A Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, Both With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes (SWITCH 1)

A Randomised, Double Blind, Cross-over Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, Both With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes (SWITCH 1)

This trial is conducted in Europe and the United States of America (USA). The aim of the trial is to compare the safety and efficacy of insulin degludec (IDeg) and insulin glargine (IGlar), both with insulin aspart (IAsp) as mealtime insulin in subjects with type 1 diabetes.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 501
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Bialystok, Poland, 15-435
    • Novo Nordisk Investigational Site
  • Gdansk, Poland, 80-858
    • Novo Nordisk Investigational Site
  • Gdansk, Poland, 80-546
    • Novo Nordisk Investigational Site
  • Szczecin, Poland, 70-506
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 04-736
    • Novo Nordisk Investigational Site
  • Zabrze, Poland, 41-800
    • Novo Nordisk Investigational Site
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35215-7502
      • Novo Nordisk Investigational Site
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Novo Nordisk Investigational Site
  • California
    • Concord, California, United States, 94520
      • Novo Nordisk Investigational Site
    • Escondido, California, United States, 92025
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • La Jolla, California, United States, 92037
      • Novo Nordisk Investigational Site
    • Long Beach, California, United States, 90807
      • Novo Nordisk Investigational Site
    • Rancho Cucamonga, California, United States, 91730-3063
      • Novo Nordisk Investigational Site
    • San Mateo, California, United States, 94401
      • Novo Nordisk Investigational Site
    • San Ramon, California, United States, 94583
      • Novo Nordisk Investigational Site
    • Santa Monica, California, United States, 90404
      • Novo Nordisk Investigational Site
    • Upland, California, United States, 91786
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80220
      • Novo Nordisk Investigational Site
  • Florida
    • Cooper City, Florida, United States, 33024
      • Novo Nordisk Investigational Site
    • Fleming Island, Florida, United States, 32003
      • Novo Nordisk Investigational Site
    • Fort Lauderdale, Florida, United States, 33312
      • Novo Nordisk Investigational Site
    • Hialeah, Florida, United States, 33012
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32204
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32207
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32256
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33156
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33175
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33130
      • Novo Nordisk Investigational Site
    • Miami Springs, Florida, United States, 33166
      • Novo Nordisk Investigational Site
    • New Port Richey, Florida, United States, 34652
      • Novo Nordisk Investigational Site
    • Pembroke Pines, Florida, United States, 33026
      • Novo Nordisk Investigational Site
    • Port Charlotte, Florida, United States, 33952
      • Novo Nordisk Investigational Site
    • Port Orange, Florida, United States, 32127
      • Novo Nordisk Investigational Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Novo Nordisk Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Novo Nordisk Investigational Site
  • Illinois
    • Arlington Heights, Illinois, United States, 60005-4144
      • Novo Nordisk Investigational Site
    • Chicago, Illinois, United States, 60611
      • Novo Nordisk Investigational Site
    • Crystal Lake, Illinois, United States, 60012
      • Novo Nordisk Investigational Site
    • Skokie, Illinois, United States, 60077
      • Novo Nordisk Investigational Site
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Novo Nordisk Investigational Site
    • Indianapolis, Indiana, United States, 46234
      • Novo Nordisk Investigational Site
  • Iowa
    • Council Bluffs, Iowa, United States, 51501
      • Novo Nordisk Investigational Site
    • West Des Moines, Iowa, United States, 50265
      • Novo Nordisk Investigational Site
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Novo Nordisk Investigational Site
    • Topeka, Kansas, United States, 66606
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
  • Michigan
    • Livonia, Michigan, United States, 48152
      • Novo Nordisk Investigational Site
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Novo Nordisk Investigational Site
    • Jefferson City, Missouri, United States, 65109
      • Novo Nordisk Investigational Site
    • Kansas City, Missouri, United States, 64106
      • Novo Nordisk Investigational Site
  • Montana
    • Billings, Montana, United States, 59101
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Novo Nordisk Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89052-2649
      • Novo Nordisk Investigational Site
    • Las Vegas, Nevada, United States, 89148
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Novo Nordisk Investigational Site
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Novo Nordisk Investigational Site
    • Harrison, New York, United States, 10528
      • Novo Nordisk Investigational Site
    • Mineola, New York, United States, 11501
      • Novo Nordisk Investigational Site
    • Syracuse, New York, United States, 13210
      • Novo Nordisk Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Novo Nordisk Investigational Site
    • Greenville, North Carolina, United States, 27834
      • Novo Nordisk Investigational Site
    • Morehead City, North Carolina, United States, 28557
      • Novo Nordisk Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Novo Nordisk Investigational Site
  • Ohio
    • Toledo, Ohio, United States, 43614
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Novo Nordisk Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15224-2215
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Novo Nordisk Investigational Site
    • Kingsport, Tennessee, United States, 37660
      • Novo Nordisk Investigational Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78758
      • Novo Nordisk Investigational Site
    • Carrollton, Texas, United States, 75007
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
    • El Paso, Texas, United States, 79912
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77024
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77079
      • Novo Nordisk Investigational Site
    • Katy, Texas, United States, 77450
      • Novo Nordisk Investigational Site
    • Mesquite, Texas, United States, 75149
      • Novo Nordisk Investigational Site
    • Richardson, Texas, United States, 75080
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
    • Schertz, Texas, United States, 78154
      • Novo Nordisk Investigational Site
    • Sugar Land, Texas, United States, 77478
      • Novo Nordisk Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Novo Nordisk Investigational Site
    • Salt Lake City, Utah, United States, 84107
      • Novo Nordisk Investigational Site
  • Virginia
    • Chesapeake, Virginia, United States, 23321
      • Novo Nordisk Investigational Site
    • Norfolk, Virginia, United States, 23510
      • Novo Nordisk Investigational Site
  • Washington
    • Federal Way, Washington, United States, 98003
      • Novo Nordisk Investigational Site
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site
    • Richland, Washington, United States, 99352
      • Novo Nordisk Investigational Site
    • Spokane, Washington, United States, 99208
      • Novo Nordisk Investigational Site
    • Walla Walla, Washington, United States, 99362-4445
      • Novo Nordisk Investigational Site
  • Wisconsin
    • 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: - Subjects fulfilling at least one of the below criteria: a) Experienced at least one severe hypo episode within the last year (according to the ADA (American Diabetes Association) definition, April 2013) b) Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m^2 per CKD-Epi (chronic kidney disease epidemiology collaboration) c) Hypoglycaemic symptom unawareness d) Diabetes mellitus duration for more than 15 years e) Recent episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (below or equal to 70 mg/dL [below or equal to 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening) - Male or female, age at least 18 years at the time of signing informed consent - Type 1 diabetes mellitus (diagnosed clinically) for at least 52 weeks prior to Visit 1 - Current treatment with a basal-bolus regimen consisting of neutral protamine Hagedorn (NPH) insulin OD (once daily) / BID (twice daily) or insulin detemir (IDet) OD / BID plus 2-4 daily injections of any rapid acting meal time insulin or CSII (with rapid acting insulin) for at least 26 weeks prior to Visit 1 - HbA1c (glycosylated haemoglobin) below or equal to 10% by central laboratory analysis - BMI (body mass index) below or equal to 45 kg/m^2 Exclusion Criteria: - Treatment with IGlar or IDeg within the last 26 weeks prior to Visit 1 (short term use [less than or equal to 2 weeks] is allowed, but not within 4 weeks prior to screening) - Use of any other anti-diabetic agent than those stated in the inclusion criteria within the last 26 weeks prior to Visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IDeg OD + IAsp followed by IGlar OD + IAsp; Each treatment period consists of a 16-week wash-out period and a 16-week maintenance period	Drug: insulin degludec; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin glargine; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin aspart; Administered 2-4 times daily injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.
Active Comparator: IGlar OD + IAsp followed by IDeg OD + IAsp; Each treatment period consists of a 16-week wash-out period and a 16-week maintenance period	Drug: insulin degludec; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin glargine; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin aspart; Administered 2-4 times daily injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Severe or BG (Blood Glucose) Confirmed Symptomatic Hypoglycaemic Episodes During the Maintenance Period	Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment. Maintenance period: 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64).	A 16-week treatment period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episodes During the Maintenance Period	Severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia and with time of onset between 00:01 and 05.59 a.m., both inclusive. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.	After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
Proportion of Subjects With One or More Severe Hypoglycaemic Episodes During the Maintenance Period	Percentage of subjects who experienced one or more severe hypoglycaemic episodes during the maintenance period. Severe hypoglycaemia (according to the American Diabetes Association 2013 definition): A hypoglycaemic episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose values may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.	After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
Incidence of Treatment Emergent Adverse Events	Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.	During 32 weeks of treatment for each treatment period
Change From Baseline in HbA1c (Glycosylated Haemoglobin)	Change from baseline in HbA1c (glycosylated haemoglobin) at week 32 (treatment period 1) and at week 64 (treatment period 2). Week 32 HbA1c absolute value was considered as baseline for calculating change from baseline in HbA1c at week 64.	Week 32, Week 64
FPG (Fasting Plasma Glucose)	Fasting plasma glucose values at week 32 and week 64.	Week 32 and Week 64

