Clinical trial NCT02500706: Efficacy and Safety of Faster-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec in Adults With Type 1 Diabetes
Official title: Efficacy and Safety of Faster-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec 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: 2015-07-16
Enrollment: 1108
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 Asia, Europe and North America. The purpose is to confirm efficacy in terms of glycaemic control of treatment with mealtime faster-acting insulin aspart in combination with insulin degludec in adults with Type 1 Diabetes Mellitus.


Eligibility criteria: Inclusion Criteria: - Male or female, age greater than or equal to 18 years ( for Japan and Taiwan: age greater than or equal to 20 years) at the time of signing informed consent - Type 1 Diabetes Mellitus (based on clinical judgement and/or supported by laboratory analysis as per local guidelines) 12 months or more prior to screening - Currently treated with a basal-bolus insulin regimen for at least 12 months prior to screening (Visit 1) - Currently treated with a basal insulin analogue for at least 4 months prior to screening (Visit 1) - HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory - Body Mass Index less than or equal to 35.0 kg/m\^2 Exclusion Criteria: - Within the past 180 days any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischemic attack - Subjects presently classified as being in New York Heart Association (NYHA) Class IV Currently planned coronary, carotid or peripheral artery revascularisation - Diabetic ketoacidosis requiring hospitalisation within the last 180 days prior to screening (Visit 1) - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of three months before screening (Visit 1)

Primary outcomes:
measure: Change From Baseline in HbA1c 26 Weeks After Randomisation
timeFrame: Week 0, week 26
Secondary outcomes:
measure: Change From Baseline in 1-hour Post Prandial Glucose (PPG) Increment 26 Weeks After Randomisation (Meal Test)
timeFrame: Week 0, week 26
measure: Change From Baseline in 1,5-anhydroglucitol 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Percentage of Subjects Reaching HbA1c Targets (HbA1c < 7.0%) 26 Weeks After Randomisation
timeFrame: 26 weeks after randomisation
measure: Percentage of Subjects Reaching HbA1c Targets (HbA1c < 7.0% Without Severe Hypoglycaemia) 26 Weeks After Randomisation
timeFrame: 26 weeks after randomisation
measure: Percentage of Subjects Reaching HbA1c Targets (HbA1c < 7.0% Without Severe Hypoglycaemia and Minimal Weight Gain [<3.0%]) 26 Weeks After Randomisation
timeFrame: 26 weeks after randomisation
measure: Change From Baseline in 30- Min, 1- Hour, 2- Hour, 3- Hour and 4- Hour PPG 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in 30- Min, 1- Hour, 2- Hour, 3- Hour and 4- Hour PPG Increment 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in 7-9-7-point Self-measured Plasma Glucose (SMPG) 26 Weeks After Randomisation: Mean of the 7-9-7-point Profile
timeFrame: Week 0, week 26
measure: Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: PPG (Mean, Breakfast, Lunch, Main Evening Meal)
timeFrame: Week 0, week 26
measure: Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: PPG Increment (Mean, Breakfast, Lunch, Main Evening Meal)
timeFrame: Week 0, week 26
measure: Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: Fluctuation in 7-9-7-point Profile
timeFrame: Week 0, week 26
measure: Change From Baseline in 7-9-7-point SMPG 26 Weeks After Randomisation: Change in the Nocturnal Self-measured Plasma Glucose Measurements
timeFrame: Week 0, week 26
measure: Percentage of Subjects Reaching PPG Target (Overall Mean of Daily PPG Measurements in SMPG) 26 Weeks After Randomisation: Overall PPG (1 Hour) ≤7.8 mmol/L
timeFrame: 26 weeks after randomisation
measure: Percentage of Subjects Reaching PPG Target (Overall Mean of Daily PPG Measurements in SMPG) 26 Weeks After Randomisation: Overall PPG (1 Hour) ≤7.8 mmol/L Without Severe Hypoglycaemia
timeFrame: 26 weeks after randomisation
measure: Percentage of Subjects Reaching PPG Target (Overall Mean of Daily PPG Measurements in SMPG) 26 Weeks After Randomisation: Overall PPG (1 Hour) ≤7.8 mmol/L and HbA1c <7.0% and Minimal Weight Gain (<3.0%) Without Severe Hypoglycaemia
timeFrame: 26 weeks after randomisation
measure: Change From Baseline in Lipids-lipoproteins Profile 26 Weeks After Randomisation (Total Cholesterol, High Density Lipoproteins [HDL] Cholesterol, Low Density Lipoproteins [LDL] Cholesterol)
timeFrame: Week 0, week 26
measure: Insulin Dose (Basal Insulin Dose, Total and Individual Meal Insulin Dose)
timeFrame: Week 0, week 26
measure: Number of Treatment Emergent Adverse Events During 26 Weeks After Randomisation
timeFrame: Week 0 to week 26 (+7 days)
measure: Number of Treatment-emergent Injection Site Reactions During the 26 Weeks After Randomisation
timeFrame: Week 0 to week 26 (+7 days)
measure: Number of Hypoglycaemic Episodes Classified Both According to the American Diabetes Association (ADA) Definition and Novo Nordisk (NN) Definition During 26 Weeks After Randomisation: Overall
timeFrame: Week 0 to week 26 (+1 day)
measure: Number of Hypoglycaemic Episodes Classified Both According to the ADA Definition and Novo Nordisk Definition During 26 Weeks After Randomisation: Daytime and Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)
timeFrame: Week 0 to week 26 (+1 day)
measure: Number of Hypoglycaemic Episodes Classified Both According to the ADA Definition and Novo Nordisk Definition During 26 Weeks After Randomisation: From Start of Meal Until 1,2, 4 Hours and From 2 Hours (Exclusive) to 4 Hours (Inclusive) After Start of Meal
timeFrame: Week 0 to week 26 (+1 day)
measure: Change From Baseline 26 Weeks After Randomisation in Clinical Evaluations (Physical Examination)
timeFrame: Week 0, week 26
measure: Change From Baseline in Blood Pressure 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Pulse 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Clinical Evaluation (Electrocardiogram) 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Clinical Evaluation (Fundoscopy/Fundus Photography) 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Erythrocytes 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Haematocrit 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Haemoglobin 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Leukocytes 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Thrombocytes 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Alanine Aminotransferase 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Albumin 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Alkaline Phosphatase 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Aspartate Aminotransferase 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Total Bilirubin 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Potassium 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Creatinine 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Total Protein 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Urinary Albumin-to-creatinine Ratio 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Urinalysis (Ketones) 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Urinalysis (Protein) 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Urinalysis (Erythrocytes) 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Anti-insulin Aspart (Specific and Cross-reacting With Human Insulin) Antibody Development 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Body Weight 26 Weeks After Randomisation
