CONCLUDE: A Trial Comparing the Efficacy and Safety of Insulin Degludec and Insulin Glargine 300 Units/mL in Subjects With Type 2 Diabetes Mellitus Inadequately Treated With Basal Insulin With or Without Oral Antidiabetic Drugs
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT03078478
Collaborator
(none)
1,609
229
2
23.7
7
0.3
Study Details
Study Description
Brief Summary
This trial is conducted in Europe and North America. The aim of the trial is to compare the efficacy and safety of insulin degludec and insulin glargine 300 units/mL in subjects with type 2 diabetes mellitus inadequately treated with basal insulin with or without oral antidiabetic drugs. Due to change in glycaemic data collection process, this trial is amended to allow for a full 36 weeks (maintenance 2 period) of the use of the new process.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1609 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Trial Comparing the Efficacy and Safety of Insulin Degludec and Insulin Glargine 300 Units/mL in Subjects With Type 2 Diabetes Mellitus Inadequately Treated With Basal Insulin With or Without Oral Antidiabetic Drugs
Actual Study Start Date
:
Mar 13, 2017
Actual Primary Completion Date
:
Feb 13, 2019
Actual Study Completion Date
:
Mar 4, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IDeg 200 U/mL
|
Drug: Insulin degludec
For subcutaneous (s.c., under the skin) injection once daily
|
| Active Comparator: IGlar 300 U/mL
|
Drug: Insulin glargine
For subcutaneous (s.c., under the skin) injection once daily
|
Outcome Measures
Primary Outcome Measures
- Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) [36 Weeks]
Severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks) period. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Secondary Outcome Measures
- Basal Insulin Dose (U) at End of Treatment (up to 88 Weeks) [88 weeks]
The observed mean daily basal insulin doses was evaluated at the end of trial (88 weeks).
- Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) [36 weeks]
Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
- Number of Severe Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) [36 weeks (maintenance 2)]
Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for maintenance 2 period. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
- Change in HbA1c From Baseline to End of Treatment (up to 88 Weeks) [Week 0, week 88]
Change in glycosylated haemoglobin (HbA1c) was evaluated from baseline to end of treatment period (week 88).
- Change in Fasting Plasma Glucose (FPG) From Baseline to End of Treatment (up to 88 Weeks) [Week 0, week 88]
Change in fasting plasma glucose (FPG) was evaluated from baseline to end of treatment period (week 88).
- Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) [At 88 weeks]
Participants achieving a fasting plasma glucose value of less than or equal to 7.2 mmol/L (130 mg/dL) at end of treatment (up to 88 weeks).
- Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) [At 88 weeks]
Participants achieving a fasting plasma glucose value of less than or equal to 5.0 mmol/L (90 mg/dL) at end of treatment (up to 88 weeks).
- Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) [End of Treatment (up to 88 Weeks)]
Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks).
- Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) [At 88 weeks]
Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without nocturnal severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks).
- Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) [Week 0, week 88]
Participants measured their pre-breakfast self-measured plasma glucose (SMPG) value until end of treatment (week 88). Mean pre-breakfast self-measured plasma glucose used for titration at baseline and end of treatment (up to 88 weeks) are presented.
- Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) [88 weeks]
Severe or BG confirmed symptomatic hypoglycaemia was evaluated during treatment (up to 88 weeks). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
- Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) [88 weeks]
Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated at the end of trial (88 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
- Number of Severe Hypoglycaemic Episodes During Treatment (up to 88 Weeks) [88 weeks]
Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for the total trial period (88 weeks). The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
- Number of Adverse Events From Randomisation to End of Maintenance Period 2 (up to 88 Weeks) [88 weeks]
The adverse events presented are treatment emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last days of randomised treatment or had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last date of randomised treatment. Number of adverse events expressed in rates, from randomisation to end of maintenance period 2 (up to 88 weeks) is presented. Rate = number of events divided by patient years of exposure multiplied by 100.
- Change in Body Weight From Baseline to End of Treatment (up to 88 Weeks) [Week 0, week 88]
Change in body weight, measured in kilograms, from baseline (week 0) to end of treatment (week 88).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria: - Male or female, age above or equal to 18 years at the time of signing informed consent. - Subjects fulfilling at least one of the below criteria (For this inclusion criterion the aim is to include minimum 80% of individuals with a previous episode of hypoglycaemia (criterion e). The remaining subjects will have to fulfil at least one of criteria a-d.): - a) Experienced at least one severe hypoglycaemic episode within the last year (according to the ADA definition, April 2013 (An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations 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.). -
- Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m2 per CKD-EPI by central laboratory analysis. - c) Hypoglycaemic symptom unawareness (History of impaired autonomic responses (tremulousness, sweating, palpitations, and hunger) during hypoglycaemia). - d) Treated with insulin for more than 5 years. - e) Episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (equal to or below 70 mg/dL [equal to or below 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening). - Subjects diagnosed (clinically) with type 2 diabetes mellitus. - Treated with basal only insulin (once daily or twice-daily insulin (insulin detemir; insulin glargine 100 U/mL, biosimilar of insulin glargine 100 U/mL or insulin Neutral Protamine Hagedorn)) equal to or above 90 days prior to the day of screening with or without any of the following anti-diabetic drugs with stable doses for equal to or above 90 days prior to screening: - a) Metformin - b) Dipeptidyl peptidase -4 inhibitor - c) Sodium-glucose co-transporter 2 inhibitor - d) Alpha-glucosidase-inhibitors (acarbose) - e) Thiazolidinediones - f) Marketed oral combination products only including the products listed in criteria 5a-5e - HbA1c equal to or below 9.5% (80 mmol/mol) at screening by central laboratory analysis. - BMI equal to or below 45 kg/m2. Exclusion Criteria: - 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 the day of screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Anniston | Alabama | United States | 36207 |
