Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Africa, Asia and North America. The aim of this trial is to compare two insulin degludec (NN1250, SIBA) formulations with each other and with insulin glargine, all in combination with metformin in insulin naive subjects with type 2 diabetes.
Interventions
DRUGinsulin glargine
Treat-to-target dose titration scheme, s.c. injection.
DRUGinsulin degludec
Formulation D: Treat-to-target dose titration scheme, s.c. injection, once daily
DRUGmetformin
Tablets, 1500-2000 mg/day
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) * Insulin naïve type 2 diabetes subjects (as diagnosed clinically) for at least 3 months (no previous insulin treatment or previous short term insulin treatment maximeum 14 days within the last 3 months) * Treatment with one or two oral anti-diabetic drug (OADs): metformin, sulphonylurea (SU) (or other insulin secretagogue e.g. repaglinide, nateglinide), alpha-glucosidase inhibitors for at least 2 months at a stable maximally tolerated dose or at least half maximally allowed dose according to the summary of product characteristics (SPC) or locally approved PI * HbA1c 7.0-11.0 % (both inclusive) * Body Mass Index (BMI) 23-42 kg/m\^2 \[lb/in\^2 x 703\] (both inclusive)
Exclusion criteria
* Metformin contraindication according to local practice * Thiazolidinedione (TZD) treatment within previous three months prior to visit 1 * Any systemic treatment with products which in the Investigator's opinion could interfere with glucose or lipid metabolism (e.g. systemic corticosteroids) three months prior to randomisation * Subject has a clinically significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary, or haematological system (except for conditions associated with type 2 diabetes) that, in the opinion of the Investigator, may confound the results of the trial or pose additional risk in administering trial drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | Week 0, Week 16 | Change from baseline in HbA1c after 16 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Major and Minor Hypoglycaemic Episodes | Week 0 to Week 16 + 5 days follow up | Rate of major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. |
| Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Week 0 to Week 16 + 5 days follow up | Rate of nocturnal major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Episodes were defined as nocturnal if the time of onset was between 23:00 (included) and 05:59 (included). |
| Rate of Treatment Emergent Adverse Events (AEs) | Week 0 to Week 16 + 5 days follow up | Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. |
| Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | Week -4, Week 16 | Mean values at Week -4 and at Week 16 |
| Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | Week -4, Week 16 | Mean values at Week -4 and at Week 16 |
| Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | Week 16 | Mean of SMPG after 16 weeks of treatment. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, before bedtime, at 4 am and before breakfast. |
| Vital Signs: Diastolic Blood Pressure (BP) | Week 0, Week 16 | Mean values at baseline (Week 0) and at Week 16 |
| Vital Signs: Systolic Blood Pressure (BP) | Week 0, Week 16 | Mean values at baseline (Week 0) and at Week 16 |
| Vital Signs: Pulse | Week 0, Week 16 | Mean values at baseline (Week 0) and at Week 16 |
| Physical Examination | Week -4, Week 0, Week 8, Week 16 | Physical examination was performed at screening (Week -4), randomisation (Week 0) and after 8 and 16 weeks of treatment. If any new findings or deterioration in previous findings were observed during the trial, these were recorded as AEs and are therefore not presented separately as no analysis was performed. |
| Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Week -4, Week 16 | Mean values at Week -4 and at Week 16 |
Countries
Canada, India, South Africa, United States
Participant flow
Recruitment details
There were 28 sites: Canada (4), India (4), South Africa (3) and the United States of America (17).
Pre-assignment details
Subjects underwent a run-in period of 3 weeks; 2 weeks of up-titration period, where metformin was up-titrated to 1500 or 2000 mg/day, followed by 1 week of maintenance period. Subjects who tolerated 1500 or 2000 mg/day of metformin for a week and had a median fasting plasma glucose ≥ 7.5 mmol/L (135 mg/dL) were randomised.