timeFrame: Week 0, week 26
measure: Change From Baseline in Body Mass Index 26 Weeks After Randomisation
timeFrame: Week 0, week 26
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Encino
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Escondido
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fullerton
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Huntington Beach
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Monterey
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Newport Beach
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: Denver
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Golden
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Palm Harbor
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Idaho Falls
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Topeka
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Flint
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Kalamazoo
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Jefferson City
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
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: Hamilton
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: Novo Nordisk Investigational Site
state: New Mexico
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Rochester
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Bend
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
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: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Beaumont
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: 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: Round Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Murray
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Ogden
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
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: Spokane
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Tacoma
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Graz
country: Austria
facility: Novo Nordisk Investigational Site
city: Salzburg
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Dimitrovgrad
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Pleven
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Plovdiv
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Ruse
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Varna
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Calgary
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: Novo Nordisk Investigational Site
state: Nova Scotia
city: Concord
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: Quebec
country: Canada
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Falkensee
country: Germany
facility: Novo Nordisk Investigational Site
city: Lingen
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: Schweinfurt
country: Germany
facility: Novo Nordisk Investigational Site
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Ahmedabad
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Rohtak
country: India
facility: Novo Nordisk Investigational Site
state: Haryana
city: Kozhikode
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Indore
country: India
facility: Novo Nordisk Investigational Site
state: Madhya Pradesh
city: Indore
country: India
facility: Novo Nordisk Investigational Site
state: Madhya Pradesh
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Bhubaneswar
country: India
facility: Novo Nordisk Investigational Site
state: Orissa
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Vellore
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Chandigarh
country: India
facility: Novo Nordisk Investigational Site
city: New Dehli
country: India
facility: Novo Nordisk Investigational Site
city: New Delhi
country: India
facility: Novo Nordisk Investigational Site
city: Pune
country: India
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Holon
country: Israel
facility: Novo Nordisk Investigational Site
city: Jerusalem
country: Israel
facility: Novo Nordisk Investigational Site
city: Jerusalem
country: Israel
facility: Novo Nordisk Investigational Site
city: Petah Tikva
country: Israel
facility: Novo Nordisk Investigational Site
city: Rishon Le Zion
country: Israel
facility: Novo Nordisk Investigational Site
city: Ancona
country: Italy
facility: Novo Nordisk Investigational Site
city: Bergamo
country: Italy
facility: Novo Nordisk Investigational Site
city: Catanzaro
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Rome
country: Italy
facility: Novo Nordisk Investigational Site
city: Sesto San Giovanni (MI)
country: Italy
facility: Novo Nordisk Investigational Site
city: Amagasaki-shi, Hyogo
country: Japan
facility: Novo Nordisk Investigational Site
city: Chuo-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Ebina-shi, Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukushima
country: Japan
facility: Novo Nordisk Investigational Site
city: Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Izumisano-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Kobe-shi, Hyogo
country: Japan
facility: Novo Nordisk Investigational Site
city: Kumamoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Matsumoto-shi, Nagano
country: Japan
facility: Novo Nordisk Investigational Site
city: Mito-shi, Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Miyazaki
country: Japan
facility: Novo Nordisk Investigational Site
city: Oita-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Ota-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Ponce
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kazan
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
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: 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: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tumen
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taoyuan
country: Taiwan
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Rose L, Kadowaki T, Pieber TR, Buchholtz K, Ekelund M, Gorst-Rasmussen A, Philis-Tsimikas A. Efficacy and Safety of Fast-Acting Insulin Aspart in People with Type 1 Diabetes Using Carbohydrate Counting: A Post Hoc Analysis of Two Randomised Controlled Trials. Diabetes Ther. 2019 Jun;10(3):1029-1041. doi: 10.1007/s13300-019-0608-4. Epub 2019 Apr 4.
citation: Buse JB, Carlson AL, Komatsu M, Mosenzon O, Rose L, Liang B, Buchholtz K, Horio H, Kadowaki T. Fast-acting insulin aspart versus insulin aspart in the setting of insulin degludec-treated type 1 diabetes: Efficacy and safety from a randomized double-blind trial. Diabetes Obes Metab. 2018 Dec;20(12):2885-2893. doi: 10.1111/dom.13545. Epub 2018 Oct 10.