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Lane W, Bailey TS, Gerety G, Gumprecht J, Philis-Tsimikas A, Hansen CT, Nielsen TSS, Warren M; Group Information; SWITCH 1. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):33-44. doi: 10.1001/jama.2017.7115.
• Evans M, Mehta R, Gundgaard J, Chubb B. Cost-Effectiveness of Insulin Degludec vs. Insulin Glargine U100 in Type 1 and Type 2 Diabetes Mellitus in a UK Setting. Diabetes Ther. 2018 Oct;9(5):1919-1930. doi: 10.1007/s13300-018-0478-1. Epub 2018 Aug 10.
• DeVries JH, Bailey TS, Bhargava A, Gerety G, Gumprecht J, Heller S, Lane W, Wysham CH, Zinman B, Bak BA, Hachmann-Nielsen E, Philis-Tsimikas A. Day-to-day fasting self-monitored blood glucose variability is associated with risk of hypoglycaemia in insulin-treated patients with type 1 and type 2 diabetes: A post hoc analysis of the SWITCH Trials. Diabetes Obes Metab. 2019 Mar;21(3):622-630. doi: 10.1111/dom.13565. Epub 2018 Nov 26.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2014
• Primary Completion (Actual): January 11, 2016
• Study Completion (Actual): January 11, 2016

Study Registration Dates

• First Submitted: January 7, 2014
• First Submitted That Met QC Criteria: January 10, 2014
• First Posted (Estimate): January 13, 2014

Study Record Updates

• Last Update Posted (Actual): January 2, 2019
• Last Update Submitted That Met QC Criteria: December 7, 2018
• Last Verified: December 1, 2018

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 Glargine
• Other Study ID Numbers: NN1250-3995; U1111-1129-9668 (Other Identifier: WHO); 2012-001930-32 (EudraCT Number)