Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)

NCT00738062 | Completed Phase 3 Results

• 1 other identifier: Droxidopa NOH303
• Study Type: interventional
• Target: 103
• Locations: 4 countries
• Sites: 54

Brief Summary

The purpose of this study is to assess the durability of effect of Droxidopa in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency.

Conditions

Neurogenic Orthostatic Hypotension; Non-Diabetic Autonomic Neuropathy; Multiple System Atrophy; Dopamine Beta Hydroxylase Deficiency

Keywords

NOH; Neurogenic Orthostatic Hypotension; Orthostatic hypotension; PAF; Pure Autonomic Failure; MSA; Multiple System Atrophy; Neuropathy; Autonomic Failure; Parkinson; Dopamine Deficiency; Dopamine; Droxidopa

Outcome Measures

Primary Outcomes (1)

• Change in Orthostatic Hypotension Questionnaire Composite Score (OHQ)

  The OHQ is the average of two sub-scales, the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). Each asks the patient to rate their symptoms or disease impact over the past week. The OHSA sub-scale is the average of six items: 1) Dizziness, lightheadedness, feeling faint or feeling like you might black out; 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. The OHDAS sub-scale is the average of four items: 1) Standing for a short time; 2) Standing for a long time; 3) Walking for a short time; and 4) Walking for a long time. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug). All patients are on open-label droxidopa for 3 months prior to randomization.

  14 days

Secondary Outcomes (7)

• Change in Orthostatic Hypotension Daily Activities (OHDAS) Score

  14 days

• Change in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score

  14 days

• Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing

  14 days

• Patient Reported Clinical Global Impression - Severity

  14 days

• Clinician Recorded Clinical Global Impression - Severity

  14 days

Study Arms (2)

Droxidopa

ACTIVE COMPARATOR

Study medication

Drug: Droxidopa

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Droxidopa DRUG

100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day

Droxidopa

Placebo DRUG

100 mg, oral, three times per day 200 mg, oral, three times per day 300 mg, oral, three times per day 400 mg, oral, three times per day 500 mg, oral, three times per day 600 mg, oral, three times per day

Also known as: Inactive drug (to look like Droxidopa)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participated in Droxidopa Protocol 302;
• 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.

You may not qualify if:

• Patients are not eligible for this study if they fulfill one or more of the following criteria:
• Currently taking ephedrine or midodrine;
• Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days 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 study start (excluding ephedrine and midodrine);
• History of more than moderate alcohol consumption;
• 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 (amenorrhea 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 urine pregnancy test must be conducted at each study visit.
• WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product.

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (54)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Dedicated Clinical Research

Litchfield Park, Arizona, 85340, United States

Location

Xenoscience Inc.

Phoenix, Arizona, 85004, United States

Location

Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

The Parkinson's and Movement Disorders Institute

Fountain Valley, California, 92708, United States

Location

Pacific Neuroscience Medical Group

Oxnard, California, 93030, United States

Location

The Parkinson's Institute

Sunnyvale, California, 94085, United States

Location

Electrophysiology Associates

Colorado Springs, Colorado, 80910, United States

Location

Parkinson's Disease & Movment Disorder Center

Boca Raton, Florida, 33486, United States

Location

Southeastern Integrated Medical

Gainesville, Florida, 32607, United States

Location

Mayo Jacksonville Florida Department of Neurology

Jacksonville, Florida, 32224, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Medical Associates of North Georgia

Canton, Georgia, 30114, United States

Location

Saint Mary of Nazareth Hospital Center

Chicago, Illinois, 60622, United States

Location

North Chicago VA Medical Center

North Chicago, Illinois, 60064, United States

Location

Indiana Medical Research

Elkhart, Indiana, 46514, United States

Location

JWM Neurology

Indianapolis, Indiana, 46237, United States

Location

Kansas City Bone and Joint, PA

Overland Park, Kansas, 66211, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Maryland Hospital

Baltimore, Maryland, 21201, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Worcester

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Health System

Southfield, Michigan, 48034, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

New Jersey Neuroscience Institute

Edison, New Jersey, 08818, United States

Location

Kingston Neurological Associates, PC

Kingston, New York, 12401, United States

Location

NYU Medical Center

New York, New York, 10016, United States

Location

Columbia University Neurological institute of NY

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14618, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

COR Clinical Research, LLC

Oklahoma City, Oklahoma, 73103, United States

Location

The Oregon Clinic

Portland, Oregon, 97213, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Jacinto Medical Group, PA

Baytown, Texas, 77521, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-9036, United States

Location

Scott & White Healthcare - Round Rock

Round Rock, Texas, 78665, United States

Location

Scott & White Memorial Hospital & Clinic

Temple, Texas, 76508, United States

Location

East Texas Medical Center - Neurological Institute Movment Disorders Center

Tyler, Texas, 75701, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Baker Heart Research Institute

Melbourne, Victoria, 3004, Australia

Location

Austin Hospital

Heidelburg, 3084, Australia

Location

McMaster University

Hamilton, Ontario, L8L2X2, Canada

Location

Centre for Movement Disorders

Markham, Ontario, L6B1C9, Canada

Location

Parkinson's & Neurodegenerative Disorders Clinic

Ottawa, Ontario, K1G4G3, Canada

Location

SMBD Jewish General Hospital - Department of Neurology

Montreal, Quebec, H3T 1E2, Canada

Location

Quebec Memory and Motor Skills Disorders Clinic

Québec, Quebec, G1R 3X5, Canada

Location

Auckland Hospital

Grafton Auckland, Private Bag, New Zealand

Location

Van der Veer Institute for Parkinson's Disease and Movement Disorders

Christchurch, New Zealand

Location

MeSH Terms

Conditions

Multiple System Atrophy; dopamine beta hydroxylase deficiency; Hypotension, Orthostatic; Pure Autonomic Failure

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Orthostatic Intolerance; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Chelsea Therapeutics Inc.

hewitt@chelsearx.com

704-973-4202

Study Officials

• Horacio Kaufmann Kaufmann, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

• Christopher J. Mathias, MD

  Imperial School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2008
• First Posted: August 20, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 16, 2014
• Results First Posted: May 16, 2014

Record last verified: 2014-04

Locations

CA (5); NZ (2); US (44); AU (3)