Trial Outcomes & Findings for Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients (NCT NCT00669942)
NCT ID: NCT00669942
Last Updated: 2015-03-30
Results Overview
Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
104 participants
Primary outcome timeframe
Day 43
Results posted on
2015-03-30
Participant Flow
Part 1: single dose escalation - sequential cohorts of patients and healthy volunteers received AIN457A or placebo. Part 2: multiple dose escalation - sequential cohorts of patients received 2 doses of AIN457A or placebo. Part 3: patients received 2 doses of AIN457 10 mg/kg (or the maximum tolerated dose) or placebo.
In parts 1 and 2, participants were randomized 3:1 to receive AIN457A or placebo. In part 3, participants were randomized 1:1 to receive AIN457A or placebo.
Participant milestones
| Measure |
Part 1 - AIN457A 0.3 mg/kg
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
|
Parts 2 and 3 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Part 1
STARTED
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6
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6
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6
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6
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8
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0
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0
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0
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0
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Part 1
COMPLETED
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6
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6
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6
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6
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8
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0
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0
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0
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0
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0
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0
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0
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Part 1
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Parts 2 and 3
STARTED
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0
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0
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0
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0
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0
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6
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6
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26
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26
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0
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Parts 2 and 3
COMPLETED
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0
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0
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0
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0
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0
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4
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6
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24
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23
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0
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0
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0
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Parts 2 and 3
NOT COMPLETED
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0
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0
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0
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0
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0
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2
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0
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2
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3
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0
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0
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0
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Healthy Volunteers
STARTED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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3
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3
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2
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Healthy Volunteers
COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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3
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2
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2
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Healthy Volunteers
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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1
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0
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Reasons for withdrawal
| Measure |
Part 1 - AIN457A 0.3 mg/kg
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
|
Parts 2 and 3 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 2 and 3
Adverse Event
|
0
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0
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0
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0
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0
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0
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0
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2
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1
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0
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0
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0
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Parts 2 and 3
Withdrawal by Subject
|
0
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0
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0
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0
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0
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1
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0
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0
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2
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0
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0
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0
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Parts 2 and 3
Protocol Violation
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0
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0
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0
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0
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0
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1
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0
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0
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0
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0
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0
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0
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Baseline Characteristics
Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients
Baseline characteristics by cohort
| Measure |
Part 1 - AIN457A 0.3 mg/kg
n=6 Participants
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 1.0 mg/kg
n=6 Participants
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=8 Participants
Placebo to AIN457A was administered intravenously as a single dose.
|
Parts 2 and 3 - AIN457A 1.0 mg/kg
n=6 Participants
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457A 10 mg/kg
n=26 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=26 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
n=3 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
n=3 Participants
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - Placebo
n=2 Participants
Placebo to AIN457A was administered intravenously as a single dose.
|
Total
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
57.6 Years
STANDARD_DEVIATION 8.04 • n=5 Participants
|
58.8 Years
STANDARD_DEVIATION 13.61 • n=7 Participants
|
51.2 Years
STANDARD_DEVIATION 9.50 • n=5 Participants
|
63.2 Years
STANDARD_DEVIATION 9.45 • n=4 Participants
|
57.8 Years
STANDARD_DEVIATION 3.41 • n=21 Participants
|
60.8 Years
STANDARD_DEVIATION 8.66 • n=10 Participants
|
56.0 Years
STANDARD_DEVIATION 12.00 • n=115 Participants
|
49.9 Years
STANDARD_DEVIATION 8.53 • n=6 Participants
|
49.8 Years
STANDARD_DEVIATION 15.19 • n=6 Participants
|
26.7 Years
STANDARD_DEVIATION 10.02 • n=64 Participants
|
22.3 Years
STANDARD_DEVIATION 2.31 • n=17 Participants
|
42.5 Years
STANDARD_DEVIATION 10.61 • n=21 Participants
|
46.07 Years
STANDARD_DEVIATION 10.83 • n=22 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
19 Participants
n=6 Participants
|
20 Participants
n=6 Participants
|
0 Participants
n=64 Participants
|
0 Participants
n=17 Participants
|
1 Participants
n=21 Participants
|
75 Participants
n=22 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
7 Participants
n=6 Participants
|
6 Participants
n=6 Participants
|
3 Participants
n=64 Participants
|
3 Participants
n=17 Participants
|
1 Participants
n=21 Participants
|
29 Participants
n=22 Participants
|
PRIMARY outcome
Timeframe: Day 43Population: The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants.
Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=26 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=26 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
|
46 percentage of participants
|
27 percentage of participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 113Population: Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=5 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants
|
0.09028 day
Interval 0.0833 to 0.167
|
0.08472 day
Interval 0.0813 to 0.167
|
0.1253 day
Interval 0.0806 to 0.167
|
0.1260 day
Interval 0.0833 to 0.99
|
PRIMARY outcome
Timeframe: Day 113Population: Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=5 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants
|
8.772 ug/mL
Standard Deviation 1.8020
|
35.22 ug/mL
Standard Deviation 18.755
|
70.95 ug/mL
Standard Deviation 9.9472
|
211.8 ug/mL
Standard Deviation 36.837
|
PRIMARY outcome
Timeframe: Day 113Population: Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=5 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants
AUCinf
|
141.3 day*ug/mL
Standard Deviation 48.781
|
430.7 day*ug/mL
Standard Deviation 48.281
|
1148 day*ug/mL
Standard Deviation 330.89
|
4080 day*ug/mL
Standard Deviation 768.87
|
|
PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants
AUClast
|
132.7 day*ug/mL
Standard Deviation 42.824
|
415.6 day*ug/mL
Standard Deviation 42.793
|
1097 day*ug/mL
Standard Deviation 291.59
|
3936 day*ug/mL
Standard Deviation 697.65
|
PRIMARY outcome
Timeframe: Day 113Population: Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=5 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants
|
7.043 Liters
Standard Deviation 2.0197
|
6.756 Liters
Standard Deviation 2.2186
|
6.506 Liters
Standard Deviation 0.83822
|
6.699 Liters
Standard Deviation 0.83967
|
PRIMARY outcome
Timeframe: Day 113Population: Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=5 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants
|
0.2249 Liters/day
Standard Deviation 0.11196
|
0.2110 Liters/day
Standard Deviation 0.064415
|
0.2077 Liters/day
Standard Deviation 0.080880
|
0.1999 Liters/day
Standard Deviation 0.049375
|
PRIMARY outcome
Timeframe: Day 113Population: Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants
|
23.21 day
Standard Deviation 6.8285
|
22.27 day
Standard Deviation 2.8478
|
23.47 day
Standard Deviation 5.7952
|
23.94 day
Standard Deviation 4.2566
|
PRIMARY outcome
Timeframe: Day 113Population: Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=26 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants
|
21.08 day
Interval 0.167 to 21.2
|
21.08 day
Interval 20.1 to 21.3
|
21.09 day
Interval 0.0736 to 21.4
|
—
|
PRIMARY outcome
Timeframe: Day 113Population: Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=26 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants
|
23.54 ug/mL
Standard Error 3.1588
|
97.78 ug/mL
Standard Error 15.543
|
322.2 ug/mL
Standard Error 96.719
|
—
|
PRIMARY outcome
Timeframe: Day 113Population: Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=26 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
AUCinf
|
808.6 day*ug/mL
Standard Deviation 251.01
|
2843 day*ug/mL
Standard Deviation 481.49
|
8371 day*ug/mL
Standard Deviation 2505.8
|
—
|
|
Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
AUClast
|
746.4 day*ug/mL
Standard Deviation 209.20
|
2704 day*ug/mL
Standard Deviation 467.60
|
7815 day*ug/mL
Standard Deviation 2102.0
|
—
|
PRIMARY outcome
Timeframe: Day 113Population: Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=26 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants
|
6.514 Liter
Standard Deviation 1.1542
|
6.062 Liter
Standard Deviation 1.0189
|
6.382 Liter
Standard Deviation 1.1336
|
—
|
PRIMARY outcome
Timeframe: Day 113Population: Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=26 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants
|
0.1834 Liters/day
Standard Deviation 0.042822
|
0.1775 Liters/day
Standard Deviation 0.034075
|
0.1994 Liters/day
Standard Deviation 0.063454
|
—
|
PRIMARY outcome
Timeframe: Day 113Population: Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis.
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=6 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=6 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
n=26 Participants
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants
|
25.60 Day
Standard Deviation 6.3100
|
23.89 Day
Standard Deviation 3.2335
|
23.68 Day
Standard Deviation 6.3048
|
—
|
SECONDARY outcome
Timeframe: Day 43Population: The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants.
Clinical response to treatment was assessed according to ACR50 and ACR70 criteria. A participant was defined as an ACR50 or ACR70 responder if the following 3 conditions were met: 1) improvement of ≥50% or ≥ 70%, respectively, in the number of tender joints, 2) improvement of ≥50% or ≥ 70%, respectively, in the number of swollen joints and 3) improvement of ≥50% or ≥ 70%, respectively, in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=26 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=26 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
ACR50
|
27 Percentage of participants
|
15 Percentage of participants
|
—
|
—
|
|
Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
ACR70
|
8 Percentage of participants
|
8 Percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 43Population: The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants.
