Trial Outcomes & Findings for Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients (NCT NCT00900146)
NCT ID: NCT00900146
Last Updated: 2012-02-20
Results Overview
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Recruitment status
TERMINATED
Study phase
PHASE2/PHASE3
Target enrollment
556 participants
Primary outcome timeframe
4 months (Period II)
Results posted on
2012-02-20
Participant Flow
Study consisted of four periods: screening (Period I), dose-finding (Period II), intermediate (Period III),and long-term continuation (Period IV). Eligible patients were randomized for 4-month treatment of Period II. Intermediate period continued until primary analysis was completed and optimal dose was selected. Study got terminated in Period III.
A total of 556 patients were randomized in Period II. 5 patients one in each 5, 15, 50mg Canakinumab arms and 2 in Placebo were randomized in error, but never received study treatment. All tables reflect the 551 treated patients.
Participant milestones
| Measure |
Canakinumab 5 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 50 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
|---|---|---|---|---|---|
|
Dose Finding: Period II (4 Months)
STARTED
|
93
|
95
|
92
|
92
|
179
|
|
Dose Finding: Period II (4 Months)
Full Analysis Set (FAS)/Safety
|
93
|
95
|
92
|
92
|
179
|
|
Dose Finding: Period II (4 Months)
COMPLETED
|
88
|
93
|
87
|
90
|
167
|
|
Dose Finding: Period II (4 Months)
NOT COMPLETED
|
5
|
2
|
5
|
2
|
12
|
|
Intermediate: Period III
STARTED
|
87
|
93
|
84
|
90
|
167
|
|
Intermediate: Period III
Safety Set
|
86
|
92
|
84
|
90
|
166
|
|
Intermediate: Period III
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Intermediate: Period III
NOT COMPLETED
|
87
|
93
|
84
|
90
|
167
|
Reasons for withdrawal
| Measure |
Canakinumab 5 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 50 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
|---|---|---|---|---|---|
|
Dose Finding: Period II (4 Months)
Withdrawal by Subject
|
2
|
2
|
5
|
1
|
9
|
|
Dose Finding: Period II (4 Months)
Lost to Follow-up
|
2
|
0
|
0
|
1
|
3
|
|
Dose Finding: Period II (4 Months)
Administrative problems
|
1
|
0
|
0
|
0
|
0
|
|
Intermediate: Period III
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
3
|
|
Intermediate: Period III
Lost to Follow-up
|
2
|
0
|
0
|
0
|
1
|
|
Intermediate: Period III
Administrative problems
|
85
|
92
|
84
|
90
|
163
|
Baseline Characteristics
Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients
Baseline characteristics by cohort
| Measure |
Canakinumab 5 mg + Metformin
n=93 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=95 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 50 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=179 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Total
n=551 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age Continuous
|
53.5 years
STANDARD_DEVIATION 10.27 • n=99 Participants
|
55.5 years
STANDARD_DEVIATION 9.70 • n=107 Participants
|
53.0 years
STANDARD_DEVIATION 9.29 • n=206 Participants
|
53.7 years
STANDARD_DEVIATION 10.36 • n=7 Participants
|
54.3 years
STANDARD_DEVIATION 10.15 • n=31 Participants
|
54.1 years
STANDARD_DEVIATION 9.99 • n=30 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=99 Participants
|
46 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
35 Participants
n=7 Participants
|
74 Participants
n=31 Participants
|
240 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=99 Participants
|
49 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
57 Participants
n=7 Participants
|
105 Participants
n=31 Participants
|
311 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: 4 months (Period II)Population: The safety set (SAF) included all patients who received at least one dose of study medication during Period II.
