Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Type 2 Diabetes (NCT NCT00605475)
NCT ID: NCT00605475
Last Updated: 2012-02-13
Results Overview
Blood was drawn after an overnight fast to measure plasma HbA1c levels. End of Study is defined as the last Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
231 participants
Primary outcome timeframe
Baseline, Day 28, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)
Results posted on
2012-02-13
Participant Flow
Participant milestones
| Measure |
Cohort 1: Canakinumab Infusion 0.3 mg/kg
Single dose intravenous (IV) infusion of canakinumab 0.3 mg/kg
|
Cohort 1: Placebo to Canakinumab 0.3 mg/kg
Single dose IV infusion of placebo to Canakinumab 0.3 mg/kg
|
Cohort 2: Canakinumab Infusion 10 mg/kg
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
Single dose IV infusion of Placebo to Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3 : Canakinumab Infusion 1.5 mg/kg
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
5
|
45
|
45
|
25
|
24
|
23
|
24
|
20
|
10
|
|
Overall Study
COMPLETED
|
10
|
5
|
45
|
45
|
24
|
22
|
22
|
24
|
18
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
2
|
1
|
0
|
2
|
2
|
Reasons for withdrawal
| Measure |
Cohort 1: Canakinumab Infusion 0.3 mg/kg
Single dose intravenous (IV) infusion of canakinumab 0.3 mg/kg
|
Cohort 1: Placebo to Canakinumab 0.3 mg/kg
Single dose IV infusion of placebo to Canakinumab 0.3 mg/kg
|
Cohort 2: Canakinumab Infusion 10 mg/kg
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
Single dose IV infusion of Placebo to Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3 : Canakinumab Infusion 1.5 mg/kg
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Abnormal Laboratory Values
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Administrative problems
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Cohort 1: Canakinumab Infusion 0.3 mg/kg
n=10 Participants
Single dose intravenous (IV) infusion of canakinumab 0.3 mg/kg
|
Cohort 1: Placebo to Canakinumab 0.3 mg/kg
n=5 Participants
Single dose IV infusion of placebo to Canakinumab 0.3 mg/kg
|
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Placebo to Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3 : Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Cohort 3: Placebo Infusion
n=24 Participants
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
n=10 Participants
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
Total
n=231 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age Continuous
|
53 years
STANDARD_DEVIATION 7.60 • n=5 Participants
|
52 years
STANDARD_DEVIATION 6.96 • n=7 Participants
|
57.1 years
STANDARD_DEVIATION 9.38 • n=5 Participants
|
57.5 years
STANDARD_DEVIATION 7.95 • n=4 Participants
|
53.9 years
STANDARD_DEVIATION 7.58 • n=21 Participants
|
55 years
STANDARD_DEVIATION 8.45 • n=8 Participants
|
55.1 years
STANDARD_DEVIATION 9.28 • n=8 Participants
|
54.7 years
STANDARD_DEVIATION 6.41 • n=24 Participants
|
53.9 years
STANDARD_DEVIATION 9.07 • n=42 Participants
|
56 years
STANDARD_DEVIATION 8.67 • n=42 Participants
|
54.6 years
STANDARD_DEVIATION 8.08 • n=42 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
17 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
16 Participants
n=24 Participants
|
10 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
116 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
8 Participants
n=24 Participants
|
10 Participants
n=42 Participants
|
8 Participants
n=42 Participants
|
