Phase 3
Completed N=472
Efficacy and Safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart Compared to NovoRapid® in Adults With Type 1 Diabetes
Diabetes · Diabetes Mellitus, Type 1
Source: ClinicalTrials.gov NCT02825251 ↗
Enrolled (actual)
472
Serious AEs
2.8%
Results posted
Jul 2018
Primary outcomePrimary: Change in Glycosylated Haemoglobin (HbA1c) — 7.49; 7.49; -0.06; -0.14 Percentage (%) of HbA1c
◆ Published Evidence
Established
77citations · ~11 / year
A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5).
Summary
This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to investigate efficacy and safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart compared to NovoRapid® in Adults with Type 1 Diabetes.
Linked Publications (3)
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A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5).
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Investigation of Pump Compatibility of Fast-Acting Insulin Aspart in Subjects With Type 1 Diabetes.
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Continuous Glucose Monitoring Sensor Glucose Levels and Insulin Pump Infusion Set Wear-Time During Treatment with Fast-Acting Insulin Aspart: A Post Hoc Analysis of Onset 5.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Glycosylated Haemoglobin (HbA1c) |
7.49; 7.49; -0.06; -0.14 | — |
| SECONDARY Change From Baseline in 1-hour PPG Increment |
4.67; 4.62; -0.89; 0.05 | — |
| SECONDARY Change From Baseline in 1,5-anhydroglucitol |
4.20; 4.13; 0.14; 0.25 | — |
| SECONDARY Change From Baseline in Time Spent in Low IG (≤3.9 mmol/L [70 mg/dL]) During CGM |
85.42; 79.88; -6.96; 2.85 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) |
7.60; 7.40; -0.03; 0.25 | — |
| SECONDARY Percentage of Subjects Reaching HbA1c <7.0% (53 mmol/Mol) |
20.3; 23.3 | — |
| SECONDARY Percentage of Subjects Reaching HbA1c <7.0% (53 mmol/Mol) Without Severe Hypoglycaemic Episodes |
18.6; 22.5 | — |
| SECONDARY Change From Baseline in 30-min, 1-hour, 2-hour, 3-hour and 4-hour PPG (Meal Test) |
10.54; 10.30; 12.18; 11.96; 13.17; 13.04 | — |
| SECONDARY Change From Baseline in 30-min, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) |
3.02; 2.95; 5.65; 5.70; 3.85; 4.13 | — |
| SECONDARY Change From Baseline in Mean of the 7-7-9 Point Self-measured Plasma Glucose (SMPG) Profile |
9.24; 9.10; 0.19; 0.10 | — |
| SECONDARY Change From Baseline of the 7-7-9 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) |
10.82; 10.28; 9.65; 9.62; 9.79; 9.34 | — |
| SECONDARY Change From Baseline of the 7-7-9 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) |
2.62; 1.93; 1.80; 1.77; 1.04; 0.52 | — |
| SECONDARY Change From Baseline of the 7-7-9 Point SMPG Profile: Pre-prandial Plasma Glucose (PG) (Mean, Pre-breakfast, Pre-lunch, Pre-main Evening Meal) |
8.40; 8.31; 8.28; 8.21; 8.68; 8.87 | — |
| SECONDARY Change From Baseline of the 7-7-9 Point SMPG Profile: Fluctuation in 7-7-9 Point Profile |
2.14; 2.05; 2.06; 2.06 | — |
| SECONDARY Change From Baseline of the 7-7-9 Point SMPG Profile: in Nocturnal SMPG Measurements |
-1.29; -1.06; -0.97; -0.56; -1.73; -1.56 | — |
| SECONDARY Percentage of Subjects Reaching Overall PPG (1 Hour) ≤7.8 mmol/L [140 mg/dL] |
8.1; 7.6 | — |
| SECONDARY Percentage of Subjects Reaching Overall PPG (1 Hour) ≤7.8 mmol/L [140 mg/dL] Without Severe Hypoglycaemia |
7.6; 6.8 | — |
| SECONDARY Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) |
4.48; 4.68; 1.70; 1.71; 2.46; 2.63 | — |
| SECONDARY Insulin Dose in Units/Day: Total Basal |
23.82; 23.87 | — |
| SECONDARY Insulin Dose in Units/Day: Total Bolus |
25.91; 25.27 | — |
| SECONDARY Insulin Dose in Units/Day: Total Daily Insulin Dose |
49.72; 49.12 | — |
| SECONDARY Insulin Dose in Units/Day: Individual Meal Insulin Dose |
— | — |
| SECONDARY Insulin Dose in Units/kg/Day: Total Basal |
0.30; 0.30 | — |
| SECONDARY Insulin Dose in Units/kg/Day: Total Bolus |
0.33; 0.31 | — |
| SECONDARY Insulin Dose in Units/kg/Day: Total Daily Insulin Dose |
0.63; 0.61 | — |
| SECONDARY Insulin Dose in Units/kg/Day: Individual Meal Insulin Dose |
— | — |