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=179 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=93 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=95 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events, Death and Clinical Significant AEs During 4 Months (Period II)
Any Adverse Events
|
45 Participants
|
43 Participants
|
76 Participants
|
33 Participants
|
43 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events, Death and Clinical Significant AEs During 4 Months (Period II)
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events, Death and Clinical Significant AEs During 4 Months (Period II)
Serious Adverse Events
|
2 Participants
|
5 Participants
|
6 Participants
|
2 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set (included all randomized patients except for mis-randomized patients who randomized in error but did not receive study drug. Last observation carried forward (LOCF) method was used for patients without Month 4 HbA1c data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
HbA1c was measured by National glycohemoglobin standardization program (NGSP) certified methodology. HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. The analysis of covariance (ANCOVA) included treatment and metformin dose group as main effects and baseline HbA1c as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=89 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=91 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=175 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=94 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c) at Month 4 During Dose-finding Period of the Study (Period II)
|
-0.31 percentage of hemoglobin A1c
Standard Error 0.073
|
-0.25 percentage of hemoglobin A1c
Standard Error 0.071
|
-0.13 percentage of hemoglobin A1c
Standard Error 0.053
|
-0.19 percentage of hemoglobin A1c
Standard Error 0.072
|
-0.29 percentage of hemoglobin A1c
Standard Error 0.071
|
PRIMARY outcome
Timeframe: Baseline, Over Month 4Population: The benefit of canakinumab for the treatment of patients with type 2 diabetes mellitus in combination with metformin was inadequate to continue patients into Period IV in the present study, and therefore decided to terminate the study during Period III.
This was planned as interim analysis and was not conducted because the study was terminated in period III.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of C-peptide prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to start of meal. C-peptide levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. The analysis of covariance included baseline C-peptide AUC 0-4 hours as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=91 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=153 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=87 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in C-peptide Area Under Curve (AUC 0-4 Hours ) Following Meal Test (Period II)
|
-0.834 nmol*hour/L
Standard Error 0.1425
|
-0.610 nmol*hour/L
Standard Error 0.1396
|
-0.588 nmol*hour/L
Standard Error 0.1070
|
-0.399 nmol*hour/L
Standard Error 0.1444
|
-0.388 nmol*hour/L
Standard Error 0.1394
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. Glucose levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. The model of analysis of covariance included baseline plasma glucose AUC 0-4 hours as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=82 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=84 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=147 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=79 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Prandial Plasma Glucose Area Under Curve (AUC0-4 Hours ) Following Meal Test (Period II)
|
-2.103 mmol*hour/L
Standard Error 0.7928
|
1.618 mmol*hour/L
Standard Error 0.7791
|
-0.851 mmol*hour/L
Standard Error 0.6053
|
-0.999 mmol*hour/L
Standard Error 0.8094
|
-1.012 mmol*hour/L
Standard Error 0.7917
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of insulin prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. Model of analysis of covariance included baseline insulin AUC 0-4 hours as covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=70 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=77 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=133 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=68 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=73 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Insulin Area Under Curve (AUC 0-4 Hours ) Following Meal Test (Period II)
|
-14.016 pmol*hour/L
Standard Error 27.9738
|
-20.583 pmol*hour/L
Standard Error 26.5602
|
0.121 pmol*hour/L
Standard Error 20.7195
|
18.623 pmol*hour/L
Standard Error 28.5445
|
66.237 pmol*hour/L
Standard Error 27.4053
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2-hour glucose level as covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=84 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=151 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=79 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=85 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in 2-hour Glucose Level Following Meal Test (Period II)
|
-0.777 mmol/L
Standard Error 0.2471
|
0.262 mmol/L
Standard Error 0.2445
|
-0.347 mmol/L
Standard Error 0.1873
|
-0.427 mmol/L
Standard Error 0.2537
|
-0.239 mmol/L
Standard Error 0.2457
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak glucose level as covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=87 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=152 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=85 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Peak Glucose Level Following Meal Test (Period II)
|
-0.565 mmol/L
Standard Error 0.2270
|
0.381 mmol/L
Standard Error 0.2208
|
-0.339 mmol/L
Standard Error 0.1711
|