115 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 28, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood was drawn after an overnight fast to measure plasma HbA1c levels. End of Study is defined as the last Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
Day 28 (n= 45, 45, 25, 23, 23, 34, 20)
|
-0.38 percent
Standard Error 0.057
|
-0.26 percent
Standard Error 0.057
|
-0.25 percent
Standard Error 0.065
|
-0.30 percent
Standard Error 0.069
|
-0.47 percent
Standard Error 0.068
|
-0.24 percent
Standard Error 0.056
|
-0.13 percent
Standard Error 0.073
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
Day 84 (n= 44, 44, 25, 23, 23, 33, 20)
|
-0.46 percent
Standard Error 0.102
|
-0.15 percent
Standard Error 0.105
|
-0.04 percent
Standard Error 0.118
|
-0.43 percent
Standard Error 0.124
|
-0.59 percent
Standard Error 0.124
|
0.32 percent
Standard Error 0.103
|
-0.15 percent
Standard Error 0.132
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
Day 126 (n= 45, 45, 21, 22, 23, 33, 20)
|
-0.29 percent
Standard Error 0.101
|
-0.02 percent
Standard Error 0.101
|
-0.08 percent
Standard Error 0.126
|
-0.22 percent
Standard Error 0.123
|
-0.40 percent
Standard Error 0.120
|
-0.19 percent
Standard Error 0.101
|
-0.11 percent
Standard Error 0.128
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
End of Study (n= 43, 45, 24, 20, 21, 33, 20)
|
-0.26 percent
Standard Error 0.121
|
-0.01 percent
Standard Error 0.118
|
0.27 percent
Standard Error 0.162
|
-0.18 percent
Standard Error 0.178
|
-0.39 percent
Standard Error 0.173
|
-0.12 percent
Standard Error 0.138
|
0.32 percent
Standard Error 0.177
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Mean Change in Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Glucose levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=43 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=24 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=22 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=33 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT )
Day 28
|
-4.7 mmol*h/L
Standard Error 0.98
|
-0.9 mmol*h/L
Standard Error 0.96
|
1.6 mmol*h/L
Standard Error 1.66
|
-0.9 mmol*h/L
Standard Error 1.65
|
-2.8 mmol*h/L
Standard Error 1.73
|
-2.3 mmol*h/L
Standard Error 1.41
|
-0.5 mmol*h/L
Standard Error 1.81
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT )
Day 84
|
-2.5 mmol*h/L
Standard Error 1.26
|
1.7 mmol*h/L
Standard Error 1.24
|
2.6 mmol*h/L
Standard Error 1.72
|
-2.8 mmol*h/L
Standard Error 1.71
|
-1.2 mmol*h/L
Standard Error 1.79
|
-2.8 mmol*h/L
Standard Error 1.46
|
-2.5 mmol*h/L
Standard Error 1.88
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were drawn after an overnight fast and standard OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. C-peptide levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT)
Day 28 (n= 41, 41, 21, 23, 23, 31, 20)
|
-335 pmol*h/L
Standard Error 178.1
|
-614 pmol*h/L
Standard Error 178.1
|
-492 pmol*h/L
Standard Error 392.4
|
-25 pmol*h/L
Standard Error 367.6
|
779 pmol*h/L
Standard Error 367.6
|
129 pmol*h/L
Standard Error 319.4
|
-553 pmol*h/L
Standard Error 394.6
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT)
Day 84 (n= 41, 43, 22, 24, 23, 32, 20)
|
-601 pmol*h/L
Standard Error 275.1
|
-205 pmol*h/L
Standard Error 268.6
|
143 pmol*h/L
Standard Error 386.5
|
143 pmol*h/L
Standard Error 361.1
|
654 pmol*h/L
Standard Error 368.9
|
240 pmol*h/L
Standard Error 316.0
|
-939 pmol*h/L
Standard Error 396.1
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
