Clinical trial NCT02825251: Efficacy and Safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart Compared to NovoRapid® in Adults With Type 1 Diabetes
Official title: Efficacy and Safety of Continuous Subcutaneous Insulin Infusion of Faster-acting Insulin Aspart Compared to NovoRapid® in Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 1
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-07-07
Enrollment: 472
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Change in Glycosylated Haemoglobin (HbA1c)
timeFrame: Week 0, week 16
Secondary outcomes:
measure: Change From Baseline in 1-hour PPG Increment
timeFrame: Week 0, Week 16
measure: Change From Baseline in 1,5-anhydroglucitol
timeFrame: Week 0, Week 16
measure: Change From Baseline in Time Spent in Low IG (≤3.9 mmol/L [70 mg/dL]) During CGM
timeFrame: Week 0, week 16
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 16
measure: Percentage of Subjects Reaching HbA1c <7.0% (53 mmol/Mol)
timeFrame: Week 16
measure: Percentage of Subjects Reaching HbA1c <7.0% (53 mmol/Mol) Without Severe Hypoglycaemic Episodes
timeFrame: Week 16
measure: Change From Baseline in 30-min, 1-hour, 2-hour, 3-hour and 4-hour PPG (Meal Test)
timeFrame: Week 0, week 16
measure: Change From Baseline in 30-min, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test)
timeFrame: Week 0, week 16
measure: Change From Baseline in Mean of the 7-7-9 Point Self-measured Plasma Glucose (SMPG) Profile
timeFrame: Week 0, week 16
measure: Change From Baseline of the 7-7-9 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal)
timeFrame: Week 0, week 16
measure: Change From Baseline of the 7-7-9 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal)
timeFrame: Week 0, week 16
measure: 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)
timeFrame: Week 0, week 16
measure: Change From Baseline of the 7-7-9 Point SMPG Profile: Fluctuation in 7-7-9 Point Profile
timeFrame: Week 0, week 16
measure: Change From Baseline of the 7-7-9 Point SMPG Profile: in Nocturnal SMPG Measurements
timeFrame: Week 0, week 16
measure: Percentage of Subjects Reaching Overall PPG (1 Hour) ≤7.8 mmol/L [140 mg/dL]
timeFrame: Week 16
measure: Percentage of Subjects Reaching Overall PPG (1 Hour) ≤7.8 mmol/L [140 mg/dL] Without Severe Hypoglycaemia
timeFrame: Week 16
measure: Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins)
timeFrame: Week 0, week 16
measure: Insulin Dose in Units/Day: Total Basal
timeFrame: Week 16
measure: Insulin Dose in Units/Day: Total Bolus
timeFrame: Week 16
measure: Insulin Dose in Units/Day: Total Daily Insulin Dose
timeFrame: Week 16
measure: Insulin Dose in Units/Day: Individual Meal Insulin Dose
timeFrame: Week 16
measure: Insulin Dose in Units/kg/Day: Total Basal
timeFrame: Week 16
measure: Insulin Dose in Units/kg/Day: Total Bolus
timeFrame: Week 16
measure: Insulin Dose in Units/kg/Day: Total Daily Insulin Dose
timeFrame: Week 16
measure: Insulin Dose in Units/kg/Day: Individual Meal Insulin Dose
timeFrame: Week 16
measure: Insulin Delivery Pump Parameter: Insulin Carbohydrate Ratio
timeFrame: Week 16
measure: Insulin Delivery Pump Parameter: Glucose Sensitivity Factor
timeFrame: Week 16
measure: Insulin Delivery Pump Parameter: Active Insulin Time
timeFrame: Week 16
measure: 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)
timeFrame: Week 0, week 16
measure: Change From Baseline in Mean Time to the IG Peak After Start of Meal (Mean, Breakfast, Lunch and Main Evening Meal)
timeFrame: Week 0, week 16
measure: Change From Baseline in Mean IG Peak After Start of Meal (Mean, Breakfast, Lunch and Main Evening Meal)
timeFrame: Week 0, week 16
measure: 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])
timeFrame: Week 16
measure: 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])
timeFrame: Week 16
measure: Change From Baseline in Mean of the IG Profile
timeFrame: Week 0, week 16
measure: 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)
timeFrame: Week 16
measure: Variation in the IG Profile
timeFrame: Week 16
measure: Area Under the Curve (AUC3.9-IG) for IG ≤3.9 mmol/L [70 mg/dL]
timeFrame: Week 16
measure: Change From Baseline in AUCIG,0-15min
timeFrame: Week 0, week 16
measure: Change From Baseline in AUCIG,0-30min
timeFrame: Week 0, week 16
measure: Change From Baseline in AUCIG,0-1h
