Healthy Volunteers
Conditions
Keywords
Healthy Volunteers, Mild Hypertension, High Blood Pressure
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
Interventions
DRUGREGN9035
Part A: Single dose administered by IV infusion on day 1. Part B: Selected doses administered by IV infusion on day 2 or 22.
DRUGREGN5381
Part B: Selected doses administered by IV infusion on day 1.
OTHERPlacebo
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.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the screening visit. 2. Normal or mildly elevated blood pressure as defined in the protocol. Key
Exclusion criteria
1. History of unexplained syncope or autonomic dysfunction. 2. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease. 3. Protocol-defined risk factors for cardiovascular disease. Note: Other protocol defined inclusion /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) | Up to Day 162 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in the mean PR obtained after study drug administration | Up to Day 3 | — |
| Percent change in the mean SV obtained after study drug administration | Up to Day 3 | — |
| Concentrations of total REGN9035 and/or total REGN5381 | Up to Day 162 | — |
| Absolute change from baseline (post-REGN5381 administration) in the mean SBP 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 diastolic blood pressure (DBP) 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 | — |
| Mean pulse rate (PR) 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 SBP 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 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 | — |
| Absolute change in the mean SV 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 DBP obtained after study drug administration | Up to Day 3 | — |
| Maximum 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 | — |
| 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 | — |
| Percent change in the mean SBP obtained after study drug administration | Up to Day 3 | — |
| Percent change in the mean DBP obtained after study drug administration | Up to Day 3 | — |
| Percent change in the mean MAP 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 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 | — |
| Absolute change from baseline (post-REGN5381 administration) in the mean PR 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 | — |
| Maximum change from baseline (post-REGN administration) in the mean SBP 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 (post-REGN administration) in the mean MAP 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 | — |
| 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 | — |
| 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 MAP 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 from baseline (post-REN5381 administration) in the mean PR 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 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 | — |
| Absolute change from baseline (pre-REGN5381 administration) in the mean PP 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 | — |
| Absolute change from baseline (pre-REGN5381 administration) in the mean SV 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 DBP 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 | — |
| Maximum change from baseline (pre-REGN 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 | — |
| Maximum change from baseline (pre-REGN administration) in the mean SV 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 | — |
| Percent change from baseline (pre-REN5381 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 from baseline (pre-REN5381 administration) in the mean PP obtained after study drug administration | Up to Day 3 | — |
| Percent change from baseline (pre-REN5381 administration) in the mean PR obtained after study drug administration | Up to Day 3 | — |
| 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) SBP obtained after study drug administration. | Baseline 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 | — |
| 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) PR 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) SBP | Up to approximately Day 162 | — |
| 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) 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) PR | 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 | — |
| DBP | Through Day 36 | — |
| MAP | Through Day 36 | — |
| PP | Through Day 36 | — |
| PR | Through Day 36 | — |
| Absolute change from baseline in SBP | Through Day 36 | — |
| Percent change in the mean PP obtained after study drug administration | Up to Day 3 | — |
| Absolute change from baseline in MAP | Through Day 36 | — |
| Absolute change from baseline in PP | Through Day 36 | — |
| Absolute change from baseline in PR | Through Day 36 | — |
| Percent change from baseline in SBP | Through Day 36 | — |
| Percent change from baseline in DBP | 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 | — |
| Concentrations of total REGN9035 | Up to Day 162 | — |
| Concentrations of total REGN5381 over time | Up to Day 162 | — |
| Absolute change from baseline in DBP | Through Day 36 | — |
Countries
Belgium, Germany
Outcome results
None listed