Open-Label Safety Study of ADS-5102 in PD Patients With LID

Sponsor
Adamas Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02202551
Collaborator
(none)
223
87
1
43.1
2.6
0.1

Study Details

Study Description

Brief Summary

This is a 105-week open-label study to evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release formulation of amantadine, in Parkinson's Disease (PD) patients with Levodopa Induced Dyskinesia (LID).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Participation in this study was offered to subjects who were described by one of the following 3 groups:

  • Group 1: Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID and chose to immediately transition into the current study without a time gap; this group was subdivided into Group 1A, consisting of subjects who received ADS-5102 in the previous Adamas efficacy study, and Group 1P, consisting of subjects who received placebo in the previous Adamas efficacy study

  • Group 2: Subjects who completed a previous Adamas efficacy study evaluating ADS-5102 in LID and entered the current study with a time gap

  • Group 3: Subjects who would have been deemed ineligible for participation in a previous Adamas efficacy study due to having undergone DBS

Consented subjects who completed Screening (Visit 1) and met study eligibility criteria were to have a Baseline Visit and receive study drug. During Week 1, subjects took 170 mg of ADS-5102 (1 capsule) daily at bedtime. For Week 2, the dose was increased to 340 mg (2 capsules) daily at bedtime; this dose was to continue through Week 100. During the final week (Week 101) of the study, the ADS-5102 dose was reduced to 170 mg (1 capsule) daily at bedtime. Subjects were enrolled into the study at Visit 2 (Baseline/Week 0) and were to return to the clinic after 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 weeks of study drug dosing. Subjects were to receive a telephone reminder at the end of Week 1 to increase their dose during Week 2. At the Week 100 Visit, subjects were instructed to reduce their dose to 1 capsule daily at bedtime for 1 week. The amount of available, unused drug was assessed during the Week 100 Visit; subjects were given an additional bottle of study drug, if needed, to complete the 1 week of reduced dosing.

Efficacy, as measured with the MDS-UPDRS, was to be evaluated at all study visits, beginning with the Screening Visit, and excluding the Baseline and Week 4 Visits. A Safety Follow-up Visit was to occur approximately 2 weeks following the completion of treatment. AEs were recorded beginning with the first dose of study drug and continued through the Safety Follow-up Visit. Concomitant medications were recorded throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
223 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-Label Safety Study of ADS-5102 (Amantadine HCl) Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia (LID)
Study Start Date :
Jul 1, 2014
Actual Primary Completion Date :
Feb 1, 2018
Actual Study Completion Date :
Feb 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: ADS-5102

amantadine HCl extended release

Drug: ADS-5102
Other Names:
  • amantadine HCl extended release
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Reported AEs and Safety-Related Study Drug Discontinuations [Up to 101 weeks]

      The primary objective of the study was to evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release (ER) formulation of amantadine, administered at a dose of 340 mg once daily at bedtime for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD).

    Secondary Outcome Measures

    1. Change From Baseline in Movement Disorder's Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Parts I-III Combined Scores) [Up to 101 weeks. MDS-UPDRS was performed at the following visits: Screening, Week 8, Week 16, Week 28, Week 40, Week 52, Week 64, Week 76, Week 88, Week 100 (or ET).]

      To evaluate clinical progression of PD as assessed by the MDS-UPDRS, combined score, Parts I, II, and III. Part I - non-motor experiences of daily living; Part II - motor experiences of daily living; Part III - motor examination. Parts I and II each contain 13 questions measured on a 5-point scale (0-4). Part III contains 18 objective rater assessments of the motor signs of PD measured on a 5-point scale (0-4). Total range for combined score (Part I-III) is = 0-176. Generally for MDS-UPDRS scores and sub-scores, the lower the score, the better. Parts I, II, and III are summed to make the total score.