| SECONDARY Insulin Delivery Pump Parameter: Insulin Carbohydrate Ratio |
9.13; 9.74 | — |
| SECONDARY Insulin Delivery Pump Parameter: Glucose Sensitivity Factor |
2.65; 2.60 | — |
| SECONDARY Insulin Delivery Pump Parameter: Active Insulin Time |
3.6; 3.6 | — |
| SECONDARY Change From Baseline in Mean IG Increment (0-30 Min, 0-1 Hour and 0-2 Hours After Start of Meal) (Mean, Breakfast, Lunch and Main Evening Meal) |
0.23; 0.21; 0.02; 0.03; 0.15; 0.09 | — |
| SECONDARY Change From Baseline in Mean Time to the IG Peak After Start of Meal (Mean, Breakfast, Lunch and Main Evening Meal) |
88.95; 97.29; 109.47; 106.94; 110.11; 106.91 | — |
| SECONDARY Change From Baseline in Mean IG Peak After Start of Meal (Mean, Breakfast, Lunch and Main Evening Meal) |
12.43; 12.25; 12.42; 12.56; 12.65; 12.70 | — |
| SECONDARY Percentage of Time Spent With IG ≤2.5, 3.0, 3.5, 3.9 mmol/L [45, 54, 63, 70 mg/dL]) and IG >10.0, 12.0, 13.9 mmol/L [180, 216, 250 mg/dL]) |
1.11; 1.03; 2.15; 2.19; 3.75; 3.93 | — |
| SECONDARY Incidence of Episodes With IG ≤2.5, 3.0, 3.5, 3.9 mmol/L [45, 54, 63, 70 mg/dL]) and IG >10.0, 12.0, 13.9 mmol/L [180, 216, 250 mg/dL]) |
1570; 1532; 2848; 2920; 4584; 4742 | — |
| SECONDARY Change From Baseline in Mean of the IG Profile |
9.38; 9.39; 0.28; 0.04 | — |
| SECONDARY Percentage of Time Spent Within IG Target Range 4.0-7.8 mmol/L (71-140 mg/dL) and 4.0-10 mmol/L (71-180 mg/dL) |
31.49; 33.11; 52.40; 54.40 | — |
| SECONDARY Variation in the IG Profile |
3.09; 3.04 | — |
| SECONDARY Area Under the Curve (AUC3.9-IG) for IG ≤3.9 mmol/L [70 mg/dL] |
3.19; 3.21 | — |
| SECONDARY Change From Baseline in AUCIG,0-15min |
7.55; 7.37; 0.16; 0.21 | — |
| SECONDARY Change From Baseline in AUCIG,0-30min |
7.98; 7.86; 0.12; 0.22 | — |
| SECONDARY Change From Baseline in AUCIG,0-1h |
9.47; 9.35; -0.07; 0.32 | — |
| SECONDARY Change From Baseline in AUCIG,0-2h |
11.27; 11.18; -0.38; 0.37 | — |
| SECONDARY Change From Baseline in AUCIG,0-4h |
11.31; 11.40; -0.32; 0.29 | — |
| SECONDARY Change From Baseline in Time to the IG Peak After Start of Meal |
111.2; 117.0; 1.2; -1.4 | — |
| SECONDARY Change From Baseline in IG Peak After Start of Meal |
14.71; 14.69; -0.57; 0.36 | — |
| SECONDARY Number of Treatment Emergent Adverse Events (AEs) |
440; 412 | — |
| SECONDARY Number of Treatment Emergent Infusion Site Reactions |
44; 32 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall |
21; 7; 8372; 8904; 2530; 2273 | — |
| 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) |
12; 5; 7508; 7889; 2321; 2071 | — |
| 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) |
9; 2; 864; 1015; 209; 202 | — |
| 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 |
0; 0; 224; 190; 31; 33 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal |
0; 0; 1258; 1077; 176; 175 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal |
5; 2; 3767; 3907; 750; 677 | — |
| 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 |
5; 2; 2509; 2830; 574; 502 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 1 Hour to 2 Hours After Start of the Meal |
0; 0; 1034; 887; 145; 142 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes Occurring Between 2 to 3 Hours After Start of the Meal |
2; 1; 1327; 1518; 277; 241 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes Occurring Between 3 to 4 Hours After Start of the Meal |
3; 1; 1182; 1312; 297; 261 | — |
| SECONDARY Number of Unexplained Episodes of Hyperglycaemia (Confirmed by SMPG) |
1185; 1058 | — |
| SECONDARY Change From Baseline in Physical Examination: Respiratory System |
234; 235; 1; 1; 1; 0 | — |
| SECONDARY Change From Baseline in Physical Examination: Cardiovascular System |
233; 229; 1; 7; 2; 0 | — |
| SECONDARY Change From Baseline in Physical Examination: Central and Peripheral Nervous System |
210; 215; 22; 18; 4; 3 | — |
| SECONDARY Change From Baseline in Physical Examination: Gastrointestinal System, Including the Mouth |
231; 231; 3; 5; 2; 0 | — |
| SECONDARY Change From Baseline in Physical Examination: Musculoskeletal System |
222; 227; 13; 9; 1; 0 | — |
| SECONDARY Change From Baseline in Physical Examination: Skin |
