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A Research Study to Compare Insulin 287 Once a Week to Insulin Glargine (100 Units/mL) Once a Day in People With Type 2 Diabetes.

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ClinicalTrials.gov Identifier: NCT03751657
Recruitment Status : Completed
First Posted : November 23, 2018
Results First Posted : February 1, 2021
Last Update Posted : April 2, 2021
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Insulin icodec
Drug: Placebo (insulin 287)
Drug: Metformin
Drug: Dipeptidyl peptidase-4 inhibitors
Drug: Insulin glargine
Drug: Placebo (insulin glargine)
Enrollment 247
Recruitment Details The trial was conducted at 49 sites in Canada (7), Czech Republic (9), Greece (5), Poland (6), Slovakia (6),Slovenia (2) and United States (14). One site in the United States screened, but didn't randomise any participant.
Pre-assignment Details Insulin-naïve participants with Type 2 Diabetes (T2D) inadequately controlled on metformin with or without dipeptidyl peptidase 4 inhibitor (DPP4i) were randomized in a 1:1 manner to receive once weekly insulin 287 and once daily placebo or once weekly placebo and once daily insulin glargine subcutaneously (s.c).
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Period Title: Overall Study
Started 125 122
Completed 122 119
Not Completed 3 3
Reason Not Completed
Physician Decision             0             1
Withdrawal by Subject             1             1
Lost to Follow-up             2             1
Arm/Group Title Insulin 287 Insulin Glargine Total
Hide Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Total of all reporting groups
Overall Number of Baseline Participants 125 122 247
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomised participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 125 participants 122 participants 247 participants
59.7  (8.2) 59.4  (9.5) 59.6  (8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 122 participants 247 participants
Female
55
  44.0%
53
  43.4%
108
  43.7%
Male
70
  56.0%
69
  56.6%
139
  56.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 122 participants 247 participants
Hispanic or Latino
10
   8.0%
6
   4.9%
16
   6.5%
Not Hispanic or Latino
115
  92.0%
116
  95.1%
231
  93.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 122 participants 247 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
8
   6.4%
4
   3.3%
12
   4.9%
Native Hawaiian or Other Pacific Islander
1
   0.8%
0
   0.0%
1
   0.4%
Black or African American
7
   5.6%
5
   4.1%
12
   4.9%
White
109
  87.2%
113
  92.6%
222
  89.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
Hide Description Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 122 120
Least Squares Mean (Standard Error)
Unit of Measure: Percentage point of HbA1c
-1.33  (0.07) -1.15  (0.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin 287, Insulin Glargine
Comments The response and change from baseline in response after 26 weeks are analysed using a linear mixed model for repeated measures (MMRM) with an unstructured covariance matrix and treatment, region, use of DPP-4 inhibitor and visit as fixed factors, and baseline response as covariate. Furthermore, the model includes the interaction between visit and all explanatory variables.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0818
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.38 to 0.02
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change in HbA1c [Millimoles/Mole (mmol/Mol)]
Hide Description Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 122 120
Least Squares Mean (Standard Error)
Unit of Measure: mmol/mol
-14.51  (0.79) -12.54  (0.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin 287, Insulin Glargine
Comments The response and change from baseline in response after 26 weeks are analysed using a linear MMRM with an unstructured covariance matrix and treatment, region, use of DPP-4 inhibitor and visit as fixed factors, and baseline response as covariate.Furthermore, the model includes the interaction between visit and all explanatory variables.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0818
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.97
Confidence Interval (2-Sided) 95%
-4.19 to 0.25
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Fasting Plasma Glucose
Hide Description Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 121 116
Least Squares Mean (Standard Error)
Unit of Measure: mmol/l
-3.20  (0.16) -2.99  (0.16)
4.Secondary Outcome
Title 9-point Profile (Individual SMPG Values)
Hide Description Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame Week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 125 122
Least Squares Mean (Standard Error)
Unit of Measure: mmol/l
Before breakfast Number Analyzed 109 participants 108 participants
5.70  (0.19) 6.19  (0.19)
90 minutes after start of breakfast Number Analyzed 103 participants 107 participants
7.90  (0.19) 8.51  (0.19)
Before lunch Number Analyzed 109 participants 106 participants
6.09  (0.19) 6.19  (0.19)
90 minutes after start of lunch Number Analyzed 107 participants 106 participants
7.83  (0.19) 8.50  (0.19)
Before main evening meal Number Analyzed 108 participants 107 participants
6.55  (0.19) 6.96  (0.19)
90 minutes after the start of main evening meal Number Analyzed 106 participants 104 participants
8.01  (0.19) 8.47  (0.19)
Before bedtime Number Analyzed 104 participants 105 participants
7.35  (0.19) 7.87  (0.19)
At 4:00 a.m. Number Analyzed 101 participants 102 participants
5.72  (0.19) 5.98  (0.19)
Before breakfast the following day Number Analyzed 109 participants 108 participants
5.74  (0.19) 6.05  (0.19)
5.Secondary Outcome
Title Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
Hide Description Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 112 111
Least Squares Mean (Standard Error)
Unit of Measure: mmol/l
-2.70  (0.12) -2.26  (0.12)
6.Secondary Outcome
Title Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
Hide Description Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame Week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 112 111
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/l
0.92
(0.84 to 1.01)
0.94
(0.86 to 1.03)
7.Secondary Outcome
Title Fasting C-peptide
Hide Description Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame At week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 115 112
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Nanomoles per liter (nmol/l)
0.44
(0.40 to 0.48)
0.47
(0.43 to 0.51)
8.Secondary Outcome
Title Change in Body Weight
Hide Description Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 122 119
Least Squares Mean (Standard Error)
Unit of Measure: Kilogram
1.49  (0.36) 1.56  (0.37)
9.Secondary Outcome
Title Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
Hide Description Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Time Frame week 25 (Visit 27) and 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 120 117
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units of Insulin
229.06
(205.08 to 255.83)
284.05
(253.97 to 317.71)
10.Secondary Outcome
Title Number of Treatment Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.
Time Frame From baseline (Visit 2) to week 31 (Visit 30)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAS) included all participants who received at least one dose of the investigational product or comparator.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 125 122
Measure Type: Number
Unit of Measure: Events
229 158
11.Secondary Outcome
Title Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
Hide Description Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and less than (<) 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of the investigational product or comparator.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 125 122
Measure Type: Number
Unit of Measure: Episodes
358 145
12.Secondary Outcome
Title Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
Hide Description Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of the investigational product or comparator.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 125 122
Measure Type: Number
Unit of Measure: Episodes
38 31
13.Secondary Outcome
Title Number of Severe Hypoglycaemic Episodes (Level 3)
Hide Description Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.
Time Frame From baseline (Visit 2) to week 26 (Visit 28)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of the investigational product or comparator.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 125 122
Measure Type: Number
Unit of Measure: Episodes
1 0
14.Secondary Outcome
Title Change in Anti-insulin 287 Antibody Titres
Hide Description Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
Time Frame From baseline (Visit 2) to week 31 (Visit 30)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of the investigational product or comparator. Overall number of participants analysed = Number of participants contributing to the analysis.
Arm/Group Title Insulin 287
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 119
Mean (Standard Deviation)
Unit of Measure: Antibody titers
979.9  (3177.9)
15.Secondary Outcome
Title Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
Hide Description Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
Time Frame From baseline (Visit 2) to week 31 (Visit 30)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of the investigational product or comparator.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 125 122
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 Number Analyzed 125 participants 122 participants
Negative
0
   0.0%
1
   0.8%
Positive
0
   0.0%
0
   0.0%
Unknown
1
   0.8%
9
   7.4%
Not Applicable
124
  99.2%
112
  91.8%
Week 31 Number Analyzed 120 participants 115 participants
Negative
9
   7.5%
0
   0.0%
Positive
86
  71.7%
26
  22.6%
Unknown
0
   0.0%
0
   0.0%
Not Applicable
25
  20.8%
89
  77.4%
16.Secondary Outcome
Title Change in Anti-insulin 287 Antibody Level
Hide Description Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.
Time Frame From baseline (Visit 2) to week 31 (Visit 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels.
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description:
Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Week 0 to Week 31 Results are based on the SAS which included all participants who received at least one dose of Insulin 287 or Insulin glargine. The SAS included all participants who received at least one dose of the investigational product or comparator.
Adverse Event Reporting Description A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.
 
Arm/Group Title Insulin 287 Insulin Glargine
Hide Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
All-Cause Mortality
Insulin 287 Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/125 (0.00%)      0/122 (0.00%)    
Hide Serious Adverse Events
Insulin 287 Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/125 (1.60%)      3/122 (2.46%)    
Blood and lymphatic system disorders     
Anaemia  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Leukocytosis  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Cardiac disorders     
Coronary artery disease  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Tachycardia  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Gastrointestinal disorders     
Melaena  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Hepatobiliary disorders     
Hepatosplenomegaly  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Infections and infestations     
Emphysematous pyelonephritis  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Injury, poisoning and procedural complications     
Lower limb fracture  1  1/125 (0.80%)  1 0/122 (0.00%)  0
Metabolism and nutrition disorders     
Hypomagnesaemia  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Nervous system disorders     
Cerebral disorder  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Renal and urinary disorders     
Acute kidney injury  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Azotaemia  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Hydronephrosis  1  0/125 (0.00%)  0 1/122 (0.82%)  1
Reproductive system and breast disorders     
Metrorrhagia  1  1/125 (0.80%)  1 0/122 (0.00%)  0
1
Term from vocabulary, MedDRA 22
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin 287 Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/125 (20.80%)      16/122 (13.11%)    
Infections and infestations     
Nasopharyngitis  1  10/125 (8.00%)  12 8/122 (6.56%)  9
Upper respiratory tract infection  1  7/125 (5.60%)  7 6/122 (4.92%)  8
Nervous system disorders     
Headache  1  14/125 (11.20%)  31 3/122 (2.46%)  3
1
Term from vocabulary, MedDRA 22
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Clinical Reporting Anchor and Disclosure (1452)
Organization: Novo Nordisk A/S
Phone: (+1)866-867-7178
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03751657    
Other Study ID Numbers: NN1436-4383
U1111-1208-4124 ( Other Identifier: World Health Organization (WHO) )
2018-000322-63 ( EudraCT Number )
First Submitted: November 16, 2018
First Posted: November 23, 2018
Results First Submitted: December 11, 2020
Results First Posted: February 1, 2021
Last Update Posted: April 2, 2021