| 2 | Novo Nordisk Investigational Site | Birmingham | Alabama | United States | 35211 |
| 3 | Novo Nordisk Investigational Site | Chandler | Arizona | United States | 85224 |
| 4 | Novo Nordisk Investigational Site | Fountain Hills | Arizona | United States | 85268 |
| 5 | Novo Nordisk Investigational Site | Glendale | Arizona | United States | 85306-4652 |
| 6 | Novo Nordisk Investigational Site | Glendale | Arizona | United States | 85306 |
| 7 | Novo Nordisk Investigational Site | Glendale | Arizona | United States | 85308 |
| 8 | Novo Nordisk Investigational Site | Phoenix | Arizona | United States | 85037 |
| 9 | Novo Nordisk Investigational Site | Tucson | Arizona | United States | 85741 |
| 10 | Novo Nordisk Investigational Site | Buena Park | California | United States | 90620 |
| 11 | Novo Nordisk Investigational Site | Concord | California | United States | 94520 |
| 12 | Novo Nordisk Investigational Site | Downey | California | United States | 90242 |
| 13 | Novo Nordisk Investigational Site | Duarte | California | United States | 91010 |
| 14 | Novo Nordisk Investigational Site | Fresno | California | United States | 93720 |
| 15 | Novo Nordisk Investigational Site | La Jolla | California | United States | 92037 |
| 16 | Novo Nordisk Investigational Site | Lancaster | California | United States | 93534 |
| 17 | Novo Nordisk Investigational Site | Lomita | California | United States | 90717 |
| 18 | Novo Nordisk Investigational Site | Los Alamitos | California | United States | 90720 |
| 19 | Novo Nordisk Investigational Site | Los Angeles | California | United States | 90057 |
| 20 | Novo Nordisk Investigational Site | Moreno Valley | California | United States | 92555 |
| 21 | Novo Nordisk Investigational Site | Northridge | California | United States | 91325 |
| 22 | Novo Nordisk Investigational Site | Palm Springs | California | United States | 92262 |
| 23 | Novo Nordisk Investigational Site | Pomona | California | United States | 91766-2007 |
| 24 | Novo Nordisk Investigational Site | Poway | California | United States | 92064 |
| 25 | Novo Nordisk Investigational Site | Riverside | California | United States | 92506 |
| 26 | Novo Nordisk Investigational Site | Roseville | California | United States | 95661 |
| 27 | Novo Nordisk Investigational Site | Sacramento | California | United States | 95821 |
| 28 | Novo Nordisk Investigational Site | San Mateo | California | United States | 94401 |
| 29 | Novo Nordisk Investigational Site | San Ramon | California | United States | 94583 |
| 30 | Novo Nordisk Investigational Site | Stanford | California | United States | 94305 |
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| 39 | Novo Nordisk Investigational Site | Clearwater | Florida | United States | 33765 |
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| 49 | Novo Nordisk Investigational Site | Pembroke Pines | Florida | United States | 33027 |
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| 67 | Novo Nordisk Investigational Site | Topeka | Kansas | United States | 66606 |
| 68 | Novo Nordisk Investigational Site | Lexington | Kentucky | United States | 40502 |
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| 70 | Novo Nordisk Investigational Site | Louisville | Kentucky | United States | 40213 |
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| 72 | Novo Nordisk Investigational Site | New Orleans | Louisiana | United States | 70119 |
| 73 | Novo Nordisk Investigational Site | Rockville | Maryland | United States | 20852 |
| 74 | Novo Nordisk Investigational Site | Bloomfield Hills | Michigan | United States | 48302 |
| 75 | Novo Nordisk Investigational Site | Richfield | Minnesota | United States | 55432 |
| 76 | Novo Nordisk Investigational Site | Chesterfield | Missouri | United States | 63017 |
| 77 | Novo Nordisk Investigational Site | Kalispell | Montana | United States | 59901 |
| 78 | Novo Nordisk Investigational Site | Elkhorn | Nebraska | United States | 68022 |
| 79 | Novo Nordisk Investigational Site | Fremont | Nebraska | United States | 68025 |
| 80 | Novo Nordisk Investigational Site | Omaha | Nebraska | United States | 68144 |
| 81 | Novo Nordisk Investigational Site | Henderson | Nevada | United States | 89052 |
| 82 | Novo Nordisk Investigational Site | Las Vegas | Nevada | United States | 89109 |
| 83 | Novo Nordisk Investigational Site | Las Vegas | Nevada | United States | 89118 |
| 84 | Novo Nordisk Investigational Site | Las Vegas | Nevada | United States | 89148 |
| 85 | Novo Nordisk Investigational Site | Nashua | New Hampshire | United States | 03063 |
| 86 | Novo Nordisk Investigational Site | East Brunswick | New Jersey | United States | 08816 |
| 87 | Novo Nordisk Investigational Site | Lawrenceville | New Jersey | United States | 08648 |
| 88 | Novo Nordisk Investigational Site | Albuquerque | New Mexico | United States | 87102 |
| 89 | Novo Nordisk Investigational Site | Albuquerque | New Mexico | United States | 87109-2134 |
| 90 | Novo Nordisk Investigational Site | Albany | New York | United States | 12203 |
| 91 | Novo Nordisk Investigational Site | New Windsor | New York | United States | 12553 |
| 92 | Novo Nordisk Investigational Site | New York | New York | United States | 10016 |
| 93 | Novo Nordisk Investigational Site | Northport | New York | United States | 11768 |
| 94 | Novo Nordisk Investigational Site | West Seneca | New York | United States | 14224 |
| 95 | Novo Nordisk Investigational Site | Charlotte | North Carolina | United States | 28210 |
| 96 | Novo Nordisk Investigational Site | Charlotte | North Carolina | United States | 28277 |
| 97 | Novo Nordisk Investigational Site | Greensboro | North Carolina | United States | 27408 |
| 98 | Novo Nordisk Investigational Site | Greenville | North Carolina | United States | 27834 |
| 99 | Novo Nordisk Investigational Site | Greenville | North Carolina | United States | 27858 |
| 100 | Novo Nordisk Investigational Site | Morehead City | North Carolina | United States | 28557-4346 |
| 101 | Novo Nordisk Investigational Site | Statesville | North Carolina | United States | 28625 |
| 102 | Novo Nordisk Investigational Site | Wilmington | North Carolina | United States | 28401 |
| 103 | Novo Nordisk Investigational Site | Columbus | Ohio | United States | 43212 |
| 104 | Novo Nordisk Investigational Site | Columbus | Ohio | United States | 43213 |
| 105 | Novo Nordisk Investigational Site | Maumee | Ohio | United States | 43537 |
| 106 | Novo Nordisk Investigational Site | Toledo | Ohio | United States | 43614 |
| 107 | Novo Nordisk Investigational Site | Norman | Oklahoma | United States | 73069 |
| 108 | Novo Nordisk Investigational Site | Beaver | Pennsylvania | United States | 15009 |
| 109 | Novo Nordisk Investigational Site | McMurray | Pennsylvania | United States | 15317 |
| 110 | Novo Nordisk Investigational Site | Philadelphia | Pennsylvania | United States | 19114 |
| 111 | Novo Nordisk Investigational Site | Anderson | South Carolina | United States | 29621 |
| 112 | Novo Nordisk Investigational Site | Gaffney | South Carolina | United States | 29341 |
| 113 | Novo Nordisk Investigational Site | Greenville | South Carolina | United States | 29615 |
| 114 | Novo Nordisk Investigational Site | Greer | South Carolina | United States | 29651 |
| 115 | Novo Nordisk Investigational Site | Mount Pleasant | South Carolina | United States | 29464 |
| 116 | Novo Nordisk Investigational Site | Pelzer | South Carolina | United States | 29669 |
| 117 | Novo Nordisk Investigational Site | West Columbia | South Carolina | United States | 29169 |
| 118 | Novo Nordisk Investigational Site | Dakota Dunes | South Dakota | United States | 57049 |
| 119 | Novo Nordisk Investigational Site | Bristol | Tennessee | United States | 37620-7352 |
| 120 | Novo Nordisk Investigational Site | Chattanooga | Tennessee | United States | 37404 |
| 121 | Novo Nordisk Investigational Site | Chattanooga | Tennessee | United States | 37411 |
| 122 | Novo Nordisk Investigational Site | Kingsport | Tennessee | United States | 37660 |
| 123 | Novo Nordisk Investigational Site | Knoxville | Tennessee | United States | 37909 |
| 124 | Novo Nordisk Investigational Site | Nashville | Tennessee | United States | 37203 |
| 125 | Novo Nordisk Investigational Site | Nashville | Tennessee | United States | 37232 |
| 126 | Novo Nordisk Investigational Site | Amarillo | Texas | United States | 79106 |
| 127 | Novo Nordisk Investigational Site | Arlington | Texas | United States | 76012-4637 |
| 128 | Novo Nordisk Investigational Site | Austin | Texas | United States | 78731 |
| 129 | Novo Nordisk Investigational Site | Dallas | Texas | United States | 75226 |
| 130 | Novo Nordisk Investigational Site | Dallas | Texas | United States | 75390-9302 |
| 131 | Novo Nordisk Investigational Site | Fort Worth | Texas | United States | 76132 |
| 132 | Novo Nordisk Investigational Site | Houston | Texas | United States | 77024 |
| 133 | Novo Nordisk Investigational Site | Houston | Texas | United States | 77066 |
| 134 | Novo Nordisk Investigational Site | Humble | Texas | United States | 77338 |
| 135 | Novo Nordisk Investigational Site | Kerrville | Texas | United States | 78028 |
| 136 | Novo Nordisk Investigational Site | New Braunfels | Texas | United States | 78130 |
| 137 | Novo Nordisk Investigational Site | Plano | Texas | United States | 75075 |
| 138 | Novo Nordisk Investigational Site | San Antonio | Texas | United States | 78215 |
| 139 | Novo Nordisk Investigational Site | San Antonio | Texas | United States | 78224 |
| 140 | Novo Nordisk Investigational Site | San Antonio | Texas | United States | 78228-6205 |
| 141 | Novo Nordisk Investigational Site | San Antonio | Texas | United States | 78229 |
| 142 | Novo Nordisk Investigational Site | San Antonio | Texas | United States | 78249 |
| 143 | Novo Nordisk Investigational Site | Waco | Texas | United States | 76710 |
| 144 | Novo Nordisk Investigational Site | Bountiful | Utah | United States | 84010 |
| 145 | Novo Nordisk Investigational Site | Murray | Utah | United States | 84123 |
| 146 | Novo Nordisk Investigational Site | Ogden | Utah | United States | 84405 |
| 147 | Novo Nordisk Investigational Site | Bennington | Vermont | United States | 05201 |
| 148 | Novo Nordisk Investigational Site | Chesapeake | Virginia | United States | 23321 |
| 149 | Novo Nordisk Investigational Site | Midlothian | Virginia | United States | 23114 |
| 150 | Novo Nordisk Investigational Site | Norfolk | Virginia | United States | 23510-2015 |
| 151 | Novo Nordisk Investigational Site | Richmond | Virginia | United States | 23219 |
| 152 | Novo Nordisk Investigational Site | Virginia Beach | Virginia | United States | 23454 |
| 153 | Novo Nordisk Investigational Site | Olympia | Washington | United States | 98502 |
| 154 | Novo Nordisk Investigational Site | Spokane | Washington | United States | 99201 |
| 155 | Novo Nordisk Investigational Site | Kenosha | Wisconsin | United States | 53144 |
| 156 | Novo Nordisk Investigational Site | West Allis | Wisconsin | United States | 53227 |
| 157 | Novo Nordisk Investigational Site | Calgary | Alberta | Canada | T2H 2G4 |
| 158 | Novo Nordisk Investigational Site | Brampton | Ontario | Canada | L6S 0C6 |
| 159 | Novo Nordisk Investigational Site | Etobicoke | Ontario | Canada | M9R 4E1 |
| 160 | Novo Nordisk Investigational Site | Hamilton | Ontario | Canada | L8N 3Z5 |
| 161 | Novo Nordisk Investigational Site | Markham | Ontario | Canada | L3P 7P2 |
| 162 | Novo Nordisk Investigational Site | Oakville | Ontario | Canada | L6M 1M1 |
| 163 | Novo Nordisk Investigational Site | Toronto | Ontario | Canada | M4G 3E8 |
| 164 | Novo Nordisk Investigational Site | Mirabel | Quebec | Canada | J7J 2K8 |
| 165 | Novo Nordisk Investigational Site | Sherbrooke | Quebec | Canada | J1L 0H8 |
| 166 | Novo Nordisk Investigational Site | Aarhus N | Denmark | 8200 | |
| 167 | Novo Nordisk Investigational Site | Esbjerg | Denmark | 6700 | |
| 168 | Novo Nordisk Investigational Site | Hellerup | Denmark | 2900 | |
| 169 | Novo Nordisk Investigational Site | Hillerød | Denmark | 3400 | |
| 170 | Novo Nordisk Investigational Site | Hvidovre | Denmark | 2650 | |
| 171 | Novo Nordisk Investigational Site | Odense | Denmark | 5000 | |
| 172 | Novo Nordisk Investigational Site | Pärnu | Estonia | 80018 | |
| 173 | Novo Nordisk Investigational Site | Tallinn | Estonia | 10138 | |
| 174 | Novo Nordisk Investigational Site | Tallinn | Estonia | 13419 | |
| 175 | Novo Nordisk Investigational Site | Viljandi | Estonia | 71024 | |
| 176 | Novo Nordisk Investigational Site | Bad Mergentheim | Germany | 97980 | |
| 177 | Novo Nordisk Investigational Site | Berlin | Germany | 13597 | |
| 178 | Novo Nordisk Investigational Site | Elsterwerda | Germany | 04910 | |
| 179 | Novo Nordisk Investigational Site | Essen | Germany | 45136 | |
| 180 | Novo Nordisk Investigational Site | Essen | Germany | 45219 | |
| 181 | Novo Nordisk Investigational Site | Falkensee | Germany | 14612 | |
| 182 | Novo Nordisk Investigational Site | Friedrichsthal | Germany | 66299 | |
| 183 | Novo Nordisk Investigational Site | Hamburg | Germany | 22041 | |
| 184 | Novo Nordisk Investigational Site | Hamburg | Germany | 22607 | |
| 185 | Novo Nordisk Investigational Site | Lingen | Germany | 49808 | |
| 186 | Novo Nordisk Investigational Site | Rehlingen-Siersburg | Germany | 66780 | |
| 187 | Novo Nordisk Investigational Site | Saint Ingbert-Oberwürzbach | Germany | 66386 | |
| 188 | Novo Nordisk Investigational Site | Athens | Greece | GR-115 27 | |
| 189 | Novo Nordisk Investigational Site | Athens | Greece | GR-11527 | |
| 190 | Novo Nordisk Investigational Site | Larissa | Greece | GR-41110 | |
| 191 | Novo Nordisk Investigational Site | Nikaia | Greece | GR-18454 | |
| 192 | Novo Nordisk Investigational Site | Thessaloniki | Greece | GR-54642 | |
| 193 | Novo Nordisk Investigational Site | Thessaloniki | Greece | GR-57001 | |
| 194 | Novo Nordisk Investigational Site | Thessaloniki | Greece | GR-57010 | |
| 195 | Novo Nordisk Investigational Site | Budapest | Hungary | 1089 | |
| 196 | Novo Nordisk Investigational Site | Budapest | Hungary | 1125 | |
| 197 | Novo Nordisk Investigational Site | Budapest | Hungary | 1131 | |
| 198 | Novo Nordisk Investigational Site | Budapest | Hungary | H-1083 | |
| 199 | Novo Nordisk Investigational Site | Debrecen | Hungary | 4043 | |
| 200 | Novo Nordisk Investigational Site | Debrecen | Hungary | H-4032 | |
