A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of REGN9035 in Healthy Adult Volunteers and Mildly Hypertensive Participants
- Registration Number
- NCT05291546
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 93
Inclusion Criteria
- Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the screening visit.
- Normal or mildly elevated blood pressure as defined in the protocol.
Key
Exclusion Criteria
- History of unexplained syncope or autonomic dysfunction.
- History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease.
- Protocol-defined risk factors for cardiovascular disease.
Note: Other protocol defined inclusion / exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B REGN5381 Selected doses of REGN5381 or matching placebo given by IV administration followed by selected doses of REGN9035 and/or matching placebo via IV infusion Part A REGN9035 Single ascending dose (SAD) of REGN9035 or matching placebo given by intravenous (IV) administration. Part B REGN9035 Selected doses of REGN5381 or matching placebo given by IV administration followed by selected doses of REGN9035 and/or matching placebo via IV infusion Part A Placebo Single ascending dose (SAD) of REGN9035 or matching placebo given by intravenous (IV) administration. Part B Placebo Selected doses of REGN5381 or matching placebo given by IV administration followed by selected doses of REGN9035 and/or matching placebo via IV infusion
- Primary Outcome Measures
Name Time Method Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) Up to Day 162
- Secondary Outcome Measures
Name Time Method Absolute change from baseline (pre-REGN5381 administration) in the mean SV obtained after study drug administration Up to Day 3 Percent change in the mean DBP obtained after study drug administration Up to Day 3 Mean diastolic blood pressure (DBP) obtained after study drug administration Up to Day 3 Mean stroke volume (SV) obtained after study drug administration Up to Day 3 Absolute change in the mean MAP obtained after study drug administration Up to Day 3 Maximum change in the mean PP obtained after study drug administration Up to Day 3 Absolute change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration Up to Day 3 Mean systolic blood pressure (SBP) obtained after study drug administration Up to Day 3 Up to 24 hours after study drug administration.
Mean pulse rate (PR) obtained after study drug administration Up to Day 3 Maximum change in the mean SBP obtained after study drug administration Up to Day 3 Maximum change in the mean MAP obtained after study drug administration Up to Day 3 Absolute change in the mean PP obtained after study drug administration Up to Day 3 Absolute change in the mean PR obtained after study drug administration Up to Day 3 Maximum change from baseline (post-REGN administration) in the mean DBP obtained after study drug administration Up to Day 3 Maximum change from baseline (pre-REGN administration) in the mean SV obtained after study drug administration Up to Day 3 Mean arterial pressure (MAP) obtained after study drug administration Up to Day 3 Mean pulse pressure (PP) obtained after study drug administration Up to Day 3 Absolute change in the mean DBP obtained after study drug administration Up to Day 3 Absolute change in the mean SBP obtained after study drug administration Up to Day 3 Absolute change in the mean SV obtained after study drug administration Up to Day 3 Maximum change in the mean DBP obtained after study drug administration Up to Day 3 Percent change from baseline (post-REN5381 administration) in the mean MAP obtained after study drug administration Up to Day 3 Percent change from baseline (pre-REN5381 administration) in the mean PP obtained after study drug administration Up to Day 3 Concentrations of total REGN9035 Up to Day 162 Percent change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration Up to Day 3 Maximum change in the mean PR obtained after study drug administration Up to Day 3 Maximum change in the mean SV obtained after study drug administration Up to Day 3 Maximum change from baseline (post-REGN administration) in the mean SBP obtained after study drug administration Up to Day 3 Maximum change from baseline (pre-REGN administration) in the mean DBP obtained after study drug administration Up to Day 3 Percent change from baseline (pre-REN5381 administration) in the mean MAP obtained after study drug administration Up to Day 3 Percent change in the mean MAP obtained after study drug administration Up to Day 3 Percent change in the mean PR obtained after study drug administration Up to Day 3 Absolute change from baseline (post-REGN5381 administration) in the mean SBP obtained after study drug administration Up to Day 3 Absolute change from baseline (post-REGN5381 administration) in the mean MAP obtained after study drug administration Up to Day 3 Absolute change from baseline (post-REGN5381 administration) in the mean PP obtained after study drug administration Up to Day 3 Maximum change from baseline (post-REN5381 administration) in the mean PR obtained after study drug administration Up to Day 3 Maximum change from baseline (post-REGN5381 administration) in the mean SV obtained after study drug administration Up to Day 3 Percent change from baseline (post-REN5381 administration) in the mean SBP obtained after study drug administration Up to Day 3 Absolute change from baseline (pre-REGN5381 administration) in the mean PR obtained after study drug administration Up to Day 3 Maximum change from baseline (pre-REGN administration) in the mean SBP obtained after study drug administration Up to Day 3 Maximum change from baseline (pre-REGN administration) in the mean MAP obtained after study drug administration Up to Day 3 Percent change in the mean SV obtained after study drug administration Up to Day 3 Maximum change from baseline (post-REGN administration) in the mean PP obtained after study drug administration Up to Day 3 Percent change from baseline (post-REN5381 administration) in the mean PP obtained after study drug administration Up to Day 3 Percent change in the mean SBP obtained after study drug administration Up to Day 3 Percent change in the mean PP obtained after study drug administration Up to Day 3 Absolute change from baseline (post-REGN5381 administration) in the mean DBP obtained after study drug administration Up to Day 3 Absolute change from baseline (post-REGN5381 administration) in the mean PR obtained after study drug administration Up to Day 3 Maximum change from baseline (post-REGN administration) in the mean MAP obtained after study drug administration Up to Day 3 Percent change from baseline (post-REN5381 administration) in the mean DBP obtained after study drug administration Up to Day 3 Percent change from baseline (post-REN5381 administration) in the mean SV obtained after study drug administration Up to Day 3 Absolute change from baseline (pre-REGN5381 administration) in the mean SBP obtained after study drug administration Up to Day 3 Absolute change from baseline (pre-REGN5381 administration) in the mean PP obtained after study drug administration Up to Day 3 Maximum change from baseline (pre-REGN administration) in the mean PR obtained after study drug administration Up to Day 3 Percent change from baseline (pre-REN5381 administration) in the mean DBP obtained after study drug administration Up to Day 3 Time to return to within 10% of baseline (pre-REGN5381) SBP Up to approximately Day 162 DBP Through Day 36 MAP Through Day 36 Absolute change from baseline (pre-REGN5381 administration) in the mean DBP obtained after study drug administration Up to Day 3 Absolute change from baseline (pre-REGN5381 administration) in the mean MAP obtained after study drug administration Up to Day 3 Percent change from baseline (pre-REN5381 administration) in the mean SBP obtained after study drug administration Up to Day 3 Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) DBP obtained after study drug administration. Baseline to Day 3 Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) MAP obtained after study drug administration. Baseline to Day 3 PR Through Day 36 Absolute change from baseline in DBP Through Day 36 Absolute change from baseline in PP Through Day 36 Percent change from baseline in MAP Through Day 36 Percent change from baseline in PP Through Day 36 Percent change from baseline in PR Through Day 36 Percent change from baseline (pre-REN5381 administration) in the mean PR obtained after study drug administration Up to Day 3 Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PR obtained after study drug administration. Baseline to Day 3 Maximum change from baseline (pre-REGN administration) in the mean PP obtained after study drug administration Up to Day 3 Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SBP obtained after study drug administration. Baseline to Day 3 Time to return to within 10% of baseline (pre-REGN5381) DBP Up to approximately Day 162 Time to return to within 10% of baseline (pre-REGN5381) PR Up to approximately Day 162 Absolute change from baseline in SBP Through Day 36 Percent change from baseline (pre-REN5381 administration) in the mean SV obtained after study drug administration Up to Day 3 Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) PP obtained after study drug administration. Baseline to Day 3 Percentage of participants who return to within 10% of baseline (pre-REGN5381 administration) SV obtained after study drug administration. Baseline to Day 3 Time to return to within 10% of baseline (pre-REGN5381) MAP Up to approximately Day 162 Time to return to within 10% of baseline (pre-REGN5381) PP Up to approximately Day 162 Time to return to within 10% of baseline (pre-REGN5381) SV Up to approximately Day 162 SBP Through Day 36 Absolute change from baseline in MAP Through Day 36 Absolute change from baseline in PR Through Day 36 PP Through Day 36 Percent change from baseline in SBP Through Day 36 Percent change from baseline in DBP Through Day 36 Concentrations of total REGN5381 over time Up to Day 162 Concentrations of total REGN9035 and/or total REGN5381 Up to Day 162
Trial Locations
- Locations (2)
Universitair Ziekenhuis Leuven Gasthuisberg Campus
🇧🇪Leuven, Belgium
Charite Research Organisation GmbH
🇩🇪Berlin, Germany