Study to Assess Droxidopa in the Treatment of Freezing Of Gait Symptoms in Patients With Parkinson's Disease

NCT01331122 | Withdrawn Phase 1

• 1 other identifier: Droxidopa FOG201
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

Freezing of Gait (FoG) is a class of symptoms that occur in Parkinson's patients. Also called motor blocks, FoG is characterized by a sudden inability to move the lower extremities which usually lasts less than 10 seconds. The exact pathophysiology of FoG is poorly understood, but treatment with levodopa appears to improve FoG observed in the off-state. As Parkinson's patients progress in severity, FoG in the on-state can increase in frequency and appears to be resistant to dopaminergic therapies. There is additional evidence that norepinephrine as well as dopaminergic systems may be involved in FoG. Droxidopa has has been approved for use in Japan since 1989 for treatment of frozen gait or dizziness associated with Parkinson's Disease. This study is to further explore the safety and efficacy of droxidopa in this indication.

Conditions

Gait Disorders, Neurologic

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of droxidopa as measured by the incidence, relatedness, and severity of adverse events.

  18 Weeks

Secondary Outcomes (3)

• Evaluate the effect of droxidopa on freezing of gait symptoms using the Freezing of Gait Questionnaire

  18 Weeks

• Evaluate the efficacy of droxidopa in the treatment of freezing of gait by using the Observed Freezing of Gait Rating (OFGR) scale

  18 Weeks

• Evaluate the effect of droxidopa on signs and symptoms associated with Parkinson's Disease utilizing the composite scores of the Unified Parkinson's Disease Rating Scale

  18 Weeks

Study Arms (2)

droxidopa

EXPERIMENTAL

Northera (2R,3S)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid L-DOPS L-threo-dihydroxyphenylserine Droxidopa SM-5688

Drug: droxidopa

placebo

PLACEBO COMPARATOR

placebo

Drug: droxidopa

Interventions

droxidopa DRUG

Oral, 100, 200, 300, 400, 500, or 600 mg TID, duration includes two crossover periods of up to a 2 week titration period followed by a 4 week treatment period,with a washout between crossover periods.

Also known as: Northera, SM-5688, L-DOPS, L-threo-dihydroxyphenylserine

droxidopa; placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, aged at least 30 years;
• Diagnosed with probable levodopa-responsive idiopathic Parkinson's Disease , and receiving levodopa. Other Parkinson's Disease medications can also be used.
• At least 3 months incidence of typical freezing of gait (FOG) symptoms, occurring while levodopa is otherwise providing an "on" mobility state (including at least one of the following FOG patterns: start hesitancy, freezing at making turns or when passing through a doorway, spontaneous freezing during continued walking, or freezing of gait related to a simultaneous mental or physical activity).
• 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
• On a stable dose of carbidopa, alone or with other Parkinson's medication, providing a range of carbidopa between 100mg and 400mg daily

You may not qualify if:

• Taking direct acting vasoconstricting agent (i.e. ephedrine or midodrine). Patients taking vasoconstrictor agents such as ephedrine or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit;
• Taking more than one anti-hypertensive medication for the treatment of high blood pressure. Short acting anti-hypertensive medication taken at night to prevent supine hypertension will be allowed.
• Have changed dose or frequency of Parkinson's medication within 2 weeks of baseline
• Known or suspected alcohol or substance abuse within 1 year
• Sustained hypertension (BP greater than 140/90 mmHg in the sitting position)
• Symptomatic coronary artery disease, severe congestive heart failure
• Women who are pregnant, lactating, or plan to become pregnant during the course of this study;
• Women of child bearing potential (WOCP) who are not using two methods of contraception (at least one barrier: i.e. condom) with their partner.
• Male patients who are sexually active with a woman of child bearing potential (WOCP) and not using two methods of contraception (at least one barrier: i.e. condom)
• Untreated closed angle glaucoma, or treated closed angle glaucoma that in the opinion of an ophthalmologist would cause increased risk to the patient;
• Active (last 6 months) atrial fibrillation or, in the investigator's opinion, any other significant cardiac arrhythmia that should preclude the patient from this trial;
• History of myocardial infarction or unstable angina
• Diabetes insipidus, insulin dependent diabetes mellitus, or diabetic neuropathy;
• In the investigator's opinion, any other significant systemic illness;
• Known or suspected malignancy (other than basal cell carcinoma);

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (2)

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

Location

University of Alberta, Movement Disorders Clinic Glenrose Rehabilitation Hospital

Edmonton, Alberta, T5G 0B7, Canada

Location

MeSH Terms

Conditions

Gait Disorders, Neurologic

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Peter A LeWitt, MD

  Henry Ford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: April 7, 2011
• Study Start: April 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 29, 2013

Record last verified: 2013-03

Locations

CA (1); US (1)