212; 211; 18; 22; 6; 3 | — |
| SECONDARY Change From Baseline in Physical Examination: Head, Ears, Eyes, Nose, Throat and Neck |
219; 221; 15; 14; 2; 1 | — |
| SECONDARY Change From Baseline in Vital Sign: Blood Pressure |
123.6; 122.0; 74.8; 74.6; -0.8; -0.7 | — |
| SECONDARY Change From Baseline in Vital Sign: Pulse |
73.7; 74.5; -0.5; -0.8 | — |
| SECONDARY Change From Screening in Electrocardiogram (ECG) |
178; 181; 58; 54; 0; 1 | — |
| SECONDARY Change From Screening in Fundus Photography/Fundoscopy |
135; 136; 94; 94; 7; 6 | — |
| SECONDARY Change From Baseline in Haematology: Haemoglobin |
8.62; 8.62; -0.01; -0.06 | — |
| SECONDARY Change From Baseline in Haematology: Haematocrit |
42.23; 42.37; 0.09; -0.30 | — |
| SECONDARY Change From Baseline in Haematology: Erythrocytes |
4.66; 4.72; 0.01; -0.03 | — |
| SECONDARY Change From Baseline in Haematology: Thrombocytes |
246.4; 243.6; 2.2; 0.2 | — |
| SECONDARY Change From Baseline in Haematology: Leucocytes |
6.41; 6.32; -0.09; -0.03 | — |
| SECONDARY Change From Baseline in Biochemistry: Total Protein |
6.73; 6.74; 0.03; -0.05 | — |
| SECONDARY Change From Baseline in Biochemistry: Creatinine |
73.8; 74.5; 0.9; -0.1 | — |
| SECONDARY Change From Baseline in Biochemistry: Alanine Aminotransferase (ALT) |
20.0; 19.1; 0.1; 0 | — |
| SECONDARY Change From Baseline in Biochemistry: Aspartate Aminotransferase (AST) |
22.2; 20.6; -0.1; -0.4 | — |
| SECONDARY Change From Baseline in Biochemistry: Alkaline Phosphatase (ALP) |
68.8; 69.7; 1.2; 0.8 | — |
| SECONDARY Change From Baseline in Biochemistry: Sodium |
140.3; 140.3; -0.2; -0.2 | — |
| SECONDARY Change From Baseline in Biochemistry: Potassium |
4.34; 4.30; -0.02; -0.01 | — |
| SECONDARY Change From Baseline in Biochemistry: Albumin |
4.32; 4.31; -0.01; -0.05 | — |
| SECONDARY Change From Baseline in Biochemistry: Total Bilirubin |
8.2; 8.8; -0.3; -1.0 | — |
| SECONDARY Change From Baseline in Urinalysis: Albumin/Creatine Ratio |
2.67; 2.00; 0.01; -0.04 | — |
| SECONDARY Change From Baseline in Urinalysis: Erythrocytes |
217; 215; 8; 10; 5; 5 | — |
| SECONDARY Change From Baseline in Urinalysis: Protein |
193; 195; 31; 27; 8; 10 | — |
| SECONDARY Change From Baseline in Urinalysis: Ketones |
192; 205; 31; 23; 11; 8 | — |
| SECONDARY Change From Baseline in Body Weight |
76.86; 78.21; 0.34; 0.80 | — |
| SECONDARY Change From Baseline in Body Mass Index (BMI) |
26.16; 26.51; 0.12; 0.28 | — |
| SECONDARY Number of Change-of-infusion-sets Per Week |
2.55; 2.49 | — |
| SECONDARY Number of Subjects With at Least One Non-routine Change-of-infusion-sets Categorised by Reasons for Change-of-infusion-sets |
50; 50; 108; 75; 23; 17 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female, age at least 18 years at the time of signing the informed consent
- Diagnosed with T1DM (Type 1 Diabetes Mellitus) (based on clinical judgement and/or supported by laboratory analysis as per local guidelines) equal or above 1 year prior to the day of screening
- Using the same Medtronic pump (Minimed 530G (551/751), Paradigm Veo (554/754), Paradigm Revel (523/723), Paradigm (522/722)) for CSII in a basal-bolus regimen with a rapid acting insulin analogue for at least six months prior to screening and willing to stay on the same pump model throughout the trial (if the model is changed the change should not exceed 7 consecutive days.)
- HbA1c (glycosylated haemoglobin) 7.0-9.0% (53-75 mmol/mol) as assessed by central laboratory at screening
- Body mass index (BMI) below or equal to 35.0 kg/m^2 at screening
- Ability and willingness to take at least 3 daily meal-time insulin bolus infusions every day throughout the trial
Exclusion Criteria
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- History of hospitalization for ketoacidosis below or equal to 180 days prior to the day of screening
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening
- Any condition which, in the opinion of the Investigator, might jeopardise a Subject's safety or compliance with the protocol
Data sourced from ClinicalTrials.gov (NCT02825251) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.