A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa

NCT00782340 | Completed Phase 3 Results

• 1 other identifier: Droxidopa NOH301
• Study Type: interventional
• Target: 263
• Locations: 2 countries
• Sites: 21

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 Orthostatic Hypotension Questionnaire 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. For the change from randomization, negative numbers represent improvement from randomization in OHQ score.

  7 days

Secondary Outcomes (8)

• Change in Ability to Conduct Activities of Daily Living Score (OHDAS Composite Score)

  7 days

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

  7 days

• Change in Activities Involving Standing a Short Time (OHDAS Item 1)

  7 days

• Change in Activities Involving Walking a Short Time (OHDAS Item 3)

  7 days

• Change in Dizziness/ Lightheadedness/ Feeling Faint/ or Feeling Like You Might Blackout (OHSA Item 1)

  7 days

Study Arms (2)

Droxidopa

ACTIVE COMPARATOR

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

Drug: Droxidopa

Placebo

PLACEBO COMPARATOR

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

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

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:

• Currently taking ephedrine or midodrine
• Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days prior to their baseline visit (Visit 2).
• 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
• For WOCP a serum beta HCG pregnancy test must be conducted at screening, and a urine pregnancy test must be conducted at baseline and study termination; the results must be negative at screening and at baseline for the patient to receive study medication.
• Sexually active males whose partner is a WOCP and who do not agree to use condoms for the duration of the study and for 30 days after the last dose;
• Women who are pregnant or breast feeding
• Known or suspected hypersensitivity to the study medication or any of its ingredients
• 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
• Any other significant systemic, hepatic, cardiac or renal illness

Sponsors & Collaborators

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

Study Sites (21)

North Alabama Neuroscience

Huntsville, Alabama, 35801, United States

Location

Mayo Clinic-Arizona

Scottsdale, Arizona, 85340, United States

Location

Arkansas Cardiology

Little Rock, Arkansas, 72205, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

Bradenton Neurology, Inc

Bradenton, Florida, 34205, United States

Location

Suncoast Neuroscience Associates, Inc

St. Petersburg, Florida, 33701, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Cncs, Ninds,Nih

Bethesda, Maryland, 20892, United States

Location

Nerological Reserch Center at Hattiesburg

Hattiesburg, Mississippi, 39401, United States

Location

North Shore Hospital

Manshasette, New York, 11030, United States

Location

Pennsylvania Hospital of the University of PA Health System- Department of Neurology

Philadelphia, Pennsylvania, 19107, United States

Location

HAN Neurological Associates

Upland, Pennsylvania, 19013, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Evergreen Hospital Medical Center; Booth Gardner Parkinson's Care Center

Kirkland, Washington, 98034, United States

Location

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

Location

University of Alberta

Edmonton, Alberta, T5G 0B7, Canada

Location

Movment Disorder Clinic Deer lodge Centre

Winnipeg, Manitoba, R3J 2H7, Canada

Location

David B. King, - Private Clinic

Halifax, Nova Scotia, GB3J 3T1, Canada

Location

London Health Sciences Centre, UH

London, Ontario, N6A 5A5, Canada

Location

UHNresearch

Toronto, Ontario, M5T 2S8, Canada

Location

IRCM

Montreal, Quebec, H2W 1 R7, Canada

Location

Related Publications (2)

• 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

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

• Stephen Greer, MD

  Arkansas Cardiology

  PRINCIPAL INVESTIGATOR

• Alberto Vasquez, MD

  Suncoast Neuroscience

  PRINCIPAL INVESTIGATOR

• Richard Hull, MD

  North Alabama Neuroscience

  PRINCIPAL INVESTIGATOR

• Brent Goodman, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Alvin McElveen, MD

  Bradenton Neurology, Inc

  PRINCIPAL INVESTIGATOR

• Mazen Dimachkie, MD

  University of Kansas Medical Center

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: September 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: May 16, 2014
• Results First Posted: May 16, 2014

Record last verified: 2014-04

Locations

CA (7); US (14)