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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03268005
Recruitment Status : Completed
First Posted : August 31, 2017
Results First Posted : February 5, 2020
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Tracking Information
First Submitted Date  ICMJE August 29, 2017
First Posted Date  ICMJE August 31, 2017
Results First Submitted Date  ICMJE January 7, 2020
Results First Posted Date  ICMJE February 5, 2020
Last Update Posted Date April 8, 2020
Actual Study Start Date  ICMJE September 19, 2017
Actual Primary Completion Date January 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2020)
Change in Glycosylated Haemoglobin (HbA1c) [ Time Frame: Week 0, week 16 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
Change from baseline in HbA1c [ Time Frame: Week 0, week 16 ]
Measured in %
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2020)
  • Change From Baseline in 1-hour PPG Increment [ Time Frame: 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. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
  • Change From Baseline in 1,5-anhydroglucitol [ Time Frame: 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. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
  • Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, week 16 ]
    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.
  • Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No) [ Time Frame: 16 weeks after randomisation ]
    Number of participants reaching HbA1c <7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
  • Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No) [ Time Frame: 16 weeks after randomisation ]
    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.
  • Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) [ Time Frame: 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. 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.
  • Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) [ Time Frame: Week 0, week 16 ]
    Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) 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.
  • Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) [ Time Frame: Week 0, week 16 ]
    Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 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.
  • Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile [ Time Frame: 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 7-9-7 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.
  • Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements [ Time Frame: 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 7-9-7 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.
  • Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No) [ Time Frame: 16 weeks after randomisation ]
    Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.
  • Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No) [ Time Frame: 16 weeks after randomisation ]
    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.
  • Total Bolus Insulin Dose: in Units/Day [ Time Frame: 16 weeks from randomisation ]
    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.
  • Total Bolus Insulin Dose: in Units/kg/Day [ Time Frame: 16 weeks from randomisation ]
    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.
  • Total Basal Insulin Dose: in Units/Day [ Time Frame: 16 weeks from randomisation ]
    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.
  • Total Basal Insulin Dose: in Units/kg/Day [ Time Frame: 16 weeks from randomisation ]
    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.
  • Individual Meal Insulin Dose: in Units [ Time Frame: 16 weeks from randomisation ]
    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.
  • Individual Meal Insulin Dose: in Units/kg [ Time Frame: 16 weeks from randomisation ]
    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.
  • Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline [ Time Frame: Week 0, week 16 ]
    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.
  • Number of Treatment Emergent Adverse Events [ Time Frame: Weeks 0-16 ]
    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.
  • Number of Treatment Emergent Injection Site Reactions [ Time Frame: Weeks 0-16 ]
    Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
  • Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall [ Time Frame: Weeks 0-16 ]
    ADA classification of hypos:
    1. Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level.
    2. Documented symptomatic: PG ≤3.9 mmol/L with symptoms.
    3. Asymptomatic: PG ≤3.9 mmol/L without symptoms.
    4. Probable symptomatic: No measurement with symptoms.
    5. Pseudo: PG >3.9 mmol/L with symptoms.
    6. Unclassifiable.
    NN classification of hypos:
    1. BG confirmed: PG <3.1 mmol/L with/without symptoms.
    2. Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with symptoms.
    3. Severe or BG confirmed: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with/without symptoms.
    4. Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.
  • Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) [ Time Frame: 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. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
  • Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) [ Time Frame: 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. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
  • Number of 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 [ Time Frame: 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. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
  • Number of 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 [ Time Frame: 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. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
  • Number of 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 [ Time Frame: 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. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.
  • Number of 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 [ Time Frame: 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. 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.
  • Change From Baseline in Physical Examination [ Time Frame: Week 0, week 16 ]
    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
  • Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Vital Signs: Pulse [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Electrocardiogram (ECG) [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Fundoscopy/Fundus Photography [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Haematology - Haematocrit [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Haematology - Haemoglobin [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Haematology - Leukocytes [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Haematology - Thrombocytes [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Haematology - Erythrocytes [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT) [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Alkaline Phosphatase [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST) [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Albumin [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Creatinine [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Potassium [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Sodium [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Total Bilirubin [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Biochemistry - Total Protein [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Body Weight [ Time Frame: Week 0, week 16 ]
    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.
