analysis as per local guidelines) equal or above 1 year prior to the day of screening
• Using the same Medtronic pump (Minimed 530G (551/751), Paradigm Veo (554/754), Paradigm Revel (523/723), Paradigm (522/722)) for CSII in a basal-bolus regimen with a rapid acting insulin analogue for at least six months prior to screening and willing to stay on the same pump model throughout the trial (if the model is changed the change should not exceed 7 consecutive days.)
• HbA1c (glycosylated haemoglobin) 7.0-9.0% (53-75 mmol/mol) as assessed by central laboratory at screening
• Body mass index (BMI) below or equal to 35.0 kg/m^2 at screening
• Ability and willingness to take at least 3 daily meal-time insulin bolus infusions every day throughout the trial

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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
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• History of hospitalization for ketoacidosis below or equal to 180 days prior to the day of screening
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening
• Any condition which, in the opinion of the Investigator, might jeopardise a Subject's safety or compliance with the protocol

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Faster-acting insulin aspart CSII	Faster-acting insulin aspart	-
NovoRapid® CSII	insulin aspart	-

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated Haemoglobin (HbA1c)	Week 0, week 16	Change from baseline (week 0) in HbA1c 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 period: the observation period from date of randomisation until last trial-related subject-site contact.

Secondary Outcome Measures

Name	Time	Method
Insulin Dose in Units/kg/Day: Total Basal	Week 16	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.
Percentage of Subjects Reaching Overall PPG (1 Hour) ≤7.8 mmol/L [140 mg/dL]	Week 16	Percentage of subjects reaching overall PPG (1 hour) ≤7.8 mmol/L \[140 mg/dL\] was evaluated after 16 weeks of randomisation. Subjects 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 in-trial period.
Insulin Dose in Units/kg/Day: Total Bolus	Week 16	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.
Insulin Dose in Units/kg/Day: Total Daily Insulin Dose	Week 16	Total 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.
Change From Baseline in 1-hour PPG Increment	Week 0, Week 16	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.
Change From Baseline in Time Spent in Low IG (≤3.9 mmol/L [70 mg/dL]) During CGM	Week 0, week 16	Change from baseline (week 0) in low interstitial glucose (IG) (≤3.9 mmol/L \[70 mg/dL\]) during continuous glucose monitoring (CGM) 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.
Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins)	Week 0, week 16	Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values at baseline (week 0) and 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.
Change From Baseline of the 7-7-9 Point SMPG Profile: in Nocturnal SMPG Measurements	Week 0, week 16	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 7-7-9 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.
Insulin Dose in Units/Day: Total Basal	Week 16	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: the observation period from date of first dose of randomised trial products (faster aspart and NovoRapid®) to no later than 7 days after the day of last dose of randomised trial products.
Insulin Dose in Units/Day: Total Bolus	Week 16	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.
Insulin Dose in Units/Day: Individual Meal Insulin Dose	Week 16	No data was collected for individual meal insulin dose.
Insulin Dose in Units/kg/Day: Individual Meal Insulin Dose	Week 16	No data was collected for individual meal insulin dose.
Percentage of Time Spent With IG ≤2.5, 3.0, 3.5, 3.9 mmol/L [45, 54, 63, 70 mg/dL]) and IG >10.0, 12.0, 13.9 mmol/L [180, 216, 250 mg/dL])	Week 16	Percentage of time spent with IG ≤2.5, 3.0, 3.5, 3.9 mmol/L \[45, 54, 63, 70 mg/dL\]) and IG \>10.0, 12.0, 13.9 mmol/L \[180, 216, 250 mg/dL\]) 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.
Change From Baseline in 1,5-anhydroglucitol	Week 0, Week 16	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.
Change From Baseline in Fasting Plasma Glucose (FPG)	Week 0, week 16	Change from baseline (week 0) in 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.
Percentage of Subjects Reaching HbA1c <7.0% (53 mmol/Mol)	Week 16	Percentage of subjects reaching HbA1c \<7.0% (53 mmol/mol) was evaluated after 16 weeks of randomisation. Subjects without an HbA1c measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the in-trial period.
Change From Baseline of the 7-7-9 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal)	Week 0, week 16	Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-7-9 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.
Insulin Dose in Units/Day: Total Daily Insulin Dose	Week 16	Total 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.
Change From Baseline in 30-min, 1-hour, 2-hour, 3-hour and 4-hour PPG (Meal Test)	Week 0, week 16	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. 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.
