Efficacy and Safety of FIAsp Compared to Insulin Aspart in Combination With Insulin Glargine and Metformin in Adults With Type 2 Diabetes (onset® 2)

This trial is conducted in Asia, Europe and North America. The aim of the trial is to compare FIAsp (faster-acting insulin aspart) to insulin aspart, both in combination with insulin glargine and metformin in adults with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: Faster-acting insulin aspart; Drug: Insulin glargine; Drug: Insulin aspart

• Study Type: Interventional
• Enrollment (Actual): 881
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1G 3Y8
    • Novo Nordisk Investigational Site
  • Quebec, Canada, G1N 4V3
    • Novo Nordisk Investigational Site
  • Alberta
    • Edmonton, Alberta, Canada, T5J 3N4
      • Novo Nordisk Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3S 2N6
      • Novo Nordisk Investigational Site
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
      • Novo Nordisk Investigational Site
    • St. John's, Newfoundland and Labrador, Canada, A1A 3R5
      • Novo Nordisk Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8M 1K7
      • Novo Nordisk Investigational Site
    • Thunder Bay, Ontario, Canada, P7B 7C7
      • Novo Nordisk Investigational Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Novo Nordisk Investigational Site
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Novo Nordisk Investigational Site
    • Montreal, Quebec, Canada, H1Y 3L1
      • Novo Nordisk Investigational Site
    • Montreal, Quebec, Canada, H2R 1V6
      • Novo Nordisk Investigational Site
    • St. Romuald, Quebec, Canada, G6W 5M6
      • Novo Nordisk Investigational Site
• Croatia
  • Cakovec, Croatia, 40000
    • Novo Nordisk Investigational Site
  • Karlovac, Croatia, 47000
    • Novo Nordisk Investigational Site
  • Osijek, Croatia, 31 000
    • Novo Nordisk Investigational Site
  • Slavonski Brod, Croatia, 35 000
    • Novo Nordisk Investigational Site
  • Split, Croatia, 21 000
    • Novo Nordisk Investigational Site
  • Varazdin, Croatia, 42 000
    • Novo Nordisk Investigational Site
  • Zagreb, Croatia, 10 000
    • Novo Nordisk Investigational Site
  • Zagreb, Croatia, 10000
    • Novo Nordisk Investigational Site
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500082
      • Novo Nordisk Investigational Site
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Novo Nordisk Investigational Site
    • Mumbai, Maharashtra, India, 400012
      • Novo Nordisk Investigational Site
    • Mumbai, Maharashtra, India, 400058
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411004
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411040
      • Novo Nordisk Investigational Site
  • New Delhi
    • Delhi, New Delhi, India, 110002
      • Novo Nordisk Investigational Site
  • Orissa
    • Bhubaneswar, Orissa, India, 751019
      • Novo Nordisk Investigational Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302006
      • Novo Nordisk Investigational Site
• Israel
  • Beer Sheva, Israel, 84101
    • Novo Nordisk Investigational Site
  • Haifa, Israel, 35152
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91120
    • Novo Nordisk Investigational Site
  • Kfar Saba, Israel, 44281
    • Novo Nordisk Investigational Site
  • Rehovot, Israel, 76100
    • Novo Nordisk Investigational Site
  • Rishon Le Zion, Israel, 75650
    • Novo Nordisk Investigational Site
• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • Novo Nordisk Investigational Site
• Russian Federation
  • Kursk, Russian Federation, 305035
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 119435
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 117036
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 127644
    • Novo Nordisk Investigational Site
  • Penza, Russian Federation, 440026
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 195257
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194358
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 199034
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 191119
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194291
    • Novo Nordisk Investigational Site
  • Saint-Petesburg, Russian Federation, 195257
    • Novo Nordisk Investigational Site
  • Stavropol, Russian Federation, 355035
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
  • Nis, Serbia, 18000
    • Novo Nordisk Investigational Site
  • Zajecar, Serbia, 19000
    • Novo Nordisk Investigational Site
• Slovakia
  • Bratislava, Slovakia, 851 01
    • Novo Nordisk Investigational Site
  • Bratislava, Slovakia, 821 02
    • Novo Nordisk Investigational Site
  • Lucenec, Slovakia, 984 01
    • Novo Nordisk Investigational Site
  • Trnava, Slovakia, 91701
    • Novo Nordisk Investigational Site
  • Zilina, Slovakia, 01001
    • Novo Nordisk Investigational Site
• United Kingdom
  • Epworth, United Kingdom, DN9 1EP
    • Novo Nordisk Investigational Site
  • Hull, United Kingdom, HU3 2RW
    • Novo Nordisk Investigational Site
  • Northampton, United Kingdom, NN1 5BD
    • Novo Nordisk Investigational Site
  • Northwood, United Kingdom, HA6 2RN
    • Novo Nordisk Investigational Site
  • Norwich, United Kingdom, NR4 7TJ
    • Novo Nordisk Investigational Site
  • Nuneaton, United Kingdom, CV10 7DJ
    • Novo Nordisk Investigational Site
  • Sidcup, United Kingdom, DA14 6LT
    • Novo Nordisk Investigational Site
  • Stoke on Trent, United Kingdom, ST4 6QG
    • Novo Nordisk Investigational Site
  • Wrexham, United Kingdom, LL13 7TD
    • Novo Nordisk Investigational Site
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306-4652
      • Novo Nordisk Investigational Site
    • Glendale, Arizona, United States, 85308
      • Novo Nordisk Investigational Site
    • Mesa, Arizona, United States, 85213
      • Novo Nordisk Investigational Site
    • Phoenix, Arizona, United States, 85020
      • Novo Nordisk Investigational Site
    • Tempe, Arizona, United States, 85283
      • Novo Nordisk Investigational Site
  • California
    • Anaheim, California, United States, 92801
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Greenbrae, California, United States, 94904
      • Novo Nordisk Investigational Site
    • Lomita, California, United States, 90717
      • Novo Nordisk Investigational Site
    • Northridge, California, United States, 91325
      • Novo Nordisk Investigational Site
    • San Diego, California, United States, 92111
      • Novo Nordisk Investigational Site
    • San Ramon, California, United States, 94583
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novo Nordisk Investigational Site
    • Colorado Springs, Colorado, United States, 80910
      • Novo Nordisk Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Novo Nordisk Investigational Site
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Novo Nordisk Investigational Site
    • Bradenton, Florida, United States, 34201
      • Novo Nordisk Investigational Site
    • Cooper City, Florida, United States, 33024
      • Novo Nordisk Investigational Site
    • Fort Lauderdale, Florida, United States, 33316
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32205
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33144
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33173
      • Novo Nordisk Investigational Site
    • Pembroke Pines, Florida, United States, 33027
      • Novo Nordisk Investigational Site
    • Plantation, Florida, United States, 33324
      • Novo Nordisk Investigational Site
    • Tampa, Florida, United States, 33603
      • Novo Nordisk Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308-2253
      • Novo Nordisk Investigational Site
    • Atlanta, Georgia, United States, 30328
      • Novo Nordisk Investigational Site
    • Decatur, Georgia, United States, 30033
      • Novo Nordisk Investigational Site
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Illinois
    • Avon, Illinois, United States, 46123
      • Novo Nordisk Investigational Site
    • Peoria, Illinois, United States, 61602
      • Novo Nordisk Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Novo Nordisk Investigational Site
    • Muncie, Indiana, United States, 47304
      • Novo Nordisk Investigational Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novo Nordisk Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Novo Nordisk Investigational Site
    • Madisonville, Kentucky, United States, 42431-1661
      • Novo Nordisk Investigational Site
    • Paducah, Kentucky, United States, 42003
      • Novo Nordisk Investigational Site
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Novo Nordisk Investigational Site
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Novo Nordisk Investigational Site
    • Detroit, Michigan, United States, 48201
      • Novo Nordisk Investigational Site
    • Troy, Michigan, United States, 48085-5524
      • Novo Nordisk Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Novo Nordisk Investigational Site
    • Jefferson City, Missouri, United States, 65109
      • Novo Nordisk Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • Novo Nordisk Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Novo Nordisk Investigational Site
  • Nebraska
    • Elkhorn, Nebraska, United States, 68022
      • Novo Nordisk Investigational Site
    • Omaha, Nebraska, United States, 68198-3020
      • Novo Nordisk Investigational Site
