A Phase 2 Double-Blind Placebo-Controlled Single-Dose Study of Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of REGN7544, an NPR1 Antagonist Monoclonal Antibody, in Patients with Postural Orthostatic Tachycardia Syndrome

Exclusion criteria:

History of hypertension or a seated SBP during screening that is >140 mm Hg.
2. SBP during AS test during screening, either supine or standing, that is >140 mm Hg systolic on ≥2 measurements.
3. Increase in HR <20 BPM within 10 minutes of changing from supine to a standing position.
4. Is judged by the investigator to have significant heart failure, cardiovascular disease, liver
disease, or renal disease (ie, eGFR <60 ml/min/1.73m2) based on medical history, physical
exam, laboratory studies, and/or ECG performed during screening period.
5. Is confined to bed more than 50% of waking hours.
6. Unwilling or unable to comply with clinic visits and study-related procedures including
study questionnaires.
7. Within 5 days of screening visit has used medications with direct effects on blood volume, BP, or HR (eg, midodrine, droxidopa, octreotide, clonidine, methyldopa, ivabradine, betablockers, calcium channel blockers, pyridostigmine, fludrocortisone, desmopressin, stimulants or IV saline).
8. Members of the clinical site study team and/or his/her immediate family, unless prior approval granted by the Sponsor.
9. Pregnant or breastfeeding women.
10. Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose.
11. Sexually active adult men who are unwilling to use the following forms of medically acceptable birth control: consistent use of a condom OR vasectomy with medical assessment of surgical success, for at least 3 months after the last dose. Sperm donation is prohibited following study drug administration throughout the study until the EOS.
12. Is committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
13. Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the subject by their participation in the study.
14. Was hospitalized (ie, >24 hours) for any reason within 30 days of the screening visit.
15. Has a history of drug or alcohol abuse within a year prior to the screening visit in the opinion of the investigator or is unwilling to forgo illegal recreational drug use during the course of the study.
16. Any malignancy, except for non-melanoma skin cancer or cervical/anus in-situ, that have been resected with no evidence of metastatic disease for 3 years prior to the screening visit.
17. Has a history of significant allergies to adhesives, hydrocolloid, hydrogel, acrylic/acrylate), or has had history of hypersensitivity to study drug or excipients.
18. Participated in any clinical research study evaluating an investigational product or therapy within 3 months or less than 5 half-lives of investigational product prior to the screening visit. Participation in clinical research studies that involve procedures or testing (eg, imaging or blood volume determinations) that will not interfere with the current study is permitted.