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

NCT01927055 | Terminated Phase 3 Results

• 1 other identifier: NOH401
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Symptomatic Neurogenic Orthostatic Hypotension; Parkinson's Disease; Multiple Systems Atrophy; Pure Autonomic Failure; Dopamine Beta Hydroxylase Deficiency

Keywords

NOH; OH; PD; MSA; PAF; DBH

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. 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

Study Arms (2)

Droxidopa

ACTIVE COMPARATOR

Droxidopa 100 mg, 200 mg, 300 mg

Drug: Droxidopa

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Droxidopa DRUG

Droxidopa at 100 mg, 200 mg, 300 mg

Also known as: L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS

Droxidopa

Placebo DRUG

Placebo to match droxidopa capsules and strength designations

Also known as: Mannitol

Placebo

Eligibility Criteria

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

You may qualify if:

• \. 18 years and older and ambulatory (defined as able to walk at least 10 meters);
• \. Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency;
• \. At the Baseline visit (Visit 2), patients must demonstrate:
• a score of at least 4 or greater on the Orthostatic Hypotension Symptom Assessment (OHSA) Item #1;
• a fall of at least 20 mmHg in their systolic blood pressure, within 3 minutes of 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:

• \. Score of 23 or lower on the mini-mental state examination (MMSE);
• \. Concomitant use of vasoconstricting agents for the purpose of increasing blood pressure;
• 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;
• \. Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV definition of alcohol or substance abuse);
• \. Women who are pregnant or breastfeeding;
• \. Women of child bearing potential (WOCP) who are not using at least one method of contraception with their partner;
• \. Male patients who are sexually active with a woman of child bearing potential (WOCP) and not using at least one method of contraception;
• \. Untreated closed angle glaucoma;
• \. 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;
• \. History of myocardial infarction, within the past 2 years;
• \. Current unstable angina;
• \. Congestive heart failure (NYHA Class 3 or 4);
• \. 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;
• \. Gastrointestinal condition that may affect the absorption of study drug (e.g. ulcerative colitis, gastric bypass);
• \. Any major surgical procedure within 30 days prior to the Baseline visit (Visit 2);

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (3)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

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

Charlotte, North Carolina, 28277, United States

Location

Wisconsin Institute for Neurology and Sleep Disorders

Milwaukee, Wisconsin, 53233, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Pure Autonomic Failure; dopamine beta hydroxylase deficiency

Interventions

Droxidopa; Mannitol

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Primary Dysautonomias; Autonomic Nervous System 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; Sugar Alcohols; Alcohols; Carbohydrates

Limitations and Caveats

The study was prematurely terminated; the limited sample size precludes meaningful conclusions on the efficacy or safety of droxidopa in this study.

Results Point of Contact

• Title: Study director
• Organization: H. Lundbeck A/S

LundbeckClinicalTrials@Lundbeck.com

Study Officials

• Horacio Kaufmann, M.D.

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: August 16, 2013
• First Posted: August 22, 2013
• Study Start: November 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: January 8, 2016
• Results First Posted: January 8, 2016

Record last verified: 2015-12

Locations

US (3)