Parkinson Disease
Conditions
Brief summary
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.
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.
Interventions
DRUGGOCOVRI
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.
Sponsors
Adamas Pharmaceuticals, Inc.
Oregon Health and Science University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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). 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 |
| 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 | 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). 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 |
| 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 | 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). 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 |
| 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) | 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 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 |
| 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) | 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 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GOCOVRI Treatment All participants will have gait, balance, dyskinesia assessed before and after receiving GOCOVRI (274 mg/day).
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. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | GOCOVRI Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 70.9 years |
| Participants with one or more falls in the last 12-months | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
| Years since Parkinson's disease diagnosis | 9.25 years |
| Years with levodopa induced dyskinesias | 3 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 2 / 8 | 1 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 5 |
Outcome results
Primary
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
Time frame: Baseline and on drug; one week of daily life monitoring at each time point
Population: 1 participant that completed the protocol was not included for analysis due to incomplete data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GOCOVRI Treatment | 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) | Baseline | 0.39 CoV, unitless (mean divided by Standard) |
| GOCOVRI Treatment | 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) | On drug | 0.42 CoV, unitless (mean divided by Standard) |
p-value: 0.012t-test, 2 sided
Primary
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
Time frame: Baseline and on drug; one week of daily life monitoring at each time point
Population: 1 participant that completed the protocol was not included for analysis due to incomplete data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GOCOVRI Treatment | 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) | Baseline | 0.55 CoV, unitless (mean divided by Standard) |
| GOCOVRI Treatment | 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) | On drug | 0.53 CoV, unitless (mean divided by Standard) |
p-value: 0.047t-test, 2 sided
Primary
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
Time frame: Baseline and on drug; one week of daily life monitoring at each time point
Population: 1 participant that completed the protocol was not included for analysis due to incomplete data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GOCOVRI Treatment | 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 | Baseline | 84.78 Average number of turns per hour | Standard Deviation 18.47 |
| GOCOVRI Treatment | 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 | On drug | 69.8 Average number of turns per hour | Standard Deviation 31.92 |
Comparison: We hypothesized that GOCOVRI would result in an increase of daily activity due to improvement in LID symptoms.p-value: >0.05t-test, 2 sided
Primary
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
Time frame: Baseline and on drug; one week of daily life monitoring at each time point
Population: 1 participant that completed the protocol was not included for analysis due to incomplete data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GOCOVRI Treatment | 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 | Baseline | 9.98 Average number of walking bouts per hour | Standard Deviation 6.23 |
| GOCOVRI Treatment | 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 | On drug | 7.68 Average number of walking bouts per hour | Standard Deviation 4.86 |
Comparison: We hypothesized that GOCOVRI would result in an increase of daily activity due to improvement in LID symptoms.p-value: >0.05t-test, 2 sided
Primary
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
Time frame: Baseline and on drug; one week of daily life monitoring at each time point
Population: 1 participant that completed the protocol was not included for analysis due to incomplete data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GOCOVRI Treatment | 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 | On drug | 4147.5 Total number of turns per day | Standard Deviation 2188.9 |
| GOCOVRI Treatment | 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 | Baseline | 6540.7 Total number of turns per day | Standard Deviation 3024.5 |
p-value: 0.037t-test, 2 sided