Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes (onset 9)

• ClinicalTrials.gov Identifier: NCT03268005
• Recruitment Status: Completed
• First Posted: August 31, 2017
• Last Update Posted: May 15, 2019
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: Faster-acting insulin aspart; Drug: Insulin aspart; Drug: Insulin degludec; Drug: Metformin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1264 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: September 19, 2017
• Actual Primary Completion Date: January 7, 2019
• Actual Study Completion Date: January 29, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Faster aspart + insulin degludec with or without metformin	Drug: Faster-acting insulin aspart; Faster aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Insulin degludec; Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Metformin; Only participants who took metformin before the study should take metformin tablets, same dose as before the study
Active Comparator: NovoRapid/NovoLog + insulin degludec with or without metformin	Drug: Insulin aspart; Insulin aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Insulin degludec; Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Metformin; Only participants who took metformin before the study should take metformin tablets, same dose as before the study

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in HbA1c [ Time Frame: Week 0, week 16 ]
   Measured in %

Secondary Outcome Measures :

1. Change from baseline in 1-hour postprandial glucose (PPG) increment (meal test) [ Time Frame: Week 0, week 16 ]
   Mean glucose values
2. Change from baseline in 1,5-anhydroglucitol [ Time Frame: Week 0, week 16 ]
   Measured in appropriate SI unit
3. Change from baseline in fasting plasma glucose (FPG) [ Time Frame: Week 0, week 16 ]
   Measured in mg/dl or other equivalent SI units
4. If a subject achieves HbA1c below 7% [ Time Frame: 16 weeks after randomisation ]
   Number of subjects
5. If a subject achieves HbA1c below 7% without severe hypoglycaemia [ Time Frame: 16 weeks after randomisation ]
   Number of subjects
6. Change from baseline in 30 minute PPG (meal test) [ Time Frame: Week 0, week 16 ]
   Mean glucose values
7. Change from baseline in 1 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
   Mean glucose values
8. Change from baseline in 2 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
   Mean glucose values
9. Change from baseline in 3 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
   Mean glucose values
10. Change from baseline in 4 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
11. Change from baseline in 30 minute PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
12. Change from baseline in 2 hour PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
13. Change from baseline in 3 hour PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
14. Change from baseline in 4 hour PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
15. Change from baseline in mean of the 7-9-7-point profile [ Time Frame: Week 0, week 16 ]
    Mean glucose values
16. Change from baseline in PPG (mean, breakfast, lunch, main evening meal) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
17. Change from baseline in PPG increment (mean, breakfast, lunch, main evening meal) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
18. Change from baseline in fluctuation in 7-9-7-point profile [ Time Frame: Week 0, week 16 ]
    Mean glucose values
19. Change from baseline in the nocturnal self-measured plasma glucose (SMPG) measurements [ Time Frame: Week 0, week 16 ]
    Mean glucose values
20. If a subject achieves overall PPG (1 hour) equal to or below 7.8 mmol/L [140 mg/dL] [ Time Frame: 16 weeks after randomisation ]
    Number of subjects
21. If a subject achieves overall PPG (1 hour) equal to or below 7.8 mmol/L [140 mg/dL] without severe hypoglycaemia [ Time Frame: 16 weeks after randomisation ]
    Number of subjects
22. Insulin dose: units/day [ Time Frame: 16 weeks after randomisation ]
    Count of units
23. Insulin dose: units/kg/day [ Time Frame: 16 weeks after randomisation ]
    Count of units
24. Insulin dose: total basal dose [ Time Frame: 16 weeks after randomisation ]
    Count of units
25. Insulin dose: total bolus dose [ Time Frame: 16 weeks after randomisation ]
    Count of units
26. Insulin dose: individual meal insulin dose [ Time Frame: 16 weeks after randomisation ]
    Count of units
27. Change from baseline in total cholesterol [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
28. Change from baseline in high density lipoproteins (HDL) cholesterol [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
29. Change from baseline in low density lipoproteins (LDL) cholesterol [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
30. Number of treatment emergent adverse events (AEs) [ Time Frame: Weeks 0-16 ]
    Count of events
31. Number of treatment emergent injection site reactions [ Time Frame: Weeks 0-16 ]
    Count of reactions
32. Number of treatment emergent hypoglycaemic episodes classified both according to the American Diabetes Association (ADA) definition and Novo Nordisk definition: Overall [ Time Frame: Weeks 0-16 ]
    Count of episodes
33. Number of treatment emergent hypoglycaemic episodes classified both according to the American Diabetes Association (ADA) definition and Novo Nordisk definition: Daytime hypoglycaemic episodes [ Time Frame: Weeks 0-16 ]
    Count of episodes
34. No. of treatment emergent hypoglycaemic episodes classified both according to the American Diabetes Association (ADA) definition and Novo Nordisk (NN) definition: Nocturnal hypoglycaemic episodes (00:01-05:59 - inclusive) [ Time Frame: Weeks 0-16 ]
    Count of episodes
35. No. of treatment emergent hypoglycaemic episodes classified both according to the ADA definition and NN definition: Hypoglycaemic episodes from start of meal until 1, 2, 4 hours and from 2 hours (exclusive) to 4 hours (inclusive) after start of meal [ Time Frame: Weeks 0-16 ]
    Count of episodes
36. Change from baseline in diastolic blood pressure [ Time Frame: Week 0, week 16 ]
    Measured in mmHg
37. Change from baseline in systolic blood pressure [ Time Frame: Week 0, week 16 ]
    Measured in mmHg
38. Change from baseline in pulse [ Time Frame: Week 0, week 16 ]
    Count of beats
39. Change from baseline in erythrocytes [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
40. Change from baseline in haematocrit [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
41. Change from baseline in haemoglobin [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
42. Change from baseline in leucocytes [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
43. Change from baseline in thrombocytes [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
44. Change from baseline in alanine aminotransferase (ALT) [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
45. Change from baseline in aspartate aminotransferase (AST) [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
46. Change from baseline in albumin [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
47. Change from baseline in alkaline phosphatase [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
48. Change from baseline in creatinine [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
49. Change from baseline in potassium [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
50. Change from baseline in sodium [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
51. Change from baseline in total bilirubin [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
52. Change from baseline in body weight [ Time Frame: Week 0, week 16 ]
    Measured in kg
53. Change from baseline in body mass index [ Time Frame: Week 0, week 16 ]
    Measured in kg/sqm

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

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Sponsors and Collaborators

Novo Nordisk A/S

More Information

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03268005 History of Changes
• Other Study ID Numbers: NN1218-4113; U1111-1180-0636 ( Other Identifier: World Health Organization (WHO) ); 2016-000878-38 ( Registry Identifier: European Medicines Agency (EudraCT) )
• First Posted: August 31, 2017
• Last Update Posted: May 15, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin; Insulin, Globin Zinc; Metformin; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Hypoglycemic Agents; Physiological Effects of Drugs