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

• ClinicalTrials.gov Identifier: NCT01927055
• Recruitment Status: Terminated
• First Posted: August 22, 2013
• Results First Posted: January 8, 2016
• Last Update Posted: January 8, 2016
• Sponsor: Chelsea Therapeutics
• Information provided by (Responsible Party): Chelsea Therapeutics

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Symptomatic Neurogenic Orthostatic Hypotension; Parkinson's Disease; Multiple Systems Atrophy; Pure Autonomic Failure; Dopamine Beta Hydroxylase Deficiency	Drug: Droxidopa; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy
• Study Start Date: November 2013
• Actual Primary Completion Date: February 2015
• Actual Study Completion Date: February 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1) [ Time Frame: Change from Randomization to Week 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, New York

NYU Langone Medical Center

New York, New York, United States, 10016

United States, North Carolina

Information on additional locations involved in this clinical trial contact Chelsea Therapeutics

Charlotte, North Carolina, United States, 28277

United States, Wisconsin

Wisconsin Institute for Neurology and Sleep Disorders

Milwaukee, Wisconsin, United States, 53233

Sponsors and Collaborators

Chelsea Therapeutics

Investigators

• Principal Investigator: Horacio Kaufmann, M.D.; NYU Langone Medical Center

More Information

• Responsible Party: Chelsea Therapeutics
• ClinicalTrials.gov Identifier: NCT01927055
• Other Study ID Numbers: NOH401
• First Posted: August 22, 2013
• Results First Posted: January 8, 2016
• Last Update Posted: January 8, 2016
• Last Verified: December 2015

Keywords provided by Chelsea Therapeutics:

NOH; OH; PD; MSA; PAF; DBH

Additional relevant MeSH terms:

Parkinson Disease; Multiple System Atrophy; Shy-Drager Syndrome; Hypotension, Orthostatic; Pure Autonomic Failure; Hypotension; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Mannitol; Droxidopa; Diuretics, Osmotic; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Antiparkinson Agents; Anti-Dyskinesia Agents