  • Change From Baseline in Body Mass Index (BMI) [ Time Frame: Week 0, week 16 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
  • Change from baseline in 1-hour postprandial glucose (PPG) increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change From Baseline in 1,5-anhydroglucitol [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
  • If a subject achieves HbA1c below 7% [ Time Frame: 16 weeks after randomisation ]
    Number of subjects
  • If a subject achieves HbA1c below 7% without severe hypoglycaemia [ Time Frame: 16 weeks after randomisation ]
    Number of subjects
  • Change from baseline in 30 minute PPG (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 1 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 2 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 3 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 4 hour PPG (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 30 minute PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 2 hour PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 3 hour PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in 4 hour PPG increment (meal test) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in mean of the 7-9-7-point profile [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in PPG (mean, breakfast, lunch, main evening meal) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in PPG increment (mean, breakfast, lunch, main evening meal) [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in fluctuation in 7-9-7-point profile [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • Change from baseline in the nocturnal self-measured plasma glucose (SMPG) measurements [ Time Frame: Week 0, week 16 ]
    Mean glucose values
  • 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
  • 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
  • Insulin dose: units/day [ Time Frame: 16 weeks after randomisation ]
    Count of units
  • Insulin dose: units/kg/day [ Time Frame: 16 weeks after randomisation ]
    Count of units
  • Insulin dose: total basal dose [ Time Frame: 16 weeks after randomisation ]
    Count of units
  • Insulin dose: total bolus dose [ Time Frame: 16 weeks after randomisation ]
    Count of units
  • Insulin dose: individual meal insulin dose [ Time Frame: 16 weeks after randomisation ]
    Count of units
  • Change from baseline in total cholesterol [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
  • Change from baseline in high density lipoproteins (HDL) cholesterol [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
  • Change from baseline in low density lipoproteins (LDL) cholesterol [ Time Frame: Week 0, week 16 ]
    Measured in mg/dl or other equivalent SI units
  • Number of treatment emergent adverse events (AEs) [ Time Frame: Weeks 0-16 ]
    Count of events
  • Number of Treatment Emergent Injection Site Reactions [ Time Frame: Weeks 0-16 ]
    Count of reactions
  • 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
  • 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
  • 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
  • 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
  • Change from baseline in diastolic blood pressure [ Time Frame: Week 0, week 16 ]
    Measured in mmHg
  • Change from baseline in systolic blood pressure [ Time Frame: Week 0, week 16 ]
    Measured in mmHg
  • Change from baseline in pulse [ Time Frame: Week 0, week 16 ]
    Count of beats
  • Change from baseline in erythrocytes [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in haematocrit [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in haemoglobin [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in leucocytes [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in thrombocytes [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in alanine aminotransferase (ALT) [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in aspartate aminotransferase (AST) [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in albumin [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in alkaline phosphatase [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in creatinine [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in potassium [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in sodium [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change from baseline in total bilirubin [ Time Frame: Week 0, week 16 ]
    Measured in appropriate SI unit
  • Change From Baseline in Body Weight [ Time Frame: Week 0, week 16 ]
    Measured in kg
  • Change from baseline in body mass index [ Time Frame: Week 0, week 16 ]
    Measured in kg/sqm
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE
  • Diabetes
  • Diabetes Mellitus, Type 2
Intervention  ICMJE
  • 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 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
Study Arms  ICMJE
  • Experimental: Faster aspart + insulin degludec with or without metformin
    Interventions:
    • Drug: Faster-acting insulin aspart
    • Drug: Insulin degludec
    • Drug: Metformin
  • Active Comparator: NovoRapid/NovoLog + insulin degludec with or without metformin
    Interventions:
    • Drug: Insulin aspart
    • Drug: Insulin degludec
    • Drug: Metformin
Publications * 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 With Insulin Degludec With or Without Metformin, in Adults With Type 2 Diabetes (Onset 9). Diabetes Care. 2020 Mar 24. pii: dc192232. doi: 10.2337/dc19-2232. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 6, 2019)
1264
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2017)
1072
Actual Study Completion Date  ICMJE January 29, 2019
Actual Primary Completion Date January 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Bulgaria,   Canada,   Croatia,   Czechia,   Germany,   Greece,   Italy,   Korea, Republic of,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Slovakia,   Spain,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03268005
Other Study ID Numbers  ICMJE NN1218-4113
U1111-1180-0636 ( Other Identifier: World Health Organization (WHO) )
2016-000878-38 ( Registry Identifier: European Medicines Agency (EudraCT) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novo Nordisk A/S
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP