Comparison of NN5401 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes (BOOST™)

NN5401-3594: A 26-week, Open-labelled, Two-arm, Parallel, Randomised Trial Comparing Efficacy and Safety of NN5401 Once Daily Plus Insulin Aspart vs. Basal-bolus Treatment With Insulin Detemir Plus Insulin Aspart in Subjects With Type 1 Diabetes / NN5401-3645: An Extension Trial Comparing Safety and Efficacy of NN5401 Plus Meal-time Insulin Aspart for the Remaining Meals With Insulin Detemir Plus Meal-time Insulin Aspart in Type 1 Diabetes (BOOST™: T1)

This trial is conducted in Europe, Oceania, and the United States of America (USA).

The aim of this clinical trial is to compare NN5401 (insulin degludec/insulin aspart (IDegAsp)) with insulin detemir (IDet) plus insulin aspart in patients with type 1 diabetes (main period) followed by the extension period comparing the long-term safety of NN5401 plus insulin aspart with insulin detemir plus insulin aspart.

The main period is registered internally at Novo Nordisk as NN5401-3594 while the extension period is registered as NN5401-3645.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin degludec/insulin aspart; Drug: insulin aspart; Drug: insulin aspart; Drug: insulin detemir

• Study Type: Interventional
• Enrollment (Actual): 548
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • Novo Nordisk Investigational Site
  • Geelong, Australia, 3220
    • Novo Nordisk Investigational Site
  • New South Wales
    • Broadmeadow, New South Wales, Australia, 2292
      • Novo Nordisk Investigational Site
    • Camperdown, New South Wales, Australia, 2050
      • Novo Nordisk Investigational Site
    • Coffs Harbour, New South Wales, Australia, 2450
      • Novo Nordisk Investigational Site
  • South Australia
    • Keswick, South Australia, Australia, 5035
      • Novo Nordisk Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Novo Nordisk Investigational Site
• Denmark
  • Aalborg, Denmark, 9100
    • Novo Nordisk Investigational Site
  • Gentofte, Denmark, 2820
    • Novo Nordisk Investigational Site
  • Århus C, Denmark, 8000
    • Novo Nordisk Investigational Site
• France
  • Auxerre, France, 89000
    • Novo Nordisk Investigational Site
  • Narbonne, France, 11108
    • Novo Nordisk Investigational Site
  • Nimes, France, 30006
    • Novo Nordisk Investigational Site
  • Pointe à Pitre, France, 97159
    • Novo Nordisk Investigational Site
• Israel
  • Petah Tikva, Israel, 49202
    • Novo Nordisk Investigational Site
  • Rishon Le Zion, Israel, 75650
    • Novo Nordisk Investigational Site
  • Tel Hashomer, Israel, 52621
    • Novo Nordisk Investigational Site
• Poland
  • Lodz, Poland, 91-738
    • Novo Nordisk Investigational Site
  • Lodz, Poland, 93-338
    • Novo Nordisk Investigational Site
  • Sopot, Poland, 81-756
    • Novo Nordisk Investigational Site
  • Szczecin, Poland, 70-376
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 02-507
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 02-692
    • Novo Nordisk Investigational Site
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Novo Nordisk Investigational Site
• Romania
  • Brasov, Romania, 500365
    • Novo Nordisk Investigational Site
  • Bucharest, Romania, 020042
    • Novo Nordisk Investigational Site
  • Bucharest, Romania, 020475
    • Novo Nordisk Investigational Site
  • Buzau, Romania, 120203
    • Novo Nordisk Investigational Site
  • Iasi, Romania, 700547
    • Novo Nordisk Investigational Site
  • Oradea, Romania, 410169
    • Novo Nordisk Investigational Site
  • Sibiu, Romania, 550245
    • Novo Nordisk Investigational Site
  • Cluj
    • Cluj Napoca, Cluj, Romania, 400006
      • Novo Nordisk Investigational Site
• Russian Federation
  • Kemerovo, Russian Federation, 650066
    • Novo Nordisk Investigational Site
  • Kursk, Russian Federation, 305035
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 117036
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 125367
    • Novo Nordisk Investigational Site
  • Penza, Russian Federation, 440026
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 195257
    • Novo Nordisk Investigational Site
  • Samara, Russian Federation, 443067
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410053
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410710
    • Novo Nordisk Investigational Site
  • Smolensk, Russian Federation, 214019
    • Novo Nordisk Investigational Site
  • Volgograd, Russian Federation, 400138
    • Novo Nordisk Investigational Site
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Novo Nordisk Investigational Site
  • Dundee, United Kingdom, DD1 9SY
    • Novo Nordisk Investigational Site
  • Edinburgh, United Kingdom, EH16 4SA
    • Novo Nordisk Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • Novo Nordisk Investigational Site
  • Liverpool, United Kingdom, L7 8XP
    • Novo Nordisk Investigational Site
  • Oxford, United Kingdom, OX3 7LE
    • Novo Nordisk Investigational Site
  • Salford, United Kingdom, M6 8HD
    • Novo Nordisk Investigational Site
  • Wirral, Merseyside, United Kingdom, CH63 4JY
    • Novo Nordisk Investigational Site
• United States
  • California
    • La Mesa, California, United States, 91942
      • Novo Nordisk Investigational Site
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
    • Mission Hills, California, United States, 91345
      • Novo Nordisk Investigational Site
    • North Hollywood, California, United States, 91606
      • Novo Nordisk Investigational Site
    • Salinas, California, United States, 93901
      • Novo Nordisk Investigational Site
    • Valencia, California, United States, 91355
      • Novo Nordisk Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novo Nordisk Investigational Site
  • Florida
    • Miami, Florida, United States, 33156
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33169
      • Novo Nordisk Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Novo Nordisk Investigational Site
    • Lawrenceville, Georgia, United States, 30046
      • Novo Nordisk Investigational Site
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novo Nordisk Investigational Site
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
  • Minnesota
    • Eagan, Minnesota, United States, 55123
      • Novo Nordisk Investigational Site
    • Minneapolis, Minnesota, United States, 55416
      • Novo Nordisk Investigational Site
  • Missouri
    • St. Peters, Missouri, United States, 63376
      • Novo Nordisk Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Novo Nordisk Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89052-2649
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Novo Nordisk Investigational Site
    • Northport, New York, United States, 11768
      • Novo Nordisk Investigational Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Novo Nordisk Investigational Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75390-9302
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78215
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78240
      • Novo Nordisk Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • 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:

