Trial Outcomes & Findings for Safety, Tolerability, and Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy (NCT NCT02024932)
NCT ID: NCT02024932
Last Updated: 2021-01-05
Results Overview
Safety was monitored throughout the study.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
37 participants
Primary outcome timeframe
After 78 days in Part A and after 85 days in Part B.
Results posted on
2021-01-05
Participant Flow
This study was conducted in 2 parts, Part A and Part B. In Part A, Cohort 1 participants received open-label BVS857. Cohort 2 participants were randomized to double-blind BVS857 or double-blind placebo in a 2:1 ratio.
In Part B, Cohort 3 was not enrolled. Cohort 4 participants received open-label BVS857. Cohort 5 participants were randomized to double-blind BVS857 or double-blind placebo in a ratio of 18:10.
Participant milestones
| Measure |
BVS857 Part A Open Label (Cohort 1)
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
2
|
4
|
2
|
2
|
18
|
9
|
|
Overall Study
Safety Analysis Set
|
2
|
4
|
2
|
2
|
18
|
9
|
|
Overall Study
Pharmacokinetic (PK) Analysis Set
|
2
|
4
|
0
|
2
|
18
|
0
|
|
Overall Study
Pharmacodynamic (PD) Analysis Set
|
2
|
4
|
2
|
2
|
18
|
9
|
|
Overall Study
COMPLETED
|
0
|
1
|
2
|
0
|
16
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
0
|
2
|
2
|
0
|
Reasons for withdrawal
| Measure |
BVS857 Part A Open Label (Cohort 1)
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
0
|
0
|
2
|
0
|
|
Overall Study
Abnormal laboratory value
|
0
|
0
|
0
|
2
|
0
|
0
|
Baseline Characteristics
Safety, Tolerability, and Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy
Baseline characteristics by cohort
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=4 Participants
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
n=2 Participants
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
n=2 Participants
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
n=18 Participants
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
n=9 Participants
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
67.0 Years
STANDARD_DEVIATION 5.66 • n=99 Participants
|
56.0 Years
STANDARD_DEVIATION 12.33 • n=107 Participants
|
59.5 Years
STANDARD_DEVIATION 7.78 • n=206 Participants
|
41.5 Years
STANDARD_DEVIATION 4.95 • n=157 Participants
|
57.0 Years
STANDARD_DEVIATION 55.5 • n=390 Participants
|
54.0 Years
STANDARD_DEVIATION 5.94 • n=16 Participants
|
56.0 Years
STANDARD_DEVIATION 10.33 • n=3 Participants
|
|
Sex/Gender, Customized
Male
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
2 Participants
n=157 Participants
|
18 Participants
n=390 Participants
|
9 Participants
n=16 Participants
|
37 Participants
n=3 Participants
|
PRIMARY outcome
Timeframe: After 78 days in Part A and after 85 days in Part B.Population: The safety analysis set, which included participants who received any study drug, was analyzed.
Safety was monitored throughout the study.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=4 Participants
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
n=2 Participants
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
n=2 Participants
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
n=18 Participants
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
n=9 Participants
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability
Non-serious AEs
|
2 Participants
|
4 Participants
|
2 Participants
|
1 Participants
|
17 Participants
|
8 Participants
|
|
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability
Deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: After 78 days in Part A and after 85 days in Part B.Population: The safety analysis set, which included participants who received any study drug, was analyzed.
Safety was monitored throughout the study.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=4 Participants
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
n=2 Participants
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
n=2 Participants
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
n=18 Participants
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
n=9 Participants
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability
Mild
|
1 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
5 Participants
|
4 Participants
|
|
Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability
Moderate
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
11 Participants
|
3 Participants
|
|
Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability
Severe
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 85Population: The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data.
