Diabetes Mellitus, Type 2
Conditions
Brief summary
The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. The study participants will either get insulin 287 or insulin glargine (100 units/mL) - which treatment the participants get is decided by chance. The participants will need to inject their selves every day about the same time. Once a week the participant will need to take 1 extra injection on the same day of the week. The participants will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter using a finger prick, 2) write down different information in a paper diary daily and return this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2 weeks 5 times during the study.
Interventions
DRUGInsulin icodec
Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL)
DRUGPlacebo (insulin 287)
Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.
DRUGMetformin
Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.
Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.
DRUGInsulin glargine
Insulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL).
Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening * HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory * Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record) OR Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records) * Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes * Body mass index (BMI) less than or equal to 40.0 kg/m\^2
Exclusion criteria
* Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation * Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation * Presently classified as being in New York Heart Association (NYHA) Class IV * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes * Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids) * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)] | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| Change in HbA1c [Millimoles/Mole (mmol/Mol)] | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time). | Week 26 (Visit 28) | 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. |
| Fasting C-peptide | At week 26 (Visit 28) | 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. |
| Change in Body Weight | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine | week 25 (Visit 27) and 26 (Visit 28) | 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. |
| Number of Treatment Emergent Adverse Events (TEAEs) | From baseline (Visit 2) to week 31 (Visit 30) | 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. |
| Change in Fasting Plasma Glucose | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| 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) | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| Number of Severe Hypoglycaemic Episodes (Level 3) | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| Change in Anti-insulin 287 Antibody Titres | From baseline (Visit 2) to week 31 (Visit 30) | 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. |
| Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | From baseline (Visit 2) to week 31 (Visit 30) | 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. |
| Change in Anti-insulin 287 Antibody Level | From baseline (Visit 2) to week 31 (Visit 30) | 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. |
| Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter) | From baseline (Visit 2) to week 26 (Visit 28) | 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. |
| 9-point Profile (Individual SMPG Values) | Week 26 (Visit 28) | 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. |
Countries
Canada, Czechia, Greece, Poland, Slovakia, Slovenia, United States
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| Insulin 287 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. | 125 |
| Insulin Glargine 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. | 122 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Insulin Glargine | Total | Insulin 287 |
|---|---|---|---|
| Age, Continuous | 59.4 Years STANDARD_DEVIATION 9.5 | 59.6 Years STANDARD_DEVIATION 8.9 | 59.7 Years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 16 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 116 Participants | 231 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 12 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 113 Participants | 222 Participants | 109 Participants |
| Sex: Female, Male Female | 53 Participants | 108 Participants | 55 Participants |
| Sex: Female, Male Male | 69 Participants | 139 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 125 | 0 / 122 |
| other Total, other adverse events | 26 / 125 | 16 / 122 |
| serious Total, serious adverse events | 2 / 125 | 3 / 122 |
Outcome results
Primary
Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin 287 | Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)] | -1.33 Percentage point of HbA1c | Standard Error 0.07 |
| Insulin Glargine | Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)] | -1.15 Percentage point of HbA1c | Standard Error 0.07 |
Comparison: 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.p-value: 0.081895% CI: [-0.38, 0.02]Mixed Models Analysis
Primary
Change in HbA1c [Millimoles/Mole (mmol/Mol)]
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin 287 | Change in HbA1c [Millimoles/Mole (mmol/Mol)] | -14.51 mmol/mol | Standard Error 0.79 |
| Insulin Glargine | Change in HbA1c [Millimoles/Mole (mmol/Mol)] | -12.54 mmol/mol | Standard Error 0.8 |
Comparison: 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.p-value: 0.081895% CI: [-4.19, 0.25]Mixed Models Analysis
Secondary
9-point Profile (Individual SMPG Values)
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin 287 | 9-point Profile (Individual SMPG Values) | 90 minutes after start of breakfast | 7.90 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | 90 minutes after the start of main evening meal | 8.01 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | Before breakfast | 5.70 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | Before bedtime | 7.35 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | Before lunch | 6.09 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | At 4:00 a.m. | 5.72 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | 90 minutes after start of lunch | 7.83 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | Before breakfast the following day | 5.74 mmol/l | Standard Error 0.19 |
| Insulin 287 | 9-point Profile (Individual SMPG Values) | Before main evening meal | 6.55 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | Before breakfast the following day | 6.05 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | Before breakfast | 6.19 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | 90 minutes after start of breakfast | 8.51 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | 90 minutes after start of lunch | 8.50 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | Before main evening meal | 6.96 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | 90 minutes after the start of main evening meal | 8.47 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | Before bedtime | 7.87 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | At 4:00 a.m. | 5.98 mmol/l | Standard Error 0.19 |
| Insulin Glargine | 9-point Profile (Individual SMPG Values) | Before lunch | 6.19 mmol/l | Standard Error 0.19 |
Secondary
Change in Anti-insulin 287 Antibody Level
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)
Population: 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.
