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Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study) (EASED)

Primary Purpose

Dyskinesia, Levodopa Induced Dyskinesia, Parkinson's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ADS-5102 (extended release amantadine HCl)
Sponsored by
Adamas Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dyskinesia focused on measuring Levodopa-induced dyskinesia, Parkinsonism

Eligibility Criteria

30 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed a current IRB/IEC-approved informed consent form
  • Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria
  • On a stable regimen of antiparkinson's medications , including any levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation
  • Experiencing troublesome dyskinesia following levodopa dosing (peak dose dyskinesia)
  • Able to understand and complete a standardized PD home diary, following training

Exclusion Criteria:

  • History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation)
  • History of seizures or stroke/TIA within 2 years of screening
  • History of cancer within 5 years of screening, except adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer
  • Estimated GFR < 50 mL/min/1.73m2
  • Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening
  • If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose
  • If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment
  • Treatment with an investigational drug or device within 30 days prior to screening
  • Treatment with an investigational biologic within 6 months prior to screening

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Treatment A

Treatment B

Treatment C

Treatment D

Arm Description

Low dose ADS-5102 (amantadine extended release)

A mid-dose ADS-5102 (amantadine extended release)

High dose ADS-5102 (amantadine extended release)

Outcomes

Primary Outcome Measures

Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score From Baseline to Week 8
The UDysRS is a dyskinesia rating scale from 0-104, and it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The last observation carried forward (LOCF) method was used for analysis. Participants were summarized according to the actual treatment received.

Secondary Outcome Measures

Change in the Fatigue Severity Score (FSS) From Baseline to Week 8
The FSS is a 9-item self-reported scale, rating subject experience of fatigue during the previous 7 days. The total score, on a scale from 1-7, is represented by the mean of all answered items. The higher the score, the greater the fatigue severity.
Change in Total Objective Score (III, IV) of the UDysRS From Baseline to Week 8
UDysRS Part III measures objective impairment (dyskinesia severity, anatomic distribution, and type, based on 4 observed activities); and Part IV measures objective disability based on Part III activities. The scores for the 2 Parts combined range from 0-44; a higher score represents more severe dyskinesia.
Change in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) From Baseline to Week 8; Based on a Standardized PD Home Diary
A PD home diary was used to score 5 different conditions in 30-minute time intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 8 visit.
Change in Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Scores (Parts I, II, III) From Baseline to Week 8
The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each part had sub scales ranging from normal = 0 to severe = 4.
Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms From Baseline to Week 8
The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement).

Full Information

First Posted
July 18, 2011
Last Updated
November 17, 2017
Sponsor
Adamas Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01397422
Brief Title
Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study)
Acronym
EASED
Official Title
Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adamas Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multi-center, randomized, double-blind, placebo-controlled, 4-arm parallel group study to evaluate the tolerability and efficacy of each of three dose levels of ADS-5102 oral capsules, an extended release formulation of amantadine, dosed once daily for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) higher amantadine plasma concentrations during daytime hours when dyskinesia as well as motor and non-motor symptoms of PD are most problematic, ii) low amantadine plasma concentrations overnight, which may reduce the sleep disturbances and vivid dreams occasionally associated with amantadine, and iii) a reduced initial rate of rise in plasma concentration, which is expected to improve overall tolerability of amantadine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyskinesia, Levodopa Induced Dyskinesia, Parkinson's Disease
Keywords
Levodopa-induced dyskinesia, Parkinsonism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
83 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment A
Arm Type
Placebo Comparator
Arm Title
Treatment B
Arm Type
Active Comparator
Arm Description
Low dose ADS-5102 (amantadine extended release)
Arm Title
Treatment C
Arm Type
Active Comparator
Arm Description
A mid-dose ADS-5102 (amantadine extended release)
Arm Title
Treatment D
Arm Type
Active Comparator
Arm Description
High dose ADS-5102 (amantadine extended release)
Intervention Type
Drug
Intervention Name(s)
ADS-5102 (extended release amantadine HCl)
Intervention Description
Oral capsules to be administered once daily at bedtime, for 8 weeks
Primary Outcome Measure Information:
Title
Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score From Baseline to Week 8
Description
The UDysRS is a dyskinesia rating scale from 0-104, and it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The last observation carried forward (LOCF) method was used for analysis. Participants were summarized according to the actual treatment received.
Time Frame
Baseline (Day 1) and Week 8
Secondary Outcome Measure Information:
Title
Change in the Fatigue Severity Score (FSS) From Baseline to Week 8
Description
The FSS is a 9-item self-reported scale, rating subject experience of fatigue during the previous 7 days. The total score, on a scale from 1-7, is represented by the mean of all answered items. The higher the score, the greater the fatigue severity.
Time Frame
Baseline (Day 1) and Week 8
Title
Change in Total Objective Score (III, IV) of the UDysRS From Baseline to Week 8
Description
UDysRS Part III measures objective impairment (dyskinesia severity, anatomic distribution, and type, based on 4 observed activities); and Part IV measures objective disability based on Part III activities. The scores for the 2 Parts combined range from 0-44; a higher score represents more severe dyskinesia.
Time Frame
Baseline (Day 1) and Week 8
Title
Change in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) From Baseline to Week 8; Based on a Standardized PD Home Diary
Description
A PD home diary was used to score 5 different conditions in 30-minute time intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 8 visit.
Time Frame
Baseline (Day 1) and Week 8
Title
Change in Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Scores (Parts I, II, III) From Baseline to Week 8
Description
The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each part had sub scales ranging from normal = 0 to severe = 4.
Time Frame
Baseline (Day 1) and Week 8
Title
Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms From Baseline to Week 8
Description
The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement).
Time Frame
Baseline (Day 1) and Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed a current IRB/IEC-approved informed consent form Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria On a stable regimen of antiparkinson's medications , including any levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation Experiencing troublesome dyskinesia following levodopa dosing (peak dose dyskinesia) Able to understand and complete a standardized PD home diary, following training Exclusion Criteria: History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation) History of seizures or stroke/TIA within 2 years of screening History of cancer within 5 years of screening, except adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer Estimated GFR < 50 mL/min/1.73m2 Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment Treatment with an investigational drug or device within 30 days prior to screening Treatment with an investigational biologic within 6 months prior to screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Director
Organizational Affiliation
Adamas Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Sun City
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Fountain Valley
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Long Beach
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Los Angeles
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Oxnard
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Pasadena
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Reseda
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Ventura
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Fairfield
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Port Charlotte
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Tampa
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Atlanta
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Augusta
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Chicago
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Winfield
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Des Moines
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Kansas City
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Boston
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West Bloomfield
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Toms River
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Durham
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Raleigh
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Toledo
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Richmond
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Virginia
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Kirkland
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Washington
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Milwaukee
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Wisconsin
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United States

12. IPD Sharing Statement

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Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study)

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