| 201 | Novo Nordisk Investigational Site | Kaposvár | Hungary | 7400 | |
| 202 | Novo Nordisk Investigational Site | Szeged | Hungary | H-6725 | |
| 203 | Novo Nordisk Investigational Site | Szombathely | Hungary | H-9700 | |
| 204 | Novo Nordisk Investigational Site | Hamar | Norway | 2318 | |
| 205 | Novo Nordisk Investigational Site | Hoenefoss | Norway | 3515 | |
| 206 | Novo Nordisk Investigational Site | Oslo | Norway | 0176 | |
| 207 | Novo Nordisk Investigational Site | Oslo | Norway | 0373 | |
| 208 | Novo Nordisk Investigational Site | Oslo | Norway | 0424 | |
| 209 | Novo Nordisk Investigational Site | Skedsmokorset | Norway | NO-2020 | |
| 210 | Novo Nordisk Investigational Site | Trondheim | Norway | 7030 | |
| 211 | Novo Nordisk Investigational Site | Bialystok | Poland | 15-445 | |
| 212 | Novo Nordisk Investigational Site | Bytom | Poland | 41-902 | |
| 213 | Novo Nordisk Investigational Site | Gdansk | Poland | 80-546 | |
| 214 | Novo Nordisk Investigational Site | Gdansk | Poland | 80-858 | |
| 215 | Novo Nordisk Investigational Site | Lublin | Poland | 20-362 | |
| 216 | Novo Nordisk Investigational Site | Lublin | Poland | 20-538 | |
| 217 | Novo Nordisk Investigational Site | Szczecin | Poland | 70-506 | |
| 218 | Novo Nordisk Investigational Site | Warsaw | Poland | 00-465 | |
| 219 | Novo Nordisk Investigational Site | Zabrze | Poland | 41-800 | |
| 220 | Novo Nordisk Investigational Site | Manati | Puerto Rico | 00674 | |
| 221 | Novo Nordisk Investigational Site | Ponce | Puerto Rico | 00716 | |
| 222 | Novo Nordisk Investigational Site | Oradea | Bihor | Romania | 410469 |
| 223 | Novo Nordisk Investigational Site | Bucharest | Romania | 022441 | |
| 224 | Novo Nordisk Investigational Site | Bucharest | Romania | 13682 | |
| 225 | Novo Nordisk Investigational Site | Buzau | Romania | 120203 | |
| 226 | Novo Nordisk Investigational Site | Galati | Romania | 800578 | |
| 227 | Novo Nordisk Investigational Site | Belgrade | Serbia | 11000 | |
| 228 | Novo Nordisk Investigational Site | Belgrade | Serbia | 11080 | |
| 229 | Novo Nordisk Investigational Site | Nis | Serbia | 18000 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT03078478
Other Study ID Numbers:
- NN1250-4252
- U1111-1184-8175
- 2016-002801-20
First Posted:
Mar 13, 2017
Last Update Posted:
Jan 11, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The trial was conducted at 230 sites in 11 countries as follows. Number of sites that screened and randomised participants to treatment are given in parenthesis. Canada:(9/9), Denmark: (6/6), Estonia: (5/5), Germany: (11 /11), Greece: (7/7), Hungary: (9/9), Norway: (4/4), Poland: (9/9), Romania: (5/4), Serbia: (8/8), United States: (157/153). |
|---|---|
| Pre-assignment Detail | The participants were previously treated with basal insulin once daily or twice daily ± oral anti-diabetic drugs excluding sulfonylureas/glinides. Pre-trial insulin was discontinued and the subjects continued their pre-trial oral anti-diabetic drugs (OADs). |
| Arm/Group Title | Insulin Degludec U200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Period Title: Titration Period (16 Weeks) | ||
| STARTED | 805 | 804 |
| Full Analysis Set | 805 | 804 |
| Safety Analysis Set | 802 | 798 |
| COMPLETED | 805 | 804 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Titration Period (16 Weeks) | ||
| STARTED | 805 | 804 |
| COMPLETED | 758 | 761 |
| NOT COMPLETED | 47 | 43 |
| Period Title: Titration Period (16 Weeks) | ||
| STARTED | 758 | 761 |
| COMPLETED | 733 | 734 |
| NOT COMPLETED | 25 | 27 |
Baseline Characteristics
| Arm/Group Title | Insulin Degludec U200 | Insulin Glargine U300 | Total |
|---|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Total of all reporting groups |
| Overall Participants | 805 | 804 | 1609 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
62.9
(10)
|
62.8
(10)
|
62.8
(10)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
333
41.4%
|
368
45.8%
|
701
43.6%
|
| Male |
472
58.6%
|
436
54.2%
|
908
56.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
84
10.4%
|
100
12.4%
|
184
11.4%
|
| Not Hispanic or Latino |
721
89.6%
|
704
87.6%
|
1425
88.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
5
0.6%
|
4
0.5%
|
9
0.6%
|
| Asian |
25
3.1%
|
29
3.6%
|
54
3.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.1%
|
1
0.1%
|
| Black or African American |
78
9.7%
|
65
8.1%
|
143
8.9%
|
| White |
693
86.1%
|
699
86.9%
|
1392
86.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
4
0.5%
|
6
0.7%
|
10
0.6%
|
Outcome Measures
| Title | Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) |
|---|---|
| Description | Severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks) period. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Time Frame | 36 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 742 | 741 |
| Number [Episodes/(PYE*100)] |
216.8
|
243.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec 200, Insulin Glargine U300 |
|---|---|---|
| Comments | The number of episodes is analysed using a negative binomial regression model (log link) with the logarithm of the time period in which a hypoglycaemic episode was considered treatment emergent as offset. The model includes treatment, number of OADs, region, sex and dosing time as fixed factors, and age as a covariate. Missing values are imputed through multiple imputation by treatment arm, based on a Poisson model. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1715 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment rate ratio |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.73 to 1.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Basal Insulin Dose (U) at End of Treatment (up to 88 Weeks) |
|---|---|
| Description | The observed mean daily basal insulin doses was evaluated at the end of trial (88 weeks). |
| Time Frame | 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 703 | 704 |
| Mean (Standard Deviation) [Units] |
66.6
(48.54)
|
73.0
(48.48)
|
| Title | Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) |
|---|---|
| Description | Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Time Frame | 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 742 | 741 |
| Number [Episodes/(PYE*100)] |
62.30
|
93.75
|
| Title | Number of Severe Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) |
|---|---|
| Description | Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for maintenance 2 period. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Time Frame | 36 weeks (maintenance 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 742 | 741 |
| Number [Episodes/(PYE*100)] |
0.98
|
4.88
|
| Title | Change in HbA1c From Baseline to End of Treatment (up to 88 Weeks) |
|---|---|
| Description | Change in glycosylated haemoglobin (HbA1c) was evaluated from baseline to end of treatment period (week 88). |
| Time Frame | Week 0, week 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) comprised all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 694 | 700 |
| Mean (Standard Deviation) [Percentage of HbA1c] |
-0.54
(0.91)
|
-0.46
(0.90)
|
| Title | Change in Fasting Plasma Glucose (FPG) From Baseline to End of Treatment (up to 88 Weeks) |
|---|---|
| Description | Change in fasting plasma glucose (FPG) was evaluated from baseline to end of treatment period (week 88). |
| Time Frame | Week 0, week 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 685 | 689 |
| Mean (Standard Deviation) [mg/dL] |
-35.50
(49.34)
|
-25.68
(56.69)
|
| Title | Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) |
|---|---|
| Description | Participants achieving a fasting plasma glucose value of less than or equal to 7.2 mmol/L (130 mg/dL) at end of treatment (up to 88 weeks). |
| Time Frame | At 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 701 | 700 |
| Yes |
84.0
10.4%
|
72.0
9%
|
| No |
16.0
2%
|
28.0
3.5%
|
| Title | Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) |
|---|---|
| Description | Participants achieving a fasting plasma glucose value of less than or equal to 5.0 mmol/L (90 mg/dL) at end of treatment (up to 88 weeks). |
| Time Frame | At 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 701 | 700 |
| Yes |
31.5
3.9%
|
21.7
2.7%
|
| No |
68.5
8.5%
|
78.3
9.7%
|
| Title | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) |
|---|---|
| Description | Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks). |
| Time Frame | End of Treatment (up to 88 Weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 694 | 700 |
| Yes |
35.3
4.4%
|
30.0
3.7%
|
| No |
64.7
8%
|
70.0
8.7%
|
| Title | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) |
|---|---|
| Description | Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without nocturnal severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks). |
| Time Frame | At 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 694 | 700 |
| Yes |
47.4
5.9%
|
39.3
4.9%
|
| No |
52.6
6.5%
|
60.7
7.5%
|
| Title | Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) |
|---|---|
| Description | Participants measured their pre-breakfast self-measured plasma glucose (SMPG) value until end of treatment (week 88). Mean pre-breakfast self-measured plasma glucose used for titration at baseline and end of treatment (up to 88 weeks) are presented. |
| Time Frame | Week 0, week 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 805 | 804 |
| Baseline (week 0) |
8.39
(2.73)
|
8.41
(2.75)
|
| End of treatment (week 88) |
5.46
(1.08)
|
5.56
(1.23)
|
| Title | Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) |
|---|---|
| Description | Severe or BG confirmed symptomatic hypoglycaemia was evaluated during treatment (up to 88 weeks). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Time Frame | 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 802 | 798 |
| Number [Episodes/(PYE*100)] |
137.8
|
163.7
|
| Title | Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) |
|---|---|
| Description | Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated at the end of trial (88 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Time Frame | 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 802 | 798 |
| Number [Episodes/(PYE*100)] |
36.93
|
60.03
|
| Title | Number of Severe Hypoglycaemic Episodes During Treatment (up to 88 Weeks) |
|---|---|
| Description | Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for the total trial period (88 weeks). The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Time Frame | 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 802 | 798 |
| Number [Episodes/(PYE*100)] |
2.06
|
5.21
|
| Title | Number of Adverse Events From Randomisation to End of Maintenance Period 2 (up to 88 Weeks) |
|---|---|
| Description | The adverse events presented are treatment emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last days of randomised treatment or had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last date of randomised treatment. Number of adverse events expressed in rates, from randomisation to end of maintenance period 2 (up to 88 weeks) is presented. Rate = number of events divided by patient years of exposure multiplied by 100. |
| Time Frame | 88 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 802 | 798 |
| Number [Episodes/(PYE*100)] |
367.32
|
365.42
|
| Title | Change in Body Weight From Baseline to End of Treatment (up to 88 Weeks) |
|---|---|
| Description | Change in body weight, measured in kilograms, from baseline (week 0) to end of treatment (week 88). |
| Time Frame | Week 0, week 88 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data. |
| Arm/Group Title | Insulin Degludec 200 | Insulin Glargine U300 |
|---|---|---|
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. |
| Measure Participants | 701 | 703 |
| Mean (Standard Deviation) [kg] |
2.9
(5.17)
|
1.7
(5.84)
|
Adverse Events
| Time Frame | From the first trial-related activity after the subject had signed the informed consent until the End of Trial (week 88) + 7 days follow-up period. Results are based on the safety analysis set (SAS), which comprised all participants who received at least one dose of trial product. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last days of randomised treatment or had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last date of randomised treatment. | |||
| Arm/Group Title | IDeg U200 | IGlar U300 | ||
| Arm/Group Description | Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | ||
All Cause Mortality |
||||
| IDeg U200 | IGlar U300 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/802 (0.9%) | 9/798 (1.1%) | ||
Serious Adverse Events |
||||
| IDeg U200 | IGlar U300 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 167/802 (20.8%) | 141/798 (17.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/802 (0.4%) | 3 | 4/798 (0.5%) | 4 |
| Iron deficiency anaemia | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Leukocytosis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Lymphadenopathy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Thrombocytopenia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Cardiac disorders | ||||
| Acute left ventricular failure | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Acute myocardial infarction | 6/802 (0.7%) | 6 | 2/798 (0.3%) | 2 |
| Angina pectoris | 3/802 (0.4%) | 3 | 2/798 (0.3%) | 2 |
| Angina unstable | 6/802 (0.7%) | 7 | 4/798 (0.5%) | 4 |
| Aortic valve stenosis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Arteriosclerosis coronary artery | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Atrial fibrillation | 9/802 (1.1%) | 9 | 5/798 (0.6%) | 5 |
| Atrial flutter | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Atrial tachycardia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Atrioventricular block second degree | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Bradycardia | 2/802 (0.2%) | 2 | 2/798 (0.3%) | 2 |
| Bundle branch block left | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Bundle branch block right | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Cardiac arrest | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Cardiac failure | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Cardiac failure acute | 1/802 (0.1%) | 1 | 2/798 (0.3%) | 2 |
| Cardiac failure congestive | 6/802 (0.7%) | 6 | 3/798 (0.4%) | 3 |
| Cardio-respiratory arrest | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Cardiogenic shock | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Cardiomyopathy | 2/802 (0.2%) | 3 | 0/798 (0%) | 0 |
| Coronary artery disease | 10/802 (1.2%) | 10 | 5/798 (0.6%) | 5 |
| Coronary artery occlusion | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Coronary artery stenosis | 2/802 (0.2%) | 2 | 1/798 (0.1%) | 1 |
| Hypertensive heart disease | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Intracardiac thrombus | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Myocardial infarction | 1/802 (0.1%) | 1 | 4/798 (0.5%) | 4 |
| Myocardial ischaemia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Sinus bradycardia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Sinus node dysfunction | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Sinus tachycardia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Ventricular hypokinesia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Vitello-intestinal duct remnant | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Ear and labyrinth disorders | ||||
| Vertigo | 3/802 (0.4%) | 3 | 0/798 (0%) | 0 |
| Vertigo positional | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Endocrine disorders | ||||
| Goitre | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Thyroid mass | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Eye disorders | ||||
| Blindness unilateral | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Diabetic retinopathy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Eye haematoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Macular degeneration | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Retinal detachment | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Retinal tear | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Retinopathy proliferative | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Rhegmatogenous retinal detachment | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Vitreous adhesions | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Vitreous haemorrhage | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Abdominal pain upper | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Diverticulum | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Diverticulum intestinal haemorrhagic | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Duodenal ulcer | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Duodenal ulcer haemorrhage | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Enteritis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Faecaloma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Gastritis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Gastritis erosive | 3/802 (0.4%) | 3 | 0/798 (0%) | 0 |
| Gastrointestinal angiodysplasia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/802 (0.1%) | 2 | 1/798 (0.1%) | 1 |
| Gastrooesophageal reflux disease | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Haematemesis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Haematochezia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hiatus hernia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Ileus | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Intestinal obstruction | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Pancreatic cyst | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Pancreatic duct dilatation | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Pancreatitis | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Pancreatitis necrotising | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Peptic ulcer perforation | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Small intestinal obstruction | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Volvulus | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| General disorders | ||||
| Asthenia | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Capsular contracture associated with breast implant | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Chest discomfort | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Chest pain | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Gait disturbance | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Multiple organ dysfunction syndrome | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Non-cardiac chest pain | 3/802 (0.4%) | 3 | 2/798 (0.3%) | 2 |
| Pyrexia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Sudden death | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Cholelithiasis | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Cirrhosis alcoholic | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Immune system disorders | ||||
| Anaphylactic reaction | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Sarcoidosis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Infections and infestations | ||||
| Abscess limb | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Appendicitis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Appendicitis perforated | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Bronchitis | 2/802 (0.2%) | 2 | 1/798 (0.1%) | 1 |
| Bronchitis bacterial | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Cellulitis | 2/802 (0.2%) | 2 | 3/798 (0.4%) | 3 |
| Chronic tonsillitis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Diabetic foot infection | 3/802 (0.4%) | 3 | 0/798 (0%) | 0 |
| Diverticulitis | 1/802 (0.1%) | 1 | 3/798 (0.4%) | 4 |
| Endocarditis staphylococcal | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Escherichia urinary tract infection | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Gangrene | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Gastroenteritis | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Gastroenteritis viral | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Helicobacter infection | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Hepatitis A | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hepatitis C | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Influenza | 3/802 (0.4%) | 3 | 1/798 (0.1%) | 1 |
| Joint abscess | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Localised infection | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Lyme disease | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Osteomyelitis | 2/802 (0.2%) | 3 | 0/798 (0%) | 0 |
| Osteomyelitis acute | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Otitis externa | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Otitis media | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Parametritis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Peritonitis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Pneumonia | 6/802 (0.7%) | 8 | 9/798 (1.1%) | 9 |
| Pneumonia fungal | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Post procedural cellulitis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Post procedural infection | 1/802 (0.1%) | 1 | 2/798 (0.3%) | 2 |
| Postoperative wound infection | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Pyelonephritis acute | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Sepsis | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Staphylococcal sepsis | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Streptococcal sepsis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Tooth abscess | 0/802 (0%) | 0 | 1/798 (0.1%) | 2 |