    • Omaha, Nebraska, United States, 68105
      • Novo Nordisk Investigational Site
  • New Jersey
    • Toms River, New Jersey, United States, 08755-8050
      • Novo Nordisk Investigational Site
  • New York
    • Mineola, New York, United States, 11501
      • Novo Nordisk Investigational Site
    • New Windsor, New York, United States, 12553
      • Novo Nordisk Investigational Site
    • North Massapequa, New York, United States, 11758-1802
      • Novo Nordisk Investigational Site
    • Northport, New York, United States, 11768
      • Novo Nordisk Investigational Site
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Novo Nordisk Investigational Site
    • Wilmington, North Carolina, United States, 28401
      • Novo Nordisk Investigational Site
  • Ohio
    • Carlisle, Ohio, United States, 45005
      • Novo Nordisk Investigational Site
    • Cleveland, Ohio, United States, 44122
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45439
      • Novo Nordisk Investigational Site
    • Franklin, Ohio, United States, 45005
      • Novo Nordisk Investigational Site
    • Mason, Ohio, United States, 45040-6815
      • Novo Nordisk Investigational Site
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Novo Nordisk Investigational Site
  • South Carolina
    • Gaffney, South Carolina, United States, 29341
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404-1192
      • Novo Nordisk Investigational Site
    • Kingsport, Tennessee, United States, 37660
      • Novo Nordisk Investigational Site
    • Spring Hill, Tennessee, United States, 37174
      • Novo Nordisk Investigational Site
    • Tullahoma, Tennessee, United States, 37388
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75251
      • Novo Nordisk Investigational Site
    • Hurst, Texas, United States, 76054
      • Novo Nordisk Investigational Site
    • Plano, Texas, United States, 75075
      • Novo Nordisk Investigational Site
  • Utah
    • Murray, Utah, United States, 84123
      • Novo Nordisk Investigational Site
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Novo Nordisk Investigational Site
  • Washington
    • Port Orchard, Washington, United States, 98366
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Novo Nordisk Investigational Site
    • Milwaukee, Wisconsin, United States, 53209
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - Type 2 diabetes (diagnosed clinically) for 6 months or longer at time of screening (visit 1) - Treated with basal insulin for at least 6 months prior to screening (visit 1) - Current once daily treatment with insulin NPH (Neutral Protamine Hagedorn), insulin detemir or glargine for at least 3 months prior to the screening visit (visit 1) - Current treatment with: a. metformin with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg or b. metformin in combination with sulfonylurea (SU) or glinide or DPP-IV (dipeptidyl peptidase-4) inhibitors and/or alpha-glucosidase inhibitors (AGI) with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg - HbA1c by central laboratory: a. 7.0 - 9.5% (53 - 80 mmol/mol) (both inclusive) in the metformin group at the screening visit (visit 1) or b. 7.0 - 9.0% (53 - 75 mmol/mol) (both inclusive) in the metformin + other OAD (oral antidiabetic drug) (SU, glinide, DDP-IV inhibitors, AGI) combination group at the screening visit (visit 1) - Body mass index (BMI) equal to or below 40.0 kg/m^2 Exclusion Criteria: - Any use of bolus insulin, except short-term use due to intermittent illness (no longer than 14 days consecutive treatment) and not 3 months prior to the screening visit (visit 1) - Use of GLP-1 (glucagon-like peptide-1) agonists and/or TZDs within the last 3 months prior to screening (visit 1) - Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months prior to screening (visit 1) - Cardiovascular disease, within the last 6 months prior to screening (visit 1), defined as: stroke, decompensated heart failure New York Heart Association (NYHA) class III or IV, myocardial infarction, unstable angina pectoris or coronary arterial bypass graft or angioplasty

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Faster-acting insulin aspart (FIAsp); Meal time faster-acting insulin aspart is given in combination with once daily insulin glargine and metformin in a basal-bolus regimen. Insulin glargine and metformin treatment are open labelled background medication.	Drug: Faster-acting insulin aspart; Mealtime FIAsp administered subcutaneously (s.c., under the skin). Dose individually adjusted.; Drug: Insulin glargine; Administered s.c. once daily at subjects' pre-trial dose. Subjects will continue their metformin treatment without changing the frequency or dose throughout the trial.
