Study of Natriuretic Peptide Receptor 1 (NPR1) Antagonist in Adult Patients With Postural Orthostatic Tachycardia Syndrome (POTS)

Key Inclusion Criteria:

1. Is diagnosed with POTS and demonstrates consensus criteria (a), (b), (c) and (d)below during screening:

2. Increase in HR ≥30 beats per minute (BPM) within 10 minutes of changing fromsupine to a standing position, as described in the protocol

3. Absence of orthostatic hypotension, defined as a decrease in systolic bloodpressure (SBP) >20 mm Hg within 3 minutes of standing

4. Absence of other conditions explaining orthostatic tachycardia in the judgmentof the investigator, as defined in the protocol

5. Ongoing episodic symptoms consistent with POTS (for example, lightheadedness,palpitations, tremulousness, generalized weakness, blurred vision, and fatigue)that are worse with standing and are relieved by lying down and which have beenpresent for ≥3 months

6. During screening, a participant must score ≥3 on the Patient Global Impressions ofSeverity (PGIS)

7. Has a body mass index between 18 and 35 kg/m2, inclusive

Key Exclusion Criteria:

1. History of hypertension or a seated SBP during screening that is >140 mm Hg

2. SBP during active stand (AS) test during screening, either supine or standing, thatis >140 mm Hg systolic on ≥2 measurements

3. Increase in HR <20 BPM within 10 minutes of changing from supine to a standingposition, as defined in protocol

4. Is judged by the investigator to have significant heart failure, cardiovasculardisease, liver disease, or renal disease (ie, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2) based on medical history, physical exam, laboratorystudies, and/or electrocardiogram (ECG) performed during screening period

5. Is confined to bed more than 50% of waking hours

6. Within 5 days of screening visit has used medications with direct effects on bloodvolume, BP, or HR (eg, midodrine, droxidopa, octreotide, clonidine, methyldopa,ivabradine, beta-blockers, calcium channel blockers, pyridostigmine,fludrocortisone, desmopressin, stimulants or intravenous (IV) saline)

NOTE: Other protocol-defined inclusion/exclusion criteria apply