Participants by arm
| Arm | Count |
|---|---|
| SIBA (D) Soluble Insulin Basal Analogue D (SIBA D, 900 nmol/mL \[1 dosing unit = 9 nmol\], insulin degludec; formulation D) was given subcutaneously once daily (OD) in the evening in combination with at least 1500 mg/day metformin (tablets) for 16 weeks. Insulin doses were initiated at 10 units (U)/day and individually adjusted. | 61 |
| SIBA (E) Soluble Insulin Basal Analogue E (SIBA E, 600 nmol/mL (1 dosing unit = 6 nmol), insulin degludec; formulation E) was given subcutaneously once daily (OD) in the evening in combination with at least 1500 mg/day metformin (tablets) for 16 weeks. Insulin doses were initiated at 10 U/day and individually adjusted. | 60 |
| SIBA (D) M, W, F Soluble Insulin Basal Analogue D (SIBA D, 900 nmol/mL (1 dosing unit = 9 nmol), insulin degludec; formulation D) was given subcutaneously thrice weekly (Monday \[M\], Wednesday\[W\], Friday\[F\]) in the evening in combination with at least 1500 mg/day metformin (tablets) for 16 weeks. Insulin doses were were initiated at 20 U/day and individually adjusted. | 62 |
| IGlar Insulin glargine (IGlar) was given subcutaneously once daily (OD) before bedtime in combination with at least 1500 mg/day metformin (tablets) for 16 weeks. Insulin doses were initiated at 10 U/day and individually adjusted. | 62 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Overall Study | Non-Compliance | 1 | 4 | 2 | 2 |
| Overall Study | Unclassified | 7 | 4 | 2 | 3 |
Baseline characteristics
| Characteristic | SIBA (D) | SIBA (E) | SIBA (D) M, W, F | IGlar | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 8.5 | 55.3 years STANDARD_DEVIATION 8.7 | 54.4 years STANDARD_DEVIATION 8.8 | 53.1 years STANDARD_DEVIATION 10.2 | 54.2 years STANDARD_DEVIATION 9.1 |
| Fasting plasma glucose (FPG) | 10.6 mmol/L STANDARD_DEVIATION 3.6 | 9.9 mmol/L STANDARD_DEVIATION 3.2 | 10.6 mmol/L STANDARD_DEVIATION 3.4 | 9.8 mmol/L STANDARD_DEVIATION 3.1 | 10.2 mmol/L STANDARD_DEVIATION 3.4 |
| Glycosylated haemoglobin (HbA1c) | 8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 | 8.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.2 | 8.8 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 | 8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 | 8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 |
| Sex: Female, Male Female | 22 Participants | 27 Participants | 34 Participants | 25 Participants | 108 Participants |
| Sex: Female, Male Male | 39 Participants | 33 Participants | 28 Participants | 37 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 57 | 16 / 59 | 19 / 62 | 23 / 61 |
| serious Total, serious adverse events | 1 / 57 | 0 / 59 | 1 / 62 | 0 / 61 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline in HbA1c after 16 weeks of treatment
Time frame: Week 0, Week 16
Population: The full analysis set (FAS) included all randomised subjects and missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIBA (D) | Change in Glycosylated Haemoglobin (HbA1c) | -1.26 percentage of glycosylated haemoglobin | Standard Deviation 1.11 |
| SIBA (E) | Change in Glycosylated Haemoglobin (HbA1c) | -1.28 percentage of glycosylated haemoglobin | Standard Deviation 1.11 |
| SIBA (D) M, W, F | Change in Glycosylated Haemoglobin (HbA1c) | -1.46 percentage of glycosylated haemoglobin | Standard Deviation 1.06 |
| IGlar | Change in Glycosylated Haemoglobin (HbA1c) | -1.49 percentage of glycosylated haemoglobin | Standard Deviation 1.12 |
Secondary
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)
Mean values at Week -4 and at Week 16
Time frame: Week -4, Week 16
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA (D) | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week -4, N=56, 59, 62, 60 | 34.6 IU/L | Standard Deviation 19.9 |
| SIBA (D) | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week 16, N=53, 53, 58, 56 | 25.7 IU/L | Standard Deviation 13.1 |
| SIBA (E) | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week 16, N=53, 53, 58, 56 | 24.7 IU/L | Standard Deviation 14.4 |
| SIBA (E) | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week -4, N=56, 59, 62, 60 | 29.2 IU/L | Standard Deviation 16.3 |
| SIBA (D) M, W, F | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week -4, N=56, 59, 62, 60 | 30.9 IU/L | Standard Deviation 16 |
| SIBA (D) M, W, F | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week 16, N=53, 53, 58, 56 | 24.3 IU/L | Standard Deviation 13 |
| IGlar | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week -4, N=56, 59, 62, 60 | 32.9 IU/L | Standard Deviation 22 |
| IGlar | Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | ALAT, Week 16, N=53, 53, 58, 56 | 30.0 IU/L | Standard Deviation 25.3 |
Secondary
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)
Mean values at Week -4 and at Week 16
Time frame: Week -4, Week 16
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA (D) | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week -4, N=56, 59, 62, 60 | 26.7 IU/L | Standard Deviation 13.6 |
| SIBA (D) | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week 16, N=53, 53, 58, 56 | 23.3 IU/L | Standard Deviation 10 |
| SIBA (E) | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week 16, N=53, 53, 58, 56 | 21.8 IU/L | Standard Deviation 7.7 |