    2. Change From Baseline in Movement Disorder's Society - Unified Parkinson's Disease Rating Scale MDS-UPDRS (Part IV - Motor Complications) [100 Weeks. MDS-UPDRS was performed at the following visits: Screening, Week 8, Week 16, Week 28, Week 40, Week 52, Week 64, Week 76, Week 88, Week 100 (or ET).]

      This component (Questions 4.1 - 4.6) includes time spent with dyskinesia, functional impact of dyskinesia, time spent in OFF state, functional impact of fluctuations, complexity of motor fluctuations, painful OFF-state dystonia. Questions 4.1-4.6 are summed to make the Part IV score. Generally for MDS-UPDRS scores and sub-scores, the lower the score, the better. Total range for Part IV is = 0-24

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Signed a current IRB/REB/IEC-approved informed consent form

    • Completed all study visits in previous Adamas efficacy study or were ineligible for participation in previous Adamas studies due to having undergone prior deep brain stimulation.

    • Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria

    • On a stable regimen of antiparkinson's medications at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily.

    • History of peak dose dyskinesia that might benefit from specific dyskinesia treatment in the judgment of the subject and clinical investigator

    Exclusion Criteria:
    • Discontinued ADS-5102 in previous Adamas efficacy study due to intolerable or unacceptable AEs considered to be related to ADS-5102

    • History of neurosurgical intervention related to Parkinson's disease, with the exception of deep brain stimulation

    • History of seizures since completion of participation in previous Adamas studies or within 2 years

    • History of stroke or TIA since completion of participation in previous Adamas studies or within 2 years

    • History of cancer since completion of participation in previous Adamas studies or within 2 years, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer

    • 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

    • 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 (other than ADS-5102) or device within 30 days prior to screening

    • Treatment with an investigational biologic within 6 months prior to screening

    • Current or planned participation in another interventional clinical trial

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35233
    2 Phoenix Arizona United States 85013
    3 Scottsdale Arizona United States 85259
    4 Sun City Arizona United States 85351
    5 Fountain Valley California United States 92708
    6 Pasadena California United States 91105
    7 Reseda California United States 91335
    8 Sacramento California United States 95817
    9 Sunnyvale California United States 94085
    10 Torrance California United States 90505
    11 Ventura California United States 93003
    12 Aurora Colorado United States 80045
    13 Manchester Connecticut United States 06040
    14 Boca Raton Florida United States 33486
    15 Gainesville Florida United States 32607
    16 Jacksonville Florida United States 32209
    17 Naples Florida United States 34102
    18 Port Charlotte Florida United States 33980
    19 Sunrise Florida United States 33351
    20 Tampa Florida United States 33612
    21 Tampa Florida United States 33613
    22 Weston Florida United States 33331
    23 Atlanta Georgia United States 30329
    24 Chicago Illinois United States 60611
    25 Chicago Illinois United States 60612
    26 Des Moines Iowa United States 45219
    27 Kansas City Kansas United States 66160
    28 Baltimore Maryland United States 21287
    29 Elkridge Maryland United States 21075
    30 Boston Massachusetts United States 02114
    31 Bingham Farms Michigan United States 48025
    32 West Bloomfield Michigan United States 48322
    33 Golden Valley Minnesota United States 55427
    34 Saint Louis Missouri United States 63110
    35 Albany New York United States 12208
    36 Commack New York United States 11725
    37 New York New York United States 10003
    38 New York New York United States 10016
    39 New York New York United States 10029
    40 Greensboro North Carolina United States 27405
    41 Raleigh North Carolina United States 27607
    42 Cincinnati Ohio United States 45219
    43 Cleveland Ohio United States 44195
    44 Toledo Ohio United States 43614
    45 Tulsa Oklahoma United States 74136
    46 Hershey Pennsylvania United States 17033
    47 Philadelphia Pennsylvania United States 19107
    48 Dallas Texas United States 75390
    49 Houston Texas United States 77030-1
    50 Houston Texas United States 77030-2
    51 Roanoke Virginia United States 24018
    52 Kirkland Washington United States 98034
    53 Morgantown West Virginia United States 26506
    54 Milwaukee Wisconsin United States 53233
    55 Innsbruck Austria 6020
    56 Vienna Austria 1080
    57 Vienna Austria 1220
    58 Edmonton Alberta Canada T6G 2B7
    59 Toronto Ontario Canada M5T 2S8
    60 Regina Saskatchewan Canada S4T 1A5
    61 Bordeaux France 33076
    62 Bron France 69677
    63 Clermont Ferrand France 63003
    64 Lille France 59037
    65 Marseille France 13385
    66 Montpellier France 34295
    67 Poitiers France 86021
    68 Rennes France 35033
    69 Rouen France 76031
    70 Strasbourg France 67098
    71 Toulouse France 31059
    72 München Bayern Germany 80804
    73 München Bayern Germany 81675
    74 Beelitz-Heilstätten Brandenburg Germany 14547
    75 Göttingen Niedersachsen Germany 37075
    76 Leipzig Sachsen Germany 04103
    77 Gera Thüringen Germany 07751
    78 Stadtroda Thüringen Germany 07646
    79 Berlin Germany 12163
    80 Berlin Germany 13353
    81 Hamburg Germany 22291
    82 Kassel Germany 34128
    83 Marburg Germany 35043
    84 Barcelona Spain 08028
    85 Barcelona Spain 08035
    86 Barcelona Spain 08036
    87 Barcelona Spain 08041

    Sponsors and Collaborators

    • Adamas Pharmaceuticals, Inc.

    Investigators

    • Study Director: Clinical Trials Director, Adamas Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Adamas Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02202551
    Other Study ID Numbers:
    • ADS-AMT-PD302
    First Posted:
    Jul 29, 2014
    Last Update Posted:
    Oct 6, 2020
    Last Verified:
    Aug 1, 2020
    Keywords provided by Adamas Pharmaceuticals, Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Group 1a Group 1P Group 2 Group 3
    Arm/Group Description Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1A received ADS-5102 in the prior study. Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1P received placebo in the prior study Subjects in Group 2 completed previous LID study, enrolled ADS-AMT-PD302 after a time gap. Subjects were not in a previous Adamas LID study and had prior DBS (deep brain stimulation)
    Period Title: Overall Study
    STARTED 60 78 24 61
    COMPLETED 35 41 14 39
    NOT COMPLETED 25 37 10 22

    Baseline Characteristics

    Arm/Group Title Group 1a Group 1P Group 2 Group 3 Total
    Arm/Group Description Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1A received ADS-5102 in the prior study. Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1P received placebo in the prior study Subjects in Group 2 completed previous LID study, enrolled ADS-AMT-PD302 after a time gap. Subjects were not in a previous Adamas LID study and had prior DBS (deep brain stimulation) Total of all reporting groups
    Overall Participants 60 78 24 61 223
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    28
    46.7%
    30
    38.5%
    12
    50%
    39
    63.9%
    109
    48.9%
    >=65 years
    32
    53.3%
    48
    61.5%
    12
    50%
    22
    36.1%
    114
    51.1%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.0
    (9.81)
    65.9
    (8.80)
    64.4
    (7.81)
    60.2
    (9.20)
    63.7
    (9.32)
    Sex: Female, Male (Count of Participants)
    Female
    26
    43.3%
    33
    42.3%
    13
    54.2%
    20
    32.8%
    92
    41.3%
    Male
    34
    56.7%
    45
    57.7%
    11
    45.8%
    41
    67.2%
    131
    58.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    3.3%
    2
    2.6%
    0
    0%
    4
    6.6%
    8
    3.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    1
    4.2%
    1
    1.6%
    2
    0.9%
    White
    57
    95%
    74
    94.9%
    23
    95.8%
    54
    88.5%
    208
    93.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    1.7%
    2
    2.6%
    0
    0%
    2
    3.3%
    5
    2.2%
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    25.86
    (25.42)
    25.72
    (24.63)
    25.26
    (23.24)
    27.29
    (4.891)
    26.14
    (5.220)
    eGFR (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL/min/1.73 m^2]
    88.7
    (24.31)
    92.2
    (19.64)
    96.3
    (20.54)
    92.1
    (19.95)
    91.6
    (21.16)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Reported AEs and Safety-Related Study Drug Discontinuations
    Description The primary objective of the study was to evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release (ER) formulation of amantadine, administered at a dose of 340 mg once daily at bedtime for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD).
    Time Frame Up to 101 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group 1a Group 1P Group 2 Group 3
    Arm/Group Description Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1A received ADS-5102 in the prior study. Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1P received placebo in the prior study Subjects in Group 2 completed previous LID study, enrolled ADS-AMT-PD302 after a time gap. Subjects were not in a previous Adamas LID study and had prior DBS (deep brain stimulation)
    Measure Participants 60 78 24 61
    AE
    57
    95%
    70
    89.7%
    23
    95.8%
    55
    90.2%
    Study drug-related AE
    31
    51.7%
    45
    57.7%
    16
    66.7%
    32
    52.5%
    SAEs
    16
    26.7%
    21
    26.9%
    6
    25%
    17
    27.9%
    Permanent discontinuation due to AE
    12
    20%
    21
    26.9%
    6
    25%
    10
    16.4%
    Permanent discontinuation due to drug-related AE
    4
    6.7%
    15
    19.2%
    4
    16.7%
    8
    13.1%
    Mild AEs
    12
    20%
    13
    16.7%
    3
    12.5%
    11
    18%
    Moderate AEs
    25
    41.7%
    36
    46.2%
    13
    54.2%
    26
    42.6%
    Mild drug-related AE
    16
    26.7%
    15
    19.2%
    3
    12.5%
    5
    8.2%
    Moderate drug-related AE
    12
    20%
    23
    29.5%
    12
    50%
    22
    36.1%
    Severe drug-related AE
    3
    5%
    7
    9%
    1
    4.2%
    5
    8.2%
    2. Secondary Outcome
    Title Change From Baseline in Movement Disorder's Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Parts I-III Combined Scores)
    Description To evaluate clinical progression of PD as assessed by the MDS-UPDRS, combined score, Parts I, II, and III. Part I - non-motor experiences of daily living; Part II - motor experiences of daily living; Part III - motor examination. Parts I and II each contain 13 questions measured on a 5-point scale (0-4). Part III contains 18 objective rater assessments of the motor signs of PD measured on a 5-point scale (0-4). Total range for combined score (Part I-III) is = 0-176. Generally for MDS-UPDRS scores and sub-scores, the lower the score, the better. Parts I, II, and III are summed to make the total score.
    Time Frame Up to 101 weeks. MDS-UPDRS was performed at the following visits: Screening, Week 8, Week 16, Week 28, Week 40, Week 52, Week 64, Week 76, Week 88, Week 100 (or ET).

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title ADS-5102 1A ADS-5102 Group 1P ADS-5102 Group 2 ADS-5102 Group 3
    Arm/Group Description Consisting of subjects who received ADS-5102 in the previous Adamas efficacy study Consisting of subjects who received placebo in the previous Adamas efficacy study Subjects who completed a previous Adamas efficacy study evaluating ADS-5102 in LID and entered the current study with a time gap Subjects who would have been deemed ineligible for participation in a previous Adamas efficacy study due to having undergone DBS
    Measure Participants 60 77 24 60
    Baseline
    41.8
    (18.43)
    45.6
    (19.24)
    52.8
    (23.06)
    52.4
    (16.55)
    Change from Baseline at Week 8
    1.2
    (10.03)
    -2.8
    (14.11)
    0.8
    (12.00)
    -5.3
    (10.74)
    Change from Baseline at Week 16
    1.6
    (13.41)
    -1.4
    (16.22)
    5.7
    (15.53)
    -5.2
    (11.33)
    Change from Baseline at Week 28
    4.8
    (10.04)
    1.5
    (12.49)
    6.5
    (14.18)
    -5.3
    (12.99)
    Change from Baseline at Week 40
    7.5
    (15.43)
    -0.4
    (15.20)
    1.6
    (18.29)
    -4.8
    (12.49)
    Change from Baseline at Week 52
    13.2
    (16.78)
    2.6
    (14.57)
    6.1
    (18.34)
    -4.6
    (15.60)
    Change from Baseline at Week 64
    8.8
    (14.83)
    2.6
    (14.57)
    6.1
    (18.34)
    -4.6
    (15.60)
    Change from Baseline at Week 76
    11.7
    (19.58)
    7.3
    (19.18)
    9.4
    (19.10)
    -4.9
    (13.83)
    Change from Baseline at Week 88
    11.3
    (16.65)
    3.7
    (13.80)
    6.4
    (22.65)
    0.9
    (16.18)
    Change from Baseline at Week 100
    11.4
    (15.66)
    3.7
    (15.29)
    6.5
    (16.46)
    4.1
    (17.48)
    3. Secondary Outcome
    Title Change From Baseline in Movement Disorder's Society - Unified Parkinson's Disease Rating Scale MDS-UPDRS (Part IV - Motor Complications)
    Description This component (Questions 4.1 - 4.6) includes time spent with dyskinesia, functional impact of dyskinesia, time spent in OFF state, functional impact of fluctuations, complexity of motor fluctuations, painful OFF-state dystonia. Questions 4.1-4.6 are summed to make the Part IV score. Generally for MDS-UPDRS scores and sub-scores, the lower the score, the better. Total range for Part IV is = 0-24
    Time Frame 100 Weeks. MDS-UPDRS was performed at the following visits: Screening, Week 8, Week 16, Week 28, Week 40, Week 52, Week 64, Week 76, Week 88, Week 100 (or ET).

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Group 1a Group 1P Group 2 Group 3
    Arm/Group Description Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1A received ADS-5102 in the prior study. Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1P received placebo in the prior study Subjects in Group 2 completed previous LID study, enrolled ADS-AMT-PD302 after a time gap. Subjects were not in a previous Adamas LID study and had prior DBS (deep brain stimulation)
    Measure Participants 60 77 24 60
    Baseline
    6.5
    (3.38)
    9.6
    (3.07)
    9.8
    (3.92)
    10.4
    (2.77)
    Change in Baseline from Week 8
    -0.2
    (3.21)
    -3.4
    (3.27)
    -3.6
    (4.16)
    -4.0
    (4.20)
    Change in Baseline from Week 16
    -0.8
    (3.61)
    -3.2
    (3.61)
    -1.1
    (5.03)
    -3.9
    (3.68)
    Change from Baseline at Week 28
    -0.3
    (3.61)
    -3.3
    (3.12)
    -1.4
    (3.84)
    -4.4
    (3.79)
    Change from Baseline at Week 40
    0.0
    (3.95)
    -2.8
    (3.39)
    -2.9
    (4.81)
    -4.7
    (4.06)
    Change from Baseline at Week 52
    0.2
    (3.64)
    -2.9
    (3.56)
    -2.5
    (4.40)
    -3.6
    (3.62)
    Change from Baseline at Week 64
    0.4
    (3.82)
    -3.3
    (3.42)
    -1.9
    (4.32)
    -2.5
    (4.22)
    Change from Baseline at Week 76
    0.9
    (4.20)
    -2.9
    (3.67)
    -2.7
    (3.90)
    -3.7
    (3.68)
    Change from Baseline at Week 88
    0.4
    (3.77)
    -2.8
    (3.60)
    -3.7
    (4.69)
    -4.3
    (3.55)
    Change from Baseline at Week 100
    0.4
    (3.28)
    -2.4
    (4.19)
    -3.6
    (3.66)
    -3.6
    (3.94)

    Adverse Events

    Time Frame 100 weeks
    Adverse Event Reporting Description Safety was assessed through adverse events (AEs), physical examinations, vital signs, and laboratory parameters (hematology, serum chemistry, urinalysis, and pregnancy testing, if appropriate).
    Arm/Group Title Group 1a Group 1P Group 2 Group 3
    Arm/Group Description Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1A received ADS-5102 in the prior study. Subjects completed previous LID study and enrolled in ADS-AMT-PD302 study immediately. Subjects in Group 1P received placebo in the prior study Subjects in Group 2 completed previous LID study, enrolled ADS-AMT-PD302 after a time gap. Subjects were not in a previous Adamas LID study and had prior DBS (deep brain stimulation)
    All Cause Mortality
    Group 1a Group 1P Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/60 (6.7%) 2/78 (2.6%) 2/24 (8.3%) 1/61 (1.6%)
    Serious Adverse Events
    Group 1a Group 1P Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/60 (26.7%) 21/78 (26.9%) 6/24 (25%) 17/61 (27.9%)
    Cardiac disorders
    Acute myocardial infarction 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Supraventricular tachycardia 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Cardiac arrest 1/60 (1.7%) 1 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Angina pectoris 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Myocardial infarction 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Arrhythmia 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Coronary artery disease 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Acute myocardial infarction 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Hypertensive cardiomyopathy 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Myocardial infarction 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Ear and labyrinth disorders
    Vertigo positional 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Gastrointestinal disorders
    Colitis 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Volvulus 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Colonic pseudo-obstruction 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Constipation 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Intestinal obstruction 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Intestinal obstruction 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Constipation 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Abdominal pain upper 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    General disorders
    Adverse drug reaction 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Death 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Abasia 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Immune system disorders
    Hypersensitivity 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Infections and infestations
    Arthritis bacteria 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Clostridium difficile sepsis 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Septic shock 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Pseudomonal sepsis 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Urinary tract infection 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Pneumonia 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Staphylococcal sepsis 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Cellulitis 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Sepsis 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 1/61 (1.6%) 1
    Injury, poisoning and procedural complications
    Laceration 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Radius fracture 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Rib fracture 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Joint dislocation 1/60 (1.7%) 1 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Hip fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Ankle fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Hip fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Femur fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Traumatic fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Acetabulum fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Pelvic fracture 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Confusion postoperative 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Wrist fracture 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Traumatic fracture 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Ankle fracture 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Fall 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Craniocerebral injury 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Forearm fracture 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Musculoskeletal and connective tissue disorders
    Ostenecrosis 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Osteoarthritis 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Rhabdomyolysis 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 1/61 (1.6%) 1
    Arthralgia 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Joint effusion 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of the colon 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Nervous system disorders
    Encephalopathy 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Lymphoadenopathy 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Neuroleptic malignant syndrome 1/60 (1.7%) 1 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Parkinson's disease 1/60 (1.7%) 2 1/78 (1.3%) 1 0/24 (0%) 0 2/61 (3.3%) 2
    Paraesthesia 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    On and Off Phenomenon 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Restless leg syndrome 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Hypokinesia 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Intercostal neuralgia 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Parkinson's disease 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Dyskinesia 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Psychiatric disorders
    Psychiatric disorder 1/60 (1.7%) 3 0/78 (0%) 0 0/24 (0%) 0 0/61 (0%) 0
    Confusional state 1/60 (1.7%) 1 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Suicide attempt 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Mental status changes 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Confusional state 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Anxiety 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Suicidal ideation 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Mania 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory arrest 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Haemothorax 0/60 (0%) 0 1/78 (1.3%) 1 0/24 (0%) 0 0/61 (0%) 0
    Respiratory distress 0/60 (0%) 0 0/78 (0%) 0 1/24 (4.2%) 1 0/61 (0%) 0
    Vascular disorders
    Hypertensive crisis 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Venous thrombosis 0/60 (0%) 0 0/78 (0%) 0 0/24 (0%) 0 1/61 (1.6%) 1
    Other (Not Including Serious) Adverse Events
    Group 1a Group 1P Group 2 Group 3
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 47/60 (78.3%) 61/78 (78.2%) 21/24 (87.5%) 45/61 (73.8%)
    Cardiac disorders
    Hypertension 2/60 (3.3%) 6/78 (7.7%) 0/24 (0%) 4/61 (6.6%)
    Gastrointestinal disorders
    Constipation 9/60 (15%) 12/78 (15.4%) 6/24 (25%) 3/61 (4.9%)
    Nausea 7/60 (11.7%) 8/78 (10.3%) 6/24 (25%) 1/61 (1.6%)
    Dry mouth 4/60 (6.7%) 6/78 (7.7%) 4/24 (16.7%) 3/61 (4.9%)
    General disorders
    Edema peripheral 10/60 (16.7%) 12/78 (15.4%) 2/24 (8.3%) 12/61 (19.7%)
    Infections and infestations
    Urinary tract infection 7/60 (11.7%) 8/78 (10.3%) 3/24 (12.5%) 5/61 (8.2%)
    Nasopharyngitis 4/60 (6.7%) 4/78 (5.1%) 1/24 (4.2%) 4/61 (6.6%)
    Upper respiratory tract infection 4/60 (6.7%) 3/78 (3.8%) 3/24 (12.5%) 2/61 (3.3%)
    Injury, poisoning and procedural complications
    Fall 13/60 (21.7%) 29/78 (37.2%) 8/24 (33.3%) 23/61 (37.7%)
    Musculoskeletal and connective tissue disorders
    Back pain 4/60 (6.7%) 5/78 (6.4%) 2/24 (8.3%) 4/61 (6.6%)
    Arthralgia 5/60 (8.3%) 5/78 (6.4%) 1/24 (4.2%) 1/61 (1.6%)
    Nervous system disorders
    Dizziness 4/60 (6.7%) 10/78 (12.8%) 5/24 (20.8%) 3/61 (4.9%)
    On and off phenomenon 7/60 (11.7%) 4/78 (5.1%) 4/24 (16.7%) 3/61 (4.9%)
    Parkinson's disease 3/60 (5%) 5/78 (6.4%) 1/24 (4.2%) 6/61 (9.8%)
    Psychiatric disorders
    Hallucination (pooled) 15/60 (25%) 24/78 (30.8%) 5/24 (20.8%) 10/61 (16.4%)
    Hallucination, visual 14/60 (23.3%) 24/78 (30.8%) 4/24 (16.7%) 10/61 (16.4%)
    Insomnia 8/60 (13.3%) 5/78 (6.4%) 4/24 (16.7%) 4/61 (6.6%)
    Depression 4/60 (6.7%) 5/78 (6.4%) 2/24 (8.3%) 4/61 (6.6%)
    Anxiety 3/60 (5%) 6/78 (7.7%) 1/24 (4.2%) 4/61 (6.6%)
    Abnormal dreams 5/60 (8.3%) 4/78 (5.1%) 2/24 (8.3%) 2/61 (3.3%)
    Skin and subcutaneous tissue disorders
    Livedo reticularis 6/60 (10%) 5/78 (6.4%) 3/24 (12.5%) 6/61 (9.8%)

    Limitations/Caveats

    [Not Specified]

    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 Reed Johnson
    Organization Adamas Pharmaceuticals, Inc.
    Phone 510-450-3500
    Email rjohnson@adamaspharma.com
    Responsible Party:
    Adamas Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02202551
    Other Study ID Numbers:
    • ADS-AMT-PD302
    First Posted:
    Jul 29, 2014
    Last Update Posted:
    Oct 6, 2020
    Last Verified:
    Aug 1, 2020