Day 28 (n= 43, 45, 18, 21,16, 29, 20)
|
-1.58 µIU*h/mL
Standard Error 6.156
|
-14.25 µIU*h/mL
Standard Error 6.017
|
-12.61 µIU*h/mL
Standard Error 8.173
|
6.06 µIU*h/mL
Standard Error 7.477
|
2.06 µIU*h/mL
Standard Error 8.494
|
-8.26 µIU*h/mL
Standard Error 6.421
|
-1.35 µIU*h/mL
Standard Error 7.637
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
Day 84 (n= 43, 45, 22, 23, 19, 31, 20)
|
-19.68 µIU*h/mL
Standard Error 11.054
|
-6.97 µIU*h/mL
Standard Error 10.805
|
-8.38 µIU*h/mL
Standard Error 9.095
|
2.44 µIU*h/mL
Standard Error 8.673
|
-6.65 µIU*h/mL
Standard Error 9.522
|
-4.09 µIU*h/mL
Standard Error 7.592
|
-10.52 µIU*h/mL
Standard Error 9.321
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
Day 28 (n= 36, 37, 22, 24, 21, 30, 20)
|
-9.9 pmol*h/L
Standard Error 8.37
|
11.0 pmol*h/L
Standard Error 8.25
|
-13.7 pmol*h/L
Standard Error 18.78
|
-15.0 pmol*h/L
Standard Error 17.64
|
26.1 pmol*h/L
Standard Error 18.81
|
-16.2 pmol*h/L
Standard Error 16.38
|
-22.3 pmol*h/L
Standard Error 19.25
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
Day 84 (n= 36, 37, 23, 24, 21, 30, 20)
|
-6.2 pmol*h/L
Standard Error 10.95
|
7.8 pmol*h/L
Standard Error 10.79
|
-25.8 pmol*h/L
Standard Error 20.96
|
-9.3 pmol*h/L
Standard Error 20.33
|
39.6 pmol*h/L
Standard Error 21.68
|
-25.9 pmol*h/L
Standard Error 18.76
|
-17.3 pmol*h/L
Standard Error 22.17
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Glucagon levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test
Day 28 (n= 41, 44, 22, 23, 23, 34, 20)
|
-3.6 pmol*h/L
Standard Error 2.30
|
-4.0 pmol*h/L
Standard Error 2.22
|
-3.1 pmol*h/L
Standard Error 3.43
|
-3.7 pmol*h/L
Standard Error 3.37
|
-0.6 pmol*h/L
Standard Error 3.36
|
-2.7 pmol*h/L
Standard Error 2.78
|
-5.5 pmol*h/L
Standard Error 3.60
|
—
|
—
|
—
|
|
Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test
Day 84 (n= 42, 45, 23, 23, 23, 33, 20)
|
-3.7 pmol*h/L
Standard Error 2.96
|
-2.0 pmol*h/L
Standard Error 2.86
|
-1.0 pmol*h/L
Standard Error 4.46
|
-1.8 pmol*h/L
Standard Error 4.48
|
14.7 pmol*h/L
Standard Error 4.46
|
2.9 pmol*h/L
Standard Error 3.74
|
-4.0 pmol*h/L
Standard Error 4.79
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were drawn after an overnight fast and OGTT at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin and proinsulin levels were measured. The insulin/proinsulin level was calculated by dividing the insulin level by the proinsulin level. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT)
Day 28 (n= 43, 45, 24, 24, 23, 34,20)
|
0.173 pmol/pmol
Standard Error 0.3902
|
-1.035 pmol/pmol
Standard Error 0.3814
|
0.160 pmol/pmol
Standard Error 0.7996
|
1.039 pmol/pmol
Standard Error 0.7996
|
0.293 pmol/pmol
Standard Error 0.8169
|
-0.031 pmol/pmol
Standard Error 0.6755
|
0.518 pmol/pmol
Standard Error 0.8832
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT)
Day 84 (n= 44, 44, 25, 24, 23, 34, 20)
|
-0.852 pmol/pmol
Standard Error 0.4890
|
-0.688 pmol/pmol
Standard Error 0.4890
|
-0.689 pmol/pmol
Standard Error 0.7973
|
0.923 pmol/pmol
Standard Error 0.8138
|
0.250 pmol/pmol
Standard Error 0.8313
|
0.682 pmol/pmol
Standard Error 0.6871
|
-0.046 pmol/pmol
Standard Error 0.8991
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Mean ISR relative to glucose over 0-4 hours was calculated as follows: Mean ISR relative to glucose = mean ISR / (glucose AUC/time interval). The mean ISR was computed as an AUC (area under the curve) using the linear trapezoidal rule divided by the corresponding time interval. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours
Day 28 (n= 41, 43, 23, 23, 22, 33, 20)
|
20.4 pmol/min/m^2/mmol/L
Standard Error 0.53
|
18.0 pmol/min/m^2/mmol/L
Standard Error 0.52
|
14.5 pmol/min/m^2/mmol/L
Standard Error 1.03
|
17.1 pmol/min/m^2/mmol/L
Standard Error 1.03
|
19.1 pmol/min/m^2/mmol/L
Standard Error 1.05
|
18.5 pmol/min/m^2/mmol/L
Standard Error 0.86
|
16.1 pmol/min/m^2/mmol/L
Standard Error 1.10
|
—
|
—
|
—
|
|
Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours
Day 84 (n= 42, 43, 24, 24, 22, 33, 20)
|
18.5 pmol/min/m^2/mmol/L
Standard Error 1.00
|
19.0 pmol/min/m^2/mmol/L
Standard Error 0.99
|
16.8 pmol/min/m^2/mmol/L
Standard Error 1.13
|
18.4 pmol/min/m^2/mmol/L
Standard Error 1.13
|
18.5 pmol/min/m^2/mmol/L
Standard Error 1.18
|
18.9 pmol/min/m^2/mmol/L
Standard Error 0.96
|
15.9 pmol/min/m^2/mmol/L
Standard Error 1.24
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. The mean ISR over 0 - 4 hours was computed as an AUC (area under the curve) using the linear trapezoidal rule divided by the corresponding time interval. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours
Day 84 (n= 43, 43, 25, 24, 23, 34, 20)
|
248 pmol/min/m^2
Standard Error 9.3
|
259 pmol/min/m^2
Standard Error 9.3
|
234 pmol/min/m^2
Standard Error 12.6
|
234 pmol/min/m^2
Standard Error 12.7
|
254 pmol/min/m^2
Standard Error 13.0
|
239 pmol/min/m^2
Standard Error 10.8
|
197 pmol/min/m^2
Standard Error 13.9
|
—
|
—
|
—
|
|
Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours
Day 28 (n= 42, 43, 23, 23, 23, 33, 20)
|
255 pmol/min/m^2
Standard Error 6.4
|
246 pmol/min/m^2
Standard Error 6.3
|
207 pmol/min/m^2
Standard Error 13.1
|
231 pmol/min/m^2
Standard Error 13.0
|
262 pmol/min/m^2
Standard Error 13.0
|
234 pmol/min/m^2
Standard Error 10.9
|
212 pmol/min/m^2
Standard Error 13.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Insulin sensitivity index (ISI) = 10000 / \[fasting insulin (μIU/mL) x fasting glucose (mg/dL) x mean 2 hour insulin(μIU/mL) x mean 2 hour glucose (mg/dL)\]1/2 where mean 2 hour insulin (or glucose) was defined as the insulin (or glucose)AUC(0-2 hr) divided by the time period (2 hr). In normal subjects the mean score ± SE is 0.366 ± 0.029. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Insulin Sensitivity Index ( ISI ) at Day 28, Day 48
Day 84 (n= 39, 43, 13, 20, 14, 27, 20)
|
2.96 units on a scale
Standard Error 0.043
|
2.80 units on a scale
Standard Error 0.041
|
3.34 units on a scale
Standard Error 0.109
|
3.04 units on a scale
Standard Error 0.085
|
2.99 units on a scale
Standard Error 0.101
|
3.63 units on a scale
Standard Error 0.074
|
3.70 units on a scale
Standard Error 0.086
|
—
|
—
|
—
|
|
Insulin Sensitivity Index ( ISI ) at Day 28, Day 48
Day 28 (n= 40, 40, 12, 17, 14, 22, 20)
|
2.91 units on a scale
Standard Error 0.049
|
2.63 units on a scale
Standard Error 0.049
|
3.13 units on a scale
Standard Error 0.093
|
2.96 units on a scale
Standard Error 0.077
|
3.57 units on a scale
Standard Error 0.083
|
3.77 units on a scale
Standard Error 0.068
|
3.39 units on a scale
Standard Error 0.071
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Insulinogenic index (0-30 min) * \[Change in insulin (0-30 min) (μIU/mL)\] / \[Change in glucose (0-30 min) (mg/dL)\] * \[insulin (μIU/mL) at 30 min - insulin (μIU/mL) at 0 min\] / \[glucose (mg/dL) at 30 min - glucose (mg/dL) at 0 min), where insulin (or glucose) at 0 min was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data..
