Clinical trial NCT02202551
Conditions: Dyskinesia Levodopa Induced Dyskinesia (LID) Parkinson's Disease (PD)
Keywords: Levodopa Induced Dyskinesia LID Parkinsonism Parkinson's Disease
Sponsor: Adamas Pharmaceuticals, Inc.
Start date: 2014-07-01; Completion date: 2018-02-01
Enrollment: 223 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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).

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.

Arms: arm 1: amantadine HCl extended release
Interventions: intervention 1: ADS-5102
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL THIS DOCUMENT IS CONFIDENTIAL AND CONTAINS PROPRIETARY 
INFORMATION OF ADAMAS PHARMACEUTICALS, INC., WHICH MAY NOT BE DISCLOSED 
WITHOUT EXPRESS PRIOR WRITTEN PERMISSION OF ADAMAS PHARMACEUTICALS, INC. 
ADS-AMT-PD302 
OPEN-LABEL SAFETY STUDY OF ADS-5102 (AMANTADINE HCL) EXTENDED 
RELEASE CAPSULES FOR THE TREATMENT OF LEVODOPA INDUCED 
DYSKINESIA  
 US IND Number: 78,671 
EudraCT Number: 2014-003739-20 
Investigational Product:  
ADS-5102 (amantadine HCl) Extended Release Capsules 
Sponsor: 
Adamas Pharmaceuticals, Inc. 
1900 Powell Street, Suite 750 
Emeryville, California 94608 
United States of America 
Telephone: +1 (510) 450-3500 
Facsimile: +1 (510) 428-0519 
Medical Monitor: 
Mary Jean Stempien, MD, FACP 
Document Date: 
16 July 2015 
Version: 
Amendment 4 


ADS-5102 forTreatment of LID
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD3O2 (Amendment 4)
16 July 2015
Pase I of74
APPROVALS:
Reviewed and Approved by:
Mary Jean
MD, F
CP
Medical Monitor
Adamas Pharmaceuticals, Inc.
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Elaine Fashana
Sr. Director, Regulatory Affairs
Adamas Pharmaceuticals, Inc.
April
Sr. Director, Clinical Operations
Adamas Pharmaceuticals, Inc.
Reed Johnson
Clinical Program
Clinical Operations
Adamas Pharmaceuticals, Inc.
Larissa Felt
Clinical Program Manager, Clinical Operations
Adamas Pharmaceuticals, [nc.
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CONFIDENTIAL and PROPRIETARY


ADS-5102 for Treatment of LID 
 
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CONFIDENTIAL and PROPRIETARY 
1. 
 SYNOPSIS 
Name of Sponsor/Company: Adamas Pharmaceuticals, Inc. 
Name of Investigational Product: ADS-5102 (amantadine HCl) Extended Release Capsules 
Name of Active Ingredient: Amantadine hydrochloride 
Title of Study: Open-Label Safety Study of ADS-5102 (amantadine HCl) Extended Release 
Capsules for the Treatment of Levodopa Induced Dyskinesia  
Study center(s): Approximately 90 sites worldwide 
Study Duration: Approximately 37 months (from 
enrollment of first subject to last subject completion 
[LSLV]) 
Phase of development: 3 
 
Objectives:  
Primary: 
 To evaluate the safety and tolerability of ADS-5102 oral capsules, an extended 
release formulation of amantadine, administered at a dose of 340 mg once nightly 
at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects 
with Parkinson’s disease (PD). 
Secondary: 
 To evaluate duration of ADS-5102 effect on dyskinesia as assessed by the Unified 
Parkinson’s Disease Rating Scale (MDS-UPDRS), Part IV. 
 To evaluate clinical progression of Parkinson’s disease as assessed by MDS-
UPDRS, Combined Score, Parts I, II, and III. 
Study Design:  
This study will be offered to subjects who are described by one of the following 3 groups:  
 Group 1 (current Adamas LID study subjects): Subjects who are participating in 
Adamas efficacy studies evaluating ADS-5102 in LID and choose to immediately 
transition into ADS-AMT-PD302 without a time gap; 
 Group 2 (previous Adamas LID study subjects): Subjects who have previously 
participated in Adamas efficacy studies evaluating ADS-5102 in LID and will 
enter ADS-AMT-PD302 after a time gap; 
 Group 3 (non Adamas LID study subjects with prior DBS): Subjects who would 
have been deemed ineligible for participation in previous or current Adamas 
efficacy studies due to having undergone deep brain stimulation. 
 
