Trial Outcomes & Findings for Study to Assess the Safety, Tolerability and PK/PD After 4 Weekly SC Injections of PB1046 in Subjects With Stable HFrEF (NCT NCT02808585)
NCT ID: NCT02808585
Last Updated: 2022-07-14
Results Overview
Number of participants with rhythm abnormalities as assessed by continuous mobile telemetry monitoring.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
29 participants
Primary outcome timeframe
Up to six weeks starting 7 to 10 days before first dose.
Results posted on
2022-07-14
Participant Flow
Participant milestones
| Measure |
PB1046 Injection, 0.2 mg/kg
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
6
|
7
|
6
|
7
|
|
Overall Study
COMPLETED
|
3
|
6
|
6
|
4
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
2
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Safety, Tolerability and PK/PD After 4 Weekly SC Injections of PB1046 in Subjects With Stable HFrEF
Baseline characteristics by cohort
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
60.7 years
STANDARD_DEVIATION 13.01 • n=5 Participants
|
69.7 years
STANDARD_DEVIATION 10.89 • n=7 Participants
|
67.6 years
STANDARD_DEVIATION 11.27 • n=5 Participants
|
64.3 years
STANDARD_DEVIATION 4.03 • n=4 Participants
|
65 years
STANDARD_DEVIATION 8.41 • n=21 Participants
|
66.0 years
STANDARD_DEVIATION 9.18 • n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
8 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
21 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
25 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7 participants
n=5 Participants
|
6 participants
n=4 Participants
|
7 participants
n=21 Participants
|
29 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Up to six weeks starting 7 to 10 days before first dose.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants with rhythm abnormalities as assessed by continuous mobile telemetry monitoring.
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Telemetry
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Seven weeks starting the first week of dosing.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants with a clinically significant change from baseline in 12-Lead ECG and presence of rhythm abnormalities and relationship to exposure of PB1046 compared to placebo
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
12-Lead ECG Assessment - Incidence of Clinically Significant Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Seven weeks starting the first week of dosing.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants with a clinically significant change from baseline in 12-Lead ECG and presence or absence of rhythm abnormalities and relationship to exposure of PB1046 compared to placebo
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
12-Lead ECG - Categorical Analysis of QT/QTc Interval - Participants With Clinically Significant Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Eight weeks starting one week before first dose.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants with clinically significant changes from baseline in laboratory parameters (serum chemistry) and the relationship to PB1046 compared to placebo
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Laboratory Parameters - Serum Chemistry - Participants With Clinically Significant Findings
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Eight weeks starting one week before first dose.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants with clinically significant changes from baseline in laboratory parameters (hematology) and the relationship to PB1046 compared to placebo
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Laboratory Parameters - Hematology - Participants With Clinically Significant Findings
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Eight weeks starting one week before first dose.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants with clinically significant changes from baseline in laboratory parameters (urinalysis) and the relationship to PB1046 compared to placebo
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Laboratory Parameters - Urinalysis - Participants With Clinically Significant Findings
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 2, 3, 4, 5 and 8.Population: Safety/Intent-to-Treat/Per Protocol Population. One subject at 0.6 mg/kg dose missed sample collection and was excluded from analysis.
Changes from baseline in laboratory parameters (eGFR) and the relationship to PB1046 compared to placebo. Calculated using Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI)
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Laboratory Parameters - eGFR
Week 2
|
-1.04 mL/min/1.73m^2
Standard Deviation 4.00
|
2.2 mL/min/1.73m^2
Standard Deviation 11.41
|
-2.9 mL/min/1.73m^2
Standard Deviation 13.23
|
1.3 mL/min/1.73m^2
Standard Deviation 7.39
|
-4.6 mL/min/1.73m^2
Standard Deviation 5.88
|
|
Laboratory Parameters - eGFR
Week 3
|
-0.3 mL/min/1.73m^2
Standard Deviation 5.77
|
0.2 mL/min/1.73m^2
Standard Deviation 10.72
|
2.3 mL/min/1.73m^2
Standard Deviation 11.40
|
1.8 mL/min/1.73m^2
Standard Deviation 7.57
|
-4.6 mL/min/1.73m^2
Standard Deviation 5.19
|
|
Laboratory Parameters - eGFR
Week 4
|
0.0 mL/min/1.73m^2
Standard Deviation 2.65
|
-1.3 mL/min/1.73m^2
Standard Deviation 7.97
|
-1.4 mL/min/1.73m^2
Standard Deviation 4.12
|
5.8 mL/min/1.73m^2
Standard Deviation 9.55
|
-6.6 mL/min/1.73m^2
Standard Deviation 6.13
|
|
Laboratory Parameters - eGFR
Week 5
|
-0.3 mL/min/1.73m^2
Standard Deviation 6.66
|
-0.7 mL/min/1.73m^2
Standard Deviation 7.26
|
-2.2 mL/min/1.73m^2
Standard Deviation 13.29
|
9.3 mL/min/1.73m^2
Standard Deviation 7.93
|
-2.3 mL/min/1.73m^2
Standard Deviation 6.63
|
|
Laboratory Parameters - eGFR
Week 8
|
-3.3 mL/min/1.73m^2
Standard Deviation 8.62
|
-5.7 mL/min/1.73m^2
Standard Deviation 11.41
|
-3.7 mL/min/1.73m^2
Standard Deviation 14.22
|
-0.2 mL/min/1.73m^2
Standard Deviation 6.79
|
-3.0 mL/min/1.73m^2
Standard Deviation 4.12
|
PRIMARY outcome
Timeframe: Eight weeks starting one week before first dose (Baseline and at Week 8).Number of participants with clinically significant changes from baseline in laboratory parameters (lipid profile) and the relationship to PB1046 compared to placebo
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Laboratory Parameters - Lipid Profile - Participants With Clinically Significant Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.Population: Safety/Intent-to-Treat/Per Protocol Population
Changes from baseline in vital signs (systolic blood pressure) and the relationship to PB1046 compared to placebo.
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Vital Signs - Systolic Blood Pressure
Day 0 1 hr
|
7.4 mmHg
Standard Deviation 10.88
|
-6.2 mmHg
Standard Deviation 19.89
|
3.1 mmHg
Standard Deviation 8.17
|
-2.6 mmHg
Standard Deviation 13.43
|
4.6 mmHg
Standard Deviation 17.41
|
|
Vital Signs - Systolic Blood Pressure
Day 0 3 hr
|
4.9 mmHg
Standard Deviation 7.17
|
-2.6 mmHg
Standard Deviation 14.06
|
1.3 mmHg
Standard Deviation 6.52
|
-8.7 mmHg
Standard Deviation 6.24
|
3.4 mmHg
Standard Deviation 11.57
|
|
Vital Signs - Systolic Blood Pressure
Day 1
|
-3.4 mmHg
Standard Deviation 2.87
|
-5.8 mmHg
Standard Deviation 14.89
|
-2.3 mmHg
Standard Deviation 4.79
|
-15.4 mmHg
Standard Deviation 18.17
|
-7.1 mmHg
Standard Deviation 14.59
|
|
Vital Signs - Systolic Blood Pressure
Day 2
|
-0.6 mmHg
Standard Deviation 7.07
|
-4.4 mmHg
Standard Deviation 13.45
|
-7.2 mmHg
Standard Deviation 7.98
|
-8.9 mmHg
Standard Deviation 12.63
|
-2.9 mmHg
Standard Deviation 23.54
|
|
Vital Signs - Systolic Blood Pressure
Day 3
|
-6.7 mmHg
Standard Deviation 8.25
|
1.8 mmHg
Standard Deviation 24.86
|
-8.9 mmHg
Standard Deviation 9.08
|
-17.8 mmHg
Standard Deviation 18.09
|
-1.8 mmHg
Standard Deviation 16.75
|
|
Vital Signs - Systolic Blood Pressure
Day 5
|
2.4 mmHg
Standard Deviation 11.42
|
-4.6 mmHg
Standard Deviation 23.37
|
1.5 mmHg
Standard Deviation 8.57
|
-11.7 mmHg
Standard Deviation 20.19
|
1.3 mmHg
Standard Deviation 10.44
|
|
Vital Signs - Systolic Blood Pressure
Day 7 pre
|
-6.9 mmHg
Standard Deviation 2.22
|
-9.4 mmHg
Standard Deviation 11.47
|
-5.9 mmHg
Standard Deviation 13.47
|
-11.7 mmHg
Standard Deviation 3.78
|
-0.3 mmHg
Standard Deviation 10.73
|
|
Vital Signs - Systolic Blood Pressure
Day 14 pre
|
4.3 mmHg
Standard Deviation 9.60
|
-8.0 mmHg
Standard Deviation 14.73
|
-1.6 mmHg
Standard Deviation 9.32
|
-8.8 mmHg
Standard Deviation 14.62
|
-3.0 mmHg
Standard Deviation 17.71
|
|
Vital Signs - Systolic Blood Pressure
Day 21 pre
|
-3.0 mmHg
Standard Deviation 6.57
|
-8.4 mmHg
Standard Deviation 9.37
|
-1.6 mmHg
Standard Deviation 9.32
|
-8.8 mmHg
Standard Deviation 14.62
|
-5.1 mmHg
Standard Deviation 13.04
|
|
Vital Signs - Systolic Blood Pressure
Day 21 1 hr
|
-7.9 mmHg
Standard Deviation 4.40
|
-14.1 mmHg
Standard Deviation 9.15
|
-4.0 mmHg
Standard Deviation 10.00
|
-12.8 mmHg
Standard Deviation 15.89
|
-3.0 mmHg
Standard Deviation 9.00
|
|
Vital Signs - Systolic Blood Pressure
Day 21 3 hr
|
-7.9 mmHg
Standard Deviation 4.40
|
-14.1 mmHg
Standard Deviation 9.15
|
-4.0 mmHg
Standard Deviation 10.00
|
-12.8 mmHg
Standard Deviation 15.89
|
-3.0 mmHg
Standard Deviation 9.00
|
|
Vital Signs - Systolic Blood Pressure
Day 22
|
-5.0 mmHg
Standard Deviation 4.81
|
-10.6 mmHg
Standard Deviation 18.27
|
-9.4 mmHg
Standard Deviation 10.46
|
-20.8 mmHg
Standard Deviation 17.19
|
-3.4 mmHg
Standard Deviation 13.67
|
|
Vital Signs - Systolic Blood Pressure
Day 23
|
-9.2 mmHg
Standard Deviation 12.16
|
-4.7 mmHg
Standard Deviation 9.18
|
-9.2 mmHg
Standard Deviation 11.77
|
-8.0 mmHg
Standard Deviation 4.33
|
-0.8 mmHg
Standard Deviation 11.38
|
|
Vital Signs - Systolic Blood Pressure
Day 24
|
0.9 mmHg
Standard Deviation 5.50
|
-1.9 mmHg
Standard Deviation 9.19
|
-1.0 mmHg
Standard Deviation 12.16
|
-21.6 mmHg
Standard Deviation 29.51
|
2.0 mmHg
Standard Deviation 20.23
|
|
Vital Signs - Systolic Blood Pressure
Day 26
|
-8.7 mmHg
Standard Deviation 8.02
|
-11.6 mmHg
Standard Deviation 8.41
|
-11.4 mmHg
Standard Deviation 5.05
|
-9.6 mmHg
Standard Deviation 19.51
|
-4.5 mmHg
Standard Deviation 14.75
|
|
Vital Signs - Systolic Blood Pressure
Day 28
|
2.1 mmHg
Standard Deviation 9.83
|
-9.4 mmHg
Standard Deviation 13.93
|
-8.1 mmHg
Standard Deviation 12.89
|
-6.3 mmHg
Standard Deviation 20.28
|
-1.2 mmHg
Standard Deviation 21.19
|
|
Vital Signs - Systolic Blood Pressure
Day 29
|
4.2 mmHg
Standard Deviation 12.05
|
-7.4 mmHg
Standard Deviation 15.88
|
-4.6 mmHg
Standard Deviation 12.30
|
-8.9 mmHg
Standard Deviation 7.54
|
-3.6 mmHg
Standard Deviation 21.02
|
|
Vital Signs - Systolic Blood Pressure
Day 30
|
0.8 mmHg
Standard Deviation 8.00
|
-7.6 mmHg
Standard Deviation 18.85
|
-5.9 mmHg
Standard Deviation 9.96
|
-11.0 mmHg
Standard Deviation 15.48
|
-4.5 mmHg
Standard Deviation 25.36
|
|
Vital Signs - Systolic Blood Pressure
Day 31
|
-3.4 mmHg
Standard Deviation 1.35
|
-10.4 mmHg
Standard Deviation 17.18
|
-9.3 mmHg
Standard Deviation 9.45
|
-12.8 mmHg
Standard Deviation 14.83
|
-0.2 mmHg
Standard Deviation 13.98
|
|
Vital Signs - Systolic Blood Pressure
Day 49
|
7.1 mmHg
Standard Deviation 14.95
|
-6.9 mmHg
Standard Deviation 12.42
|
-10.2 mmHg
Standard Deviation 11.97
|
-16.8 mmHg
Standard Deviation 22.45
|
-3.0 mmHg
Standard Deviation 14.78
|
PRIMARY outcome
Timeframe: Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.Population: Safety/Intent-to-Treat/Per Protocol Population
Changes from baseline in vital signs (heart rate) and the relationship to PB1046 compared to placebo.
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Vital Signs - Heart Rate
Day 0 1 hr
|
-1.8 Beats/min
Standard Deviation 4.55
|
-2.1 Beats/min
Standard Deviation 6.23
|
-2.5 Beats/min
Standard Deviation 9.66
|
2.3 Beats/min
Standard Deviation 3.64
|
-3.0 Beats/min
Standard Deviation 5.79
|
|
Vital Signs - Heart Rate
Day 0 3 hr
|
2.7 Beats/min
Standard Deviation 6.49
|
-2.4 Beats/min
Standard Deviation 5.39
|
0.0 Beats/min
Standard Deviation 8.67
|
1.2 Beats/min
Standard Deviation 2.83
|
3.0 Beats/min
Standard Deviation 9.64
|
|
Vital Signs - Heart Rate
Day 1
|
-0.7 Beats/min
Standard Deviation 1.15
|
4.1 Beats/min
Standard Deviation 3.38
|
-1.6 Beats/min
Standard Deviation 9.66
|
4.1 Beats/min
Standard Deviation 5.53
|
3.2 Beats/min
Standard Deviation 4.09
|
|
Vital Signs - Heart Rate
Day 2
|
1.7 Beats/min
Standard Deviation 2.31
|
-6.0 Beats/min
Standard Deviation 15.58
|
-3.3 Beats/min
Standard Deviation 8.73
|
2.6 Beats/min
Standard Deviation 3.83
|
4.5 Beats/min
Standard Deviation 8.66
|
|
Vital Signs - Heart Rate
Day 3
|
3.8 Beats/min
Standard Deviation 1.35
|
-0.8 Beats/min
Standard Deviation 5.51
|
-2.2 Beats/min
Standard Deviation 4.24
|
1.4 Beats/min
Standard Deviation 5.86
|
-.04 Beats/min
Standard Deviation 6.82
|
|
Vital Signs - Heart Rate
Day 5
|
-1.2 Beats/min
Standard Deviation 3.67
|
-2.9 Beats/min
Standard Deviation 5.06
|
-3.2 Beats/min
Standard Deviation 9.09
|
2.9 Beats/min
Standard Deviation 5.85
|
3.1 Beats/min
Standard Deviation 8.62
|
|
Vital Signs - Heart Rate
Day 7 pre
|
0.6 Beats/min
Standard Deviation 2.67
|
-0.4 Beats/min
Standard Deviation 5.74
|
-4.5 Beats/min
Standard Deviation 6.05
|
1.6 Beats/min
Standard Deviation 1.83
|
-1.7 Beats/min
Standard Deviation 8.01
|
|
Vital Signs - Heart Rate
Day 14 pre
|
-2.4 Beats/min
Standard Deviation 2.14
|
-3.7 Beats/min
Standard Deviation 6.26
|
-0.6 Beats/min
Standard Deviation 2.65
|
0.5 Beats/min
Standard Deviation 1.29
|
-1.9 Beats/min
Standard Deviation 7.16
|
|
Vital Signs - Heart Rate
Day 21 pre
|
3.6 Beats/min
Standard Deviation 4.67
|
-2.6 Beats/min
Standard Deviation 7.62
|
-2.7 Beats/min
Standard Deviation 2.72
|
0.2 Beats/min
Standard Deviation 0.96
|
-4.7 Beats/min
Standard Deviation 5.84
|
|
Vital Signs - Heart Rate
Day 21 1 hr
|
3.6 Beats/min
Standard Deviation 4.67
|
-1.4 Beats/min
Standard Deviation 7.49
|
0.9 Beats/min
Standard Deviation 2.23
|
1.2 Beats/min
Standard Deviation 1.00
|
-4.7 Beats/min
Standard Deviation 5.84
|
|
Vital Signs - Heart Rate
Day 21 3 hr
|
8.3 Beats/min
Standard Deviation 4.93
|
3.6 Beats/min
Standard Deviation 3.62
|
-0.9 Beats/min
Standard Deviation 3.51
|
0.9 Beats/min
Standard Deviation 1.83
|
0.2 Beats/min
Standard Deviation 10.92
|
|
Vital Signs - Heart Rate
Day 22
|
2.2 Beats/min
Standard Deviation 3.02
|
-3.3 Beats/min
Standard Deviation 10.02
|
0.3 Beats/min
Standard Deviation 5.37
|
0.4 Beats/min
Standard Deviation 1.07
|
0.3 Beats/min
Standard Deviation 8.10
|
|
Vital Signs - Heart Rate
Day 23
|
-1.8 Beats/min
Standard Deviation 1.68
|
-2.4 Beats/min
Standard Deviation 13.10
|
-2.5 Beats/min
Standard Deviation 5.92
|
1.4 Beats/min
Standard Deviation 1.32
|
-0.9 Beats/min
Standard Deviation 10.13
|
|
Vital Signs - Heart Rate
Day 24
|
-2.4 Beats/min
Standard Deviation 3.15
|
-0.8 Beats/min
Standard Deviation 8.52
|
-2.1 Beats/min
Standard Deviation 4.65
|
1.4 Beats/min
Standard Deviation 1.40
|
-1.5 Beats/min
Standard Deviation 7.49
|
|
Vital Signs - Heart Rate
Day 26
|
1.4 Beats/min
Standard Deviation 3.91
|
-2.2 Beats/min
Standard Deviation 10.56
|
-1.6 Beats/min
Standard Deviation 6.97
|
0.4 Beats/min
Standard Deviation 1.13
|
-0.8 Beats/min
Standard Deviation 7.77
|
|
Vital Signs - Heart Rate
Day 28
|
-2.0 Beats/min
Standard Deviation 8.09
|
-0.5 Beats/min
Standard Deviation 11.09
|
-1.5 Beats/min
Standard Deviation 2.10
|
0.2 Beats/min
Standard Deviation 1.97
|
-2.8 Beats/min
Standard Deviation 7.52
|
|
Vital Signs - Heart Rate
Day 29
|
0.3 Beats/min
Standard Deviation 3.18
|
-2.5 Beats/min
Standard Deviation 8.62
|
-2.1 Beats/min
Standard Deviation 9.99
|
2.9 Beats/min
Standard Deviation 7.47
|
-1.1 Beats/min
Standard Deviation 6.84
|
|
Vital Signs - Heart Rate
Day 30
|
-2.4 Beats/min
Standard Deviation 2.50
|
-3.9 Beats/min
Standard Deviation 11.54
|
-3.6 Beats/min
Standard Deviation 7.61
|
0.8 Beats/min
Standard Deviation 1.67
|
1.7 Beats/min
Standard Deviation 8.13
|
|
Vital Signs - Heart Rate
Day 31
|
-3.4 Beats/min
Standard Deviation 3.10
|
-4.9 Beats/min
Standard Deviation 8.27
|
-1.4 Beats/min
Standard Deviation 4.96
|
-1.6 Beats/min
Standard Deviation 1.95
|
0.5 Beats/min
Standard Deviation 7.43
|
|
Vital Signs - Heart Rate
Day 49
|
-2.0 Beats/min
Standard Deviation 2.33
|
-2.9 Beats/min
Standard Deviation 14.19
|
-2.3 Beats/min
Standard Deviation 4.67
|
1.8 Beats/min
Standard Deviation 4.84
|
-2.4 Beats/min
Standard Deviation 5.70
|
PRIMARY outcome
Timeframe: Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.Population: Safety/Intent-to-Treat/Per Protocol Population
Changes from baseline in vital signs (temperature) and the relationship to PB1046 compared to placebo.
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Vital Signs - Temperature
Day 0 1 hr
|
0.0 Celsius
Standard Deviation 0.10
|
-0.1 Celsius
Standard Deviation 0.35
|
0.0 Celsius
Standard Deviation 0.34
|
0.0 Celsius
Standard Deviation 0.33
|
-0.1 Celsius
Standard Deviation 0.28
|
|
Vital Signs - Temperature
Day 0 3 hr
|
-0.1 Celsius
Standard Deviation 0.06
|
-0.2 Celsius
Standard Deviation 0.36
|
0.0 Celsius
Standard Deviation 0.39
|
0.1 Celsius
Standard Deviation 0.24
|
0.2 Celsius
Standard Deviation 0.53
|
|
Vital Signs - Temperature
Day 1
|
0.1 Celsius
Standard Deviation 0.12
|
-0.3 Celsius
Standard Deviation 0.52
|
-0.1 Celsius
Standard Deviation 0.40
|
0.3 Celsius
Standard Deviation 0.14
|
0.2 Celsius
Standard Deviation 0.38
|
|
Vital Signs - Temperature
Day 2
|
-1.1 Celsius
Standard Deviation 2.06
|
-0.5 Celsius
Standard Deviation 0.65
|
-0.0 Celsius
Standard Deviation 0.45
|
0.1 Celsius
Standard Deviation 0.23
|
-0.1 Celsius
Standard Deviation 0.59
|
|
Vital Signs - Temperature
Day 3
|
-1.2 Celsius
Standard Deviation 2.20
|
-0.2 Celsius
Standard Deviation 0.46
|
0.0 Celsius
Standard Deviation 0.49
|
0.1 Celsius
Standard Deviation 0.39
|
0.0 Celsius
Standard Deviation 0.66
|
|
Vital Signs - Temperature
Day 5
|
0.1 Celsius
Standard Deviation 0.21
|
-0.2 Celsius
Standard Deviation 0.36
|
0.1 Celsius
Standard Deviation 0.26
|
0.1 Celsius
Standard Deviation 0.39
|
0.0 Celsius
Standard Deviation 0.52
|
|
Vital Signs - Temperature
Day 7 pre
|
-0.1 Celsius
Standard Deviation 0.06
|
0.0 Celsius
Standard Deviation 1.22
|
0.1 Celsius
Standard Deviation 0.27
|
0.0 Celsius
Standard Deviation 0.25
|
0.1 Celsius
Standard Deviation 0.37
|
|
Vital Signs - Temperature
Day 14 pre
|
-0.2 Celsius
Standard Deviation 0.49
|
-0.1 Celsius
Standard Deviation 0.39
|
0.2 Celsius
Standard Deviation 0.27
|
0.1 Celsius
Standard Deviation 0.29
|
0.1 Celsius
Standard Deviation 0.48
|
|
Vital Signs - Temperature
Day 21 1 hr
|
0.1 Celsius
Standard Deviation 0.36
|
0.1 Celsius
Standard Deviation 0.48
|
0.0 Celsius
Standard Deviation 0.42
|
0.1 Celsius
Standard Deviation 0.34
|
0.1 Celsius
Standard Deviation 0.50
|
|
Vital Signs - Temperature
Day 21 3 hr
|
0.1 Celsius
Standard Deviation 0.23
|
-0.2 Celsius
Standard Deviation 0.29
|
-0.1 Celsius
Standard Deviation 0.39
|
-0.1 Celsius
Standard Deviation 0.36
|
0.0 Celsius
Standard Deviation 0.55
|
|
Vital Signs - Temperature
Day 22
|
0.1 Celsius
Standard Deviation 0.31
|
0.1 Celsius
Standard Deviation 0.24
|
0.2 Celsius
Standard Deviation 0.24
|
-0.1 Celsius
Standard Deviation 0.22
|
0.0 Celsius
Standard Deviation 0.49
|
|
Vital Signs - Temperature
Day 23
|
0.3 Celsius
Standard Deviation 0.25
|
0.2 Celsius
Standard Deviation 0.25
|
0.1 Celsius
Standard Deviation 0.23
|
0.1 Celsius
Standard Deviation 0.26
|
0.1 Celsius
Standard Deviation 0.48
|
|
Vital Signs - Temperature
Day 24
|
0.3 Celsius
Standard Deviation 0.40
|
0.1 Celsius
Standard Deviation 0.28
|
0.2 Celsius
Standard Deviation 0.30
|
-0.1 Celsius
Standard Deviation 0.51
|
0.1 Celsius
Standard Deviation 0.47
|
|
Vital Signs - Temperature
Day 26
|
0.2 Celsius
Standard Deviation 0.15
|
0.0 Celsius
Standard Deviation 0.66
|
0.1 Celsius
Standard Deviation 0.34
|
-0.1 Celsius
Standard Deviation 0.15
|
0.0 Celsius
Standard Deviation 0.44
|
|
Vital Signs - Temperature
Day 28
|
-0.6 Celsius
Standard Deviation 1.42
|
0.2 Celsius
Standard Deviation 0.53
|
-0.2 Celsius
Standard Deviation 0.43
|
0.3 Celsius
Standard Deviation 0.30
|
0.0 Celsius
Standard Deviation 0.44
|
|
Vital Signs - Temperature
Day 29
|
0.1 Celsius
Standard Deviation 0.21
|
-0.3 Celsius
Standard Deviation 0.69
|
0.0 Celsius
Standard Deviation 0.40
|
0.1 Celsius
Standard Deviation 0.38
|
0.1 Celsius
Standard Deviation 0.52
|
|
Vital Signs - Temperature
Day 30
|
-1.0 Celsius
Standard Deviation 1.91
|
-0.1 Celsius
Standard Deviation 0.69
|
0.1 Celsius
Standard Deviation 0.30
|
0.0 Celsius
Standard Deviation 0.44
|
0.1 Celsius
Standard Deviation 0.51
|
|
Vital Signs - Temperature
Day 31
|
0.3 Celsius
Standard Deviation 0.25
|
0.1 Celsius
Standard Deviation 0.57
|
0.1 Celsius
Standard Deviation 0.37
|
-0.2 Celsius
Standard Deviation 0.29
|
-0.1 Celsius
Standard Deviation 0.73
|
|
Vital Signs - Temperature
Day 49
|
0.1 Celsius
Standard Deviation 0.36
|
0.1 Celsius
Standard Deviation 0.55
|
0.1 Celsius
Standard Deviation 0.42
|
0.0 Celsius
Standard Deviation 0.43
|
8.7 Celsius
Standard Deviation 22.71
|
PRIMARY outcome
Timeframe: Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.Population: Safety/Intent-to-Treat/Per Protocol Population
Changes from baseline in vital signs (respiratory rate) and the relationship to PB1046 compared to placebo.
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Vital Signs - Respiratory Rate
Day 0 1 hr
|
0.7 Breaths/min
Standard Deviation 1.15
|
0.3 Breaths/min
Standard Deviation 1.51
|
0.9 Breaths/min
Standard Deviation 1.57
|
-0.3 Breaths/min
Standard Deviation 1.51
|
0.4 Breaths/min
Standard Deviation 1.51
|
|
Vital Signs - Respiratory Rate
Day 0 3hr
|
1.3 Breaths/min
Standard Deviation 2.31
|
0.7 Breaths/min
Standard Deviation 2.07
|
0.0 Breaths/min
Standard Deviation 1.15
|
0.0 Breaths/min
Standard Deviation 1.26
|
0.8 Breaths/min
Standard Deviation 1.83
|
|
Vital Signs - Respiratory Rate
Day 1
|
0.7 Breaths/min
Standard Deviation 1.15
|
0.3 Breaths/min
Standard Deviation 2.25
|
-0.6 Breaths/min
Standard Deviation 1.51
|
-1.0 Breaths/min
Standard Deviation 1.10
|
0.3 Breaths/min
Standard Deviation 1.25
|
|
Vital Signs - Respiratory Rate
Day 2
|
1.0 Breaths/min
Standard Deviation 1.00
|
0.3 Breaths/min
Standard Deviation 1.77
|
0.3 Breaths/min
Standard Deviation 0.76
|
-0.3 Breaths/min
Standard Deviation 1.51
|
-0.1 Breaths/min
Standard Deviation 1.81
|
|
Vital Signs - Respiratory Rate
Day 3
|
0.7 Breaths/min
Standard Deviation 1.15
|
-1.2 Breaths/min
Standard Deviation 2.15
|
0.3 Breaths/min
Standard Deviation 2.14
|
0.3 Breaths/min
Standard Deviation 1.51
|
0.1 Breaths/min
Standard Deviation 1.07
|
|
Vital Signs - Respiratory Rate
Day 5
|
0.0 Breaths/min
Standard Deviation 0.00
|
0.4 Breaths/min
Standard Deviation 1.75
|
-0.1 Breaths/min
Standard Deviation 0.90
|
0.3 Breaths/min
Standard Deviation 0.082
|
0.6 Breaths/min
Standard Deviation 1.62
|
|
Vital Signs - Respiratory Rate
Day 21 1hr
|
-1.3 Breaths/min
Standard Deviation 1.15
|
0.7 Breaths/min
Standard Deviation 2.07
|
-0.3 Breaths/min
Standard Deviation 1.51
|
-0.5 Breaths/min
Standard Deviation 1.00
|
-0.4 Breaths/min
Standard Deviation 3.05
|
|
Vital Signs - Respiratory Rate
Day 21 3 hr
|
0.0 Breaths/min
Standard Deviation 2.00
|
0.0 Breaths/min
Standard Deviation 0.00
|
-0.3 Breaths/min
Standard Deviation 1.97
|
0.5 Breaths/min
Standard Deviation 1.00
|
0.4 Breaths/min
Standard Deviation 2.44
|
|
Vital Signs - Respiratory Rate
Day 21 pre
|
-1.3 Breaths/min
Standard Deviation 1.15
|
1.0 Breaths/min
Standard Deviation 3.52
|
0.7 Breaths/min
Standard Deviation 1.63
|
0.0 Breaths/min
Standard Deviation 0.00
|
0.6 Breaths/min
Standard Deviation 1.81
|
|
Vital Signs - Respiratory Rate
Day 22
|
0.0 Breaths/min
Standard Deviation 2.00
|
1.5 Breaths/min
Standard Deviation 2.51
|
0.0 Breaths/min
Standard Deviation 2.19
|
-0.5 Breaths/min
Standard Deviation 1.00
|
0.2 Breaths/min
Standard Deviation 2.28
|
|
Vital Signs - Respiratory Rate
Day 23
|
0.0 Breaths/min
Standard Deviation 2.00
|
0.8 Breaths/min
Standard Deviation 1.60
|
-1.0 Breaths/min
Standard Deviation 2.10
|
-0.5 Breaths/min
Standard Deviation 1.00
|
-0.4 Breaths/min
Standard Deviation 3.15
|
|
Vital Signs - Respiratory Rate
Day 24
|
-0.7 Breaths/min
Standard Deviation 1.15
|
1.2 Breaths/min
Standard Deviation 2.56
|
0.0 Breaths/min
Standard Deviation 1.79
|
-0.5 Breaths/min
Standard Deviation 1.00
|
0.2 Breaths/min
Standard Deviation 1.56
|
|
Vital Signs - Respiratory Rate
Day 26
|
-0.7 Breaths/min
Standard Deviation 1.15
|
1.2 Breaths/min
Standard Deviation 2.56
|
0.0 Breaths/min
Standard Deviation 1.79
|
-0.5 Breaths/min
Standard Deviation 1.00
|
0.3 Breaths/min
Standard Deviation 1.89
|
|
Vital Signs - Respiratory Rate
Day 28
|
0.0 Breaths/min
Standard Deviation 2.00
|
1.2 Breaths/min
Standard Deviation 3.37
|
0.3 Breaths/min
Standard Deviation 1.97
|
-0.5 Breaths/min
Standard Deviation 1.00
|
0.6 Breaths/min
Standard Deviation 2.44
|
|
Vital Signs - Respiratory Rate
Day 29
|
-0.7 Breaths/min
Standard Deviation 1.15
|
1.7 Breaths/min
Standard Deviation 3.44
|
-0.3 Breaths/min
Standard Deviation 1.51
|
-1.0 Breaths/min
Standard Deviation 1.15
|
-0.3 Breaths/min
Standard Deviation 2.06
|
|
Vital Signs - Respiratory Rate
Day 30
|
0.7 Breaths/min
Standard Deviation 1.15
|
1.3 Breaths/min
Standard Deviation 2.42
|
0.0 Breaths/min
Standard Deviation 1.26
|
-1.0 Breaths/min
Standard Deviation 1.15
|
0.3 Breaths/min
Standard Deviation 2.43
|
|
Vital Signs - Respiratory Rate
Day 49
|
-0.7 Breaths/min
Standard Deviation 1.15
|
1.2 Breaths/min
Standard Deviation 2.40
|
0.7 Breaths/min
Standard Deviation 1.03
|
0.0 Breaths/min
Standard Deviation 1.26
|
-0.3 Breaths/min
Standard Deviation 1.38
|
PRIMARY outcome
Timeframe: Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.Population: Safety/Intent-to-Treat/Per Protocol Population
Changes from baseline in vital signs (systolic blood pressure) and the relationship to PB1046 compared to placebo.
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Vital Signs - Diastolic Blood Pressure
Day 0 3 hr
|
-0.1 mmHg
Standard Deviation 2.50
|
-3.1 mmHg
Standard Deviation 11.89
|
-4.4 mmHg
Standard Deviation 11.10
|
-3.9 mmHg
Standard Deviation 4.08
|
2.6 mmHg
Standard Deviation 3.50
|
|
Vital Signs - Diastolic Blood Pressure
Day 0 1 hr
|
-2.3 mmHg
Standard Deviation 3.38
|
-5.7 mmHg
Standard Deviation 13.53
|
-2.5 mmHg
Standard Deviation 10.64
|
-1.4 mmHg
Standard Deviation 5.68
|
7.8 mmHg
Standard Deviation 9.34
|
|
Vital Signs - Diastolic Blood Pressure
Day 1
|
-2.7 mmHg
Standard Deviation 1.76
|
-1.9 mmHg
Standard Deviation 9.52
|
-1.5 mmHg
Standard Deviation 7.77
|
-9.5 mmHg
Standard Deviation 11.69
|
3.8 mmHg
Standard Deviation 7.99
|
|
Vital Signs - Diastolic Blood Pressure
Day 2
|
-0.9 mmHg
Standard Deviation 5.09
|
-1.7 mmHg
Standard Deviation 7.48
|
-3.0 mmHg
Standard Deviation 9.41
|
-5.7 mmHg
Standard Deviation 7.20
|
3.6 mmHg
Standard Deviation 10.18
|
|
Vital Signs - Diastolic Blood Pressure
Day 3
|
-5.8 mmHg
Standard Deviation 2.17
|
0.1 mmHg
Standard Deviation 10.36
|
-2.0 mmHg
Standard Deviation 8.14
|
-11.3 mmHg
Standard Deviation 7.33
|
2.8 mmHg
Standard Deviation 7.93
|
|
Vital Signs - Diastolic Blood Pressure
Day 5
|
1.1 mmHg
Standard Deviation 7.88
|
1.3 mmHg
Standard Deviation 9.01
|
-1.1 mmHg
Standard Deviation 6.61
|
-6.9 mmHg
Standard Deviation 12.32
|
1.2 mmHg
Standard Deviation 5.82
|
|
Vital Signs - Diastolic Blood Pressure
Day 7 pre
|
-2.2 mmHg
Standard Deviation 8.60
|
-2.5 mmHg
Standard Deviation 6.88
|
-1.4 mmHg
Standard Deviation 12.28
|
-2.5 mmHg
Standard Deviation 15.60
|
3.6 mmHg
Standard Deviation 6.05
|
|
Vital Signs - Diastolic Blood Pressure
Day 14 pre
|
3.1 mmHg
Standard Deviation 4.44
|
-2.9 mmHg
Standard Deviation 7.07
|
-0.2 mmHg
Standard Deviation 7.73
|
-4.7 mmHg
Standard Deviation 7.88
|
6.0 mmHg
Standard Deviation 6.28
|
|
Vital Signs - Diastolic Blood Pressure
Day 21 pre
|
0.7 mmHg
Standard Deviation 2.40
|
-1.3 mmHg
Standard Deviation 8.50
|
2.1 mmHg
Standard Deviation 10.83
|
-5.8 mmHg
Standard Deviation 5.91
|
4.2 mmHg
Standard Deviation 7.23
|
|
Vital Signs - Diastolic Blood Pressure
Day 21 1 hr
|
-3.4 mmHg
Standard Deviation 1.26
|
-4.9 mmHg
Standard Deviation 11.98
|
-2.2 mmHg
Standard Deviation 9.70
|
-9.8 mmHg
Standard Deviation 6.43
|
2.2 mmHg
Standard Deviation 8.35
|
|
Vital Signs - Diastolic Blood Pressure
Day 21 3 hr
|
-1.4 mmHg
Standard Deviation 3.91
|
-7.3 mmHg
Standard Deviation 6.34
|
-0.9 mmHg
Standard Deviation 10.82
|
-9.8 mmHg
Standard Deviation 8.03
|
4.3 mmHg
Standard Deviation 6.82
|
|
Vital Signs - Diastolic Blood Pressure
Day 22
|
-2.1 mmHg
Standard Deviation 4.40
|
-6.1 mmHg
Standard Deviation 10.52
|
-2.2 mmHg
Standard Deviation 9.80
|
-10.8 mmHg
Standard Deviation 8.63
|
1.8 mmHg
Standard Deviation 9.89
|
|
Vital Signs - Diastolic Blood Pressure
Day 23
|
-2.1 mmHg
Standard Deviation 5.00
|
-2.1 mmHg
Standard Deviation 8.88
|
-3.2 mmHg
Standard Deviation 12.10
|
-6.1 mmHg
Standard Deviation 5.39
|
4.5 mmHg
Standard Deviation 7.81
|
|
Vital Signs - Diastolic Blood Pressure
Day 24
|
1.0 mmHg
Standard Deviation 2.91
|
1.3 mmHg
Standard Deviation 7.61
|
1.7 mmHg
Standard Deviation 9.05
|
-12.8 mmHg
Standard Deviation 14.55
|
3.0 mmHg
Standard Deviation 10.50
|
|
Vital Signs - Diastolic Blood Pressure
Day 26
|
-1.4 mmHg
Standard Deviation 7.13
|
-6.1 mmHg
Standard Deviation 9.86
|
-3.2 mmHg
Standard Deviation 10.03
|
-6.4 mmHg
Standard Deviation 6.58
|
0.8 mmHg
Standard Deviation 6.74
|
|
Vital Signs - Diastolic Blood Pressure
Day 28
|
-1.4 mmHg
Standard Deviation 1.58
|
-1.4 mmHg
Standard Deviation 9.43
|
-0.2 mmHg
Standard Deviation 8.64
|
-8.3 mmHg
Standard Deviation 12.66
|
3.7 mmHg
Standard Deviation 10.41
|
|
Vital Signs - Diastolic Blood Pressure
Day 29
|
1.6 mmHg
Standard Deviation 7.34
|
-2.0 mmHg
Standard Deviation 6.72
|
-1.5 mmHg
Standard Deviation 9.98
|
-3.7 mmHg
Standard Deviation 9.64
|
2.9 mmHg
Standard Deviation 6.22
|
|
Vital Signs - Diastolic Blood Pressure
Day 30
|
2.8 mmHg
Standard Deviation 2.52
|
-2.8 mmHg
Standard Deviation 7.92
|
-1.9 mmHg
Standard Deviation 11.77
|
-8.8 mmHg
Standard Deviation 5.47
|
3.6 mmHg
Standard Deviation 9.02
|
|
Vital Signs - Diastolic Blood Pressure
Day 31
|
-4.3 mmHg
Standard Deviation 4.04
|
-4.6 mmHg
Standard Deviation 10.98
|
0.3 mmHg
Standard Deviation 10.02
|
-8.9 mmHg
Standard Deviation 6.10
|
3.9 mmHg
Standard Deviation 6.99
|
|
Vital Signs - Diastolic Blood Pressure
Day 49
|
2.6 mmHg
Standard Deviation 2.22
|
-3.1 mmHg
Standard Deviation 7.86
|
-5.3 mmHg
Standard Deviation 11.08
|
-5.0 mmHg
Standard Deviation 10.27
|
5.1 mmHg
Standard Deviation 4.89
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures \[AUC(0-t)\] during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=2 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Area Under the Curve Over the Dosing Interval [AUC(0-t)]
Week 1
|
5791.391 h*ng/mL
Standard Error 1639.3
|
12382.716 h*ng/mL
Standard Error 4869.3
|
14789.912 h*ng/mL
Standard Error 4269.7
|
25555.798 h*ng/mL
Standard Error 11248.6
|
—
|
|
Pharmacokinetic Profile - Area Under the Curve Over the Dosing Interval [AUC(0-t)]
Week 4
|
7440.721 h*ng/mL
Standard Error 6183.8
|
19007.517 h*ng/mL
Standard Error 12655.5
|
16689.657 h*ng/mL
Standard Error 7313.0
|
21997.727 h*ng/mL
Standard Error 7709.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures (Cmax) during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Maximum Serum Concentration (Cmax)
Week 1
|
47.433 ng/mL
Standard Error 17.3
|
128.317 ng/mL
Standard Error 64.1
|
218.471 ng/mL
Standard Error 106.3
|
207.600 ng/mL
Standard Error 112.3
|
—
|
|
Pharmacokinetic Profile - Maximum Serum Concentration (Cmax)
Week 4
|
53.600 ng/mL
Standard Error 40.2
|
233.450 ng/mL
Standard Error 189.6
|
211.967 ng/mL
Standard Error 110.1
|
239.000 ng/mL
Standard Error 102.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures (Tmax) during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Time to Cmax (Tmax)
Week 1
|
39.533 hours
Standard Error 14.1
|
57.594 hours
Standard Error 54.0
|
27.645 hours
Standard Error 15.7
|
55.578 hours
Standard Error 35.8
|
—
|
|
Pharmacokinetic Profile - Time to Cmax (Tmax)
Week 4
|
32.028 hours
Standard Error 13.7
|
32.042 hours
Standard Error 12.2
|
36.153 hours
Standard Error 13.6
|
35.804 hours
Standard Error 13.9
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures (lambda z) during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=2 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Elimination Rate Constant (Lambda z)
Week 1
|
0.015 1/hour
Standard Error 0.0
|
0.018 1/hour
Standard Error 0.0
|
0.017 1/hour
Standard Error 0.0
|
0.010 1/hour
Standard Error 0.0
|
—
|
|
Pharmacokinetic Profile - Elimination Rate Constant (Lambda z)
Week 4
|
0.015 1/hour
Standard Error 0.0
|
0.026 1/hour
Standard Error 0.0
|
0.021 1/hour
Standard Error 0.0
|
0.019 1/hour
Standard Error 0.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures (t½) during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=2 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Elimination Half-life (t½)
Week 1
|
45.787 hours
Standard Error 4.7
|
40.806 hours
Standard Error 7.8
|
54.735 hours
Standard Error 35.8
|
103.951 hours
Standard Error 94.6
|
—
|
|
Pharmacokinetic Profile - Elimination Half-life (t½)
Week 4
|
78.382 hours
Standard Error 69.3
|
28.333 hours
Standard Error 6.5
|
34.602 hours
Standard Error 8.5
|
44.902 hours
Standard Error 28.5
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures (CL/F) during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=2 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Clearance (CL/F), Uncorrected for Bioavailability
Week 1
|
31.992 mL/h/kg
Standard Error 10.1
|
33.145 mL/h/kg
Standard Error 11.8
|
37.376 mL/h/kg
Standard Error 8.2
|
36.067 mL/h/kg
Standard Error 15.0
|
—
|
|
Pharmacokinetic Profile - Clearance (CL/F), Uncorrected for Bioavailability
Week 4
|
26.981 mL/h/kg
Standard Error 16.2
|
28.443 mL/h/kg
Standard Error 16.7
|
39.940 mL/h/kg
Standard Error 17.7
|
49.220 mL/h/kg
Standard Error 11.3
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.Population: Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.
Comparison of dose exposures (Vz/F) during once weekly administration of various doses of PB1046
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=2 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=4 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Profile - Volume of Distribution (Vz/F), Uncorrected for Bioavailability (F)
Week 1
|
2079.049 mL/kg
Standard Error 451.5
|
1955.795 mL/kg
Standard Error 826.8
|
2983.922 mL/kg
Standard Error 1951.6
|
4774.976 mL/kg
Standard Error 3297.6
|
—
|
|
Pharmacokinetic Profile - Volume of Distribution (Vz/F), Uncorrected for Bioavailability (F)
Week 4
|
3860.362 mL/kg
Standard Error 4528.5
|
1246.900 mL/kg
Standard Error 979.1
|
2122.745 mL/kg
Standard Error 1412.1
|
3401.624 mL/kg
Standard Error 2650.3
|
—
|
SECONDARY outcome
Timeframe: Eleven weeks starting the first week of dosing.Population: Safety/Intent-to-Treat/Per Protocol Population
Number of participants reporting positive immunogenicity (four-fold increase of pre-dose titer)
Outcome measures
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 Participants
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 Participants
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 Participants
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 Participants
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Immunogenicity
|
2 subjects
|
2 subjects
|
3 subjects
|
6 subjects
|
0 subjects
|
Adverse Events
PB1046 Injection, 0.2 mg/kg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
PB1046 Injection, 0.4 mg/kg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
PB1046 Injection, 0.6 mg/kg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
PB1046 Injection, 1.2 mg/kg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo Comparator
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 participants at risk
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 participants at risk
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 participants at risk
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 participants at risk
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 participants at risk
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/3 • 18 months
|
16.7%
1/6 • 18 months
|
0.00%
0/7 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
|
Cardiac disorders
Blood creatinine increased
|
0.00%
0/3 • 18 months
|
16.7%
1/6 • 18 months
|
0.00%
0/7 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
|
Cardiac disorders
White blood cell count
|
0.00%
0/3 • 18 months
|
16.7%
1/6 • 18 months
|
0.00%
0/7 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
Other adverse events
| Measure |
PB1046 Injection, 0.2 mg/kg
n=3 participants at risk
Four weekly doses of PB1046 Injection, 0.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.4 mg/kg
n=6 participants at risk
Four weekly doses of PB1046 Injection, 0.4 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 0.6 mg/kg
n=7 participants at risk
Four weekly doses of PB1046 Injection, 0.6 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
PB1046 Injection, 1.2 mg/kg
n=6 participants at risk
Four weekly doses of PB1046 Injection, 1.2 mg/kg
PB1046 Injection: Four weekly subcutaneous injections of PB1046.
|
Placebo Comparator
n=7 participants at risk
Four weekly doses of Placebo (0.9% NaCl) Injection
Placebo Injection: Four weekly subcutaneous injections of placebo.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
2/3 • Number of events 2 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
16.7%
1/6 • Number of events 1 • 18 months
|
0.00%
0/7 • 18 months
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
16.7%
1/6 • Number of events 1 • 18 months
|
0.00%
0/7 • 18 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
14.3%
1/7 • Number of events 3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
33.3%
1/3 • Number of events 1 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
|
Vascular disorders
Dizziness
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
16.7%
1/6 • Number of events 1 • 18 months
|
0.00%
0/7 • 18 months
|
|
Vascular disorders
Flushing
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
16.7%
1/6 • Number of events 2 • 18 months
|
0.00%
0/7 • 18 months
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/3 • 18 months
|
16.7%
1/6 • Number of events 1 • 18 months
|
28.6%
2/7 • Number of events 2 • 18 months
|
16.7%
1/6 • Number of events 1 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Injection site erythema
|
100.0%
3/3 • Number of events 20 • 18 months
|
100.0%
6/6 • Number of events 40 • 18 months
|
100.0%
7/7 • Number of events 34 • 18 months
|
100.0%
6/6 • Number of events 28 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Injection site induration
|
0.00%
0/3 • 18 months
|
33.3%
2/6 • Number of events 3 • 18 months
|
28.6%
2/7 • Number of events 3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Injection site pain
|
66.7%
2/3 • Number of events 9 • 18 months
|
33.3%
2/6 • Number of events 5 • 18 months
|
28.6%
2/7 • Number of events 10 • 18 months
|
100.0%
6/6 • Number of events 14 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Injection site pruritus
|
33.3%
1/3 • Number of events 1 • 18 months
|
0.00%
0/6 • 18 months
|
14.3%
1/7 • Number of events 1 • 18 months
|
33.3%
2/6 • Number of events 4 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Injection site swelling
|
33.3%
1/3 • Number of events 4 • 18 months
|
33.3%
2/6 • Number of events 4 • 18 months
|
57.1%
4/7 • Number of events 5 • 18 months
|
33.3%
2/6 • Number of events 3 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Injection site warmth
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
14.3%
1/7 • Number of events 1 • 18 months
|
16.7%
1/6 • Number of events 1 • 18 months
|
0.00%
0/7 • 18 months
|
|
General disorders
Malaise
|
0.00%
0/3 • 18 months
|
0.00%
0/6 • 18 months
|
0.00%
0/7 • 18 months
|
16.7%
1/6 • Number of events 2 • 18 months
|
0.00%
0/7 • 18 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PIs are not permitted to publish or discuss trial results until 5 years after study completion.
- Publication restrictions are in place
Restriction type: OTHER