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

NCT00633880 | Completed Phase 3 Results DMC

• 1 other identifier: Droxidopa NOH302
• Study Type: interventional
• Target: 181
• Locations: 4 countries
• Sites: 54

Brief Summary

The purpose of this study is to see whether droxidopa is effective 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

Symptomatic Neurogenic Orthostatic Hypotension (NOH); Non-diabetic Neuropathy; Primary Autonomic Failure; 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 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. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug) .

  14 days

Secondary Outcomes (9)

• Change in Fatigue (OHSA Item 4)

  14 days

• Change in Weakness (OHSA Item 3)

  14 days

• Change in Vision (OHSA Item 2)

  14 days

• Change in Concentration (OHSA Item 5)

  14 days

• Change in Head/Neck Discomfort (OHSA Item 6)

  14 days

Study Arms (2)

Droxidopa

EXPERIMENTAL

Double-blind

Drug: Droxidopa

Placebo

PLACEBO COMPARATOR

Double-blind

Drug: Placebo

Interventions

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

Placebo

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

Also known as: L-DOPS, L-threo-DOPS, Northera

Droxidopa

Eligibility Criteria

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

You may qualify if:

• Male or female and aged 18 years or over;
• Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Autonomic Neuropathies;
• A documented fall in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing;
• 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:

• Taking ephedrine or midodrine; Patients taking ephedrine or midodrine may enroll after a minimum 7 day washout period;
• Taking anti-hypertensive medication;
• Have a history of more than moderate alcohol consumption;
• Women who are pregnant or lactating;
• Have a history of closed angle glaucoma;
• Have pre-existing sustained severe hypertension (BP \> 180/110 mmHg in the sitting position);
• Have atrial fibrillation or, in the investigator's opinion, have any other significant cardiac arrhythmia;
• In the investigator's opinion, have any other significant systemic, hepatic, cardiac or renal illness;
• Have diabetes mellitus or insipidus;
• Have a known or suspected malignancy;
• Have known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug;
• In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing;
• Have a serum creatinine level \> 130 µmol/L;

Sponsors & Collaborators

• Chelsea Therapeutics: lead
• Chiltern International Inc.: collaborator

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

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

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

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

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

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

Related Publications (3)

• Biaggioni I, Arthur Hewitt L, Rowse GJ, Kaufmann H. Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension. BMC Neurol. 2017 May 12;17(1):90. doi: 10.1186/s12883-017-0867-5.

  PMID: 28494751 DERIVED

• Francois C, Rowse GJ, Hewitt LA, Vo P, Hauser RA. Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension. BMC Neurol. 2016 Aug 18;16(1):143. doi: 10.1186/s12883-016-0665-5.

  PMID: 27538531 DERIVED

• Biaggioni I, Freeman R, Mathias CJ, Low P, Hewitt LA, Kaufmann H; Droxidopa 302 Investigators. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension. 2015 Jan;65(1):101-7. doi: 10.1161/HYPERTENSIONAHA.114.04035. Epub 2014 Oct 27.

  PMID: 25350981 DERIVED

MeSH Terms

Conditions

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

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

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

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Christopher J Mathias, MD

  Imperial School of Medicine

  PRINCIPAL INVESTIGATOR

• Roy Freeman, MD

  Harvard Medicine School

  PRINCIPAL INVESTIGATOR

• Phillip A Low, MD

  Mayo Foundation

  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: March 5, 2008
• First Posted: March 12, 2008
• Study Start: January 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: September 1, 2009
• Last Updated: May 20, 2014
• Results First Posted: May 20, 2014

Record last verified: 2014-04

Locations

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