Neurogenic Orthostatic HypotensionPhase 2NCT07089043
A Study in Subjects With Neurogenic Orthostatic Hypotension
A Phase 2 study testing CST-3056 in people with Neurogenic Orthostatic Hypotension, run by CuraSen Therapeutics, Inc. at 5 sites in United States.
Trial summary
This is a study to evaluate the effects of CST-3056 on orthostatic symptoms and signs in subjects with neurogenic orthostatic hypotension (nOH). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Neurogenic Orthostatic Hypotension
- What is being tested?
- CST-3056
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 5 sitesUnited States
- Study dates
- 12 Sep 2025to Oct 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects ≥ 18 and ≤ 85 years of age, at time of informed consent.
- Diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease or pure autonomic failure (i.e. neurogenic orthostatic hypotension).
- At Screening, subjects must meet the diagnostic criteria of neurogenic orthostatic hypotension, as demonstrated by a decrease ≥20 mm Hg in systolic or ≥10 mm Hg in diastolic BP upon standing ≤3 minutes from a supine position.
- At Screening, subjects must have a score ≥4 on the Orthostatic Hypotension Symptom Assessment (OHSA) scale question #1.
- Currently receiving, or known to be responsive to, direct or indirect α1-AR agonists (e.g., midodrine, droxidopa) for treatment of nOH.
- If the Investigator determines that additional autonomic function testing is required to confirm the diagnosis of autonomic dysfunction, the Valsalva maneuver may be performed to show the absence of BP overshoot during phase IV.
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- Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 35 kg/m2, inclusive at Screening.
- Stable medical conditions for 3 months prior to Screening.
- For patients taking antiparkinsonian medication: stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1 month.
- Subject is ambulatory with/without the use of an assistive device.
- Willing to follow the protocol requirements and comply with protocol restrictions.
- Capable of providing informed consent and complying with study procedures.
- Able to speak, understand, and read English.
Who cannot join
- Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies.
- Concomitant use of vasoconstricting agents for the purpose of increasing blood pressure (BP) such as ephedrine, dihydroergotamine, or midodrine must be stopped at least 1 day or 5 half-lives (whichever is longer) prior to dosing on Day 1 and throughout the duration of the study. Fludrocortisone use in the study will be limited to a stable dose of 0.1 mg once-daily (QD).
- Supine SBP ≥ 170 mm Hg or seated SBP ≥ 140 mm Hg at Screening.
- Subjects with clinically meaningful urinary retention who use or are likely to use α1-AR antagonists (e.g., tamsulosin [Flomax]), or other medications (e.g., trazodone).
- Concomitant use of anti-hypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
- Evidence of any significant or unstable clinical disorder or laboratory finding that renders the subject unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine (excluding managed hypo and hyperthyroidism), metabolic, renal, or other systemic disease or laboratory abnormality.
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- History of malignant disease within 5 years, including solid tumors and hematologic malignancies (except [a] basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured; [b] low-grade adenocarcinoma of the prostate).
- Any clinically significant illness or disease (apart from those typically associated with neurodegenerative disease) as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening.
- History of suicidal ideation or an episode of clinically severe depression as determined by the Investigator.
- Clinically significant abnormalities of ECG, including QTcF > 450 ms, for males and QTcF > 470 ms for females, and/or HR < 50 beats per minute, or evidence of clinically significant bundle branch blocks, as indicated by 12-lead ECG in a supine position at Screening.
- A calculated eGFR of ≤60 mL/min/1.73m2 according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation at Screening.
- Current use of any prohibited prescription medication during Screening or throughout study, unless approved by both the Investigator and the Sponsor Medical Monitor.
- Prior treatment with any investigational drug ≤90 days prior to dosing (Day 1), or ≤5 half-lives of the drug (whichever is longer), or current enrollment in any other study treatment or disease study, except for observational studies.
- Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse at Screening.
- Positive screening test for human immunodeficiency virus (HIV), hepatitis C antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HbsAg] at Screening).
- Females who are breastfeeding.
- Any other reason for which the Investigator considers it is not in the best interest of the subject to undertake the study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
CuraSen Investigational Site
Eatontown, New Jersey, 07724
CuraSen Investigational Site
Farmington Hills, Michigan, 48334
CuraSen Investigational Site
Nashville, Tennessee, 37240
CuraSen Investigational Site
New York, New York, 10019
CuraSen Investigational Site
Scottsdale, Arizona, 85251
About this study
Official title: A Single-Blind Dose-Ranging Study in Subjects With Neurogenic Orthostatic Hypotension to Evaluate the Effect of CST-3056 on Symptoms and Signs of Orthostatic Hypotension
This is a study to evaluate the effects of CST-3056 on orthostatic symptoms and signs in subjects with neurogenic orthostatic hypotension (nOH).
Read the detailed description
This is a study to evaluate the effects of CST-3056 on orthostatic symptoms in subjects with nOH.
Subjects who use direct or indirect α1-AR agonists for treatment of nOH will need to discontinue those treatments for at least 1 day or 5 half-lives (whichever is longer) prior to assessment of orthostatic measures during Screening, and again prior to initiation of dosing for study drug on Day 1.
Following confirmation of eligibility, subjects will be enrolled and participate in a single-blind dose ranging study. Single oral doses of CST-3056 will be administered once-daily for five days (Days 1 through 4 and the Optimal Dose Day [Day 5]), as tolerated. The Individual Optimal Dose will be determined based on observations for each subject over Day 1 through Day 4, including standing blood pressure, and safety/tolerability of the dose.
Between 3-7 days after discharge from the in-patient stay, the Investigator or designee will contact the subject by telephone to review the subject's health status. Any adverse events reported by phone will be recorded and followed as medically appropriate as determined by the Investigator.
- Conditions
- Neurogenic Orthostatic Hypotension
- Being tested
- CST-3056, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CST-3056Drug
Administered as an oral solution
PlaceboDrug
Administered as an oral solution
| Study group | Role | What they receive |
|---|---|---|
| CST-3056 | Experimental | Subjects will receive single doses of CST-3056 over 3 days and on the Optimal Dose Day (Day 5) Receives: Drug: CST-3056 |
| Placebo | Placebo comparator | Subjects will receive a single dose of placebo on 1 day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Standing Systolic Blood Pressure
Baseline is defined as the pre-dose measurement on Day 1
Measured: Baseline and 1, 2, 3, and 4 hours post-dose on Days 1 to 4
Secondary outcomes (3)
Change from Baseline in Seated Systolic Blood Pressure relative to placebo
Baseline is defined as the pre-dose measurement on Day 1
Measured: Baseline and 5 minutes post-dose on Days 1 to 4
Change from Baseline in the Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 relative to placebo
The question asks subjects to rate the severity of their orthostatic hypotension symptoms (dizziness, lightheaded, feeling faint, or felling like you might black out) on an 11-point scale from 0-10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference. A higher score indicates a worse outcome. Baseline is defined as the pre-dose measurement on Day 1.
Measured: Baseline and 3 hours post-dose on Days 1 to 4
Change from Baseline in the heads-up tilt table test (HUTT)
Subjects will have blood pressure and heart rate measured continuously and/or intermittently after resting in the supine position and pre-dose measurements will be taken twice. After dosing, subjects will undergo a graded HUTT at 30, 45 and 60 degrees. Measurements will be taken continuously and/or intermittently and at 1 and 3 minutes after each degree of tilt.
Measured: Baseline and 3 hours post-dose on Optimal Dose Day (Day 5)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2025
- Study start12 Sep 2025
- Primary completion24 Sep 2026
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurogenic Orthostatic HypotensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is a single-blind dose ranging study
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- CuraSen Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, CuraSen Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07089043
- Sponsor's protocol ID
- CST3056-CLIN-021
- Status last verified
- Oct 2026
- First submitted
- 14 Jul 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No