Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— onset 9  

Official title:

Efficacy and Safety of Fast-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec With or Without Metformin in Adults With Type 2 Diabetes (Onset® 9)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03268005
• Other study ID #: NN1218-4113
• Secondary ID: U1111-1180-06362
• Status: Completed
• Phase: Phase 3
• Start date: September 19, 2017
• Est. completion date: January 29, 2019

Study information

• Verified date: January 2022
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1264
• Est. completion date: January 29, 2019
• Est. primary completion date: January 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Faster-acting insulin aspart
Faster aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.
• Insulin aspart
Insulin aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.
• Insulin degludec
Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.
• Metformin
Only participants who took metformin before the study should take metformin tablets, same dose as before the study

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Cordoba
Argentina	Novo Nordisk Investigational Site	Córdoba
Bulgaria	Novo Nordisk Investigational Site	Kozloduy
Bulgaria	Novo Nordisk Investigational Site	Razgrad
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Canada	Novo Nordisk Investigational Site	Barrie	Ontario
Canada	Novo Nordisk Investigational Site	Concord	Ontario
Canada	Novo Nordisk Investigational Site	Edmonton	Alberta
Canada	Novo Nordisk Investigational Site	Etobicoke	Ontario
Canada	Novo Nordisk Investigational Site	Halifax	Nova Scotia
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Newmarket	Ontario
Canada	Novo Nordisk Investigational Site	Thunder Bay	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Victoria	British Columbia
Croatia	Novo Nordisk Investigational Site	Karlovac
Croatia	Novo Nordisk Investigational Site	Osijek
Croatia	Novo Nordisk Investigational Site	Varazdin
Croatia	Novo Nordisk Investigational Site	Zagreb
Czechia	Novo Nordisk Investigational Site	Hradec Kralove
Czechia	Novo Nordisk Investigational Site	Plzen
Czechia	Novo Nordisk Investigational Site	Plzen
Czechia	Novo Nordisk Investigational Site	Trutnov
Germany	Novo Nordisk Investigational Site	Dresden
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Lingen
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach
Germany	Novo Nordisk Investigational Site	Schweinfurt
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Ioannina
Greece	Novo Nordisk Investigational Site	Larissa
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Italy	Novo Nordisk Investigational Site	Catanzaro
Italy	Novo Nordisk Investigational Site	Chieti
Italy	Novo Nordisk Investigational Site	Cittadella (PD)
Italy	Novo Nordisk Investigational Site	Milano (MI)
Italy	Novo Nordisk Investigational Site	Olbia
Italy	Novo Nordisk Investigational Site	Palermo
Korea, Republic of	Novo Nordisk Investigational Site	Bucheon
Korea, Republic of	Novo Nordisk Investigational Site	Daegu
Korea, Republic of	Novo Nordisk Investigational Site	Seongnam-si
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Wonju
Poland	Novo Nordisk Investigational Site	Bialystok
Poland	Novo Nordisk Investigational Site	Skorzewo
Poland	Novo Nordisk Investigational Site	Warsaw
Poland	Novo Nordisk Investigational Site	Warsaw
Poland	Novo Nordisk Investigational Site	Warszawa
Poland	Novo Nordisk Investigational Site	Wroclaw
Puerto Rico	Novo Nordisk Investigational Site	Ponce
Romania	Novo Nordisk Investigational Site	Baia Mare	Maramures
Romania	Novo Nordisk Investigational Site	Brasov
Romania	Novo Nordisk Investigational Site	Brasov
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Timisoara	Timis
Romania	Novo Nordisk Investigational Site	Tirgu Mures	Mures
Russian Federation	Novo Nordisk Investigational Site	Arkhangelsk
Russian Federation	Novo Nordisk Investigational Site	Kazan
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Tumen
Russian Federation	Novo Nordisk Investigational Site	Voronezh
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Kragujevac
Serbia	Novo Nordisk Investigational Site	Nis
Serbia	Novo Nordisk Investigational Site	Novi Sad
Serbia	Novo Nordisk Investigational Site	Zajecar
Slovakia	Novo Nordisk Investigational Site	Kosice
Slovakia	Novo Nordisk Investigational Site	Kysucke Nove Mesto
Slovakia	Novo Nordisk Investigational Site	Lubochna
Slovakia	Novo Nordisk Investigational Site	Lucenec
Slovakia	Novo Nordisk Investigational Site	Zilina
Spain	Novo Nordisk Investigational Site	Alcobendas
Spain	Novo Nordisk Investigational Site	Almería
Spain	Novo Nordisk Investigational Site	Girona
Spain	Novo Nordisk Investigational Site	La Coruña
Spain	Novo Nordisk Investigational Site	Pozuelo de Alarcon
Spain	Novo Nordisk Investigational Site	Sabadell
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Sevilla
Ukraine	Novo Nordisk Investigational Site	Dnipro
Ukraine	Novo Nordisk Investigational Site	Kharkiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Lviv
Ukraine	Novo Nordisk Investigational Site	Ternopil
Ukraine	Novo Nordisk Investigational Site	Vinnytsia
United States	Novo Nordisk Investigational Site	Alpharetta	Georgia
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Asheville	North Carolina
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Beaumont	Texas
United States	Novo Nordisk Investigational Site	Bennington	Vermont
United States	Novo Nordisk Investigational Site	Boynton Beach	Florida
United States	Novo Nordisk Investigational Site	Bradenton	Florida
United States	Novo Nordisk Investigational Site	Chapel Hill	North Carolina
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Chesapeake	Virginia
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Concord	California
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Denver	Colorado
United States	Novo Nordisk Investigational Site	Fort Lauderdale	Florida
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Fullerton	California
United States	Novo Nordisk Investigational Site	Golden	Colorado
United States	Novo Nordisk Investigational Site	Green Bay	Wisconsin
United States	Novo Nordisk Investigational Site	Greenville	South Carolina
United States	Novo Nordisk Investigational Site	Henderson	Nevada
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Lawrenceville	Georgia
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Longview	Texas
United States	Novo Nordisk Investigational Site	Mentor	Ohio
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	Norco	California
United States	Novo Nordisk Investigational Site	Northport	New York
United States	Novo Nordisk Investigational Site	Ogden	Utah
United States	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Pearland	Texas
United States	Novo Nordisk Investigational Site	Peoria	Illinois
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Sacramento	California
United States	Novo Nordisk Investigational Site	Seattle	Washington
United States	Novo Nordisk Investigational Site	South Burlington	Vermont
United States	Novo Nordisk Investigational Site	Spokane	Washington
United States	Novo Nordisk Investigational Site	Springfield	Illinois
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Valparaiso	Indiana
United States	Novo Nordisk Investigational Site	Ventura	California
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Waltham	Massachusetts
United States	Novo Nordisk Investigational Site	Waterbury	Connecticut
United States	Novo Nordisk Investigational Site	West Des Moines	Iowa
United States	Novo Nordisk Investigational Site	West Seneca	New York
United States	Novo Nordisk Investigational Site	Winchester	Virginia
United States	Novo Nordisk Investigational Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Croatia,  Czechia,  Germany,  Greece,  Italy,  Korea, Republic of,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Ukraine, 

References & Publications (1)

Lane WS, Favaro E, Rathor N, Jang HC, Kjærsgaard MIS, Oviedo A, Rose L, Senior P, Sesti G, Soto Gonzalez A, Franek E. A Randomized Trial Evaluating the Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination Wit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	16 weeks after randomisation
Secondary	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.	16 weeks after randomisation
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	16 weeks after randomisation
Secondary	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.	16 weeks after randomisation
Secondary	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.	16 weeks from randomisation
Secondary	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.	16 weeks from randomisation
Secondary	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.	16 weeks from randomisation
Secondary	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.	16 weeks from randomisation
Secondary	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.	16 weeks from randomisation
Secondary	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.	16 weeks from randomisation
Secondary	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.	Week 0, week 16
Secondary	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.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall	ADA classification of hypos: 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.; Documented symptomatic: PG =3.9 mmol/L with symptoms.; Asymptomatic: PG =3.9 mmol/L without symptoms.; Probable symptomatic: No measurement with symptoms.; Pseudo: PG >3.9 mmol/L with symptoms.; Unclassifiable.; NN classification of hypos: BG confirmed: PG <3.1 mmol/L with/without symptoms.; Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with symptoms.; Severe or BG confirmed: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with/without symptoms.; Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	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.	Weeks 0-16
Secondary	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	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16
Secondary	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.	Week 0, week 16