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Insulinogenic Index, 0 - 30 Minutes
Day 28 (n=44, 44, 17, 23 17, 32, 18)
|
0.174 units on a scale
Standard Error 0.0754
|
0.140 units on a scale
Standard Error 0.0754
|
0.090 units on a scale
Standard Error 0.1995
|
0.105 units on a scale
Standard Error 0.1735
|
0.139 units on a scale
Standard Error 0.1991
|
0.102 units on a scale
Standard Error 0.1464
|
0.137 units on a scale
Standard Error 0.1942
|
—
|
—
|
—
|
|
Insulinogenic Index, 0 - 30 Minutes
Day 84 (n=43, 44, 17, 24, 20, 31, 17)
|
0.157 units on a scale
Standard Error 0.0987
|
0.134 units on a scale
Standard Error 0.0976
|
0.092 units on a scale
Standard Error 0.1928
|
0.098 units on a scale
Standard Error 0.1651
|
0.111 units on a scale
Standard Error 0.1777
|
0.124 units on a scale
Standard Error 0.1445
|
0.121 units on a scale
Standard Error 0.1937
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Mean Change in Peak Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Change from baseline assessed at Day 28 and 84. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=44 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=24 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=33 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT )
Day 28
|
-1.3 mmol/L
Standard Error 0.30
|
0.0 mmol/L
Standard Error 0.30
|
0.2 mmol/L
Standard Error 0.55
|
-0.2 mmol/L
Standard Error 0.55
|
-0.8 mmol/L
Standard Error 0.57
|
-1.0 mmol/L
Standard Error 0.47
|
0.1 mmol/L
Standard Error 0.61
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT )
Day 84
|
-0.9 mmol/L
Standard Error 0.38
|
0.6 mmol/L
Standard Error 0.37
|
0.2 mmol/L
Standard Error 0.58
|
-0.7 mmol/L
Standard Error 0.58
|
0.3 mmol/L
Standard Error 0.60
|
-0.9 mmol/L
Standard Error 0.50
|
-0.3 mmol/L
Standard Error 0.64
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 14, Day 28, Day 56, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Blood was drawn to measure change in plasma Fructosamine Level, from baseline to Day 14, 28, 56, 84, 126 and End of Study ( defined as the final available post-randomization assessment up to the last regularly scheduled visit at Day 168 \[+/- 5\]). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Peak Plasma Fructosamine Level
Day 126 (n= 45, 45)
|
1.6 µmol/L
Standard Error 4.84
|
-1.1 µmol/L
Standard Error 4.84
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Fructosamine Level
Day 14 (n= 44, 45)
|
4.8 µmol/L
Standard Error 3.0
|
-0.7 µmol/L
Standard Error 2.97
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Fructosamine Level
Day 28 (n= 45, 45)
|
-9.2 µmol/L
Standard Error 3.72
|
-13.9 µmol/L
Standard Error 3.72
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Fructosamine Level
Day 56 (n= 43, 44)
|
1.4 µmol/L
Standard Error 4.88
|
-0.9 µmol/L
Standard Error 4.82
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Fructosamine Level
Day 84 (n= 44, 45)
|
-16.6 µmol/L
Standard Error 4.71
|
-12.1 µmol/L
Standard Error 4.65
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline in Peak Plasma Fructosamine Level
End of Study (n = 45, 45)
|
-2.2 µmol/L
Standard Error 7.25
|
4.9 µmol/L
Standard Error 7.25
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
Insulin Resistance is measured via the Homeostatic Model Assessment (HOMA-IR) using a computer to model insulin sensitivity. Insulin Sensitivity (HOMA-%S), where 100% is normal, is the reciprocal of insulin resistance (100/S%). HOMA IR = \[fasting insulin (μU/mL)\] x \[fasting plasma glucose (mmol/L)\] / 22.5 where fasting insulin (or glucose) was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR)
Day 84 (n= 44, 45, 24, 24, 23, 33, 20)
|
3.37 units on a scale
Standard Error 0.054
|
3.62 units on a scale
Standard Error 0.053
|
3.87 units on a scale
Standard Error 0.103
|
3.43 units on a scale
Standard Error 0.101
|
4.09 units on a scale
Standard Error 0.103
|
3.06 units on a scale
Standard Error 0.087
|
2.94 units on a scale
Standard Error 0.113
|
—
|
—
|
—
|
|
Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR)
Day 28 (n= 44, 45, 24, 24, 22, 33, 20)
|
3.30 units on a scale
Standard Error 0.059
|
3.74 units on a scale
Standard Error 0.058
|
4.03 units on a scale
Standard Error 0.092
|
3.34 units on a scale
Standard Error 0.091
|
3.31 units on a scale
Standard Error 0.095
|
3.25 units on a scale
Standard Error 0.078
|
3.31 units on a scale
Standard Error 0.101
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 84Population: All randomized participants who received study drug were included in the intent to treat population (ITT). Last observation carried forward (LOCF) was used to impute missing values.
