Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

February 14, 2022 updated by: Loma Linda University
The purpose of this study is to determine the efficacy of Droxidopa for the treatment of fatigue in patients with Parkinsonism by the Visual Analog Fatigue Scale (VAFS). This is a randomized, placebo-controlled, double-blind clinical trial for 3 months where half the subjects will receive placebo and the other half will receive Droxidopa. Following this will be a wash-out period of 7 days and then all subjects will receive Droxidopa for 3 months during the open-label phase.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Parkinsonism, is a group of symptoms seen in several diseases, including Parkinson's Disease. In Parkinsonism, a patient may become stiff, have smaller and slower movements, develop a tremor (shaking of the arms or legs), have decreased facial expression, and a softer voice.

Fatigue is a common symptom that causes suffering and stress in diseases that affect the brain. Over 50% of patients with Parkinsonism report fatigue as one of their top three symptoms that make their life more difficult. Currently, there are no evidence-based guidelines for treating fatigue in Parkinson's Disease, and no effective medications or therapeutic modalities exist for fatigue symptoms in patients with Parkinson's Disease.

Droxidopa (also known by the trade name NORTHERA) is a safe and well tolerated medication which has been approved in USA for the treatment of orthostatic dizziness or light headedness in patients with a clinical diagnosis of symptomatic Neurogenic Orthostatic Hypotension associated with primary autonomic failure (Parkinson's Disease and Multiple System Atrophy), Dopamine Beta Hydroxylase Deficiency, or Non Diabetic Autonomic Neuropathy.

Fatigue may be due to diminished levels of norepinephrine in Parkinson's Disease. The locus coeruleus, one of the major sources of norepinephrine, is affected during the preclinical phase of Parkinson's Disease during stage 2 of Braak pathology staging. Norepinephrine is the final metabolite of dopamine, therefore by adding exogenous norepinephrine, it may be possible to control some of the motor and non-motor symptoms of Parkinsonism. Norepinephrine is the final metabolite of droxidopa, and it is still unclear if it passes the blood-brain barrier. This pilot study is to measure the efficacy and safety of droxidopa in Parkinsonism patients with fatigue.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University Faculty Medical Offices - Neurology Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age of 50 years or older.
  • Clinical diagnosis of Parkinsons Disease or Atypical Parkinsonism (including multiple system atrophy (MSA), PSP)
  • Fluent in English
  • Reported fatigue and must have a mean VAFS score of 4 or more at baseline
  • Written informed consent

Exclusion Criteria:

  • Inability to understand or cooperate with study procedures
  • Alcohol or substance use disorder within the past 12 months (as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria)
  • Women who are pregnant or breastfeeding
  • Women of childbearing potential (WOCP) as indicated by one of the following:
  • Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic. Sustained is defined as the average of 3 observations each at least 10 minutes apart with the patient having been supine and at rest for at least 5 minutes prior to each measurement
  • Untreated closed angle glaucoma
  • Diagnosis of hypertension that requires treatment with antihypertensive medications
  • 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)
  • Diabetic autonomic neuropathy
  • 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 Investigational Medicinal Product (e.g. ulcerative colitis, gastric bypass)
  • Any major surgical procedure within 30 days prior to the first titration visit.
  • Currently receiving any investigational drug or have received an investigational drug within 28 days prior to the first titration visit
  • Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study
  • Dementia or non-treated depression
  • Subjects who have a mean VAFS score of less than 4 at baseline
  • Vulnerable populations
  • Uncontrolled intercurrent illnesses including, but not limited to severe lung disease, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, and situations that would limit compliance with study requirements will be excluded
  • Orthostatic hypotension (OH)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Droxidopa
The Droxidopa starting dose for all eligible patients in the Titration Periods are 100mg three times daily (TID). Doses will be titrated by 100mg TID; increments will be made weekly until the optimal dose is achieved or the subject doesn't notice an improvement in their subjective fatigue on a higher dose compared to the most recent dose. Half of the subjects will be on Droxidopa for 3 months during the double-blind phase. All subjects will be on Droxidopa for 3 months during the open-label phase.
Drug: Droxidopa
Droxidopa in 100, 200, and 300mg capsules. Maximum dose to be used in this study is 600mg.
Other Names:
  • Northera
Placebo Comparator: Placebo Oral Tablet
The placebo starting dose for all eligible patients in the Titration Period is 100mg TID. Doses will be titrated by 100mg TID; increments will be made weekly until the optimal dose is achieved. Half of the subjects will be on placebo for 3 months during the double-blind phase.
Drug: Placebo Oral Tablet
Placebo capsules to match Droxidopa 100, 200, and 300mg capsules.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS)
Time Frame: Change between baseline and 12 weeks
Subjects will complete the VAFS which measures level of fatigue with zero being equivalent to energetic with no fatigue to ten being worst possible fatigue
Change between baseline and 12 weeks
Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS)
Time Frame: Change between 18 weeks and 28 weeks
Subjects will complete the VAFS which measures level of fatigue with zero being equivalent to energetic with no fatigue to ten being worst possible fatigue
Change between 18 weeks and 28 weeks
Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS)
Time Frame: Week 29
Subjects will complete the VAFS which measures level of fatigue with zero being equivalent to energetic with no fatigue to ten being worst possible fatigue
Week 29

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS)
Time Frame: Change between baseline and 12 weeks
The UPDRS is a composite measurement of motor and non-motor symptoms divided into six domains. Domain I measures Mentation, Behavior and Mood. Domain II measures Activities of Daily Living. Domain III measures Motor Examination. Domain IV measures Complications of Therapy. Domain V is Modified Hoehn and Yahr Staging. Domain 6 is Schwab and England Activities of Daily Living Scale
Change between baseline and 12 weeks
Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS)
Time Frame: Change between 18 weeks and 28 weeks
The UPDRS is a composite measurement of motor and non-motor symptoms divided into six domains. Domain I measures Mentation, Behavior and Mood. Domain II measures Activities of Daily Living. Domain III measures Motor Examination. Domain IV measures Complications of Therapy. Domain V is Modified Hoehn and Yahr Staging. Domain 6 is Schwab and England Activities of Daily Living Scale
Change between 18 weeks and 28 weeks
Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS)
Time Frame: Week 29
The UPDRS is a composite measurement of motor and non-motor symptoms divided into six domains. Domain I measures Mentation, Behavior and Mood. Domain II measures Activities of Daily Living. Domain III measures Motor Examination. Domain IV measures Complications of Therapy. Domain V is Modified Hoehn and Yahr Staging. Domain 6 is Schwab and England Activities of Daily Living Scale
Week 29

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loma Linda University

Collaborators

H. Lundbeck A/S

Investigators

  • Principal Investigator: Khashayar Dashtipour, M.D. Ph.D., Loma Linda University Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2021

Primary Completion (Anticipated)

July 1, 2023

Study Completion (Anticipated)

July 1, 2023

Study Registration Dates

First Submitted

February 20, 2018

First Submitted That Met QC Criteria

February 23, 2018

First Posted (Actual)

February 27, 2018

Study Record Updates

Last Update Posted (Actual)

March 2, 2022

Last Update Submitted That Met QC Criteria

February 14, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5170406

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Lundbeck is funding this study and will be providing the study drug. If Lundbeck requests, they will be provided with protocol, statistical analysis plan, clinical study report, and any other study data they request. All adverse events will be reported to Lundbeck.

IPD Sharing Time Frame

The data will be available to Lundbeck from the start of the study through it's completion.

IPD Sharing Access Criteria

This material will be provided to Lundbeck in person, not electronically.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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