A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy

Study Overview
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Brief Summary
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Evaluate the clinical efficacy and safety of droxidopa versus placebo over a 17 week (maximum) treatment period in patients with symptomatic NOH.

Detailed Description
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This is a multi-center, multi-national, randomized, parallel-group, placebo-controlled, double-blind study with a 17 week (maximum) treatment period consisting of an initial, open-label dose titration (up to 2 weeks), followed by a washout period (up to 3 weeks), followed by a 12 week treatment period on a stable dose.

Official Title
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A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy

Conditions
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Parkinson's Disease, Symptomatic Neurogenic Orthostatic Hypotension, Multiple Systems Atrophy, Pure Autonomic Failure, Dopamine Beta Hydroxylase Deficiency

Intervention / Treatment
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* Drug: Droxidopa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 18 years and older and ambulatory (defined as able to walk at least 10 meters); 2. Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency; 3. At the Baseline visit (Visit 2), patients must demonstrate: a score of at least 4 or greater on the Orthostatic Hypotension Symptom Assessment (OHSA) Item #1; a fall of at least 20 mmHg in their systolic blood pressure, within 3 minutes of standing; 4. 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; Exclusion Criteria: 1. Score of 23 or lower on the mini-mental state examination (MMSE); 2. Concomitant use of vasoconstricting agents for the purpose of increasing blood pressure; 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 baseline visit (Visit 2) and throughout the duration of the study; 3. Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV definition of alcohol or substance abuse); 4. Women who are pregnant or breastfeeding; 5. Women of child bearing potential (WOCP) who are not using at least one method of contraception with their partner; 6. Male patients who are sexually active with a woman of child bearing potential (WOCP) and not using at least one method of contraception; 7. Untreated closed angle glaucoma; 8. Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine HTN are allowed in this study) Any significant uncontrolled cardiac arrhythmia; 9. History of myocardial infarction, within the past 2 years; 10. Current unstable angina; 11. Congestive heart failure (NYHA Class 3 or 4); 12. History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ; 13. Gastrointestinal condition that may affect the absorption of study drug (e.g. ulcerative colitis, gastric bypass); 14. Any major surgical procedure within 30 days prior to the Baseline visit (Visit 2); 15. Previously treated with droxidopa within 30 days prior to the Baseline visit (Visit 2); 16. Currently receiving any other investigational drug or have received an investigational drug within 30 days prior to the Baseline visit (Visit 2); 17. Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study; 18. The Investigator has the ability to exclude a patient if for any reason they feel the subject is not a good candidate for the study or will not be able to follow study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Droxidopa<br>Droxidopa 100 mg, 200 mg, 300 mg | Drug: Droxidopa<br>* Droxidopa at 100 mg, 200 mg, 300 mg<br>* Other names: L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo to match droxidopa capsules and strength designations<br>* Other names: Mannitol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1) | OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at end of study minus score at randomization. A positive score indicates worsening during the double-blind randomized phase relative to value at randomization, while a negative score indicates an improvement in symptom severity. | Change from Randomization to Week 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NOH, OH, PD, MSA, PAF, DBH