| SIBA (E) | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week -4, N=56, 59, 62, 60 | 22.5 IU/L | Standard Deviation 9.9 |
| SIBA (D) M, W, F | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week -4, N=56, 59, 62, 60 | 23.9 IU/L | Standard Deviation 8.5 |
| SIBA (D) M, W, F | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week 16, N=53, 53, 58, 56 | 21.7 IU/L | Standard Deviation 7.7 |
| IGlar | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week -4, N=56, 59, 62, 60 | 24.2 IU/L | Standard Deviation 12.6 |
| IGlar | Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | ASAT, Week 16, N=53, 53, 58, 56 | 24.1 IU/L | Standard Deviation 13.7 |
Secondary
Laboratory Safety Parameters (Biochemistry): Serum Creatinine
Mean values at Week -4 and at Week 16
Time frame: Week -4, Week 16
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA (D) | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week -4, N=56, 59, 62, 60 | 74.5 umol/L | Standard Deviation 15.2 |
| SIBA (D) | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week 16, N=53, 53, 58, 56 | 76.1 umol/L | Standard Deviation 15.9 |
| SIBA (E) | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week 16, N=53, 53, 58, 56 | 76.6 umol/L | Standard Deviation 19.1 |
| SIBA (E) | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week -4, N=56, 59, 62, 60 | 75.4 umol/L | Standard Deviation 19 |
| SIBA (D) M, W, F | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week -4, N=56, 59, 62, 60 | 73.2 umol/L | Standard Deviation 16.1 |
| SIBA (D) M, W, F | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week 16, N=53, 53, 58, 56 | 71.5 umol/L | Standard Deviation 15.6 |
| IGlar | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week -4, N=56, 59, 62, 60 | 72.4 umol/L | Standard Deviation 13.9 |
| IGlar | Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Creatinine, Week 16, N=53, 53, 58, 56 | 74.2 umol/L | Standard Deviation 14.4 |
Secondary
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)
Mean of SMPG after 16 weeks of treatment. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, before bedtime, at 4 am and before breakfast.
Time frame: Week 16
Population: The full analysis set (FAS) included all randomised subjects and missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SIBA (D) | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.30 mmol/L | Standard Error 0.42 |
| SIBA (E) | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.55 mmol/L | Standard Error 0.42 |
| SIBA (D) M, W, F | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.45 mmol/L | Standard Error 0.42 |
| IGlar | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.42 mmol/L | Standard Error 0.41 |
Secondary
Physical Examination
Physical examination was performed at screening (Week -4), randomisation (Week 0) and after 8 and 16 weeks of treatment. If any new findings or deterioration in previous findings were observed during the trial, these were recorded as AEs and are therefore not presented separately as no analysis was performed.
Time frame: Week -4, Week 0, Week 8, Week 16
Secondary
Rate of Major and Minor Hypoglycaemic Episodes
Rate of major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time frame: Week 0 to Week 16 + 5 days follow up
Population: The full analysis set (FAS) included all randomised subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIBA (D) | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes/100 years of patient exposure |
| SIBA (D) | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 89 Episodes/100 years of patient exposure |
| SIBA (E) | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 60 Episodes/100 years of patient exposure |
| SIBA (E) | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 221 Episodes/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Major and Minor Hypoglycaemic Episodes | Major | 6 Episodes/100 years of patient exposure |
| IGlar | Rate of Major and Minor Hypoglycaemic Episodes | Minor | 113 Episodes/100 years of patient exposure |
| IGlar | Rate of Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes/100 years of patient exposure |
Secondary
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
Rate of nocturnal major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Episodes were defined as nocturnal if the time of onset was between 23:00 (included) and 05:59 (included).
Time frame: Week 0 to Week 16 + 5 days follow up
Population: The full analysis set (FAS) included all randomised subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIBA (D) | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes/100 years of patient exposure |
| SIBA (D) | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 6 Episodes/100 years of patient exposure |
| SIBA (E) | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 12 Episodes/100 years of patient exposure |
| SIBA (E) | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 6 Episodes/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 17 Episodes/100 years of patient exposure |
| IGlar | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Major | 0 Episodes/100 years of patient exposure |
| IGlar | Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Minor | 0 Episodes/100 years of patient exposure |
Secondary
Rate of Treatment Emergent Adverse Events (AEs)
Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.
