Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus, Canakinumab, ACZ885, IL-1B antagonist, metformin, glycemic control, insulin sensitivity
Brief summary
The purpose of this study was to evaluate, in patients with Type 2 Diabetes Mellitus, whether Canakinumab can lower Glycosylated hemoglobin / hemoglobin A1c (HbA1c) and/or peak glucose levels in response to an oral glucose tolerance test (OGTT).
Interventions
DRUGCanakinumab
Canakinumab given as single dose IV injection of 0.03 mg/kg, or single dose IV infusion at doses of 0.1 mg/kg 0.3 mg/kg, 1.5 mg/kg or 10 mg/kg.
DRUGPlacebo
Placebo to Canakinumab given as single dose IV injection of 0.03 mg/kg, or single dose IV infusion at doses of 0.1 mg/kg 0.3 mg/kg, 1.5 mg/kg or 10 mg/kg.
DRUGMetformin
Participants continued on their stable daily dose of metformin throughout the study
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients aged 18 to 70 years, with type 2 diabetes mellitus (non-insulin dependent diabetes) for at least 6 months prior to study start * HbA1c between 7.0 and 9.5% * On stable dose metformin monotherapy * Stable body weight
Exclusion criteria
* Poorly controlled type 2 diabetes (very low or very high blood sugar levels, or other indicators of poor control) * Acute infections prior to dosing * Patients with type 1 diabetes (insulin-dependent diabetes) * Taking diabetes medication (other than metformin) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Baseline, Day 28, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing) | Blood was drawn after an overnight fast to measure plasma HbA1c levels. End of Study is defined as the last Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Baseline, Day 28, Day 84 | Mean Change in Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Glucose levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Baseline, Day 28, Day 84 | Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Baseline, Day 28, Day 84 | Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Glucagon levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Baseline, Day 28, Day 84 | Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin and proinsulin levels were measured. The insulin/proinsulin level was calculated by dividing the insulin level by the proinsulin level. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28, Day 84 | Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Mean ISR relative to glucose over 0-4 hours was calculated as follows: Mean ISR relative to glucose = mean ISR / (glucose AUC/time interval). The mean ISR was computed as an AUC (area under the curve) using the linear trapezoidal rule divided by the corresponding time interval. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28, Day 84 | Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. The mean ISR over 0 - 4 hours was computed as an AUC (area under the curve) using the linear trapezoidal rule divided by the corresponding time interval. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28, Day 84 | Insulin sensitivity index (ISI) = 10000 / \[fasting insulin (μIU/mL) x fasting glucose (mg/dL) x mean 2 hour insulin(μIU/mL) x mean 2 hour glucose (mg/dL)\]1/2 where mean 2 hour insulin (or glucose) was defined as the insulin (or glucose)AUC(0-2 hr) divided by the time period (2 hr). In normal subjects the mean score ± SE is 0.366 ± 0.029. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data. |
| Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Baseline, Day 28, Day 84 | Blood samples were drawn after an overnight fast and standard OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. C-peptide levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Baseline, Day 28, Day 84 | Mean Change in Peak Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Change from baseline assessed at Day 28 and 84. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Mean Change From Baseline in Peak Plasma Fructosamine Level | Baseline, Day 14, Day 28, Day 56, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing) | Blood was drawn to measure change in plasma Fructosamine Level, from baseline to Day 14, 28, 56, 84, 126 and End of Study ( defined as the final available post-randomization assessment up to the last regularly scheduled visit at Day 168 \[+/- 5\]). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
| Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Baseline, Day 28, Day 84 | Insulin Resistance is measured via the Homeostatic Model Assessment (HOMA-IR) using a computer to model insulin sensitivity. Insulin Sensitivity (HOMA-%S), where 100% is normal, is the reciprocal of insulin resistance (100/S%). HOMA IR = \[fasting insulin (μU/mL)\] x \[fasting plasma glucose (mmol/L)\] / 22.5 where fasting insulin (or glucose) was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data. |
| β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Baseline, Day 28, Day 84 | β cell function is measured by the Homeostatic Model Assessment(HOMA-β) using a computer to model β cell function and insulin sensitivity . β cell function is related to Insulin Sensitivity (HOMA-%S) and is the reciprocal of insulin resistance (100/S%). HOMA β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\] where fasting insulin (or glucose) was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data. |
| Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Baseline to End of Study (56[+/-2] and 168 [+/- 5] days after dosing for Cohort 1 and Cohorts 2-4, respectively) | An adverse event is any unwanted event, whether related to study drug or not occurring during the study period. A Serious Adverse Event (SAE) is an event resulting in death, requiring or prolonging hospitalization, a congenital anomaly or other important medical event. AEs and SAEs were recorded at each visit. |
| Insulinogenic Index, 0 - 30 Minutes | Day 28, Day 84 | Insulinogenic index (0-30 min) * \[Change in insulin (0-30 min) (μIU/mL)\] / \[Change in glucose (0-30 min) (mg/dL)\] * \[insulin (μIU/mL) at 30 min - insulin (μIU/mL) at 0 min\] / \[glucose (mg/dL) at 30 min - glucose (mg/dL) at 0 min), where insulin (or glucose) at 0 min was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.. |
| Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Baseline, Day 28, Day 84 | Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed. |
Countries
Germany, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Canakinumab Infusion 0.3 mg/kg Single dose intravenous (IV) infusion of canakinumab 0.3 mg/kg | 10 |
| Cohort 1: Placebo to Canakinumab 0.3 mg/kg Single dose IV infusion of placebo to Canakinumab 0.3 mg/kg | 5 |
| Cohort 2: Canakinumab Infusion 10 mg/kg Single dose IV infusion of Canakinumab 10 mg/kg | 45 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg Single dose IV infusion of Placebo to Canakinumab 10 mg/kg | 45 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg Single dose IV infusion Canakinumab 0.1 mg/kg | 25 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg Single dose IV infusion of Canakinumab 0.3 mg/kg | 24 |
| Cohort 3 : Canakinumab Infusion 1.5 mg/kg Single dose IV infusion of canakinumab 1.5 mg/kg | 23 |
| Cohort 3: Placebo Infusion Single dose IV infusion of Placebo | 24 |
| Cohort 4 : Canakinumab Injection 0.03 mg/kg Single dose IV injection of Canakinumab 0.03 mg/kg | 20 |
| Cohort 4: Placebo to Canakinumab 0.03 mg/kg Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg | 10 |
| Total | 231 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal Laboratory Values | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Administrative problems | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Canakinumab Infusion 0.3 mg/kg | Cohort 1: Placebo to Canakinumab 0.3 mg/kg | Cohort 2: Canakinumab Infusion 10 mg/kg | Cohort 2: Placebo to Canakinumab 10 mg/kg | Cohort 3: Canakinumab Infusion 0.1 mg/kg | Cohort 3: Canakinumab Infusion 0.3 mg/kg | Cohort 3 : Canakinumab Infusion 1.5 mg/kg | Cohort 3: Placebo Infusion | Cohort 4 : Canakinumab Injection 0.03 mg/kg | Cohort 4: Placebo to Canakinumab 0.03 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 53 years STANDARD_DEVIATION 7.6 | 52 years STANDARD_DEVIATION 6.96 | 57.1 years STANDARD_DEVIATION 9.38 | 57.5 years STANDARD_DEVIATION 7.95 | 53.9 years STANDARD_DEVIATION 7.58 | 55 years STANDARD_DEVIATION 8.45 | 55.1 years STANDARD_DEVIATION 9.28 | 54.7 years STANDARD_DEVIATION 6.41 | 53.9 years STANDARD_DEVIATION 9.07 | 56 years STANDARD_DEVIATION 8.67 | 54.6 years STANDARD_DEVIATION 8.08 |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 21 Participants | 14 Participants | 13 Participants | 17 Participants | 14 Participants | 16 Participants | 10 Participants | 2 Participants | 116 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 24 Participants | 31 Participants | 12 Participants | 7 Participants | 9 Participants | 8 Participants | 10 Participants | 8 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 10 | 2 / 5 | 9 / 45 | 6 / 45 | 4 / 25 | 4 / 24 | 2 / 23 | 6 / 24 | 10 / 20 | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 | 1 / 45 | 2 / 45 | 0 / 25 | 0 / 24 | 0 / 23 | 0 / 24 | 0 / 20 | 0 / 10 |
Outcome results
Primary
Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT )
Mean Change in Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Glucose levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | -4.7 mmol*h/L | Standard Error 0.98 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | -2.5 mmol*h/L | Standard Error 1.26 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | -0.9 mmol*h/L | Standard Error 0.96 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | 1.7 mmol*h/L | Standard Error 1.24 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | 1.6 mmol*h/L | Standard Error 1.66 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | 2.6 mmol*h/L | Standard Error 1.72 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | -0.9 mmol*h/L | Standard Error 1.65 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | -2.8 mmol*h/L | Standard Error 1.71 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | -2.8 mmol*h/L | Standard Error 1.73 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | -1.2 mmol*h/L | Standard Error 1.79 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | -2.3 mmol*h/L | Standard Error 1.41 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | -2.8 mmol*h/L | Standard Error 1.46 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 84 | -2.5 mmol*h/L | Standard Error 1.88 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT ) | Day 28 | -0.5 mmol*h/L | Standard Error 1.81 |
Primary
Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
Blood was drawn after an overnight fast to measure plasma HbA1c levels. End of Study is defined as the last Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.38 percent | Standard Error 0.057 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | -0.46 percent | Standard Error 0.102 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.29 percent | Standard Error 0.101 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | -0.26 percent | Standard Error 0.121 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | -0.15 percent | Standard Error 0.105 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.26 percent | Standard Error 0.057 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | -0.01 percent | Standard Error 0.118 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.02 percent | Standard Error 0.101 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.25 percent | Standard Error 0.065 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | -0.04 percent | Standard Error 0.118 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.08 percent | Standard Error 0.126 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | 0.27 percent | Standard Error 0.162 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.30 percent | Standard Error 0.069 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.22 percent | Standard Error 0.123 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | -0.18 percent | Standard Error 0.178 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | -0.43 percent | Standard Error 0.124 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | -0.59 percent | Standard Error 0.124 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | -0.39 percent | Standard Error 0.173 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.47 percent | Standard Error 0.068 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.40 percent | Standard Error 0.12 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | 0.32 percent | Standard Error 0.103 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | -0.12 percent | Standard Error 0.138 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.19 percent | Standard Error 0.101 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.24 percent | Standard Error 0.056 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | End of Study (n= 43, 45, 24, 20, 21, 33, 20) | 0.32 percent | Standard Error 0.177 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 84 (n= 44, 44, 25, 23, 23, 33, 20) | -0.15 percent | Standard Error 0.132 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 126 (n= 45, 45, 21, 22, 23, 33, 20) | -0.11 percent | Standard Error 0.128 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c) | Day 28 (n= 45, 45, 25, 23, 23, 34, 20) | -0.13 percent | Standard Error 0.073 |
Secondary
Insulinogenic Index, 0 - 30 Minutes
Insulinogenic index (0-30 min) * \[Change in insulin (0-30 min) (μIU/mL)\] / \[Change in glucose (0-30 min) (mg/dL)\] * \[insulin (μIU/mL) at 30 min - insulin (μIU/mL) at 0 min\] / \[glucose (mg/dL) at 30 min - glucose (mg/dL) at 0 min), where insulin (or glucose) at 0 min was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data..
Time frame: Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.174 units on a scale | Standard Error 0.0754 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.157 units on a scale | Standard Error 0.0987 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.140 units on a scale | Standard Error 0.0754 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.134 units on a scale | Standard Error 0.0976 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.090 units on a scale | Standard Error 0.1995 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.092 units on a scale | Standard Error 0.1928 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.105 units on a scale | Standard Error 0.1735 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.098 units on a scale | Standard Error 0.1651 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.139 units on a scale | Standard Error 0.1991 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.111 units on a scale | Standard Error 0.1777 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.102 units on a scale | Standard Error 0.1464 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.124 units on a scale | Standard Error 0.1445 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 28 (n=44, 44, 17, 23 17, 32, 18) | 0.137 units on a scale | Standard Error 0.1942 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Insulinogenic Index, 0 - 30 Minutes | Day 84 (n=43, 44, 17, 24, 20, 31, 17) | 0.121 units on a scale | Standard Error 0.1937 |
Secondary
Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR)
Insulin Resistance is measured via the Homeostatic Model Assessment (HOMA-IR) using a computer to model insulin sensitivity. Insulin Sensitivity (HOMA-%S), where 100% is normal, is the reciprocal of insulin resistance (100/S%). HOMA IR = \[fasting insulin (μU/mL)\] x \[fasting plasma glucose (mmol/L)\] / 22.5 where fasting insulin (or glucose) was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 3.30 units on a scale | Standard Error 0.059 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 3.37 units on a scale | Standard Error 0.054 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 3.74 units on a scale | Standard Error 0.058 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 3.62 units on a scale | Standard Error 0.053 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 4.03 units on a scale | Standard Error 0.092 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 3.87 units on a scale | Standard Error 0.103 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 3.43 units on a scale | Standard Error 0.101 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 3.34 units on a scale | Standard Error 0.091 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 3.31 units on a scale | Standard Error 0.095 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 4.09 units on a scale | Standard Error 0.103 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 3.25 units on a scale | Standard Error 0.078 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 3.06 units on a scale | Standard Error 0.087 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 2.94 units on a scale | Standard Error 0.113 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 3.31 units on a scale | Standard Error 0.101 |
Secondary
Insulin Sensitivity Index ( ISI ) at Day 28, Day 48
Insulin sensitivity index (ISI) = 10000 / \[fasting insulin (μIU/mL) x fasting glucose (mg/dL) x mean 2 hour insulin(μIU/mL) x mean 2 hour glucose (mg/dL)\]1/2 where mean 2 hour insulin (or glucose) was defined as the insulin (or glucose)AUC(0-2 hr) divided by the time period (2 hr). In normal subjects the mean score ± SE is 0.366 ± 0.029. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.
Time frame: Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 2.96 units on a scale | Standard Error 0.043 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 2.91 units on a scale | Standard Error 0.049 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 2.63 units on a scale | Standard Error 0.049 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 2.80 units on a scale | Standard Error 0.041 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 3.13 units on a scale | Standard Error 0.093 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 3.34 units on a scale | Standard Error 0.109 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 2.96 units on a scale | Standard Error 0.077 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 3.04 units on a scale | Standard Error 0.085 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 3.57 units on a scale | Standard Error 0.083 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 2.99 units on a scale | Standard Error 0.101 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 3.63 units on a scale | Standard Error 0.074 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 3.77 units on a scale | Standard Error 0.068 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 28 (n= 40, 40, 12, 17, 14, 22, 20) | 3.39 units on a scale | Standard Error 0.071 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Insulin Sensitivity Index ( ISI ) at Day 28, Day 48 | Day 84 (n= 39, 43, 13, 20, 14, 27, 20) | 3.70 units on a scale | Standard Error 0.086 |
Secondary
Mean Change From Baseline in Peak Plasma Fructosamine Level
Blood was drawn to measure change in plasma Fructosamine Level, from baseline to Day 14, 28, 56, 84, 126 and End of Study ( defined as the final available post-randomization assessment up to the last regularly scheduled visit at Day 168 \[+/- 5\]). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 14, Day 28, Day 56, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 14 (n= 44, 45) | 4.8 µmol/L | Standard Error 3 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 28 (n= 45, 45) | -9.2 µmol/L | Standard Error 3.72 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 56 (n= 43, 44) | 1.4 µmol/L | Standard Error 4.88 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 84 (n= 44, 45) | -16.6 µmol/L | Standard Error 4.71 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 126 (n= 45, 45) | 1.6 µmol/L | Standard Error 4.84 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | End of Study (n = 45, 45) | -2.2 µmol/L | Standard Error 7.25 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 126 (n= 45, 45) | -1.1 µmol/L | Standard Error 4.84 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 14 (n= 44, 45) | -0.7 µmol/L | Standard Error 2.97 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 84 (n= 44, 45) | -12.1 µmol/L | Standard Error 4.65 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 28 (n= 45, 45) | -13.9 µmol/L | Standard Error 3.72 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | End of Study (n = 45, 45) | 4.9 µmol/L | Standard Error 7.25 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Fructosamine Level | Day 56 (n= 43, 44) | -0.9 µmol/L | Standard Error 4.82 |
Secondary
Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT )
Mean Change in Peak Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Change from baseline assessed at Day 28 and 84. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | -0.9 mmol/L | Standard Error 0.38 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | -1.3 mmol/L | Standard Error 0.3 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | 0.0 mmol/L | Standard Error 0.3 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | 0.6 mmol/L | Standard Error 0.37 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | 0.2 mmol/L | Standard Error 0.55 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | 0.2 mmol/L | Standard Error 0.58 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | -0.2 mmol/L | Standard Error 0.55 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | -0.7 mmol/L | Standard Error 0.58 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | 0.3 mmol/L | Standard Error 0.6 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | -0.8 mmol/L | Standard Error 0.57 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | -1.0 mmol/L | Standard Error 0.47 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | -0.9 mmol/L | Standard Error 0.5 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 | 0.1 mmol/L | Standard Error 0.61 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 | -0.3 mmol/L | Standard Error 0.64 |
Secondary
Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT)
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin and proinsulin levels were measured. The insulin/proinsulin level was calculated by dividing the insulin level by the proinsulin level. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | 0.173 pmol/pmol | Standard Error 0.3902 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | -0.852 pmol/pmol | Standard Error 0.489 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | -1.035 pmol/pmol | Standard Error 0.3814 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | -0.688 pmol/pmol | Standard Error 0.489 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | -0.689 pmol/pmol | Standard Error 0.7973 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | 0.160 pmol/pmol | Standard Error 0.7996 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | 0.923 pmol/pmol | Standard Error 0.8138 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | 1.039 pmol/pmol | Standard Error 0.7996 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | 0.293 pmol/pmol | Standard Error 0.8169 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | 0.250 pmol/pmol | Standard Error 0.8313 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | -0.031 pmol/pmol | Standard Error 0.6755 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | 0.682 pmol/pmol | Standard Error 0.6871 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 44, 44, 25, 24, 23, 34, 20) | -0.046 pmol/pmol | Standard Error 0.8991 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 43, 45, 24, 24, 23, 34,20) | 0.518 pmol/pmol | Standard Error 0.8832 |
Secondary
Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT)
Blood samples were drawn after an overnight fast and standard OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. C-peptide levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | -601 pmol*h/L | Standard Error 275.1 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | -335 pmol*h/L | Standard Error 178.1 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | -614 pmol*h/L | Standard Error 178.1 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | -205 pmol*h/L | Standard Error 268.6 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | -492 pmol*h/L | Standard Error 392.4 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | 143 pmol*h/L | Standard Error 386.5 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | -25 pmol*h/L | Standard Error 367.6 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | 143 pmol*h/L | Standard Error 361.1 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | 779 pmol*h/L | Standard Error 367.6 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | 654 pmol*h/L | Standard Error 368.9 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | 129 pmol*h/L | Standard Error 319.4 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | 240 pmol*h/L | Standard Error 316 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 28 (n= 41, 41, 21, 23, 23, 31, 20) | -553 pmol*h/L | Standard Error 394.6 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT) | Day 84 (n= 41, 43, 22, 24, 23, 32, 20) | -939 pmol*h/L | Standard Error 396.1 |
Secondary
Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Glucagon levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -3.6 pmol*h/L | Standard Error 2.3 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | -3.7 pmol*h/L | Standard Error 2.96 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | -2.0 pmol*h/L | Standard Error 2.86 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -4.0 pmol*h/L | Standard Error 2.22 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | -1.0 pmol*h/L | Standard Error 4.46 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -3.1 pmol*h/L | Standard Error 3.43 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -3.7 pmol*h/L | Standard Error 3.37 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | -1.8 pmol*h/L | Standard Error 4.48 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | 14.7 pmol*h/L | Standard Error 4.46 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -0.6 pmol*h/L | Standard Error 3.36 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -2.7 pmol*h/L | Standard Error 2.78 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | 2.9 pmol*h/L | Standard Error 3.74 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 84 (n= 42, 45, 23, 23, 23, 33, 20) | -4.0 pmol*h/L | Standard Error 4.79 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test | Day 28 (n= 41, 44, 22, 23, 23, 34, 20) | -5.5 pmol*h/L | Standard Error 3.6 |
Secondary
Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | -19.68 µIU*h/mL | Standard Error 11.054 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | -1.58 µIU*h/mL | Standard Error 6.156 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | -6.97 µIU*h/mL | Standard Error 10.805 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | -14.25 µIU*h/mL | Standard Error 6.017 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | -8.38 µIU*h/mL | Standard Error 9.095 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | -12.61 µIU*h/mL | Standard Error 8.173 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | 6.06 µIU*h/mL | Standard Error 7.477 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | 2.44 µIU*h/mL | Standard Error 8.673 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | 2.06 µIU*h/mL | Standard Error 8.494 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | -6.65 µIU*h/mL | Standard Error 9.522 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | -8.26 µIU*h/mL | Standard Error 6.421 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | -4.09 µIU*h/mL | Standard Error 7.592 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 43, 45, 22, 23, 19, 31, 20) | -10.52 µIU*h/mL | Standard Error 9.321 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 43, 45, 18, 21,16, 29, 20) | -1.35 µIU*h/mL | Standard Error 7.637 |
Secondary
Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | -9.9 pmol*h/L | Standard Error 8.37 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | -6.2 pmol*h/L | Standard Error 10.95 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | 11.0 pmol*h/L | Standard Error 8.25 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | 7.8 pmol*h/L | Standard Error 10.79 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | -13.7 pmol*h/L | Standard Error 18.78 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | -25.8 pmol*h/L | Standard Error 20.96 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | -15.0 pmol*h/L | Standard Error 17.64 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | -9.3 pmol*h/L | Standard Error 20.33 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | 39.6 pmol*h/L | Standard Error 21.68 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | 26.1 pmol*h/L | Standard Error 18.81 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | -16.2 pmol*h/L | Standard Error 16.38 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | -25.9 pmol*h/L | Standard Error 18.76 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 84 (n= 36, 37, 23, 24, 21, 30, 20) | -17.3 pmol*h/L | Standard Error 22.17 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT ) | Day 28 (n= 36, 37, 22, 24, 21, 30, 20) | -22.3 pmol*h/L | Standard Error 19.25 |
Secondary
Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours
Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. The mean ISR over 0 - 4 hours was computed as an AUC (area under the curve) using the linear trapezoidal rule divided by the corresponding time interval. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 255 pmol/min/m^2 | Standard Error 6.4 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 248 pmol/min/m^2 | Standard Error 9.3 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 246 pmol/min/m^2 | Standard Error 6.3 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 259 pmol/min/m^2 | Standard Error 9.3 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 207 pmol/min/m^2 | Standard Error 13.1 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 234 pmol/min/m^2 | Standard Error 12.6 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 231 pmol/min/m^2 | Standard Error 13 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 234 pmol/min/m^2 | Standard Error 12.7 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 262 pmol/min/m^2 | Standard Error 13 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 254 pmol/min/m^2 | Standard Error 13 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 234 pmol/min/m^2 | Standard Error 10.9 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 239 pmol/min/m^2 | Standard Error 10.8 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 84 (n= 43, 43, 25, 24, 23, 34, 20) | 197 pmol/min/m^2 | Standard Error 13.9 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours | Day 28 (n= 42, 43, 23, 23, 23, 33, 20) | 212 pmol/min/m^2 | Standard Error 13.9 |
Secondary
Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours
Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Mean ISR relative to glucose over 0-4 hours was calculated as follows: Mean ISR relative to glucose = mean ISR / (glucose AUC/time interval). The mean ISR was computed as an AUC (area under the curve) using the linear trapezoidal rule divided by the corresponding time interval. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Time frame: Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 20.4 pmol/min/m^2/mmol/L | Standard Error 0.53 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 18.5 pmol/min/m^2/mmol/L | Standard Error 1 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 18.0 pmol/min/m^2/mmol/L | Standard Error 0.52 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 19.0 pmol/min/m^2/mmol/L | Standard Error 0.99 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 14.5 pmol/min/m^2/mmol/L | Standard Error 1.03 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 16.8 pmol/min/m^2/mmol/L | Standard Error 1.13 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 17.1 pmol/min/m^2/mmol/L | Standard Error 1.03 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 18.4 pmol/min/m^2/mmol/L | Standard Error 1.13 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 19.1 pmol/min/m^2/mmol/L | Standard Error 1.05 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 18.5 pmol/min/m^2/mmol/L | Standard Error 1.18 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 18.5 pmol/min/m^2/mmol/L | Standard Error 0.86 |
| Pooled (Cohort 3 and 4): Placebo Infusion | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 18.9 pmol/min/m^2/mmol/L | Standard Error 0.96 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 28 (n= 41, 43, 23, 23, 22, 33, 20) | 16.1 pmol/min/m^2/mmol/L | Standard Error 1.1 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours | Day 84 (n= 42, 43, 24, 24, 22, 33, 20) | 15.9 pmol/min/m^2/mmol/L | Standard Error 1.24 |
Secondary
Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency
An adverse event is any unwanted event, whether related to study drug or not occurring during the study period. A Serious Adverse Event (SAE) is an event resulting in death, requiring or prolonging hospitalization, a congenital anomaly or other important medical event. AEs and SAEs were recorded at each visit.