• FOR THE MAIN TRIAL, NN5401-3594:
• Type 1 diabetes mellitus for at least 12 months
• Ongoing daily treatment with insulin (in a basal bolus regimen, premix insulin regimen, self mix regimen) for at least 12 months
• HbA1c 7.0-10.0% (both inclusive)
• BMI (Body Mass Index) below or equal to 35.0 kg/m^2
• FOR THE EXTENSION TRIAL, NN5401-3645:
• The subject must have completed the six-month treatment period in trial NN5401-3594

Exclusion Criteria:

• FOR THE MAIN TRIAL, NN5401-3594:
• Treatment with other insulin regimens than insulin in a basal bolus regimen/premix insulin regimen/self mix regimen within 3 months
• Cardiovascular disease within the last 6 months
• Uncontrolled treated/untreated severe hypertension
• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements
• Cancer and medical history of cancer
• FOR THE EXTENSION TRIAL, NN5401-3645:
• Anticipated significant lifestyle changes during the trial
• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IDegAsp OD	Drug: insulin degludec/insulin aspart; Injected subcutaneously (under the skin) once daily with a meal. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) at the remaining meals. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) as meal time insulin. Dose was individually adjusted.
Active Comparator: IDet	Drug: insulin aspart; Injected subcutaneously (under the skin) at the remaining meals. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) as meal time insulin. Dose was individually adjusted.; Drug: insulin detemir; Injected subcutaneously (under the skin) once daily or twice daily. Dose was individually adjusted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	Change from baseline in HbA1c after 26 weeks of treatment	Week 0, Week 26
Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol /L.	Week 0 to Week 53 + 7 days follow up
Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.	Week 0 to Week 53 + 7 days follow up
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs)	Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.	Week 0 to Week 53 + 7 days of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.	Week 0 to Week 26 + 7 days follow up
Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26	Overall mean of 9-point SMPG at 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.	Week 26
Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment	Change from baseline in HbA1c after 52 weeks of treatment	Week 0, Week 53
Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.	Week 0 to Week 26 + 7 days follow up
Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment	Change from baseline in FPG after 52 weeks of treatment.	Week 0, Week 53

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Hirsch IB, Franek E, Mersebach H, Bardtrum L, Hermansen K. Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with Type 1 diabetes: 1-year results from a randomized clinical trial (BOOST(R) T1). Diabet Med. 2017 Feb;34(2):167-173. doi: 10.1111/dme.13068. Epub 2016 Feb 19.
• Hirsch IB, Bode B, Courreges JP, Dykiel P, Franek E, Hermansen K, King A, Mersebach H, Davies M. Insulin degludec/insulin aspart administered once daily at any meal, with insulin aspart at other meals versus a standard basal-bolus regimen in patients with type 1 diabetes: a 26-week, phase 3, randomized, open-label, treat-to-target trial. Diabetes Care. 2012 Nov;35(11):2174-81. doi: 10.2337/dc11-2503. Epub 2012 Aug 28.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: September 16, 2009
• First Submitted That Met QC Criteria: September 16, 2009
• First Posted (Estimate): September 17, 2009

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir
• Other Study ID Numbers: NN5401-3594; 2008-005769-71 (EudraCT Number); U1111-1111-8943 (Other Identifier: WHO); 2009-013412-13 (EudraCT Number); U1111-1113-2475 (Other Identifier: WHO)