 


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CONFIDENTIAL and PROPRIETARY 
Detailed inclusion/exclusion criteria and a schedule of events are described in this protocol 
Section 7 and Appendix A, respectively for each of these groups: 
 Current Adamas LID study subjects (Group 1) should have their Screening Visit 
(Visit 1), including consent, for the ADS-AMT-PD302 study occur at the same 
visit as the final efficacy visit for the previous Adamas efficacy study, as outlined 
in the previous protocol. Subsequently, they should also have their Baseline Visit 
(Visit 2) for the ADS-AMT-PD302 study occur during the final study visit (not 
including any safety follow up visit) of the previous Adamas efficacy study visit, 
as outlined in the previous protocol. 
 Previous Adamas LID study subjects (Group 2) and Non Adamas LID study 
subjects with prior DBS (Group 3) will not have overlapping visits with any 
previous protocol. 
A study design schematic for study entry differences between these groups can be found in 
Appendix B.   
Consented subjects who complete screening (Visit 1) and meet study eligibility criteria will 
have a baseline visit (Visit 2) and receive 1 week of 170 mg ADS-5102 (1 capsule) nightly at 
bedtime, followed by 340 mg ADS-5102 (2 capsules) nightly at bedtime for up to  99 
additional weeks. The final week ( Week 101) of dosing will be at the reduced dose of  
170 mg ADS-5102 (1 capsule) nightly at bedtime.  
Subjects will be enrolled into the study at Visit 2 (Week 0, Baseline) and return to the clinic 
after 4, 8, 16, 28, 40, 52, 64, 76, 88,  and 100 weeks dosing.  Subjects will receive a 
telephone reminder at the end of Week 1 to increase their dose to two capsules nightly at 
bedtime.  At the Week 100 visit, subjects will be instructed to reduce their dose for 1 week, 
taking 1 capsule nightly at bedtime.   
An efficacy assessment using the MDS-UPDRS will be completed at all study visits, 
beginning with the Screening Visit, with the exception of the Baseline/Week 0, Week 4, and 
Safety Follow Up visit.  A safety follow-up visit will occur approximately 2 weeks following 
the completion of treatment.  Women of childbearing potential will also have a pregnancy 
test performed at the early termination visit or 2 weeks following the completion of treatment 
at the final safety follow up visit.  
Subjects who discontinue study drug before Week 101 will have an early termination visit 
that includes MDS-UPDRS assessments and safety follow-up.   
Subjects who discontinue study drug after Week 4 should receive a reduced dose of 170 mg 
ADS-5102 for one additional week.  The additional week of dosing at a reduced dose will not 
be needed for subjects who discontinue study drug before Week 4. 
Adverse events (AEs) will be recorded beginning with the first dose of study drug and will 
continue through the safety follow-up visit.  Concomitant medications will be recorded 
throughout the study.   
 
 
 


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CONFIDENTIAL and PROPRIETARY 
Methodology:  
The safety analysis population will include all enrolled subjects who receive at least one dose 
of study drug.  Safety data will be summarized from the time of first dose and include all 
available safety data.  No formal statistical testing will be done. 
All AE data will be listed and will be summarized by system organ class, preferred term, and 
analysis group, as well as for all analysis groups combined.  Quantitative safety variables 
(e.g., vital signs and clinical laboratory tests) will be summarized at each visit by analysis 
group, as well as for all analysis groups combined and changes from baseline will be 
summarized by analysis group at selected visits. 
The efficacy analysis population will include all enrolled subjects who receive at least one 
dose of study drug and provide at least one post-enrollment MDS-UPDRS assessment.  
MDS-UPDRS, Part IV and Combined Score, Parts I, II, and III data will be summarized 
across study visits and include all available data.  The baseline MDS-UPDRS scores for a 
subject will be their MDS-UPDRS scores from the Screening Visit.  
Sample Size Justification: 
It is expected that a study size of  up to 250 subjects and duration of treatment up to 101 
weeks will support the goal of 100 subjects completing one year of treatment. 
Number of subjects (planned): Up to 250  
Diagnosis and eligibility criteria for inclusion: 
Group 1: Current Adamas LID study subjects:  
Below are the eligibility criteria for subjects who are continuing directly into ADS-AMT-
PD302 without a time gap between their Adamas LID efficacy study and ADS-AMT-PD302:   
INCLUSION CRITERIA: 
1. Signed a current IRB/REB/IEC-approved informed consent form; 
2. Completed study visits per protocol in a previous Adamas efficacy study; 
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the 
subject can complete study assessments;  
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the 
subject to study visits and assist in completion of study assessments, as needed and 
allowed; 
5. History of peak dose dyskinesia that might benefit from specific dyskinesia treatment 
in the judgment of the subject and clinical investigator;  
6. On a stable regimen of antiparkinson’s medications, including a levodopa preparation 
administered not less than three times daily. 