-0.386 mmol/L
Standard Error 0.2302
|
-0.380 mmol/L
Standard Error 0.2257
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on the day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of C-peptide prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak C-peptide level as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=84 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=89 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=154 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=84 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=89 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Peak C-peptide Following Meal Test (Period II)
|
-0.227 nmol/L
Standard Error 0.0523
|
-0.207 nmol/L
Standard Error 0.0506
|
-0.212 nmol/L
Standard Error 0.0394
|
-0.075 nmol/L
Standard Error 0.0524
|
-0.115 nmol/L
Standard Error 0.0509
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of insulin prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2-hour insulin level as covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=82 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=84 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=148 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=76 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Peak Insulin Level Following Meal Test (Period II)
|
2.0 pmol/L
Standard Error 13.88
|
-7.0 pmol/L
Standard Error 13.61
|
1.7 pmol/L
Standard Error 10.59
|
13.1 pmol/L
Standard Error 14.40
|
26.0 pmol/L
Standard Error 14.00
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. A standard liquid mixed-meal challenge was done at baseline and Month 4. Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. The model of analysis of covariance included baseline Insulin secretion rate relative to glucose AUC at 0-2 hours as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=82 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=149 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=77 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Insulin Secretion Rates Relative to Glucose AUC (0-2 Hours) at Month 4 Following Meal Test (Period II)
|
-1.761 pmol/min/m²/mmol *hour/L
Standard Error 0.6744
|
-2.428 pmol/min/m²/mmol *hour/L
Standard Error 0.6681
|
-1.635 pmol/min/m²/mmol *hour/L
Standard Error 0.5084
|
-0.369 pmol/min/m²/mmol *hour/L
Standard Error 0.6922
|
-0.331 pmol/min/m²/mmol *hour/L
Standard Error 0.6705
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
A standard liquid mixed-meal challenge was done at baseline and Month 4. A 2 hour insulin secretion rate using deconvolution was performed. The deconvolution was an algorithm that analyzed the insulin secretion rate relative to glucose and C-peptide combined. Blood samples were taken prior to and after meal at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2 hour Insulin secretion rate as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=86 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=152 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=80 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=88 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in 2 Hour Insulin Secretion Rate Derived Based on Glucose and C-peptide Following at Month 4 Following Meal Test (Period II)
|
-31.296 pmol/min/m²
Standard Error 10.2302
|
-38.515 pmol/min/m²
Standard Error 10.0176
|
-24.812 pmol/min/m²
Standard Error 7.6980
|
-17.022 pmol/min/m²
Standard Error 10.4317
|
-9.607 pmol/min/m²
Standard Error 9.9815
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
Patients were asked to check their glucose level (7 times) using their glucose meter on one of the seven days prior to the Meal Challenge Visits (Period II: baseline, Month 4. Patient was instructed to test at following timepoints: fasting before breakfast, 2 hours after starting breakfast, before lunch, 2 hours after starting lunch, before dinner, 2 hours after dinner and at bedtime. The patient documented the results in their Study Diary. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak plasma glucose level as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=82 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=86 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=152 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=85 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Peak Plasma Glucose Level (7-point Glucose Testing) at Month 4(Period II)
|
-0.421 mmol/L
Standard Error 0.2653
|
-0.333 mmol/L
Standard Error 0.2578
|
-0.212 mmol/L
Standard Error 0.1975
|
-0.549 mmol/L
Standard Error 0.2669
|
-0.129 mmol/L
Standard Error 0.2610
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
Patients were asked to check their glucose level (7 times) using their glucose meter on one of the seven days prior to the Meal Challenge Visits (Period II: Month 0 (Baseline), Month 4. Patient was instructed to test at following timepoints: fasting before breakfast, 2 hours after starting breakfast, before lunch, 2 hours after starting lunch, before dinner, 2 hours after dinner and at bedtime. Patient documented the results in their Study Diary. The analysis of covariance included treatment and metformin dose group as main effects and baseline average plasma glucose level as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=82 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=86 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=152 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=85 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Average Plasma Glucose Level (7-point Glucose Testing) at Month 4 (Period II)
|
-0.275 mmol/L
Standard Error 0.1614
|
-0.040 mmol/L
Standard Error 0.1569
|
-0.091 mmol/L
Standard Error 0.1203
|
-0.357 mmol/L
Standard Error 0.1626
|
-0.218 mmol/L
Standard Error 0.1589
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
Change in Fasting Glucose Level measured from plasma taken at Baseline and at Month 4. The analysis of covariance included treatment and metformin dose group as main effects and baseline fasting plasma glucose level as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=88 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=90 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=172 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=89 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=93 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose at Month 4 (Period II)
|
-0.29 mmol/L
Standard Error 0.162
|
0.19 mmol/L
Standard Error 0.160
|
0.01 mmol/L
Standard Error 0.118
|
0.25 mmol/L
Standard Error 0.162
|
-0.19 mmol/L
Standard Error 0.159
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
Change in fasting insulin Level measured from blood samples taken at Baseline and at Month 4. The analysis of covariance included treatment and metformin dose group as main effects and baseline fasting insulin level as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=77 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=143 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=75 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Fasting Insulin at Month 4 (Period II)
|
7.0 pmol/L
Standard Error 4.67
|
4.4 pmol/L
Standard Error 4.47
|
-0.4 pmol/L
Standard Error 3.50
|
4.3 pmol/L
Standard Error 4.74
|
7.2 pmol/L
Standard Error 4.57
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). Time profile of postprandial glucose, insulin and C-peptide were assessed as measures of β-cell response to stimulation. The analysis of covariance included treatment and metformin dose group as main effects and baseline HOMA-B as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=77 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=143 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=75 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=79 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Homeostatic Model Assessment B (HOMA2 B) Beta Cell Function (%B) at Month 4 (Period II)
|
8.215 percentage of beta cell function
Standard Error 5.9727
|
6.217 percentage of beta cell function
Standard Error 5.7307
|
-2.182 percentage of beta cell function
Standard Error 4.4846
|
-1.067 percentage of beta cell function
Standard Error 6.0549
|
2.259 percentage of beta cell function
Standard Error 5.9304
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S)as a percentage of a normal reference population (normal young adults). The analysis of covariance included treatment and metformin dose group as main effects and baseline HOMA2 IR as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=77 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=143 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=75 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Homeostatic Model Assessment Insulin Resistance (HOMA2 IR) at Month 4 (Period II)
|
0.255 percentage of insulin resistance
Standard Error 0.3054
|
0.252 percentage of insulin resistance
Standard Error 0.2925
|
0.013 percentage of insulin resistance
Standard Error 0.2286
|
0.245 percentage of insulin resistance
Standard Error 0.3107
|
0.517 percentage of insulin resistance
Standard Error 0.2990
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. The score is calculated by the equation: 1 /(log(fasting insulin µU/mL) + log(fasting glucose mg/dL)). In normal subjects, the mean score ± SE is 0.366 ± 0.029. The analysis of covariance included treatment and metformin dose group as main effects and baseline QUICKI as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=77 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=83 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=143 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=75 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=81 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) at Month 4 (Period II)
|
-0.003 units on a scale
Standard Error 0.0017
|
-0.001 units on a scale
Standard Error 0.0016
|
0.000 units on a scale
Standard Error 0.0013
|
-0.001 units on a scale
Standard Error 0.0017
|
0.000 units on a scale
Standard Error 0.0016
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin.
The change from baseline in hsCRP (on the logarithmic scale) at Month 4 was measured for this analysis. The analysis of covariance included treatment and metformin dose group as main effects and baseline hsCRP as a covariate.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=87 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=91 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=168 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=89 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=93 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at Month 4 (Period II)
|
-0.44 log (mg/L)
Standard Error 0.037
|
-0.40 log (mg/L)
Standard Error 0.036
|
-0.08 log (mg/L)
Standard Error 0.027
|
-0.19 log (mg/L)
Standard Error 0.037
|
-0.32 log (mg/L)
Standard Error 0.036
|
SECONDARY outcome
Timeframe: Baseline, Month 4Population: The full analysis set included all randomized patients except for mis-randomized patients who randomized in error, did not receive study drug. LOCF method was used for patients without Month 4 data for any reason and who used rescue drug or any other glucose lowering agents other than metformin. 'n' = patients with baseline and endpoints data.
The fasting lipid profiles included triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), calculated very low-density lipoprotein (VLDL), non-HDL cholesterol. Percentage change was measured as \[(value at month 4 - baseline value)/baseline value\]\*100%. The analysis of covariance model included treatment and metformin dose group as main effects and baseline triglycerides, total cholesterol, LDL, HDL, VLDL and non-HDL as covariates.
Outcome measures
| Measure |
Canakinumab 50 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=92 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=179 Participants
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
Canakinumab 5 mg + Metformin
n=93 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=95 Participants
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
|---|---|---|---|---|---|
|
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
Total cholesterol (n = 91, 93, 88, 91, 172)
|
5.334 percent change
Standard Error 1.5542
|
6.265 percent change
Standard Error 1.5234
|
2.697 percent change
Standard Error 1.1334
|
3.163 percent change
Standard Error 1.5364
|
3.922 percent change
Standard Error 1.5188
|
|
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
Triglycerides (n = 91, 93, 88, 91, 172)
|
19.937 percent change
Standard Error 4.3684
|
18.795 percent change
Standard Error 4.2786
|
7.009 percent change
Standard Error 3.1813
|
16.127 percent change
Standard Error 4.3130
|
7.903 percent change
Standard Error 4.2688
|
|
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
LDL (n = 90, 90, 85, 87, 165)
|
2.705 percent change
Standard Error 2.5137
|
5.938 percent change
Standard Error 2.4752
|
5.129 percent change
Standard Error 1.8351
|
2.624 percent change
Standard Error 2.4606
|
4.741 percent change
Standard Error 2.4582
|
|
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
HDL (n = 91, 93, 88, 91, 172)
|
8.074 percent change
Standard Error 1.6853
|
6.780 percent change
Standard Error 1.6494
|
3.963 percent change
Standard Error 1.2303
|
1.438 percent change
Standard Error 1.6619
|
5.346 percent change
Standard Error 1.6441
|
|
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
VLDL (n= 90, 90, 85, 87, 165)
|
16.533 percent change
Standard Error 3.9986
|
16.618 percent change
Standard Error 3.9373
|
7.370 percent change
Standard Error 2.9203
|
15.646 percent change
Standard Error 3.9196
|
6.711 percent change
Standard Error 3.9118
|
|
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
Non-HDL (n = 91, 93, 88, 91, 172)
|
5.17 percent change
Standard Error 2.046
|
7.25 percent change
Standard Error 2.005
|
3.04 percent change
Standard Error 1.491
|
4.25 percent change
Standard Error 2.022
|
4.40 percent change
Standard Error 1.999
|
Adverse Events
Canakinumab 5 mg + Metformin
Serious events: 3 serious events
Other events: 9 other events
Deaths: 0 deaths
Canakinumab 15 mg + Metformin
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Canakinumab 50 mg + Metformin
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Canakinumab 150 mg + Metformin
Serious events: 7 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo + Metformin
Serious events: 8 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Canakinumab 5 mg + Metformin
n=93 participants at risk
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=95 participants at risk
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 50 mg + Metformin
n=92 participants at risk
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=92 participants at risk
Experimental: Canakinumab 150 mg + Metformin In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=179 participants at risk
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
|---|---|---|---|---|---|
|
Cardiac disorders
Acute left ventricular failure
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
General disorders
Oedema peripheral
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Breast abscess
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Gastroenteritis bacterial
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Graft infection
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Urosepsis
|
1.1%
1/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
1.1%
1/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Nervous system disorders
Haemorrhagic stroke
|
1.1%
1/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Nervous system disorders
Ischaemic cerebral infarction
|
1.1%
1/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.1%
1/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Renal and urinary disorders
Renal mass
|
0.00%
0/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.56%
1/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.1%
1/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
Other adverse events
| Measure |
Canakinumab 5 mg + Metformin
n=93 participants at risk
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 15 mg + Metformin
n=95 participants at risk
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 50 mg + Metformin
n=92 participants at risk
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Canakinumab 150 mg + Metformin
n=92 participants at risk
Experimental: Canakinumab 150 mg + Metformin In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy.
The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
|
Placebo + Metformin
n=179 participants at risk
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.2%
2/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
2.1%
2/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
5.4%
5/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
0.00%
0/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
1.7%
3/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
5/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
4.2%
4/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
9.8%
9/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
4.3%
4/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
8.4%
15/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
|
Infections and infestations
Urinary tract infection
|
3.2%
3/93 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
4.2%
4/95 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
5.4%
5/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
5.4%
5/92 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
6.1%
11/179 • Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER