Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

NCT03446807 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 5170406
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Multiple System Atrophy; Progressive Supranuclear Palsy

Keywords

fatigue; Droxidopa

Outcome Measures

Primary Outcomes (3)

• Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS)

  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)

  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)

  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 Outcomes (3)

• Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS)

  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)

  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)

  Week 29

Study Arms (2)

Droxidopa

EXPERIMENTAL

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

Placebo Oral Tablet

PLACEBO COMPARATOR

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

Interventions

Droxidopa DRUG

Droxidopa in 100, 200, and 300mg capsules. Maximum dose to be used in this study is 600mg.

Also known as: Northera

Droxidopa

Placebo Oral Tablet DRUG

Placebo capsules to match Droxidopa 100, 200, and 300mg capsules.

Also known as: Placebo

Placebo Oral Tablet

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Loma Linda University: lead
• H. Lundbeck A/S: collaborator

Study Sites (1)

Loma Linda University Faculty Medical Offices - Neurology Clinic

Loma Linda, California, 92354, United States

Location

Related Publications (9)

• Friedman J, Friedman H. Fatigue in Parkinson's disease. Neurology. 1993 Oct;43(10):2016-8. doi: 10.1212/wnl.43.10.2016.

  PMID: 8413960 BACKGROUND

• Friedman JH, Brown RG, Comella C, Garber CE, Krupp LB, Lou JS, Marsh L, Nail L, Shulman L, Taylor CB; Working Group on Fatigue in Parkinson's Disease. Fatigue in Parkinson's disease: a review. Mov Disord. 2007 Feb 15;22(3):297-308. doi: 10.1002/mds.21240.

  PMID: 17133511 BACKGROUND

• Friedman JH, Beck JC, Chou KL, Clark G, Fagundes CP, Goetz CG, Herlofson K, Kluger B, Krupp LB, Lang AE, Lou JS, Marsh L, Newbould A, Weintraub D. Fatigue in Parkinson's disease: report from a mutidisciplinary symposium. NPJ Parkinsons Dis. 2016;2:15025-. doi: 10.1038/npjparkd.2015.25. Epub 2016 Jan 14.

  PMID: 27239558 BACKGROUND

• Mendonca DA, Menezes K, Jog MS. Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial. Mov Disord. 2007 Oct 31;22(14):2070-6. doi: 10.1002/mds.21656.

  PMID: 17674415 BACKGROUND

• Smith KM, Eyal E, Weintraub D; ADAGIO Investigators. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA Neurol. 2015 Jan;72(1):88-95. doi: 10.1001/jamaneurol.2014.2472.

  PMID: 25420207 BACKGROUND

• Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, Mauney J, Feirtag M, Mathias CJ; NOH301 Investigators. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014 Jul 22;83(4):328-35. doi: 10.1212/WNL.0000000000000615. Epub 2014 Jun 18.

  PMID: 24944260 BACKGROUND

• Herlofson K, Larsen JP. Measuring fatigue in patients with Parkinson's disease - the Fatigue Severity Scale. Eur J Neurol. 2002 Nov;9(6):595-600. doi: 10.1046/j.1468-1331.2002.00444.x.

  PMID: 12453074 BACKGROUND

• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.

  PMID: 2803071 BACKGROUND

• Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995 Apr;39(3):315-25. doi: 10.1016/0022-3999(94)00125-o.

  PMID: 7636775 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Multiple System Atrophy; Supranuclear Palsy, Progressive; Fatigue

Interventions

Droxidopa

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; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Paralysis; Neurologic Manifestations; Eye 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

• Khashayar Dashtipour, M.D. Ph.D.

  Loma Linda University Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The first phase is double-blind and the second phase is open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: February 27, 2018
• Study Start: December 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: The data will be available to Lundbeck from the start of the study through it's completion.
• Access Criteria: This material will be provided to Lundbeck in person, not electronically.

Locations

US (1)