Thigh muscle volume was assessed by magnetic resonance imaging (MRI). Change from baseline was calculated from the ratio of the post-baseline mean value to the baseline mean value: \[(Day 85/baseline) - 1)\] x 100. A positive change from baseline indicates improvement.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=15 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=9 Participants
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5
|
0.0 Percent change
Standard Deviation 2.42
|
-3.4 Percent change
Standard Deviation 4.79
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 85Population: The PD set included, which included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data, was analyzed.
The AMAT rated physical function and muscle endurance, with higher scores indicating better performance. The tool includes 7 timed functional tasks rated on a scale from 0 - 21 and 6 endurance tasks rated on a scale from 0 - 24. The range for the total score was from 0 (worst) to 45 (best). A positive change from baseline indicates improvement.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=18 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=9 Participants
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5
|
1.0 score on a scale
Standard Deviation 4.20
|
2.3 score on a scale
Standard Deviation 1.87
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 85Population: The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data.
LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=17 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=8 Participants
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5
|
0.77 kilograms
Standard Deviation 1.556
|
0.16 kilograms
Standard Deviation 1.199
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1
Day 1, 0.01 mg/kg BVS857 i.v.
|
184 ng/mL
Standard Deviation 6.36
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1
Day 15, 0.01 mg/kg BVS857 s.c.
|
34.6 ng/mL
Standard Deviation 48.9
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1
Day 29, 0.03 mg/kg BVS857 s.c
|
83.1 ng/mL
Standard Deviation 20.3
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1
Day 43, 0.06 mg/kg BVS857 s.c.
|
74.2 ng/mL
Standard Deviation 16.1
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=4 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Day 1, 0.03 mg/kg BVS857 i.v. (n=4)
|
393 ng/mL
Standard Deviation 30.1
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Day 15, 0.03 mg/kg BVS857 s.c. (n=3)
|
77.3 ng/mL
Standard Deviation 46.5
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Day 29, 0.06 mg/kg BVS857 s.c. (n=2)
|
113 ng/mL
Standard Deviation 2.12
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Day 43, 0.10 mg/kg BVS857 s.c. (n=3)
|
191 ng/mL
Standard Deviation 19.2
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Day 57, 0.10 mg/kg BVS857 s.c. (n=1)
|
232 ng/mL
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1
Day 1, 0.01 mg/kg BVS857 i.v. (n=2)
|
4.04 hours
Standard Deviation 0.0566
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1
Day 15, 0.01 mg/kg BVS857 s.c. (n=1)
|
12.1 hours
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1
Day 29, 0.03 mg/kg BVS857 s.c.(n=2)
|
18.1 hours
Standard Deviation 8.41
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1
Day 43, 0.06 mg/kg BVS857 s.c. (n=2)
|
36.0 hours
Standard Deviation 16.8
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=4 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Day 1, 0.03 mg/kg BVS857 i.v. (n=4)
|
2.53 hours
Standard Deviation 1.70
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Day 15, 0.03 mg/kg BVS857 s.c.(n=3)
|
24.1 hours
Standard Deviation 0.100
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Day 29, 0.06 mg/kg BVS857 s.c. (n=2)
|
24.0 hours
Standard Deviation 0
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Day 43, 0.10 mg/kg BVS857 s.c. (n=3)
|
24.0 hours
Standard Deviation 0.200
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Day 57, 0.10 mg/kg BVS857 s.c. (n=1)
|
48.0 hours
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1
Day 1, 0.01 mg/kg BVS857 i.v.(n=2)
|
4630 h*ng/mL
Standard Deviation 1200
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1
Day 15, 0.01 mg/kg BVS857 s.c. (n=2)
|
1060 h*ng/mL
Standard Deviation 1500
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1
Day 29, 0.03 mg/kg BVS857 s.c.(n=2)
|
2720 h*ng/mL
Standard Deviation 870
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1
Day 43, 0.06 mg/kg BVS857 s.c.(n=2)
|
5310 h*ng/mL
Standard Deviation 4720
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=4 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Day 1, 0.03 mg/kg BVS857 i.v.(n=4)
|
9850 H*ng/mL
Standard Deviation 4480
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Day 15, 0.03 mg/kg BVS857 s.c. (n=3)
|
6480 H*ng/mL
Standard Deviation 5850