Change From Baseline in 30-min, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test)	Week 0, week 16	Change from baseline (week 0) in 30-min, 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. 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 PPG was evaluated after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.
Change From Baseline of the 7-7-9 Point SMPG Profile: Pre-prandial Plasma Glucose (PG) (Mean, Pre-breakfast, Pre-lunch, Pre-main Evening Meal)	Week 0, week 16	Change from baseline (week 0) in pre-prandial PG (pre-breakfast, pre-lunch, pre-main evening meal and mean over all meals) of the 7-7-9 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.
Change From Baseline of the 7-7-9 Point SMPG Profile: Fluctuation in 7-7-9 Point Profile	Week 0, week 16	Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-7-9 point SMPG profile at baseline (week 0) and after 16 weeks of randomisation (i.e., week 16). The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Percentage of Subjects Reaching Overall PPG (1 Hour) ≤7.8 mmol/L [140 mg/dL] Without Severe Hypoglycaemia	Week 16	Percentage of subjects reaching overall PPG (1 hour) ≤7.8 mmol/L \[140 mg/dL\] without treatment emergent severe hypoglycaemia was evaluated after 16 weeks of randomisation. Subjects without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal was considered sufficient evidence that the event was induced by a low PG concentration. The results are based on the in-trial period.
Percentage of Subjects Reaching HbA1c <7.0% (53 mmol/Mol) Without Severe Hypoglycaemic Episodes	Week 16	Percentage of subjects reaching HbA1c \<7.0% (53 mmol/mol) without treatment emergent severe hypoglycaemic episodes was evaluated after 16 weeks of randomisation. Subjects without an HbA1c measurement at week 16 were considered not to have achieved HbA1c target at week 16. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal was considered sufficient evidence that the event was induced by a low PG concentration. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of IMP administration after randomisation (in week 0) and no later than one day after the last day on IMP (i.e., maximum week 16 + 1 day). The results are based on the in-trial period.
Change From Baseline in Mean of the 7-7-9 Point Self-measured Plasma Glucose (SMPG) Profile	Week 0, week 16	Change from baseline (week 0) in mean of the 7-7-9 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. 7-7-9 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.
Change From Baseline of the 7-7-9 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal)	Week 0, week 16	Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-7-9 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.
Insulin Delivery Pump Parameter: Insulin Carbohydrate Ratio	Week 16	Insulin carbohydrate ratio 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.
Insulin Delivery Pump Parameter: Glucose Sensitivity Factor	Week 16	Glucose sensitivity factor 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.
Incidence of Episodes With IG ≤2.5, 3.0, 3.5, 3.9 mmol/L [45, 54, 63, 70 mg/dL]) and IG >10.0, 12.0, 13.9 mmol/L [180, 216, 250 mg/dL])	Week 16	Incidence of episodes with IG ≤2.5, 3.0, 3.5, 3.9 mmol/L \[45, 54, 63, 70 mg/dL\]) and IG \>10.0, 12.0, 13.9 mmol/L \[180, 216, 250 mg/dL\]) 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.
Insulin Delivery Pump Parameter: Active Insulin Time	Week 16	Active insulin time 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.
Change From Baseline in Mean IG Increment (0-30 Min, 0-1 Hour and 0-2 Hours After Start of Meal) (Mean, Breakfast, Lunch and Main Evening Meal)	Week 0, week 16	Change from baseline (week 0) in mean interstitial glucose (IG) increment (0-30 minutes (min), 0-1 hour (h) and 0-2 h after start of meal) (breakfast, lunch, main evening meal and mean across all meals) 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.
Change From Baseline in Mean Time to the IG Peak After Start of Meal (Mean, Breakfast, Lunch and Main Evening Meal)	Week 0, week 16	Change from baseline (week 0) in mean time to the IG peak after start of meal (breakfast, lunch, main evening meal and mean across all meals) 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.
Change From Baseline in Mean IG Peak After Start of Meal (Mean, Breakfast, Lunch and Main Evening Meal)	Week 0, week 16	Change from baseline (week 0) in mean IG peak after start of meal (breakfast, lunch, main evening meal and mean across all meals) 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.
Change From Baseline in Mean of the IG Profile	Week 0, week 16	Change from baseline (week 0) in mean of the IG profile was evaluated after 16 weeks of randomisation. The mean of an IG profile is defined as the time integral of the profile over the profile's length, divided by the profile's length. The results are based on the last in-trial value, which included the last available measurement in the in-trial period.
Percentage of Time Spent Within IG Target Range 4.0-7.8 mmol/L (71-140 mg/dL) and 4.0-10 mmol/L (71-180 mg/dL)	Week 16	Percentage of time spent within IG target range 4.0-7.8 mmol/L (71-140 mg/dL) and 4.0-10 mmol/L (71-180 mg/dL) 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.
Variation in the IG Profile	Week 16	Variation in IG profile was the average absolute difference from the mean of the IG profile. Variation in the IG 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.
