Primary Autonomic FailurePhase 3NOH304NCT01132326
Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (Droxi-304)
A Phase 3 study testing Droxidopa in people with Primary Autonomic Failure and Dopamine Beta Hydroxylase Deficiency, run by Chelsea Therapeutics.
Trial summary
Symptomatic NOH in patients with primary autonomic failure is thought to be a consequence of norepinephrine depletion leading to a diminished capacity to effect an appropriate cardiovascular response to an orthostatic challenge resulting in symptomatic cerebral-hypoperfusion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency, Non-Diabetic Neuropathy
- What is being tested?
- Droxidopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- No sites listed yet
- Study dates
- Jan 2009to Feb 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for inclusion, each patient must fulfill the following criteria:
- Demonstrated a symptomatic response (an improvement of at least 1 point in Item #1 of the OHSA) to treatment with droxidopa during open-label titration in Droxidopa Protocol 301 ;
- Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.
Who cannot join
- Patients are not eligible for this study if they fulfill one or more of the following criteria:
- Currently taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine; patients taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their study entry visit (Visit 1).
- Currently taking anti-hypertensive medication; the use of short-acting anti-hypertensive medications at bedtime is permitted.
- Currently taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors;
- Have changed dose, frequency and or type of prescribed medication, within two weeks of starting droxidopa treatment within Protocol 304, with the following exceptions:
- vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine (see exclusion a),
Show all 27Show fewer
- short courses of antibiotics or other medications/treatments that do not interfere with, or exacerbate the patient's condition under study.
- History of known or suspected drug or substance abuse;
- Women of childbearing potential who are not using a medically accepted contraception;
- Reproductive potential: Female subjects should be either post-menopausal (amenorrhoea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception. Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
- For WOCP a serum beta HCG pregnancy test must be conducted at screening, and a urine pregnancy test must be conducted at baseline and study termination; the results must be negative at screening and at baseline for the patient to receive study medication. WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product. If hormonal contraceptives are used they should be taken according to the package insert. WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 30 days after the last dose of investigational product.
- Sexually active males whose partner is a WOCP and who do not agree to use condoms for the duration of the study and for 30 days after the last dose;
- Women who are pregnant or breast feeding;
- Known or suspected hypersensitivity to the study medication or any of its ingredients;
- Pre-existing, sustained, severe hypertension (BP greater than or equal to 180/110 mmHg in the sitting position);
- Have atrial fibrillation or, in the investigator's opinion, have any other significant cardiac arrhythmia;
- Any other significant systemic, hepatic, cardiac or renal illness;
- Diabetes mellitus or insipidus;
- Have a history of closed angle glaucoma;
- Have a known or suspected malignancy;
- Patients with known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug;
- In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing;
- In the investigator's opinion, are unable to adequately co-operate because of individual or family situation;
- In the investigator's opinion, are suffering from a mental disorder that interferes with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major depression, dementia;
- Are not able or willing to comply with the study requirements for the duration of the study;
- Have participated in another clinical trial with an investigational agent other than droxidopa (including named patient or compassionate use protocol) within 4 weeks before starting droxidopa treatment within Protocol 304;
- Previous enrolment in the study.
About this study
Official title: A Multi-center, Open-label Study to Assess the Long-term Safety of Droxidopa in Subjects With Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Neuropathy and Symptomatic Neurogenic Orthostatic Hypotension
Symptomatic NOH in patients with primary autonomic failure is thought to be a consequence of norepinephrine depletion leading to a diminished capacity to effect an appropriate cardiovascular response to an orthostatic challenge resulting in symptomatic cerebral-hypoperfusion. Droxidopa augments norepinephrine levels which should lead to improved cerebral perfusion following orthostatic challenge thereby reducing the symptoms of NOH. The present study will evaluate the long-term safety of droxidopa.
Read the detailed description
This is a Phase III, multi-center, open-label study designed to evaluate the long-term safety of droxidopa in subjects with neurogenic orthostatic hypotension (NOH) associated with Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Autonomic Neuropathy.
Patients will be initially treated with droxidopa at their individualized dose identified during the titration phase in Protocol 301. Patients will not require adjustment of their dose, unless their physician feels a dose change will benefit their symptoms, or side effects. At any point in the study a patient's physician may elect to titrate the subject to a higher or lower dose if they feel additional benefit can be safely derived or to deal with any unwanted side-effect.
Patients will return to the clinic for study visits at 1, 3, 6, 9 and 12 months (± 1 week allowed for 1 month visit, ± 2 weeks allowed for subsequent study visits). Patients who prematurely withdraw from the study will be asked to attend the study center for a final assessment At the conclusion of the 12 month treatment period, all patients who benefit from treatment with droxidopa will be offered the option to continue to receive open-label droxidopa through a separate access program.
At any time during the study, patients can schedule a visit with their study physician if they experience a worsening of symptoms and wish to have their dose adjusted or to remove themselves from the trial.
Patients who decide to terminate their participation in the study will receive a phone call 1 month after leaving the trial to follow-up on any new or ongoing adverse events (AEs).
It is a recognized best practice that patients with neurogenic orthostatic hypotension are advised not to lay fully supine because of the associated increased risk of supine hypertension inherent with their condition. Patients participating in this study should be advised to sleep in a semi-recumbent position. .
Patients will attend the study center as out-patients. Patients will be identified using the unique identification number assigned during Protocol 301.
- Conditions
- Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency, Non-Diabetic Neuropathy, Neurogenic Orthostatic Hypotension
- Being tested
- Droxidopa
- Keywords
- Symptomatic NOH
- Medical subject headings
- dopamine beta hydroxylase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Also called L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS
Oral, 100, 200, 300, 400, 500, 600 mg TID, 12 months
| Study group | Role | What they receive |
|---|---|---|
| Droxidopa | Experimental | Open-Label Droxidopa Receives: Drug: Droxidopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients With Treatment-emergent Adverse Events
Number of patients reporting any treatment emergent adverse events (SAE and or AEs) during the study
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2010 (estimated)
- Study startJan 2009
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Autonomic FailureStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chelsea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Horacio Kaufmann, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01132326
- Sponsor's protocol ID
- Droxidopa NOH304
- Acronym
- NOH304
- Status last verified
- Feb 2024
- First submitted
- 9 Sep 2009
- Last updated
- 9 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Open-label Study to Assess the Long-term Safety of Droxidopa in Subjects With Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Neuropathy and Symptomatic Neurogenic Orthostatic Hypotension
- ClinicalTrials.gov ID
- NCT01132326
- Acronym / sponsor ID
- NOH304 / Droxidopa NOH304
- Conditions
- Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency, Non-Diabetic Neuropathy, Neurogenic Orthostatic Hypotension
- Keywords
- Symptomatic NOH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Chelsea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 28 May 2010 (estimated)
- Results
- Posted 21 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Symptomatic NOH in patients with primary autonomic failure is thought to be a consequence of norepinephrine depletion leading to a diminished capacity to effect an appropriate cardiovascular response to an orthostatic challenge resulting in symptomatic cerebral-hypoperfusion. Droxidopa augments norepinephrine levels which should lead to improved cerebral perfusion following orthostatic challenge thereby reducing the symptoms of NOH. The present study will evaluate the long-term safety of droxidopa.
Detailed description
This is a Phase III, multi-center, open-label study designed to evaluate the long-term safety of droxidopa in subjects with neurogenic orthostatic hypotension (NOH) associated with Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Autonomic Neuropathy.
Patients will be initially treated with droxidopa at their individualized dose identified during the titration phase in Protocol 301. Patients will not require adjustment of their dose, unless their physician feels a dose change will benefit their symptoms, or side effects. At any point in the study a patient's physician may elect to titrate the subject to a higher or lower dose if they feel additional benefit can be safely derived or to deal with any unwanted side-effect.
Patients will return to the clinic for study visits at 1, 3, 6, 9 and 12 months (± 1 week allowed for 1 month visit, ± 2 weeks allowed for subsequent study visits). Patients who prematurely withdraw from the study will be asked to attend the study center for a final assessment At the conclusion of the 12 month treatment period, all patients who benefit from treatment with droxidopa will be offered the option to continue to receive open-label droxidopa through a separate access program.
At any time during the study, patients can schedule a visit with their study physician if they experience a worsening of symptoms and wish to have their dose adjusted or to remove themselves from the trial.
Patients who decide to terminate their participation in the study will receive a phone call 1 month after leaving the trial to follow-up on any new or ongoing adverse events (AEs).
It is a recognized best practice that patients with neurogenic orthostatic hypotension are advised not to lay fully supine because of the associated increased risk of supine hypertension inherent with their condition. Patients participating in this study should be advised to sleep in a semi-recumbent position. .
Patients will attend the study center as out-patients. Patients will be identified using the unique identification number assigned during Protocol 301.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Droxidopa | Experimental | Drug: DroxidopaOpen-Label Droxidopa |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Demonstrated a symptomatic response (an improvement of at least 1 point in Item #1 of the OHSA) to treatment with droxidopa during open-label titration in Droxidopa Protocol 301 ;
- Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.
Key exclusion criteria (27 listed)
- Patients are not eligible for this study if they fulfill one or more of the following criteria:
- Currently taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine; patients taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their study entry visit (Visit 1).
- Currently taking anti-hypertensive medication; the use of short-acting anti-hypertensive medications at bedtime is permitted.
- Currently taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors;
- Have changed dose, frequency and or type of prescribed medication, within two weeks of starting droxidopa treatment within Protocol 304, with the following exceptions:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DroxidopaAlso: L-threo-3,4-dihydroxyphenylserine, L-threo-DOPSOral, 100, 200, 300, 400, 500, 600 mg TID, 12 months | Drug | Droxidopa |
Primary outcome
Patients With Treatment-emergent Adverse Events
Time frame: up to 2 years
Number of patients reporting any treatment emergent adverse events (SAE and or AEs) during the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Primary Autonomic Failure
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Recruiting
Treatment of Supine Hypertension in Autonomic Failure (CPAP)
Supine Hypertension, Autonomic Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Horacio Kaufmann, MD principal investigator
NYU Langone Health
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Droxidopa in people with Primary Autonomic Failure and Dopamine Beta Hydroxylase Deficiency, run by Chelsea Therapeutics.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients With Treatment-emergent Adverse Events (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2024; AzTrials last refreshed its copy on 8 Nov 2026.