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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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)
Enrollment 83
Recruitment Details 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 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.
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks 260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks 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) 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)
Period Title: Overall Study
Started 22 20 21 [1] 20
Completed 20 17 18 [2] 12
Not Completed 2 3 3 8
Reason Not Completed
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
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg) Total
Hide Arm/Group Description ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks 260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks 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) 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 of all reporting groups
Overall Number of Baseline Participants 22 20 21 20 83
Hide Baseline Analysis Population Description
Safety Analysis Population (all randomized subjects who received ≥ 1 dose of study drug)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
65.5  (10.17) 67.5  (8.59) 64.7  (10.03) 66.4  (9.38) 66.0  (9.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 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] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
4.86  (1.211) 4.40  (1.488) 4.80  (1.425) 4.78  (1.120) 4.71  (1.307)
[1]
Measure 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.
Hoehn and Yahr Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
2.5  (0.7) 2.5  (0.9) 2.5  (0.6) 2.4  (0.8) 2.5  (0.7)
[1]
Measure Description: 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  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
10.66  (7.057) 8.94  (3.395) 9.33  (4.913) 9.00  (3.484) 9.51  (4.964)
Levodopa daily dose  
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
801.1  (431.94) 714.5  (449.33) 694.0  (278.33) 862.5  (585.94) 768.6  (444.41)
Duration of LID  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
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] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 22 participants 20 participants 21 participants 20 participants 83 participants
Levodopa (Sinemet or Stalevo)
22
 100.0%
20
 100.0%
21
 100.0%
20
 100.0%
83
 100.0%
Dopamine Agonist
14
  63.6%
14
  70.0%
10
  47.6%
16
  80.0%
54
  65.1%
MAO-B Inhibitor
14
  63.6%
11
  55.0%
12
  57.1%
12
  60.0%
49
  59.0%
COMT Inhibitor
3
  13.6%
1
   5.0%
6
  28.6%
4
  20.0%
14
  16.9%
Anticholinergic
1
   4.5%
0
   0.0%
0
   0.0%
1
   5.0%
2
   2.4%
[1]
Measure Description: Participants may have been taking more than 1 antiparkinson medication at baseline.
1.Primary Outcome
Title Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score From Baseline to Week 8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the MITT population with available data were analyzed.
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description:
ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
260 mg dose of ADS-5102 (amantadine HClextended release): oral capsules administered once daily at bedtime for 8 weeks
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)
420 mg dose of ADS-5102 (amantadine HClextended release): oral capsules administered once daily at bedtime for 8 weeks (260 mg Week 1; 340 mg Week 2; 420 mg Weeks 3-8)
Overall Number of Participants Analyzed 22 19 20 19
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.7  (2.68) -12.3  (2.88) -17.9  (2.82) -16.7  (2.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ADS-5102 (340 mg)
Comments 20 subjects per treatment arm provided 80% power using a 2-sided 2-sample test at 5% significance. The null hypothesis for the primary endpoint was that the response of the ADS-5102 340 mg group was equal to that of the placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0051
Comments [Not Specified]
Method ANCOVA
Comments Change from baseline is a dependent variable, treatment group is a factor, and the baseline value is a covariate.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -11.3
Confidence Interval (2-Sided) 95%
-19.1 to -3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ADS-5102 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0131
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -10.0
Confidence Interval (2-Sided) 95%
-17.8 to -2.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ADS-5102 (260 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1595
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-13.4 to 2.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in the Fatigue Severity Score (FSS) From Baseline to Week 8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description:
ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
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)
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)
Overall Number of Participants Analyzed 22 19 20 19
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.25  (0.267) -0.06  (0.289) -0.55  (0.280) 0.00  (0.287)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ADS-5102 (340 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4314
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.1 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ADS-5102 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5223
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.5 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ADS-5102 (260 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6298
Comments [Not Specified]
Method ANCOVA
Comments Change from baseline is a dependent variable, treatment group is a factor, baseline value is a covariate
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.6 to 1.0
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Total Objective Score (III, IV) of the UDysRS From Baseline to Week 8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
MITT Population
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description:
ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
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)
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)
Overall Number of Participants Analyzed 22 19 20 19
