Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (Droxi-304)

Last updated: February 7, 2024
Sponsor: Chelsea Therapeutics
Overall Status: Completed

Phase

3

Condition

Circulation Disorders

Vascular Diseases

Neurologic Disorders

Treatment

Droxidopa

Clinical Study ID

NCT01132326
Droxidopa NOH304
  • Ages > 18
  • All Genders

Study 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. 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.

Eligibility Criteria

Inclusion

Inclusion Criteria: 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 ofthe OHSA) to treatment with droxidopa during open-label titration in DroxidopaProtocol 301 ;
  • Provide written informed consent to participate in the study and understand that theymay withdraw their consent at any time without prejudice to their future medical care.

Exclusion

Exclusion Criteria: Patients are not eligible for this study if they fulfill one or more of the followingcriteria:

  • Currently taking vasoconstricting agents such as ephedrine, dihydroergotamine, ormidodrine; patients taking vasoconstricting agents such as ephedrine,dihydroergotamine, or midodrine must stop taking these drugs at least 2 days or 5half-lives (whichever is longer) prior to their study entry visit (Visit 1).
  • Currently taking anti-hypertensive medication; the use of short-actinganti-hypertensive medications at bedtime is permitted.
  • Currently taking tri-cyclic antidepressant medication or other norepinephrinere-uptake inhibitors;
  • Have changed dose, frequency and or type of prescribed medication, within two weeks ofstarting droxidopa treatment within Protocol 304, with the following exceptions:
  • vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine (seeexclusion a),
  • short courses of antibiotics or other medications/treatments that do notinterfere 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 ofchild-bearing potential (WOCP) who are using or agree to use acceptable methodsof contraception. Acceptable contraceptives include intrauterine devices (IUDs),hormonal contraceptives (oral, depot, patch or injectable) and double barriermethods such as condoms or diaphragms with spermicidal gel or foam.
  • For WOCP a serum beta HCG pregnancy test must be conducted at screening, and aurine pregnancy test must be conducted at baseline and study termination; theresults must be negative at screening and at baseline for the patient to receivestudy medication. WOCP must be advised to use acceptable contraceptivesthroughout the study period and for 30 days after the last dose ofinvestigational product. If hormonal contraceptives are used they should be takenaccording to the package insert. WOCP who are not currently sexually active mustagree to use acceptable contraception, as defined above, if they decide to becomesexually active during the period of the study and for 30 days after the lastdose of investigational product.
  • Sexually active males whose partner is a WOCP and who do not agree to use condoms forthe 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 mmHgin the sitting position);
  • Have atrial fibrillation or, in the investigator's opinion, have any other significantcardiac 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 thatmay, in the investigator's opinion, affect the absorption of study drug;
  • In the investigator's opinion, have clinically significant abnormalities on clinicalexamination or laboratory testing;
  • In the investigator's opinion, are unable to adequately co-operate because ofindividual or family situation;
  • In the investigator's opinion, are suffering from a mental disorder that interfereswith the diagnosis and/or with the conduct of the study, e.g. schizophrenia, majordepression, dementia;
  • Are not able or willing to comply with the study requirements for the duration of thestudy;
  • Have participated in another clinical trial with an investigational agent other thandroxidopa (including named patient or compassionate use protocol) within 4 weeksbefore starting droxidopa treatment within Protocol 304;
  • Previous enrolment in the study.

Study Design

Total Participants: 350
Treatment Group(s): 1
Primary Treatment: Droxidopa
Phase: 3
Study Start date:
January 01, 2009
Estimated Completion Date:
February 28, 2013

Study 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.