timeFrame: Week 0, week 16
measure: Change From Baseline in AUCIG,0-2h
timeFrame: Week 0, week 16
measure: Change From Baseline in AUCIG,0-4h
timeFrame: Week 0, week 16
measure: Change From Baseline in Time to the IG Peak After Start of Meal
timeFrame: Week 0, week 16
measure: Change From Baseline in IG Peak After Start of Meal
timeFrame: Week 0, week 16
measure: Number of Treatment Emergent Adverse Events (AEs)
timeFrame: Weeks 0-16
measure: Number of Treatment Emergent Infusion Site Reactions
timeFrame: Weeks 0-16
measure: Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall
timeFrame: Weeks 0-16
measure: Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive)
timeFrame: Weeks 0-16
measure: Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: 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
timeFrame: Weeks 0-16
measure: Number of Unexplained Episodes of Hyperglycaemia (Confirmed by SMPG)
timeFrame: Weeks 0-16
measure: Change From Baseline in Physical Examination: Respiratory System
timeFrame: Week 0, week 16
measure: Change From Baseline in Physical Examination: Cardiovascular System
timeFrame: Week 0, week 16
measure: Change From Baseline in Physical Examination: Central and Peripheral Nervous System
timeFrame: Week 0, week 16
measure: Change From Baseline in Physical Examination: Gastrointestinal System, Including the Mouth
timeFrame: Week 0, week 16
measure: Change From Baseline in Physical Examination: Musculoskeletal System
timeFrame: Week 0, week 16
measure: Change From Baseline in Physical Examination: Skin
timeFrame: Week 0, week 16
measure: Change From Baseline in Physical Examination: Head, Ears, Eyes, Nose, Throat and Neck
timeFrame: Week 0, week 16
measure: Change From Baseline in Vital Sign: Blood Pressure
timeFrame: Week 0, week 16
measure: Change From Baseline in Vital Sign: Pulse
timeFrame: Week 0, week 16
measure: Change From Screening in Electrocardiogram (ECG)
timeFrame: Week 0, week 16
measure: Change From Screening in Fundus Photography/Fundoscopy
timeFrame: Week 0, week 16
measure: Change From Baseline in Haematology: Haemoglobin
timeFrame: Week 0, week 16
measure: Change From Baseline in Haematology: Haematocrit
timeFrame: Week 0, week 16
measure: Change From Baseline in Haematology: Erythrocytes
timeFrame: Week 0, week 16
measure: Change From Baseline in Haematology: Thrombocytes
timeFrame: Week 0, week 16
measure: Change From Baseline in Haematology: Leucocytes
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Total Protein
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Creatinine
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Alanine Aminotransferase (ALT)
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Aspartate Aminotransferase (AST)
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Alkaline Phosphatase (ALP)
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Sodium
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Potassium
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Albumin
timeFrame: Week 0, week 16
measure: Change From Baseline in Biochemistry: Total Bilirubin
timeFrame: Week 0, week 16
measure: Change From Baseline in Urinalysis: Albumin/Creatine Ratio
timeFrame: Week 0, week 16
measure: Change From Baseline in Urinalysis: Erythrocytes
timeFrame: Week 0, week 16
measure: Change From Baseline in Urinalysis: Protein
timeFrame: Week 0, week 16
measure: Change From Baseline in Urinalysis: Ketones
timeFrame: Week 0, week 16
measure: Change From Baseline in Body Weight
timeFrame: Week 0, week 16
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Week 0, week 16
measure: Number of Change-of-infusion-sets Per Week
timeFrame: Week 0-16
measure: Number of Subjects With at Least One Non-routine Change-of-infusion-sets Categorised by Reasons for Change-of-infusion-sets
timeFrame: Week 0-16
Other outcomes:
Locations:
city: Encino
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Roseville
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Mateo
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Ramon
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Santa Barbara
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Newark
country: United States
facility: Novo Nordisk Investigational Site
state: Delaware
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Idaho Falls