Time frame: Baseline to End of Study (56[+/-2] and 168 [+/- 5] days after dosing for Cohort 1 and Cohorts 2-4, respectively)
Population: All randomized participants who received study medication were included in the Safety Analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 2: Canakinumab Infusion 10 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 1 Participants |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 2 Participants |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 1 Participants |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 9 Participants |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 2 Participants |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 6 Participants |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 4 Participants |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Pooled (Cohort 3 and 4): Placebo Infusion | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 4 Participants |
| Pooled (Cohort 3 and 4): Placebo Infusion | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Pooled (Cohort 3 and 4): Placebo Infusion | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 2 Participants |
| Cohort 3: Placebo Infusion | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 6 Participants |
| Cohort 3: Placebo Infusion | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 3: Placebo Infusion | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 4 : Canakinumab Injection 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 10 Participants |
| Cohort 4 : Canakinumab Injection 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 4 : Canakinumab Injection 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 4: Placebo to Canakinumab 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Serious Adverse Events | 0 Participants |
| Cohort 4: Placebo to Canakinumab 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Death | 0 Participants |
| Cohort 4: Placebo to Canakinumab 0.03 mg/kg | Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency | Adverse Events Above 5 % Frequency | 2 Participants |
Secondary
β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β )
β cell function is measured by the Homeostatic Model Assessment(HOMA-β) using a computer to model β cell function and insulin sensitivity . β cell function is related to Insulin Sensitivity (HOMA-%S) and is the reciprocal of insulin resistance (100/S%). HOMA β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\] where fasting insulin (or glucose) was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.
Time frame: Baseline, Day 28, Day 84
Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: Canakinumab Infusion 10 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 35.6 percent β-cell Function | Standard Error 0.06 |
| Cohort 2: Canakinumab Infusion 10 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 40.2 percent β-cell Function | Standard Error 0.05 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 35.9 percent β-cell Function | Standard Error 0.05 |
| Cohort 2: Placebo to Canakinumab 10 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 34.3 percent β-cell Function | Standard Error 0.06 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 38.1 percent β-cell Function | Standard Error 0.1 |
| Cohort 3: Canakinumab Infusion 0.1 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 34.6 percent β-cell Function | Standard Error 0.1 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 38.2 percent β-cell Function | Standard Error 0.1 |
| Cohort 3: Canakinumab Infusion 0.3 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 37.6 percent β-cell Function | Standard Error 0.1 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 42.0 percent β-cell Function | Standard Error 0.11 |
| Cohort 3: Canakinumab Infusion 1.5 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 43.3 percent β-cell Function | Standard Error 0.1 |
| Pooled (Cohort 3 and 4): Placebo Infusion | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 37.9 percent β-cell Function | Standard Error 0.09 |
| Pooled (Cohort 3 and 4): Placebo Infusion | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 37.2 percent β-cell Function | Standard Error 0.09 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 84 (n= 44, 45, 24, 24, 23, 33, 20) | 33.7 percent β-cell Function | Standard Error 0.11 |
| Cohort 4: Canakinumab Injection 0.03 mg/kg | β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β ) | Day 28 (n= 44, 45, 24, 24, 22, 33, 20) | 38.3 percent β-cell Function | Standard Error 0.11 |