| Tuberculosis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Urinary tract infection | 2/802 (0.2%) | 2 | 5/798 (0.6%) | 5 |
| Urosepsis | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Vestibular neuronitis | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Viral infection | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Viral pharyngitis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Wound infection | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Wound infection staphylococcal | 1/802 (0.1%) | 3 | 0/798 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Acetabulum fracture | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Ankle fracture | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Arterial bypass occlusion | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Cartilage injury | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Cervical vertebral fracture | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Craniocerebral injury | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Drug administered in wrong device | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Fall | 3/802 (0.4%) | 3 | 3/798 (0.4%) | 3 |
| Femur fracture | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Gastrointestinal procedural complication | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hip fracture | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Incision site haemorrhage | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Intentional product misuse | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Jaw fracture | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Joint dislocation | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Joint injury | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Ligament rupture | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Post procedural haemorrhage | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Post procedural oedema | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Post procedural pulmonary embolism | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Post-traumatic pain | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Postoperative respiratory failure | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Procedural hypertension | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Procedural nausea | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Radiation oesophagitis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Road traffic accident | 1/802 (0.1%) | 1 | 2/798 (0.3%) | 2 |
| Spinal column injury | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Tibia fracture | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Toxicity to various agents | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Vascular graft thrombosis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Investigations | ||||
| Blood lactic acid increased | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Haemoglobin decreased | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Lipase increased | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Weight decreased | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/802 (0.4%) | 4 | 0/798 (0%) | 0 |
| Diabetes mellitus | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Diabetic ketoacidosis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hyperammonaemia | 0/802 (0%) | 0 | 1/798 (0.1%) | 2 |
| Hyperglycaemia | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Hyperkalaemia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hypoglycaemia | 8/802 (1%) | 8 | 19/798 (2.4%) | 21 |
| Hypokalaemia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hyponatraemia | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Metabolic acidosis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Back pain | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Cervical spinal stenosis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Intervertebral disc degeneration | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Intervertebral disc protrusion | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Lumbar spinal stenosis | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Musculoskeletal chest pain | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Myofascial pain syndrome | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Neuropathic arthropathy | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Osteoarthritis | 2/802 (0.2%) | 2 | 5/798 (0.6%) | 5 |
| Osteochondrosis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Osteopenia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Polymyalgia rheumatica | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Rhabdomyolysis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Rotator cuff syndrome | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Spinal osteoarthritis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Vertebral foraminal stenosis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma of colon | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Bladder transitional cell carcinoma | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Bladder transitional cell carcinoma stage I | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Breast cancer | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Colon adenoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Colorectal adenocarcinoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Diffuse large B-cell lymphoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Endometrial adenocarcinoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Hepatic cancer metastatic | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hepatocellular carcinoma | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Intraductal proliferative breast lesion | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Invasive ductal breast carcinoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Malignant melanoma | 1/802 (0.1%) | 2 | 0/798 (0%) | 0 |
| Malignant melanoma stage IV | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Neoplasm malignant | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Neuroendocrine carcinoma of the skin | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Oesophageal cancer metastatic | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Oesophageal squamous cell carcinoma stage 0 | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Pancreatic carcinoma stage IV | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Prostate cancer | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Prostate cancer metastatic | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Rectal cancer stage I | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Nervous system disorders | ||||
