Effect of GOCOVRI (Amantadine, Extended Release Capsules) on Gait in Parkinson's Disease

Effect of GOCOVRI on Quantity and Quality of Gait in Parkinson's Disease

The purpose of the study is to learn about the effect of GOCOVRI (Amantadine extended release) on activity levels and measures of gait and balance quality in people with Parkinson's disease (PD) and levodopa induced dyskinesia (LID) during daily activities using body-worn sensors.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: GOCOVRI

Detailed Description

Levodopa induced dyskinesia (LID) is a symptom of Parkinson's disease for which there are limited treatment options. LID leads to reduced quality of life, increased caregiver burden and an increased risk of falls (Rascol et al., 2015, Chapuis et al., 2005). GOCOVRI™ is an extended release capsule prescription medication shown to reduce LID in people with PD (Pahwa et al., 2017, Pahwa et al., 2018). However, a number of studies have identified an increase in falls in those on the active medication study arm but not the placebo arm (13% increase in active and 7% in placebo) (Pahwa et al., 2017). In order to understand this increase in falls, comprehensive measurements of quantity of activity (gait measured in the home environment) and quality of activity (comprehensive gait characteristics that may increase risk of falls) need to be assessed in participants taking GOCOVRI™. In addition, the evidence for the effect of GOCOVRI™ on gait and balance in PD is limited (Smulders et al., 2016).

This study is an open label study in which the following Aims will be studied:

Aim I: Investigate the effect of GOCOVRI™ on activity levels in people with Parkinson's disease (PD) and Levodopa induced dyskinesia (LID) Hypothesis I: We hypothesize that GOCOVRI™ will result in an increase of daily activity due to improvement in LID symptoms. Primary outcome measures: Total amount of activity per day

Aim II: Investigate the effect of GOCOVRI™ on comprehensive measures of gait and balance quality in people with PD with LID Hypothesis II: We hypothesize GOCOVRI™ may improve discrete characteristics of gait and balance that is evident even within the first hour of the day walking.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Idiopathic Parkinson'd Disease in accordance with the United Kingdom (UK) Brain Bank Criteria
• Hoehn & Yahr scores of II-IV
• subjective report of experiencing at least 1hr/day (two, half-hour periods) of ON time with troublesome Levodopa-Induced Dyskinesia (LID)
• ambulation with or without aids (e.g., walker or cane)
• ≥30 days of a stable regimen of anti-Parkinson's medications that includes a levodopa dose administered ≥3 times daily
• a stable dose of levodopa throughout the study
• no amantadine for a minimum of 30 days prior to enrollment in the study

Exclusion Criteria:

• neurological or musculoskeletal disorders
• orthostatic hypotension at screening (defined as a drop of ≥20mm mercury (HG) systolic and ≥10mm HG diastolic at 2 or 5 minutes of quiet standing after 5 minutes of supine rest)
• a major psychotic disorder
• contraindication to GOCOVRI™ at time of screening, especially renal impairment estimated by glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2) as impaired renal function can increase the chances of adverse reactions to the study drug
• mild to severe cognitive impairment as measured by Montreal Cognitive Assessment (MoCA) score ≤ 23
• concurrent use of immediate release amantadine
• are pregnant or plan to become pregnant
• an implanted deep brain stimulator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GOCOVRI Treatment; All participants will have gait, balance, dyskinesia assessed before and after receiving GOCOVRI (274 mg/day).