Secondary
Change in Anti-insulin 287 Antibody Titres
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin 287 | Change in Anti-insulin 287 Antibody Titres | 979.9 Antibody titers | Standard Deviation 3177.9 |
Secondary
Change in Body Weight
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin 287 | Change in Body Weight | 1.49 Kilogram | Standard Error 0.36 |
| Insulin Glargine | Change in Body Weight | 1.56 Kilogram | Standard Error 0.37 |
Secondary
Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
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)
Population: SAS included all participants who received at least one dose of the investigational product or comparator.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Negative | 0 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Unknown | 1 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Positive | 86 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Unknown | 0 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Positive | 0 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Not Applicable | 124 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Negative | 9 Participants |
| Insulin 287 | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Not Applicable | 25 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Not Applicable | 89 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Negative | 1 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Positive | 0 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Not Applicable | 112 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Negative | 0 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 0 | Unknown | 9 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Positive | 26 Participants |
| Insulin Glargine | Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) | Week 31 | Unknown | 0 Participants |
Secondary
Change in Fasting Plasma Glucose
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin 287 | Change in Fasting Plasma Glucose | -3.20 mmol/l | Standard Error 0.16 |
| Insulin Glargine | Change in Fasting Plasma Glucose | -2.99 mmol/l | Standard Error 0.16 |
Secondary
Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin 287 | Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time | -2.70 mmol/l | Standard Error 0.12 |
| Insulin Glargine | Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time | -2.26 mmol/l | Standard Error 0.12 |
Secondary
Fasting C-peptide
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin 287 | Fasting C-peptide | 0.44 Nanomoles per liter (nmol/l) |
| Insulin Glargine | Fasting C-peptide | 0.47 Nanomoles per liter (nmol/l) |
Secondary
Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin 287 | Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time). | 0.92 mmol/l |
| Insulin Glargine | Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time). | 0.94 mmol/l |
Secondary
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)
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)
Population: SAS included all participants who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin 287 | 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) | 38 Episodes |
| Insulin Glargine | 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) | 31 Episodes |
Secondary
Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
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)
Population: SAS included all participants who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin 287 | Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter) | 358 Episodes |
| Insulin Glargine | Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter) | 145 Episodes |
Secondary
Number of Severe Hypoglycaemic Episodes (Level 3)
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)
Population: SAS included all participants who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin 287 | Number of Severe Hypoglycaemic Episodes (Level 3) | 1 Episodes |
| Insulin Glargine | Number of Severe Hypoglycaemic Episodes (Level 3) | 0 Episodes |
Secondary
Number of Treatment Emergent Adverse Events (TEAEs)
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)
Population: The safety analysis set (SAS) included all participants who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin 287 | Number of Treatment Emergent Adverse Events (TEAEs) | 229 Events |
| Insulin Glargine | Number of Treatment Emergent Adverse Events (TEAEs) | 158 Events |
Secondary
Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
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)
Population: FAS included all randomised participants. Number of Participants Analyzed = Number of participants contributing to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Insulin 287 | Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine | 229.06 Units of Insulin |
| Insulin Glargine | Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine | 284.05 Units of Insulin |