The DAS28 is a composite score based on tender and swollen joint counts, C reactive protein (CRP) concentrations, and the participant's global disease activity based on a visual analogue scale (VAS). The tender joint count (based on 28 joints) was calculated by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. The information on various types of tenderness was then collapsed into a single tender versus non-tender dichotomy, and the number of joints that were classified as tender was recorded. The swollen joint count was calculated in the same manner. For CRP concentrations, blood samples were collected and sent to a central laboratory for assessment. For the VAS assessment, the participant used a 100 mm horizontal VAS to assess the severity of his or her arthritis where 0 = none and 100 = most severe. DAS28 scores range from \<2.6 (disease remission) to \>5.1 (high disease activity).
Outcome measures
| Measure |
Parts 2 and 3 - AIN457A 10 mg/kg
n=25 Participants
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=23 Participants
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|
|
Disease Activity Score (DAS28) of Parts 2 and 3 Participants
|
4.306 scores on a scale
Standard Error 1.4787
|
4.598 scores on a scale
Standard Error 1.2618
|
—
|
—
|
Adverse Events
Part 1 - AIN457A 0.3 mg/kg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 1 - AIN457A 1.0 mg/kg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 - AIN457A 3.0 mg/kg
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Part 1 - AIN457A 10 mg/kg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 - Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Parts 2 and 3 - AIN457 1.0 mg/kg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Parts 2 and 3 - AIN457 3.0 mg/kg
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Parts 2 and 3 - AIN457 10 mg/kg
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
Parts 2 and 3 - Placebo
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part 1 - Healthy Volunteers - Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part 1 - AIN457A 0.3 mg/kg
n=6 participants at risk
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 1.0 mg/kg
n=6 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 participants at risk
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 participants at risk
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=8 participants at risk
Placebo to AIN457A was administered intravenously as a single dose.
|
Parts 2 and 3 - AIN457 1.0 mg/kg
n=6 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457 3.0 mg/kg
n=6 participants at risk
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457 10 mg/kg
n=26 participants at risk
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=26 participants at risk
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
n=3 participants at risk
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - Placebo
n=2 participants at risk
Placebo to AIN457A was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
n=3 participants at risk
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Nervous system disorders
Brachial plexopathy
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
Other adverse events
| Measure |
Part 1 - AIN457A 0.3 mg/kg
n=6 participants at risk
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 1.0 mg/kg
n=6 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 3.0 mg/kg
n=6 participants at risk
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - AIN457A 10 mg/kg
n=6 participants at risk
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Placebo
n=8 participants at risk
Placebo to AIN457A was administered intravenously as a single dose.
|
Parts 2 and 3 - AIN457 1.0 mg/kg
n=6 participants at risk
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457 3.0 mg/kg
n=6 participants at risk
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - AIN457 10 mg/kg
n=26 participants at risk
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Parts 2 and 3 - Placebo
n=26 participants at risk
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
n=3 participants at risk
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - Placebo
n=2 participants at risk
Placebo to AIN457A was administered intravenously as a single dose.
|
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
n=3 participants at risk
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/8
|
16.7%
1/6
|
16.7%
1/6
|
3.8%
1/26
|
7.7%
2/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
11.5%
3/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
3.8%
1/26
|
11.5%
3/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
General disorders
Asthenia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
General disorders
Fatigue
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
2/6
|
0.00%
0/6
|
7.7%
2/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
General disorders
Oedema peripheral
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
General disorders
Pain
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Bronchitis
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Fungal infection
|
0.00%
0/6
|
0.00%
0/6
|
33.3%
2/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Influenza
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
12.5%
1/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Paronychia
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
12.5%
1/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
7.7%
2/26
|
0.00%
0/3
|
50.0%
1/2
|
0.00%
0/3
|
|
Infections and infestations
Urinary tract infection
|
33.3%
2/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
7.7%
2/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
3.8%
1/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
50.0%
1/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
3.8%
1/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
33.3%
1/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
12.5%
1/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
12.5%
1/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
11.5%
3/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
16.7%
1/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
16.7%
1/6
|
11.5%
3/26
|
7.7%
2/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
11.5%
3/26
|
11.5%
3/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
7.7%
2/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Nervous system disorders
Tremor
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
3.8%
1/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
3.8%
1/26
|
7.7%
2/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Vascular disorders
Haematoma
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Vascular disorders
Hypertension
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
7.7%
2/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
|
Vascular disorders
Hypotension
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/3
|
0.00%
0/2
|
0.00%
0/3
|
Additional Information
Study Director
Novartis
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 or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER