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

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ClinicalTrials.gov Identifier: NCT01397422
Recruitment Status : Completed
First Posted : July 19, 2011
Results First Posted : November 6, 2017
Last Update Posted : December 13, 2017
Sponsor:
Information provided by (Responsible Party):
Adamas Pharmaceuticals, Inc.

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Dyskinesia
Levodopa Induced Dyskinesia
Parkinson's Disease
Intervention: Drug: ADS-5102 (extended release amantadine HCl)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants with Parkinson's disease (PD) and Levodopa-induced Dyskinesia (LID) were enrolled at 31 study sites in the United States. The first subject was randomized on 03 August 2011 and the last subject completed on 15 April 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All randomized subjects (83) were treated and analyzed for safety; 80 were analyzed for efficacy and included in the Modified Intent to Treat (MITT) population. Subjects in the MITT had mild to severe dyskinesia, had periods of troublesome dyskinesia during the day, received ≥ 1 dose of study drug, and provided ≥ 1 postbaseline efficacy assessment.

Reporting Groups
  Description
Placebo ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
ADS-5102 (260 mg) 260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
ADS-5102 (340 mg) 340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks (260 mg Week 1; 340 mg Weeks 2-8)
ADS-5102 (420 mg) 420 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks (260 mg Week 1; 340 mg Week 2; 420 mg Weeks 3-8)

Participant Flow:   Overall Study
    Placebo   ADS-5102 (260 mg)   ADS-5102 (340 mg)   ADS-5102 (420 mg)
STARTED   22   20   21 [1]   20 
COMPLETED   20   17   18 [2]   12 
NOT COMPLETED   2   3   3   8 
Adverse Event                0                3                3                8 
Withdrawal by Subject                1                0                0                0 
Increased bradykinesia related to PD                1                0                0                0 
[1] Of the 3 participants who discontinued, 1 withdrew due to both an AE and an eGFR < 50 mL/min/1.73m^2
[2] AE = adverse event; eGFR = estimated glomerular filtration rate



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Population (all randomized subjects who received ≥ 1 dose of study drug)

Reporting Groups
  Description
Placebo ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
ADS-5102 (260 mg) 260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
ADS-5102 (340 mg) 340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks (260 mg Week 1; 340 mg Weeks 2-8)
ADS-5102 (420 mg) 420 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks (260 mg Week 1; 340 mg Week 2; 420 mg Weeks 3-8)
Total Total of all reporting groups

Baseline Measures
   Placebo   ADS-5102 (260 mg)   ADS-5102 (340 mg)   ADS-5102 (420 mg)   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 22   20   21   20   83 
Age 
[Units: Years]
Mean (Standard Deviation) 		 65.5  (10.17)   67.5  (8.59)   64.7  (10.03)   66.4  (9.38)   66.0  (9.47) 
Sex: Female, Male 
[Units: Participants]
Count of Participants 		         
Female      8  36.4%      12  60.0%      8  38.1%      10  50.0%      38  45.8% 
Male      14  63.6%      8  40.0%      13  61.9%      10  50.0%      45  54.2% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants 		         
Hispanic or Latino      1   4.5%      2  10.0%      0   0.0%      2  10.0%      5   6.0% 
Not Hispanic or Latino      21  95.5%      18  90.0%      21 100.0%      18  90.0%      78  94.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants 		         
American Indian or Alaska Native      0   0.0%      2  10.0%      0   0.0%      0   0.0%      2   2.4% 
Asian      1   4.5%      0   0.0%      0   0.0%      3  15.0%      4   4.8% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      1   4.5%      0   0.0%      1   4.8%      0   0.0%      2   2.4% 
White      20  90.9%      18  90.0%      20  95.2%      17  85.0%      75  90.4% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Fatigue Severity Score (FSS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation) 		 4.86  (1.211)   4.40  (1.488)   4.80  (1.425)   4.78  (1.120)   4.71  (1.307) 
[1] 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.
Hoehn and Yahr Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation) 		 2.5  (0.7)   2.5  (0.9)   2.5  (0.6)   2.4  (0.8)   2.5  (0.7) 
[1] Hoehn and Yahr assessed at screening only. The scale, from 1-5, describes the patient's PD progression. The higher the score the more severe the symptoms of PD.
Time since PD diagnosis 
[Units: Years]
Mean (Standard Deviation) 		 10.66  (7.057)   8.94  (3.395)   9.33  (4.913)   9.00  (3.484)   9.51  (4.964) 
Levodopa daily dose 
[Units: Mg]
Mean (Standard Deviation) 		 801.1  (431.94)   714.5  (449.33)   694.0  (278.33)   862.5  (585.94)   768.6  (444.41) 
Duration of LID 
[Units: Years]
Mean (Standard Deviation) 		 4.08  (4.051)   3.35  (2.585)   4.37  (3.364)   3.57  (2.049)   3.85  (3.106) 
Subjects taking Antiparkinson Medication [1] 
[Units: Participants]
Count of Participants 		         
Levodopa (Sinemet or Stalevo)   22   20   21   20   83 
Dopamine Agonist   14   14   10   16   54 
MAO-B Inhibitor   14   11   12   12   49 
COMT Inhibitor   3   1   6   4   14 
Anticholinergic   1   0   0   1   2 
[1] Participants may have been taking more than 1 antiparkinson medication at baseline.


  Outcome Measures

1.  Primary:   Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score From Baseline to Week 8   [ Time Frame: Baseline (Day 1) and Week 8 ]
  Show Outcome Measure 1

2.  Secondary:   Change in the Fatigue Severity Score (FSS) From Baseline to Week 8   [ Time Frame: Baseline (Day 1) and Week 8 ]
  Show Outcome Measure 2

3.  Secondary:   Change in Total Objective Score (III, IV) of the UDysRS From Baseline to Week 8   [ Time Frame: Baseline (Day 1) and Week 8 ]
  Show Outcome Measure 3

4.  Secondary:   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   [ Time Frame: Baseline (Day 1) and Week 8 ]
  Show Outcome Measure 4

5.  Secondary:   Change in Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Combined Scores (Parts I, II, III) From Baseline to Week 8   [ Time Frame: Baseline (Day 1) and Week 8 ]
  Show Outcome Measure 5

6.  Secondary:   Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms From Baseline to Week 8   [ Time Frame: Baseline (Day 1) and Week 8 ]
  Show Outcome Measure 6


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Head, Regulatory Affairs
Organization: Adamas Pharmaceuticals, Inc.
phone: +1 (510) 450-3500
e-mail: drugsafety@adamaspharma.com



Responsible Party: Adamas Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01397422     History of Changes
Other Study ID Numbers: ADS-PAR-AM201
First Submitted: July 18, 2011
First Posted: July 19, 2011
Results First Submitted: October 7, 2017
Results First Posted: November 6, 2017
Last Update Posted: December 13, 2017