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.9  (1.19) -4.4  (1.26) -7.1  (1.24) -8.3  (1.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ADS-5102 (340 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -5.2
Confidence Interval (2-Sided) 95%
-8.7 to -1.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ADS-5102 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -6.4
Confidence Interval (2-Sided) 95%
-9.8 to -2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ADS-5102 (260 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1469
Comments [Not Specified]
Method ANCOVA
Comments Change from baseline is a dependent variable, treatment group is a factor, and the baseline value is a covariate.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-6.0 to 0.9
Estimation Comments [Not Specified]
4.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description:
ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
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)
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)
Overall Number of Participants Analyzed 22 19 20 19
Least Squares Mean (Standard Error)
Unit of Measure: hours
0.9  (0.76) 4.1  (0.82) 3.8  (0.79) 3.6  (0.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ADS-5102 (340 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
0.8 to 5.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ADS-5102 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0179
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
0.5 to 5.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ADS-5102 (260 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0040
Comments [Not Specified]
Method ANCOVA
Comments Change from baseline is a dependent variable, treatment group is a factor, and the baseline value is a covariate
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
1.1 to 5.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Combined Scores (Parts I, II, III) From Baseline to Week 8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description:
ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
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)
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)
Overall Number of Participants Analyzed 22 19 20 19
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.2  (3.08) 0.0  (3.22) -3.4  (3.31) 0.5  (3.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ADS-5102 (340 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6355
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-11.2 to 6.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ADS-5102 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7053
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-7.2 to 10.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ADS-5102 (260 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7862
Comments [Not Specified]
Method ANCOVA
Comments Change from baseline is a dependent variable, treatment group is a factor, and the baseline value is a covariate
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-7.7 to 10.1
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms From Baseline to Week 8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description:
ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks
260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks
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)
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)
Overall Number of Participants Analyzed 22 19 20 19
Measure Type: Count of Participants
Unit of Measure: Participants
Marked Improvement
1
   4.5%
2
  10.5%
7
  35.0%
4
  21.1%
Moderate Improvement
6
  27.3%
8
  42.1%
8
  40.0%
6
  31.6%
Minimal Improvement
4
  18.2%
5
  26.3%
1
   5.0%
5
  26.3%
No Change
10
  45.5%
3
  15.8%
4
  20.0%
2
  10.5%
Minimal Worsening
1
   4.5%
1
   5.3%
0
   0.0%
0
   0.0%
Moderate Worsening
0
   0.0%
0
   0.0%
0
   0.0%
2
  10.5%
Marked Worsening
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ADS-5102 (340 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0036
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ADS-5102 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2158
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ADS-5102 (260 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1042
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Equally spaced scores
Time Frame Baseline through Week 8
Adverse Event Reporting Description The reporting threshold of 5% for Other (Not Including Serious) AEs reflects events that occurred at 5% or greater in any treatment arm.
 
Arm/Group Title Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Hide Arm/Group Description ADS-5102 matching placebo: oral capsules administered once daily at bedtime for 8 weeks 260 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once daily at bedtime for 8 weeks 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) 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)
All-Cause Mortality
Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/20 (0.00%)   0/21 (0.00%)   0/20 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   1/20 (5.00%)   0/21 (0.00%)   4/20 (20.00%) 
Immune system disorders         
Hypersensitivity † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Infections and infestations         
Cellulitis † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Lobar pneumonia † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Urinary tract Infection † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications         
Subdural haematoma † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Psychiatric disorders         
Mental Status Change † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Psychotic disorder † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
1
Term from vocabulary, MedDRA (15.1)
†
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo ADS-5102 (260 mg) ADS-5102 (340 mg) ADS-5102 (420 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/22 (81.82%)   16/20 (80.00%)   20/21 (95.24%)   18/20 (90.00%) 
Blood and lymphatic system disorders         
Leukocytosis † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Cardiac disorders         
Angina pectoris † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Eye disorders         
Vision blurred † 1  1/22 (4.55%)  1/20 (5.00%)  1/21 (4.76%)  1/20 (5.00%) 
Altered visual depth perception † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  2/20 (10.00%) 
Dry eye † 1  0/22 (0.00%)  1/20 (5.00%)  1/21 (4.76%)  0/20 (0.00%) 
Eye irritation † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Photophobia † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders         
Constipation † 1  2/22 (9.09%)  7/20 (35.00%)  5/21 (23.81%)  3/20 (15.00%) 
Dry mouth † 1  0/22 (0.00%)  3/20 (15.00%)  4/21 (19.05%)  2/20 (10.00%) 
Nausea † 1  1/22 (4.55%)  1/20 (5.00%)  3/21 (14.29%)  1/20 (5.00%) 
Diarrhoea † 1  1/22 (4.55%)  1/20 (5.00%)  1/21 (4.76%)  0/20 (0.00%) 
Abdominal discomfort † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Dysphagia † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Salivary hypersecretion † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
General disorders         
Oedema peripheral † 1  1/22 (4.55%)  1/20 (5.00%)  2/21 (9.52%)  2/20 (10.00%) 
Asthenia † 1  1/22 (4.55%)  0/20 (0.00%)  3/21 (14.29%)  1/20 (5.00%) 
Malaise † 1  0/22 (0.00%)  1/20 (5.00%)  1/21 (4.76%)  0/20 (0.00%) 
Chills † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Irritability † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Pain † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Immune system disorders         
Hypersensitivity † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Infections and infestations         
Urinary tract infection † 1  0/22 (0.00%)  1/20 (5.00%)  2/21 (9.52%)  1/20 (5.00%) 
Nasopharyngitis † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  2/20 (10.00%) 
Upper respiratory tract infection † 1  1/22 (4.55%)  1/20 (5.00%)  1/21 (4.76%)  0/20 (0.00%) 
Injury, poisoning and procedural complications         
Fall † 1  3/22 (13.64%)  1/20 (5.00%)  3/21 (14.29%)  3/20 (15.00%) 
Contusion † 1  1/22 (4.55%)  2/20 (10.00%)  0/21 (0.00%)  0/20 (0.00%) 
Tooth fracture † 1  0/22 (0.00%)  0/20 (0.00%)  1/21 (4.76%)  1/20 (5.00%) 
Concussion † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Corneal abrasion † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Excoriation † 1  1/22 (4.55%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Hand fracture † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Joint dislocation † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Laceration † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Investigations         
Blood urea increased † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  1/20 (5.00%) 
Blood creatinine increased † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Blood glucose increased † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Glomerular filtration rate decreased † 1  1/22 (4.55%)  1/20 (5.00%)  0/21 (0.00%)  1/20 (5.00%) 
Blood pressure increased † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Hepatic enzyme increased † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Liver function test abnormal † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Metabolism and nutrition disorders         
Hyperglycaemia † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Hypokalaemia † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Hypomagnesaemia † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders         
Muscle spasms † 1  1/22 (4.55%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Pain in extremity † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  2/20 (10.00%) 
Groin pain † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Musculoskeletal pain † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Neck pain † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Nervous system disorders         
Dizziness † 1  1/22 (4.55%)  3/20 (15.00%)  6/21 (28.57%)  3/20 (15.00%) 
Headache † 1  1/22 (4.55%)  1/20 (5.00%)  3/21 (14.29%)  1/20 (5.00%) 
Balance disorder † 1  0/22 (0.00%)  1/20 (5.00%)  1/21 (4.76%)  1/20 (5.00%) 
Somnolence † 1  2/22 (9.09%)  0/20 (0.00%)  1/21 (4.76%)  2/20 (10.00%) 
Syncope † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Cerebral infarction † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Intracranial pressure increased † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Subarachnoid haemorrhage † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Psychiatric disorders         
Hallucination, visual † 1  0/22 (0.00%)  3/20 (15.00%)  3/21 (14.29%)  2/20 (10.00%) 
Confusional state † 1  1/22 (4.55%)  1/20 (5.00%)  3/21 (14.29%)  2/20 (10.00%) 
Hallucination † 1  0/22 (0.00%)  1/20 (5.00%)  2/21 (9.52%)  2/20 (10.00%) 
Mental status changes † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  1/20 (5.00%) 
Hallucination, auditory † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Insomnia † 1  2/22 (9.09%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Nightmare † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Paranoia † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  1/20 (5.00%) 
Psychotic disorder † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Abnormal dreams † 1  1/22 (4.55%)  0/20 (0.00%)  1/21 (4.76%)  0/20 (0.00%) 
Anxiety † 1  1/22 (4.55%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Suicidal ideation † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Renal and urinary disorders         
Urinary hesitation † 1  0/22 (0.00%)  0/20 (0.00%)  2/21 (9.52%)  0/20 (0.00%) 
Haematuria † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Pyuria † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea † 1  0/22 (0.00%)  1/20 (5.00%)  1/21 (4.76%)  0/20 (0.00%) 
Atelectasis † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Dysphonia † 1  0/22 (0.00%)  1/20 (5.00%)  0/21 (0.00%)  0/20 (0.00%) 
Respiratory failure † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Rhinorrhoea † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders         
Hyperhydrosis † 1  1/22 (4.55%)  0/20 (0.00%)  0/21 (0.00%)  2/20 (10.00%) 
Rash † 1  2/22 (9.09%)  0/20 (0.00%)  0/21 (0.00%)  2/20 (10.00%) 
Vascular disorders         
Hypertension † 1  1/22 (4.55%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
Orthostatic hypertension † 1  0/22 (0.00%)  0/20 (0.00%)  0/21 (0.00%)  1/20 (5.00%) 
1
Term from vocabulary, MedDRA (15.1)
†
Indicates events were collected by systematic assessment
[Not Specified]
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
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