Area Under the Curve (AUC3.9-IG) for IG ≤3.9 mmol/L [70 mg/dL]	Week 16	Area under the curve (AUC3.9-IG) for IG ≤3.9 mmol/L \[70 mg/dL\] 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.
Change From Baseline in AUCIG,0-2h	Week 0, week 16	Change from baseline (week 0) in AUCIG,0-2 hours during 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.
Change From Baseline in AUCIG,0-4h	Week 0, week 16	Change from baseline (week 0) in AUCIG,0-24hours during 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.
Number of Treatment Emergent Infusion Site Reactions	Weeks 0-16	Number of treatment emergent infusion site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period.
Change From Baseline in AUCIG,0-15min	Week 0, week 16	Change from baseline (week 0) in area under the curve for interstitial glucose (AUCIG),0-15 minutes during 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.
Change From Baseline in AUCIG,0-30min	Week 0, week 16	Change from baseline (week 0) in AUCIG,0-30 minutes during 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.
Change From Baseline in AUCIG,0-1h	Week 0, week 16	Change from baseline (week 0) in AUCIG,0-1 hour during 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.
Change From Baseline in IG Peak After Start of Meal	Week 0, week 16	Change from baseline (week 0) in IG peak after start of meal-test meal 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.
Number of Treatment Emergent Adverse Events (AEs)	Weeks 0-16	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 16. A TEAE was defined as an event that has an onset date on or after the first day of exposure to randomised treatment (in week 0), and no later than seven days after the last day of randomised treatment (i.e., maximum week 16 + 7 days). The results are based on the on-treatment period.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall	Weeks 0-16	ADA classification of hypo: 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 hypo: 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 hypo.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)	Weeks 0-16	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.
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	Weeks 0-16	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.
Change From Baseline in Time to the IG Peak After Start of Meal	Week 0, week 16	Change from baseline (week 0) in time to the IG peak after start of meal-test meal 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.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive)	Weeks 0-16	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal	Weeks 0-16	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal	Weeks 0-16	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 1 Hour to 2 Hours After Start of the Meal	Weeks 0-16	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 1 hour to 2 hours after start of the meal. The results are based on the on-treatment period.
Number of Unexplained Episodes of Hyperglycaemia (Confirmed by SMPG)	Weeks 0-16	Unexplained hyperglycaemia was defined as a confirmed PG value ≥16.7 mmol/L (300 mg/dL) and was unexplained (i.e. no apparent medical, dietary, insulin dosage or pump failure reason). The results are based on the on-treatment period.
Change From Baseline in Physical Examination: Cardiovascular System	Week 0, week 16	Reported results are cardiovascular system-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Physical Examination: Central and Peripheral Nervous System	Week 0, week 16	Reported results are central and peripheral nervous system-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Physical Examination: Gastrointestinal System, Including the Mouth	Week 0, week 16	Reported results are gastrointestinal system-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Physical Examination: Musculoskeletal System	Week 0, week 16	Reported results are musculoskeletal system-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
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	Weeks 0-16	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.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes Occurring Between 2 to 3 Hours After Start of the Meal	Weeks 0-16	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 3 hours after start of the meal. The results are based on the on-treatment period.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes Occurring Between 3 to 4 Hours After Start of the Meal	Weeks 0-16	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 3 to 4 hours after start of the meal. The results are based on the on-treatment period.
Change From Baseline in Physical Examination: Respiratory System	Week 0, week 16	Reported results are respiratory system-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Physical Examination: Skin	Week 0, week 16	Reported results are skin-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Physical Examination: Head, Ears, Eyes, Nose, Throat and Neck	Week 0, week 16	Reported results are head, ears, eyes, nose, throat and neck-examination findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Vital Sign: Blood Pressure	Week 0, week 16	Change from baseline (week 0) in blood pressure (both systolic and diastolic) 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.
