Clinical Trials

Inclusion Criteria:

Healthy Participants

• Is 18 (or age of adult) to 80 years of age at the screening visit.
• Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and ECGs performed at screening and/or at the start of in-clinic visit 1.
• Is in good health based on laboratory safety testing.
• Must be age-matched (±5 years), BMI-matched (± 3 kg/m2) and sex-matched to currently enrolled participants with POTS or participants with nOH, as applicable. This will be decided by the investigators in discussion with the sponsor.
• Has normal BP and pulse rate readings defined as:
  • Normal supine oscillometric BP measurements at the screening visit:
    • SBP ≤ 140 and ≥ 90;
    • DBP ≤ 90 and ≥ 50; and
    • Resting pulse ≤ 100 and ≥ 40.
  • 1 recheck is allowed at screening visit.
  • Normal upright BP measurements with normal range orthostatic responses (measured after approximately 1, 3, and 10 minutes of upright posture following approximately 20 minutes of supine position) at screening visit:
    • Drop of < 20 mmHg SBP and drop of < 10 mmHg DBP; AND increase in HR of < 30 bpm;
    • 1 recheck is allowed at screening visit after a period of quiet rest if the orthostatic changes from the first set of measurements are abnormal.

Participants with POTS

• Is 18 (or age of adult) to 55 years of age at time of screening.
• Diagnosis of POTS based on the following consensus criteria (Raj, 2022) (Sheldon, 2015), confirmed within 12 months of enrollment:
  • An increase in heart rate ≥ 30 beats per minute within 10 minutes of changing from the supine to standing position ( ≥ 40 beats per minute if age ≤ 19);
  • Absence of orthostatic hypotension (defined as a decrease in systolic blood pressure ≥ 20 mmHg or diastolic blood pressure ≥ 10 mmHg upon standing);
  • Absence of other conditions that could explain sinus tachycardia such as acute hypovolemia, anemia, endocrinopathy;
  • Ongoing chronic symptoms (≥ 6 months) consistent with POTS that are worse with standing and are relieved by lying down.
• Active symptoms of moderate to severe intensity, as judged by impact of POTS on overall quality of life and ability to execute activities of daily living.

Participants with nOH

• Is 18 (or age of adult) to 80 years of age at time of screening.
• Diagnosis of nOH based on the following criteria (Freeman, 2011) confirmed within 12 months of enrollment:
  • Presence of neurodegenerative disease (Parkinson’s disease [PD], multiple system atrophy [MSA], Lewy body dementia [LBD], or pure autonomic failure [PAF]);
  • Prior documentation of hemodynamic abnormality: reproducible fall in SBP ≥ 20 mmHg and/or a fall in DBP ≥ 10 mmHg between readings obtained after supine rest and within 3 min of standing;
  • Ongoing chronic symptoms (≥ 6 months) consistent with nOH that are worse with standing and are relieved by lying down.
• Ongoing symptoms of moderate to severe intensity, as judged by impact of nOH on overall quality of life and ability to execute activities of daily living.

All Participants

• Has a body mass index between 18 and 32 kg/m2 , inclusive.
• Able to perform all planned study procedures safely and successfully in the opinion of the investigator.
• Willing and able to comply with clinic visits and study-related procedures.
• Provide informed consent signed by study participant.
• Able to understand and complete study-related questionnaires.

Exclusion Criteria:

Healthy Participants

• History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation.

Participants with POTS and participants with nOH 2.

• History of heart failure, cirrhosis, chronic kidney disease (eGFR of ≤ 60 ml/min/1.73m^2 ), or diabetes mellitus as detected on review during screening of history, physical exam data, laboratory studies, or ECG collected in 12 months prior to enrollment.
• Any mental disorder that, in the opinion of the investigator, interferes with diagnosis and/or conduct of study.
• Clinically significant abnormalities on clinical examination performed within 12 months of enrollment that may interfere with study conduct (eg, amputations, wounds, etc).
• Inability to forgo use of prohibited concomitant medication prescribed for treatment of orthostatic intolerance as described in the protocol.

All Participants

• Members of the clinical site study team and/or is an immediate family member of the clinical site study staff.
• History of more than moderate alcohol consumption ( > 2 drinks/day), history of known or suspected drug or substance abuse within a year prior to the screening visit based on the investigator’s discretion.
• Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study.
• Was hospitalized (ie, > 24 hours) for any reason within 30 days of the screening visit.
• Any malignancy, except for non-melanoma skin cancer or cervical/anus in-situ, that has been resected with no evidence of metastatic disease for 3 years prior to the screening visit.
• Participated in any clinical research study evaluating an investigational drug within 90 days or at least 5 half-lives (whichever is longer) of an investigational biologic drug, or at least 4 weeks for other investigational drug, prior to screening.
• History of allergy or intolerance to skin adhesives.
• Pregnant or breastfeeding women at screening or study day 1:
  • Pregnancy testing is required for WOCBP;
  • Pregnancy testing is not required for women who are postmenopausal or permanently sterile;
  • WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy;
  • A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Pregnancy testing is not required for women with documented hysterectomy.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 7/10/23. Questions regarding updates should be directed to the study team contact.