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

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

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

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease; Pure Autonomic Failure; Dopamine Beta Hydroxylase Deficiency; Symptomatic Neurogenic Orthostatic Hypotension; Multiple Systems Atrophy
• Intervention / Treatment: Drug: Droxidopa; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Information on additional locations involved in this clinical trial contact Chelsea Therapeutics
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Wisconsin Institute for Neurology and Sleep Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. a score of at least 4 or greater on the Orthostatic Hypotension Symptom Assessment (OHSA) Item #1;

  2. 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;

  1. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chelsea Therapeutics
• Investigators: Principal Investigator: Horacio Kaufmann, M.D., NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: August 16, 2013
• First Submitted That Met QC Criteria: August 21, 2013
• First Posted (Estimate): August 22, 2013

Study Record Updates

• Last Update Posted (Estimate): January 8, 2016
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: MSA; NOH; PD; PAF; OH; DBH
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Parkinson Disease; Hypotension; Multiple System Atrophy; Shy-Drager Syndrome; Hypotension, Orthostatic; Pure Autonomic Failure; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Antiparkinson Agents; Anti-Dyskinesia Agents; Mannitol; Droxidopa
• Other Study ID Numbers: NOH401