ACTIVE_COMPARATOR: Insulin aspart; Meal time insulin aspart is given in combination with once daily insulin glargine and metformin in a basal-bolus regimen. Insulin glargine and metformin treatment are open labelled background medication.	Drug: Insulin glargine; Administered s.c. once daily at subjects' pre-trial dose. Subjects will continue their metformin treatment without changing the frequency or dose throughout the trial.; Drug: Insulin aspart; Mealtime insulin aspart administered subcutaneously (s.c., under the skin). Dose individually adjusted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c	The primary endpoint was change from baseline in HbA1c after 26 weeks of randomized treatment. For this endpoint baseline (week 0) and week 26 have been presented, where week 26 data is end of trial containing last available measurement.	Week 0, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 2-hour PPG Increment (Meal Test)	For this endpoint baseline (week 0) and week 26 have been presented, where week 26 data is end of trial containing last available measurement.	Week 0, week 26
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes	A hypoglycaemic episode was defined as treatment-emergent if the onset of the episode was on or after the first day of exposure to randomized treatment and no later than 1 day after the last day of randomized treatment. A severe or blood glucose (BG) confirmed hypoglycaemic episode was an episode that was severe according to the American Diabetes Association (ADA) classification (an episode that required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.	From Week 0 to Week 26.
Change From Baseline in Body Weight	For this endpoint baseline (week 0) and week 26 have been presented, where week 26 data is end of trial containing last available measurement.	Week 0, week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Bowering K, Case C, Harvey J, Reeves M, Sampson M, Strzinek R, Bretler DM, Bang RB, Bode BW. Faster Aspart Versus Insulin Aspart as Part of a Basal-Bolus Regimen in Inadequately Controlled Type 2 Diabetes: The onset 2 Trial. Diabetes Care. 2017 Jul;40(7):951-957. doi: 10.2337/dc16-1770. Epub 2017 May 8.
• Bode BW, Bowering K, Russell-Jones D. Response to Comment on Russell-Jones et al. Diabetes Care 2017;40:943-950. Comment on Bowering et al. Diabetes Care 2017;40:951-957. Diabetes Care. 2018 Mar;41(3):e29-e30. doi: 10.2337/dci17-0051. No abstract available.
• Bowering K, Rodbard HW, Russell-Jones D, Bode B, Harris S, Piletic M, Heller S, Woo V, Babu V, Dethlefsen C, Mathieu C. Investigating the Association Between Baseline Characteristics (HbA1c and Body Mass Index) and Clinical Outcomes of Fast-Acting Insulin Aspart in People with Diabetes: A Post Hoc Analysis. Diabetes Ther. 2019 Feb;10(1):177-188. doi: 10.1007/s13300-018-0553-7. Epub 2018 Dec 13.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 9, 2013
• Primary Completion (ACTUAL): January 22, 2015
• Study Completion (ACTUAL): January 22, 2015

Study Registration Dates

• First Submitted: March 21, 2013
• First Submitted That Met QC Criteria: March 22, 2013
• First Posted (ESTIMATE): March 27, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Glargine
• Other Study ID Numbers: NN1218-3853; 2010-024051-93 (EUDRACT_NUMBER); U1111-1118-2509 (OTHER: WHO); CTRI/2014/01/004285 (REGISTRY: Clinical Trials Registry - India (CTRI))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No