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Arlington Heights
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Boston
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Nashua
country: United States
facility: Novo Nordisk Investigational Site
state: New Hampshire
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Asheville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Federal Way
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Arlon
country: Belgium
facility: Novo Nordisk Investigational Site
city: Bonheiden
country: Belgium
facility: Novo Nordisk Investigational Site
city: Brussels
country: Belgium
facility: Novo Nordisk Investigational Site
city: Edegem
country: Belgium
facility: Novo Nordisk Investigational Site
city: Leuven
country: Belgium
facility: Novo Nordisk Investigational Site
city: Sint-Niklaas
country: Belgium
facility: Novo Nordisk Investigational Site
city: Wilrijk
country: Belgium
facility: Novo Nordisk Investigational Site
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Barrie
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Concord
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: London
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: Novo Nordisk Investigational Site
city: Caen
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Le Creusot
country: France
facility: Novo Nordisk Investigational Site
city: MONTPELLIER cedex 5
country: France
facility: Novo Nordisk Investigational Site
city: Narbonne
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Saint Herblain
country: France
facility: Novo Nordisk Investigational Site
city: Strasbourg
country: France
facility: Novo Nordisk Investigational Site
city: TOULOUSE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Venissieux
country: France
facility: Novo Nordisk Investigational Site
city: Bad Mergentheim
country: Germany
facility: Novo Nordisk Investigational Site
city: Essen
country: Germany
facility: Novo Nordisk Investigational Site
city: Friedrichsthal
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Ludwigshafen
country: Germany
facility: Novo Nordisk Investigational Site
city: Münster
country: Germany
facility: Novo Nordisk Investigational Site
city: Neuwied
country: Germany
facility: Novo Nordisk Investigational Site
city: Rehlingen-Siersburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Rostock
country: Germany
facility: Novo Nordisk Investigational Site
city: Amsterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Apeldoorn
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Eindhoven
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Hoofddorp
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Hoogeveen
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Leiden
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Nijmegen
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Rotterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Utrecht
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Venlo
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Cheboksary
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yoshkar-Ola
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Ljubljana
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Novo mesto
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Cambridge
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Guildford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Harrogate, North Yorkshire
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Manchester
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: St Helens
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Zijlstra E, Demissie M, Graungaard T, Heise T, Nosek L, Bode B. Investigation of Pump Compatibility of Fast-Acting Insulin Aspart in Subjects With Type 1 Diabetes. J Diabetes Sci Technol. 2018 Jan;12(1):145-151. doi: 10.1177/1932296817730375. Epub 2017 Sep 18.
citation: Klonoff DC, Evans ML, Lane W, Kempe HP, Renard E, DeVries JH, Graungaard T, Hyseni A, Gondolf T, Battelino T. 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). Diabetes Obes Metab. 2019 Apr;21(4):961-967. doi: 10.1111/dom.13610. Epub 2019 Jan 13.
citation: Gorst-Rasmussen A, Sturis J, Ekelund M. 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. Diabetes Technol Ther. 2022 Jan;24(1):10-17. doi: 10.1089/dia.2021.0199. Epub 2021 Dec 14.