The primary objective of the study is to: • Evaluate the safety and tolerability of REGN5381 and REGN9035 administered alone or sequentially. The secondary objectives of the study are to: * Evaluate the ability of single intravenous (IV) doses of REGN9035 (compared to placebo) to reverse the acute hemodynamic effects of REGN5381 * Evaluate the hemodynamic effects of single IV doses of REGN5381 * Evaluate the persistence of the hemodynamic effects of single IV doses of REGN5381 and the reversal of REGN5381 effects by REGN9035 (compared to placebo) * Evaluate the pharmacokinetics of single IV doses of REGN5381 and REGN9035 administered alone or sequentially
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
93
Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.
Part B: Selected doses administered by IV infusion on day 1.
Part A: Single dose administered by IV infusion on day1. Part B: Single dose administered by IV infusion on day 1, day 2 and/or day 22.
Universitair Ziekenhuis Leuven Gasthuisberg Campus
Leuven, Belgium
Charite Research Organisation GmbH
Berlin, Germany
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to Day 162
Mean systolic blood pressure (SBP) obtained after study drug administration
Up to 24 hours after study drug administration.
Time frame: Up to Day 3
Mean diastolic blood pressure (DBP) obtained after study drug administration
Time frame: Up to Day 3
Mean arterial pressure (MAP) obtained after study drug administration
Time frame: Up to Day 3
Mean pulse pressure (PP) obtained after study drug administration
Time frame: Up to Day 3
Mean pulse rate (PR) obtained after study drug administration
Time frame: Up to Day 3
Mean stroke volume (SV) obtained after study drug administration
Time frame: Up to Day 3
Absolute change in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Absolute change in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Absolute change in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Absolute change in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Absolute change in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Absolute change in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Maximum change in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Maximum change in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Maximum change in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Maximum change in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Maximum change in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Maximum change in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Percent change in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Percent change in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Percent change in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Percent change in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Percent change in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Percent change in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (post-REGN5381 administration) in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (post-REGN5381 administration) in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (post-REGN5381 administration) in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (post-REGN5381 administration) in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (post-REGN5381 administration) in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (post-REGN administration) in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (post-REGN administration) in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (post-REGN administration) in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (post-REGN administration) in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (post-REN5381 administration) in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (post-REN5381 administration) in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (post-REN5381 administration) in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (post-REN5381 administration) in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (post-REN5381 administration) in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (pre-REGN5381 administration) in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (pre-REGN5381 administration) in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (pre-REGN5381 administration) in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (pre-REGN5381 administration) in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (pre-REGN5381 administration) in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Absolute change from baseline (pre-REGN5381 administration) in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (pre-REGN administration) in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (pre-REGN administration) in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (pre-REGN administration) in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (pre-REGN administration) in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (pre-REGN administration) in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Maximum change from baseline (pre-REGN administration) in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (pre-REN5381 administration) in the mean SBP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (pre-REN5381 administration) in the mean DBP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (pre-REN5381 administration) in the mean MAP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (pre-REN5381 administration) in the mean PP obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (pre-REN5381 administration) in the mean PR obtained after study drug administration
Time frame: Up to Day 3
Percent change from baseline (pre-REN5381 administration) in the mean SV obtained after study drug administration
Time frame: Up to Day 3
Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SBP obtained after study drug administration.
Time frame: Baseline to Day 3
Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) DBP obtained after study drug administration.
Time frame: Baseline to Day 3
Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) MAP obtained after study drug administration.
Time frame: Baseline to Day 3
Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PP obtained after study drug administration.
Time frame: Baseline to Day 3
Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PR obtained after study drug administration.
Time frame: Baseline to Day 3
Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SV obtained after study drug administration.
Time frame: Baseline to Day 3
Time to return to within 10% of baseline (pre-REGN5381) SBP
Time frame: Up to approximately Day 162
Time to return to within 10% of baseline (pre-REGN5381) DBP
Time frame: Up to approximately Day 162
Time to return to within 10% of baseline (pre-REGN5381) MAP
Time frame: Up to approximately Day 162
Time to return to within 10% of baseline (pre-REGN5381) PP
Time frame: Up to approximately Day 162
Time to return to within 10% of baseline (pre-REGN5381) PR
Time frame: Up to approximately Day 162
Time to return to within 10% of baseline (pre-REGN5381) SV
Time frame: Up to approximately Day 162
SBP
Time frame: Through Day 36
DBP
Time frame: Through Day 36
MAP
Time frame: Through Day 36
PP
Time frame: Through Day 36
PR
Time frame: Through Day 36
Absolute change from baseline in SBP
Time frame: Through Day 36
Absolute change from baseline in DBP
Time frame: Through Day 36
Absolute change from baseline in MAP
Time frame: Through Day 36
Absolute change from baseline in PP
Time frame: Through Day 36
Absolute change from baseline in PR
Time frame: Through Day 36
Percent change from baseline in SBP
Time frame: Through Day 36
Percent change from baseline in DBP
Time frame: Through Day 36
Percent change from baseline in MAP
Time frame: Through Day 36
Percent change from baseline in PP
Time frame: Through Day 36
Percent change from baseline in PR
Time frame: Through Day 36
Concentrations of total REGN9035
Time frame: Up to Day 162
Concentrations of total REGN5381 over time
Time frame: Up to Day 162
Concentrations of total REGN9035 and/or total REGN5381
Time frame: Up to Day 162
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