β cell function is measured by the Homeostatic Model Assessment(HOMA-β) using a computer to model β cell function and insulin sensitivity . β cell function is related to Insulin Sensitivity (HOMA-%S) and is the reciprocal of insulin resistance (100/S%). HOMA β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\] where fasting insulin (or glucose) was defined as the arithmetic mean of the -15, -10 and 0 min pre-glucose load values. Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed on log transformed data.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=23 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=34 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β )
Day 84 (n= 44, 45, 24, 24, 23, 33, 20)
|
35.6 percent β-cell Function
Standard Error 0.06
|
34.3 percent β-cell Function
Standard Error 0.06
|
34.6 percent β-cell Function
Standard Error 0.10
|
37.6 percent β-cell Function
Standard Error 0.10
|
43.3 percent β-cell Function
Standard Error 0.10
|
37.2 percent β-cell Function
Standard Error 0.09
|
33.7 percent β-cell Function
Standard Error 0.11
|
—
|
—
|
—
|
|
β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β )
Day 28 (n= 44, 45, 24, 24, 22, 33, 20)
|
40.2 percent β-cell Function
Standard Error 0.05
|
35.9 percent β-cell Function
Standard Error 0.05
|
38.1 percent β-cell Function
Standard Error 0.10
|
38.2 percent β-cell Function
Standard Error 0.10
|
42.0 percent β-cell Function
Standard Error 0.11
|
37.9 percent β-cell Function
Standard Error 0.09
|
38.3 percent β-cell Function
Standard Error 0.11
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to End of Study (56[+/-2] and 168 [+/- 5] days after dosing for Cohort 1 and Cohorts 2-4, respectively)Population: All randomized participants who received study medication were included in the Safety Analysis
An adverse event is any unwanted event, whether related to study drug or not occurring during the study period. A Serious Adverse Event (SAE) is an event resulting in death, requiring or prolonging hospitalization, a congenital anomaly or other important medical event. AEs and SAEs were recorded at each visit.
Outcome measures
| Measure |
Cohort 2: Canakinumab Infusion 10 mg/kg
n=10 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=5 Participants
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=45 Participants
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=45 Participants
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3: Canakinumab Infusion 1.5 mg/kg
n=25 Participants
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Pooled (Cohort 3 and 4): Placebo Infusion
n=24 Participants
Pooled Placebo of Cohort 3 and 4. Single dose IV infusion of Placebo
|
Cohort 4: Canakinumab Injection 0.03 mg/kg
n=23 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 3: Placebo Infusion
n=24 Participants
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
n=20 Participants
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
n=10 Participants
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency
Serious Adverse Events
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency
Adverse Events Above 5 % Frequency
|
1 Participants
|
2 Participants
|
9 Participants
|
6 Participants
|
4 Participants
|
4 Participants
|
2 Participants
|
6 Participants
|
10 Participants
|
2 Participants
|
Adverse Events
Cohort 1: Canakinumab Infusion 0.3 mg/kg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 1: Placebo to Canakinumab 0.3 mg/kg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 2: Canakinumab Infusion 10 mg/kg
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Cohort 2: Placebo to Canakinumab 10 mg/kg
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 3: Canakinumab Infusion 0.1 mg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 3: Canakinumab Infusion 0.3 mg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 3 : Canakinumab Infusion 1.5 mg/kg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 3: Placebo Infusion
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 4 : Canakinumab Injection 0.03 mg/kg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1: Canakinumab Infusion 0.3 mg/kg
n=10 participants at risk
Single dose intravenous (IV) infusion of canakinumab 0.3 mg/kg
|
Cohort 1: Placebo to Canakinumab 0.3 mg/kg
n=5 participants at risk
Single dose IV infusion of placebo to Canakinumab 0.3 mg/kg
|
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 participants at risk
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 participants at risk
Single dose IV infusion of Placebo to Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 participants at risk
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 participants at risk
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3 : Canakinumab Infusion 1.5 mg/kg
n=23 participants at risk
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Cohort 3: Placebo Infusion
n=24 participants at risk
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
n=20 participants at risk
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
n=10 participants at risk
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Gastrointestinal disorders
Intestinal polyp
|
0.00%
0/10
|
0.00%
0/5
|
2.2%
1/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/20
|
0.00%
0/10
|
Other adverse events
| Measure |
Cohort 1: Canakinumab Infusion 0.3 mg/kg
n=10 participants at risk
Single dose intravenous (IV) infusion of canakinumab 0.3 mg/kg
|
Cohort 1: Placebo to Canakinumab 0.3 mg/kg
n=5 participants at risk
Single dose IV infusion of placebo to Canakinumab 0.3 mg/kg
|
Cohort 2: Canakinumab Infusion 10 mg/kg
n=45 participants at risk
Single dose IV infusion of Canakinumab 10 mg/kg
|
Cohort 2: Placebo to Canakinumab 10 mg/kg
n=45 participants at risk
Single dose IV infusion of Placebo to Canakinumab 10 mg/kg
|
Cohort 3: Canakinumab Infusion 0.1 mg/kg
n=25 participants at risk
Single dose IV infusion Canakinumab 0.1 mg/kg
|
Cohort 3: Canakinumab Infusion 0.3 mg/kg
n=24 participants at risk
Single dose IV infusion of Canakinumab 0.3 mg/kg
|
Cohort 3 : Canakinumab Infusion 1.5 mg/kg
n=23 participants at risk
Single dose IV infusion of canakinumab 1.5 mg/kg
|
Cohort 3: Placebo Infusion
n=24 participants at risk
Single dose IV infusion of Placebo
|
Cohort 4 : Canakinumab Injection 0.03 mg/kg
n=20 participants at risk
Single dose IV injection of Canakinumab 0.03 mg/kg
|
Cohort 4: Placebo to Canakinumab 0.03 mg/kg
n=10 participants at risk
Single dose IV injection of Placebo to Canakinumab 0.03 mg/kg
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
5.0%
1/20
|
10.0%
1/10
|
|
Eye disorders
Cataract
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
5.0%
1/20
|
0.00%
0/10
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/10
|
20.0%
1/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
10.0%
2/20
|
0.00%
0/10
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
0.00%
0/5
|
2.2%
1/45
|
4.4%
2/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
5.0%
1/20
|
0.00%
0/10
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
2.2%
1/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
8.3%
2/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Infections and infestations
Bronchitis
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
4.0%
1/25
|
8.3%
2/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Infections and infestations
Cystitis
|
0.00%
0/10
|
0.00%
0/5
|
4.4%
2/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
5.0%
1/20
|
0.00%
0/10
|
|
Infections and infestations
Influenza
|
10.0%
1/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/10
|
0.00%
0/5
|
15.6%
7/45
|
4.4%
2/45
|
16.0%
4/25
|
8.3%
2/24
|
4.3%
1/23
|
4.2%
1/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
15.0%
3/20
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
5.0%
1/20
|
0.00%
0/10
|
|
Nervous system disorders
Headache
|
0.00%
0/10
|
20.0%
1/5
|
6.7%
3/45
|
4.4%
2/45
|
0.00%
0/25
|
4.2%
1/24
|
0.00%
0/23
|
8.3%
2/24
|
0.00%
0/20
|
0.00%
0/10
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
5.0%
1/20
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/10
|
0.00%
0/5
|
2.2%
1/45
|
2.2%
1/45
|
0.00%
0/25
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/20
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10
|
0.00%
0/5
|
0.00%
0/45
|
0.00%
0/45
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/23
|
8.3%
2/24
|
0.00%
0/20
|
0.00%
0/10
|
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