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Day 29, 0.06 mg/kg BVS857 s.c. (n=2)
|
7340 H*ng/mL
Standard Deviation 5610
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Day 43, 0.10 mg/kg BVS857 s.c. (n=3)
|
14400 H*ng/mL
Standard Deviation 3320
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Day 57, 0.10 mg/kg BVS857 s.c. (n=1)
|
28400 H*ng/mL
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1
Day 15, 0.01 mg/kg BVS857 s.c. (n=1)
|
2120 h*ng/mL
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1
Day 29, 0.03 mg/kg BVS857 s.c. (n=2)
|
2720 h*ng/mL
Standard Deviation 870
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1
Day 43, 0.06 mg/kg BVS857 s.c. (n=2)
|
2210 h*ng/mL
Standard Deviation 339
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1
Day 1, 0.01 mg/kg BVS857 i.v.(n=2)
|
4620 h*ng/mL
Standard Deviation 1200
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dosePopulation: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=4 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Day 57, 0.10 mg/kg BVS857 s.c. (n=1)
|
7360 h*ng/mL
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Day 1, 0.03 mg/kg BVS857 i.v. (n=4)
|
7980 h*ng/mL
Standard Deviation 1710
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Day 15, 0.03 mg/kg BVS857 s.c. (n=3)
|
2640 h*ng/mL
Standard Deviation 1500
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Day 29, 0.06 mg/kg BVS857 s.c. (n=2)
|
3880 h*ng/mL
Standard Deviation 735
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Day 43, 0.10 mg/kg BVS857 s.c. (n=3)
|
6390 h*ng/mL
Standard Deviation 925
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1: pre-dose, 1, 4, 24, 48 hours post-dosePopulation: The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4
|
2490 ng/mL
Standard Deviation 799
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=18 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5
Day 1, 0.06 mg/kg BVS857 i.v. (n=18)
|
854 ng/mL
Standard Deviation 669
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5
Day 36, 0.06 mg/kg BVS857 i.v. (n=16)
|
790 ng/mL
Standard Deviation 184
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5
Day 78, 0.06 mg/kg BVS857 i.v. (n=16)
|
712 ng/mL
Standard Deviation 218
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1: pre-dose, 1, 4, 24, 48 hours post-dosePopulation: The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4
|
1.08 hours
Standard Deviation 0.0707
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=18 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5
Day 1, 0.06 mg/kg BVS857 i.v. (n=18)
|
2.39 hours
Standard Deviation 1.54
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5
Day 36, 0.06 mg/kg BVS857 i.v. (n=16)
|
1.73 hours
Standard Deviation 1.20
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5
Day 78, 0.06 mg/kg BVS857 i.v. (n=16)
|
1.49 hours
Standard Deviation 1.04
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Serum samples were obtained for PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=18 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5
Day 78, 0.06 mg/kg BVS857 i.v. (n=15)
|
28000 h*ng/mL
Standard Deviation 13500
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5
Day 36, 0.06 mg/kg BVS857 i.v. (n=1)
|
13100 h*ng/mL
Standard Deviation NA
Standard deviation does not apply when n = 1.
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1: pre-dose, 1, 4, 24, 48 hours post-dosePopulation: The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
Serum samples were obtained for the PK assessment.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4
|
40600 H*ng/mL
Standard Deviation 1270
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Outcome measures
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=18 Participants
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
BVS857 Part A Double Blind (Cohort 2)
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
Placebo Part A Double Blind (Cohort 2)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part B Open-label (Cohort 4)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5
Day 1, 0.06 mg/kg BVS857 i.v. (n=18)
|
19400 h*ng/mL
Standard Deviation 4160
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5
Day 36, 0.06 mg/kg BVS857 i.v.(n=16)
|
19600 h*ng/mL
Standard Deviation 5240
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5
Day 78, 0.06 mg/kg BVS857 i.v. (n=16)
|
18100 h*ng/mL
Standard Deviation 5850
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Serum samples were obtained for PK assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Serum samples were obtained for PK assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Serum samples were obtained for PK assessment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose.Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Serum samples were obtained for PK assessment.
Outcome measures
Outcome data not reported
Adverse Events
BVS857 Part A Open Label (Cohort 1)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo Part A Double Blind (Cohort 2)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
BVS857 Part A Double Blind (Cohort 2)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
BVS857 Part B Open-label (Cohort 4)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
BVS857 Part B Double Blind (Cohort 5)
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Placebo Part B Double Blind (Cohort 5)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BVS857 Part A Open Label (Cohort 1)
n=2 participants at risk
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
|
Placebo Part A Double Blind (Cohort 2)
n=2 participants at risk
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
|
BVS857 Part A Double Blind (Cohort 2)
n=4 participants at risk
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
|
BVS857 Part B Open-label (Cohort 4)
n=2 participants at risk
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
|
BVS857 Part B Double Blind (Cohort 5)
n=18 participants at risk
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
|
Placebo Part B Double Blind (Cohort 5)
n=9 participants at risk
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Nervous system disorders
Dizziness
|
0.00%
0/2
|
0.00%
0/2
|
50.0%
2/4
|
0.00%
0/2
|
11.1%
2/18
|
0.00%
0/9
|
|
Nervous system disorders
Headache
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
16.7%
3/18
|
11.1%
1/9
|
|
Nervous system disorders
Hypoaesthesia
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
11.1%
2/18
|
0.00%
0/9
|
|
Nervous system disorders
Presyncope
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Nervous system disorders
Somnolence
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Psychiatric disorders
Irritability
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
5.6%
1/18
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Vascular disorders
Flushing
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Vascular disorders
Hypertension
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
11.1%
1/9
|
|
Vascular disorders
Hypotension
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Ear and labyrinth disorders
Eustachian tube dysfunction
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Eye disorders
Eyelid haematoma
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Eye disorders
Glaucoma
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Eye disorders
Ocular discomfort
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Eye disorders
Scleral hyperaemia
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Eye disorders
Vision blurred
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Lip disorder
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Lip oedema
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
11.1%
1/9
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Paraesthesia oral
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Periodontal disease
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Sensitivity of teeth
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
General disorders
Administration site hypersensitivity
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Asthenia
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Catheter site extravasation
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
General disorders
Fatigue
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
11.1%
2/18
|
0.00%
0/9
|
|
General disorders
Feeling hot
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Infusion site erythema
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Infusion site pruritus
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Injection site erythema
|
100.0%
2/2
|
0.00%
0/2
|
75.0%
3/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
General disorders
Injection site rash
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
General disorders
Injection site swelling
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
General disorders
Malaise
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Puncture site pain
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
11.1%
2/18
|
0.00%
0/9
|
|
General disorders
Pyrexia
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
General disorders
Therapeutic response unexpected
|
100.0%
2/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Infections and infestations
Bronchitis
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Infections and infestations
Influenza
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/2
|
100.0%
2/2
|
25.0%
1/4
|
0.00%
0/2
|
22.2%
4/18
|
11.1%
1/9
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Injury, poisoning and procedural complications
Bone contusion
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Injury, poisoning and procedural complications
Fall
|
50.0%
1/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
50.0%
1/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Investigations
Blood potassium increased
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Investigations
Blood pressure increased
|
0.00%
0/2
|
0.00%
0/2
|
25.0%
1/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Investigations
Neutralising antibodies positive
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
11.1%
2/18
|
0.00%
0/9
|
|
Investigations
Weight increased
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
22.2%
2/9
|
|
Musculoskeletal and connective tissue disorders
Exostosis of jaw
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/18
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
50.0%
1/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
11.1%
2/18
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
0.00%
0/2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/2
|
5.6%
1/18
|
0.00%
0/9
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-1873
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