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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Dyskinesia; Levodopa Induced Dyskinesia
• Intervention / Treatment: Drug: ADS-5102 (extended release amantadine HCl)

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Sun City, Arizona, United States
  • California
    • Fountain Valley, California, United States
    • Long Beach, California, United States
    • Los Angeles, California, United States
    • Oxnard, California, United States
    • Pasadena, California, United States
    • Reseda, California, United States
    • Sunnyvale, California, United States
    • Ventura, California, United States
  • Connecticut
    • Fairfield, Connecticut, United States
  • Florida
    • Boca Raton, Florida, United States
    • Bradenton, Florida, United States
    • Port Charlotte, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Augusta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
    • Winfield, Illinois, United States
  • Iowa
    • Des Moines, Iowa, United States
  • Kansas
    • Kansas City, Kansas, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • West Bloomfield, Michigan, United States
  • New Jersey
    • Toms River, New Jersey, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
    • Raleigh, North Carolina, United States
  • Ohio
    • Toledo, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Texas
    • Houston, Texas, United States
    • San Antonio, Texas, United States
  • Virginia
    • Richmond, Virginia, United States
  • Washington
    • Kirkland, Washington, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Treatment A	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks
ACTIVE_COMPARATOR: Treatment B; Low dose ADS-5102 (amantadine extended release)	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks
ACTIVE_COMPARATOR: Treatment C; A mid-dose ADS-5102 (amantadine extended release)	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks
ACTIVE_COMPARATOR: Treatment D; High dose ADS-5102 (amantadine extended release)	Drug: ADS-5102 (extended release amantadine HCl); Oral capsules to be administered once daily at bedtime, for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) and Week 8
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.	Baseline (Day 1) and Week 8
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.	Baseline (Day 1) and Week 8
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.	Baseline (Day 1) and Week 8
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).	Baseline (Day 1) and Week 8

Collaborators and Investigators

• Sponsor: Adamas Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): May 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: July 18, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (ESTIMATE): July 19, 2011

Study Record Updates

• Last Update Posted (ACTUAL): December 13, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Parkinsonism; Levodopa-induced dyskinesia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Dyskinesias; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: ADS-PAR-AM201