Time frame: Week 0 to Week 16 + 5 days follow up
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIBA (D) | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 6 Events/100 years of patient exposure |
| SIBA (D) | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 468 Events/100 years of patient exposure |
| SIBA (D) | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 594 Events/100 years of patient exposure |
| SIBA (D) | Rate of Treatment Emergent Adverse Events (AEs) | Fatal | 0 Events/100 years of patient exposure |
| SIBA (D) | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 12 Events/100 years of patient exposure |
| SIBA (D) | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 114 Events/100 years of patient exposure |
| SIBA (E) | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 6 Events/100 years of patient exposure |
| SIBA (E) | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 323 Events/100 years of patient exposure |
| SIBA (E) | Rate of Treatment Emergent Adverse Events (AEs) | Fatal | 0 Events/100 years of patient exposure |
| SIBA (E) | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 0 Events/100 years of patient exposure |
| SIBA (E) | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 430 Events/100 years of patient exposure |
| SIBA (E) | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 102 Events/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 0 Events/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 110 Events/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 488 Events/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 5 Events/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 379 Events/100 years of patient exposure |
| SIBA (D) M, W, F | Rate of Treatment Emergent Adverse Events (AEs) | Fatal | 0 Events/100 years of patient exposure |
| IGlar | Rate of Treatment Emergent Adverse Events (AEs) | Fatal | 0 Events/100 years of patient exposure |
| IGlar | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs | 452 Events/100 years of patient exposure |
| IGlar | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs | 0 Events/100 years of patient exposure |
| IGlar | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (AEs) | 622 Events/100 years of patient exposure |
| IGlar | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs | 141 Events/100 years of patient exposure |
| IGlar | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs | 28 Events/100 years of patient exposure |
Secondary
Vital Signs: Diastolic Blood Pressure (BP)
Mean values at baseline (Week 0) and at Week 16
Time frame: Week 0, Week 16
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA (D) | Vital Signs: Diastolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 79 mmHg | Standard Deviation 8 |
| SIBA (D) | Vital Signs: Diastolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 81 mmHg | Standard Deviation 9 |
| SIBA (E) | Vital Signs: Diastolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 82 mmHg | Standard Deviation 9 |
| SIBA (E) | Vital Signs: Diastolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 82 mmHg | Standard Deviation 8 |
| SIBA (D) M, W, F | Vital Signs: Diastolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 78 mmHg | Standard Deviation 9 |
| SIBA (D) M, W, F | Vital Signs: Diastolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 80 mmHg | Standard Deviation 8 |
| IGlar | Vital Signs: Diastolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 77 mmHg | Standard Deviation 8 |
| IGlar | Vital Signs: Diastolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 79 mmHg | Standard Deviation 7 |
Secondary
Vital Signs: Pulse
Mean values at baseline (Week 0) and at Week 16
Time frame: Week 0, Week 16
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA (D) | Vital Signs: Pulse | Week 0 (Baseline), N=57, 59, 62, 61 | 79 beats/minute | Standard Deviation 10 |
| SIBA (D) | Vital Signs: Pulse | Week 16, N=55, 55, 60, 56 | 77 beats/minute | Standard Deviation 11 |
| SIBA (E) | Vital Signs: Pulse | Week 16, N=55, 55, 60, 56 | 78 beats/minute | Standard Deviation 10 |
| SIBA (E) | Vital Signs: Pulse | Week 0 (Baseline), N=57, 59, 62, 61 | 79 beats/minute | Standard Deviation 9 |
| SIBA (D) M, W, F | Vital Signs: Pulse | Week 0 (Baseline), N=57, 59, 62, 61 | 79 beats/minute | Standard Deviation 9 |
| SIBA (D) M, W, F | Vital Signs: Pulse | Week 16, N=55, 55, 60, 56 | 79 beats/minute | Standard Deviation 9 |
| IGlar | Vital Signs: Pulse | Week 0 (Baseline), N=57, 59, 62, 61 | 76 beats/minute | Standard Deviation 9 |
| IGlar | Vital Signs: Pulse | Week 16, N=55, 55, 60, 56 | 74 beats/minute | Standard Deviation 9 |
Secondary
Vital Signs: Systolic Blood Pressure (BP)
Mean values at baseline (Week 0) and at Week 16
Time frame: Week 0, Week 16
Population: The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIBA (D) | Vital Signs: Systolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 129 mmHg | Standard Deviation 14 |
| SIBA (D) | Vital Signs: Systolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 126 mmHg | Standard Deviation 14 |
| SIBA (E) | Vital Signs: Systolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 131 mmHg | Standard Deviation 15 |
| SIBA (E) | Vital Signs: Systolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 131 mmHg | Standard Deviation 13 |
| SIBA (D) M, W, F | Vital Signs: Systolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 129 mmHg | Standard Deviation 15 |
| SIBA (D) M, W, F | Vital Signs: Systolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 126 mmHg | Standard Deviation 16 |
| IGlar | Vital Signs: Systolic Blood Pressure (BP) | Week 0 (Baseline), N=57, 59, 62, 61 | 127 mmHg | Standard Deviation 14 |
| IGlar | Vital Signs: Systolic Blood Pressure (BP) | Week 16, N=55, 55, 60, 56 | 128 mmHg | Standard Deviation 13 |