Drug: GOCOVRI; Participants will have gait and balance baseline assessment and then repeat assessment after being on full-dose of GOCOVRI for two weeks. The assessments will include measures of gait, balance and dyskinesia. Participants will also wear body-worn sensors (on wrist, feet and lumbar area) during daily-life for seven days to quantify mobility. GOCOVRI will be started at 137mg/day for two weeks and then increased to 274mg/day for two weeks. Participants will repeat baseline assessments and then decrease to a dose of 137mg/day of GOCOVRI for one week, before stopping the medication completely. All participants will receive GOCOVRI and they will know that they are on study drug. No placebo group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim I: Investigate the Effect of GOCOVRI™ on Activity Levels in People With Parkinson's Disease (PD) and Levodopa Induced Dyskinesia (LID) Measure: Number of Walking Bouts Per Hour	Aim I: Investigate the effect of GOCOVRI™ on activity levels in people with Parkinson's disease (PD) and Levodopa induced dyskinesia (LID). Hypothesis I: We hypothesized that GOCOVRI™ would result in an increase of daily activity due to improvement in LID symptoms. Measure: number of walking bouts per hour	Baseline and on drug; one week of daily life monitoring at each time point
Aim I: Investigate the Effect of GOCOVRI™ on Activity Levels in People With Parkinson's Disease (PD) and Levodopa Induced Dyskinesia (LID) Measure: Number of Turns Per Hour	Aim I: Investigate the effect of GOCOVRI™ on activity levels in people with Parkinson's disease (PD) and Levodopa induced dyskinesia (LID). Hypothesis I: We hypothesized that GOCOVRI™ would result in an increase of daily activity due to improvement in LID symptoms. Measure: number of turns per hour	Baseline and on drug; one week of daily life monitoring at each time point
Aim I: Investigate the Effect of GOCOVRI™ on Activity Levels in People With Parkinson's Disease (PD) and Levodopa Induced Dyskinesia (LID) Measure: Total Number of Turns During the Day	Aim I: Investigate the effect of GOCOVRI™ on activity levels in people with Parkinson's disease (PD) and Levodopa induced dyskinesia (LID). Hypothesis I: We hypothesized that GOCOVRI™ would result in an increase of daily activity due to improvement in LID symptoms. Measure: total number of turns during the day	Baseline and on drug; one week of daily life monitoring at each time point
Aim II: Investigate the Effect of GOCOVRI™ on Comprehensive Measures of Gait and Balance Quality in People With PD With LID Measure: Variability in the Turn Rate Per Step (CoV, Coefficient of Variation)	Aim II: Investigate the effect of GOCOVRI™ on comprehensive measures of gait and balance quality in people with PD with LID Hypothesis II: We hypothesize GOCOVRI™ may improve discrete characteristics of gait and balance that is evident even within the first hour of the day walking. Measure: Variability in the turn rate per step (CoV, Coefficient of Variation) Collection methods: wearable sensors worn during daily life used to measure participant walking characteristics; analysis extracts bouts of walking and turning, and specific gait measures for each are averaged across the weeklong collections; CoV calculated using standard deviation and mean of turn rate per step	Baseline and on drug; one week of daily life monitoring at each time point
Aim II: Investigate the Effect of GOCOVRI™ on Comprehensive Measures of Gait and Balance Quality in People With PD With LID Measure: Variability in Total Number of Steps During Turns (CoV, Coefficient of Variation)	Aim II: Investigate the effect of GOCOVRI™ on comprehensive measures of gait and balance quality in people with PD with LID Hypothesis II: We hypothesize GOCOVRI™ may improve discrete characteristics of gait and balance that is evident even within the first hour of the day walking. Measure: variability in total number of steps during turns (CoV, Coefficient of Variation) Collection methods: wearable sensors worn during daily life used to measure participant walking characteristics; analysis extracts bouts of walking and turning, and specific gait measures for each are averaged across the weeklong collections; CoV calculated using standard deviation and mean of the number of steps to complete turns	Baseline and on drug; one week of daily life monitoring at each time point

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Activity during first waking hour	Using body-worn sensors will quantify the amount of activity during the first awake hour of each day over a week.	6 weeks
Change in stride duration variability	Body-worn sensors will be used to quantify stride duration variability during gait in daily life.	6 weeks
Change turning speed	Body-worn sensors will be used to identify turns and quantify turning speed during daily life.	6 weeks
Change in Parkinson's Disease Questionnaire 39 Score	The Parkinson's Disease Quality of Life questionnaire with 39 questions (PDQ-39) reflects eight domains of quality of life (Mobility, Activities of Daily Living, Emotional well-being, Stigma, Social support, Cognition, Communication, and Bodily discomfort). Each item scores from 0 (never) to 4 (always). Sub-scale scores and a Parkinson's Disease summary index (PDSI; sum of eight subsections/8) representing the global health-related quality of life will be calculated, with higher scores representing worse quality of life. Convergent validity is very good and discriminative validity for PD severity levels has been established. The PDQ-39 will be a Patient Reported Outcome to reflect limitations to participation in community mobility.	6 weeks
Change in International Physical Activity Questionnaire	This measure assesses the types of intensity of physical activity and sitting time that people do as part of their daily lives are considered to estimate total physical activity in metabolic expenditure (MET) minutes a week and time spent sitting. Subjects score as low, moderate, or high levels of activity categories. It will be used as a second Patient Reported Outcome to reflect the level of activity during the day.	6 weeks
Change in Movement Disorders Society - Unified Dyskinesia Rating Scale	This will be one of two assessments for Levodopa Induce Dyskinesias (LID). This scale evaluates the involuntary movements often associated with treated Parkinson's disease. There are two primary sections: Historical [Part 1 (On-Dyskinesia) and Part 2 (Off-Dystonia)] and Objective [Part 3 (Impairment) and Part 4 (Disability)]. Score ranges are 0 to 44 for Part I, 0 to 16for Part II, 0 to 28 for Part III, and 0 to 16 for Part IV,with a total score range of 0 to 104. Higher scores reflect more severe dyskinesia.	6 weeks
Change in modified Abnormal Involuntary Movement Scale	The Abnormal Involuntary Movement Scale (AIMS) is an assessment of the occurrence of tardive dyskinesia The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Total score ranges from 0 to 48 with higher scores reflecting more severe dyskinesia. We will compare total scores.	6 weeks

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Adamas Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Amie Hiller, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 20105 (Arthritis Research UK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participants' data will be available (including data dictionary) after de-identification and will include all data collected during the trial. The study protocol, statistical analysis plan, informed consent, clinical study report, and analytic code will all be available 3 months after study publication to 5 years after publication. This data will be shared with anyone providing a methodologically sound proposal. To gain access to the data proposals should be directed to carlsonp@ohsu.edu and requesters will need to sign a data access agreement.
• IPD Sharing Time Frame: 3 months to 5 years after study publication
• IPD Sharing Access Criteria: Requesters will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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
• product manufactured in and exported from the U.S.: No