Change From Baseline in Vital Sign: Pulse	Week 0, week 16	Change from baseline (week 0) in pulse 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.
Change From Screening in Electrocardiogram (ECG)	Week 0, week 16	Reported results are ECG findings at screening (week -6) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) Abnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Screening in Fundus Photography/Fundoscopy	Week 0, week 16	Reported results are fundus photography/fundoscopy (for both left and right eye) findings at screening (week -6) and after 16 weeks of randomisation. The findings are presented as: 1) Normal. 2) AAbnormal (not clinically significant \[NCS\]). 3) Abnormal (clinically significant \[CS\]). The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Haematology: Haemoglobin	Week 0, week 16	Change from baseline (week 0) in haemoglobin 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.
Change From Baseline in Haematology: Haematocrit	Week 0, week 16	Change from baseline (week 0) in haematocrit 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.
Change From Baseline in Haematology: Erythrocytes	Week 0, week 16	Change from baseline (week 0) in erythrocytes 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.
Change From Baseline in Haematology: Thrombocytes	Week 0, week 16	Change from baseline (week 0) in thrombocytes 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.
Change From Baseline in Haematology: Leucocytes	Week 0, week 16	Change from baseline (week 0) in leucocytes 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.
Change From Baseline in Biochemistry: Total Protein	Week 0, week 16	Change from baseline (week 0) in total protein 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.
Change From Baseline in Biochemistry: Creatinine	Week 0, week 16	Change from baseline (week 0) in creatinine 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.
Change From Baseline in Biochemistry: Alanine Aminotransferase (ALT)	Week 0, week 16	Change from baseline (week 0) in ALT 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.
Change From Baseline in Biochemistry: Alkaline Phosphatase (ALP)	Week 0, week 16	Change from baseline (week 0) in ALP 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.
Change From Baseline in Urinalysis: Protein	Week 0, week 16	Reported results are urine protein-test findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: a) Negative, b) Trace, c) 1+, d) 2+ e) 3+ and f) 4+. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Urinalysis: Albumin/Creatine Ratio	Week 0, week 16	Change from baseline (week 0) in albumin/creatine ratio 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.
Change From Baseline in Urinalysis: Erythrocytes	Week 0, week 16	Reported results are urine erythrocytes-test findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: a) Negative, b) Trace, c) 1+, d) 2+ and e) 3+. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Change From Baseline in Biochemistry: Aspartate Aminotransferase (AST)	Week 0, week 16	Change from baseline (week 0) in AST 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.
Change From Baseline in Biochemistry: Total Bilirubin	Week 0, week 16	Change from baseline (week 0) in bilirubin 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.
Change From Baseline in Body Mass Index (BMI)	Week 0, week 16	Change from baseline (week 0) in BMI 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.
Change From Baseline in Biochemistry: Sodium	Week 0, week 16	Change from baseline (week 0) in sodium 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.
Change From Baseline in Biochemistry: Potassium	Week 0, week 16	Change from baseline (week 0) in potassium 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.
Change From Baseline in Biochemistry: Albumin	Week 0, week 16	Change from baseline (week 0) in albumin 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.
Change From Baseline in Body Weight	Week 0, week 16	Change from baseline (week 0) in body weight 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.
Number of Subjects With at Least One Non-routine Change-of-infusion-sets Categorised by Reasons for Change-of-infusion-sets	Week 0-16	Number of subjects with at least one non-routine change-of-infusion-sets categorised by reasons for change-of-infusion-sets was evaluated 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.; Reasons for change-of-infusion-sets are categorised as follows: Category-1: A perceived occlusion by the subject Category-2: Any problems related to the infusion set Category-3: Any technical issues with the pump Category-4: Changes in the insulin solution in the infusion set or reservoir Category-5: High BG with no other explanation which made the subject change the infusion set Category-6: Infusion site reaction Category-7: Missing
Change From Baseline in Urinalysis: Ketones	Week 0, week 16	Reported results are urine ketone-test findings at baseline (week 0) and after 16 weeks of randomisation. The findings are presented as: a) Negative, b) Trace, c) 1+, d) 2+ e) 3+ and f) 4+. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period.
Number of Change-of-infusion-sets Per Week	Week 0-16	Number of change-of-infusion-sets per week was evaluated 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.

Trial Locations

Locations (1)

Novo Nordisk Investigational Site; 🇬🇧 St Helens, United Kingdom