| Ataxia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Carotid artery disease | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Carotid artery occlusion | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Carotid artery stenosis | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Cerebral infarction | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Cerebrovascular disorder | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Cervical radiculopathy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Dementia Alzheimer's type | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Dizziness | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Dysarthria | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Embolic stroke | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Encephalopathy | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Haemorrhagic stroke | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Headache | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hypoaesthesia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hypoglycaemic coma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Hypoglycaemic unconsciousness | 3/802 (0.4%) | 4 | 9/798 (1.1%) | 11 |
| Hypotonia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Ischaemic stroke | 5/802 (0.6%) | 5 | 4/798 (0.5%) | 4 |
| Lacunar stroke | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Loss of consciousness | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Lumbar radiculopathy | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Metabolic encephalopathy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Presyncope | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Sciatica | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Seizure | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Subarachnoid haemorrhage | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Syncope | 3/802 (0.4%) | 3 | 2/798 (0.3%) | 2 |
| Transient ischaemic attack | 3/802 (0.4%) | 3 | 5/798 (0.6%) | 5 |
| Psychiatric disorders | ||||
| Alcohol withdrawal syndrome | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Confusional state | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Delirium | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Depression | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Suicidal ideation | 2/802 (0.2%) | 2 | 1/798 (0.1%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 4/802 (0.5%) | 4 | 8/798 (1%) | 9 |
| Bladder prolapse | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Nephrolithiasis | 2/802 (0.2%) | 2 | 2/798 (0.3%) | 2 |
| Polyuria | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Renal failure | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Renal mass | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Uterine prolapse | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute interstitial pneumonitis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Acute respiratory failure | 3/802 (0.4%) | 3 | 2/798 (0.3%) | 2 |
| Chronic obstructive pulmonary disease | 2/802 (0.2%) | 2 | 4/798 (0.5%) | 6 |
| Dyspnoea | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Emphysema | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Epistaxis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hypoxia | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Interstitial lung disease | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Pleural effusion | 1/802 (0.1%) | 2 | 1/798 (0.1%) | 1 |
| Pulmonary embolism | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Pulmonary mass | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Pulmonary oedema | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Respiratory failure | 0/802 (0%) | 0 | 2/798 (0.3%) | 2 |
| Sinus polyp | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Diabetic foot | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Erythema | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Hidradenitis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Skin ulcer | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Stasis dermatitis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Surgical and medical procedures | ||||
| Abdominal wall operation | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Cardiac ablation | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Cardiac pacemaker insertion | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Gastric bypass | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Gastroenterostomy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Intervertebral disc operation | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Large intestinal polypectomy | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Medical device removal | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Metabolic surgery | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Multiple drug therapy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Rehabilitation therapy | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 1/802 (0.1%) | 1 | 2/798 (0.3%) | 2 |
| Embolism venous | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Haematoma | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Hypertension | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Hypertensive crisis | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Hypertensive emergency | 2/802 (0.2%) | 2 | 0/798 (0%) | 0 |
| Internal haemorrhage | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Orthostatic hypotension | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Peripheral arterial occlusive disease | 1/802 (0.1%) | 1 | 1/798 (0.1%) | 1 |
| Peripheral artery occlusion | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Peripheral artery stenosis | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Peripheral artery thrombosis | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
| Peripheral vascular disorder | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Peripheral venous disease | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Steal syndrome | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Thrombophlebitis superficial | 0/802 (0%) | 0 | 1/798 (0.1%) | 1 |
| Varicose vein | 1/802 (0.1%) | 1 | 0/798 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| IDeg U200 | IGlar U300 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 496/802 (61.8%) | 476/798 (59.6%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 72/802 (9%) | 90 | 79/798 (9.9%) | 97 |
| Nausea | 43/802 (5.4%) | 53 | 50/798 (6.3%) | 56 |
| Vomiting | 26/802 (3.2%) | 30 | 40/798 (5%) | 52 |
| Infections and infestations | ||||
| Bronchitis | 48/802 (6%) | 54 | 46/798 (5.8%) | 46 |
| Influenza | 59/802 (7.4%) | 64 | 41/798 (5.1%) | 44 |
| Nasopharyngitis | 152/802 (19%) | 253 | 161/798 (20.2%) | 265 |
| Sinusitis | 45/802 (5.6%) | 58 | 40/798 (5%) | 53 |
| Upper respiratory tract infection | 145/802 (18.1%) | 199 | 122/798 (15.3%) | 177 |
| Urinary tract infection | 49/802 (6.1%) | 58 | 47/798 (5.9%) | 65 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 51/802 (6.4%) | 59 | 65/798 (8.1%) | 84 |
| Back pain | 59/802 (7.4%) | 73 | 62/798 (7.8%) | 70 |
| Pain in extremity | 45/802 (5.6%) | 49 | 43/798 (5.4%) | 49 |
| Nervous system disorders | ||||
| Headache | 51/802 (6.4%) | 61 | 62/798 (7.8%) | 70 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 48/802 (6%) | 60 | 46/798 (5.8%) | 53 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Results Point of Contact
| Name/Title | Clinical Reporting Anchor and Disclosure (1452) |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | (+1) 866-867-7178 |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT03078478
Other Study ID Numbers:
- NN1250-4252
- U1111-1184-8175
- 2016-002801-20
First Posted:
Mar 13, 2017
Last Update Posted:
Jan 11, 2022
Last Verified:
Jan 1, 2022