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CONFIDENTIAL and PROPRIETARY 
EXCLUSION CRITERIA: 
1. Discontinued study drug in previous Adamas studies due to intolerable or 
unacceptable AEs considered to be related to ADS-5102;  
2. Hoehn and Yahr Stage 5; 
3. Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure 
(at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes 
of the subject standing up, compared to pressures obtained while sitting; 
4. Estimated GFR < 50 mL/min/1.73m2 (calculated using Modification of Diet in Renal 
Disease (MDRD)); 
5. If female, is pregnant or lactating;  
6. If a sexually active female, is not surgically sterile or at least 2 years postmenopausal, 
or does not agree to utilize a highly effective hormonal method of contraception (an 
IUD, or vasectomized male partner is also acceptable), in combination with a barrier 
method, from screening through at least 4 weeks after the completion of study 
treatment;  
7. Anticipated need for treatment with restricted medication (reference Appendix E); 
8. Planned participation in another interventional clinical trial. 
Group 2: Previous Adamas LID study subjects  
Below are the eligibility criteria for subjects who participated in a previous Adamas efficacy 
study evaluating ADS-5102 in LID and will enter ADS-AMT-PD302 with a time gap 
INCLUSION CRITERIA: 
1. Signed a current IRB/REB/IEC-approved informed consent form; 
2. Completed study visits in as described per protocol in  a previous Adamas efficacy 
study; 
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the 
subject can complete study assessments;   
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the 
subject to study visits and assist in completion of study instruments, as needed and 
allowed; 
5. Peak dose dyskinesia during Screening that might benefit from specific dyskinesia 
treatment in the judgment of the subject and clinical investigator OR a history of peak 
dose dyskinesia that is currently being managed by amantadine treatment; 
6. 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; 
7. Parkinson’s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank 
Clinical Diagnostic Criteria (see Appendix C). 


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CONFIDENTIAL and PROPRIETARY 
EXCLUSION CRITERIA: 
 
1. Discontinued study drug in previous Adamas studies due to intolerable or 
unacceptable AEs considered to be related to ADS-5102; 
2. History of neurosurgical intervention related to Parkinson’s disease, with the 
exception of deep brain stimulation; 
3. History of other neurological disease that, in the opinion of the investigator, would  
affect motor function or cognition, including, but not limited to Alzheimer’s 
dementia, Huntington’s disease, Lewy body dementia, frontotemporal dementia, 
corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy, 
motor or sensory dysfunction secondary to stroke or brain trauma, or multi-infarct 
dementia with lacunae;  
4. Current sensory impairments (e.g., hearing, vision) that, in the opinion of the 
investigator, would impair the subject’s ability to complete study assessments, or 
presence of untreated angle closure glaucoma; 
5. History of alcohol or substance dependence or abuse since completion of participation 
in previous Adamas trial;  
6. History of seizures since completion of participation in previous Adamas trial;  
7. History of stroke or TIA since completion of participation in previous Adamas trial;  
8. History of myocardial infarction, or NYHA Functional Classification of Heart Failure 
Class 3 or 4 since completion of participation in previous Adamas trial (see  
Appendix D); 
9. Any clinically significant ECG abnormalities, including any findings of abnormal 
ventricular conduction or rhythm other than isolated PVCs or first degree AV block; 
10. History of cancer since completion of participation in previous Adamas trial, with the 
following exceptions: adequately treated non-melanomatous skin cancers, localized 
bladder cancer, non-metastatic prostate cancer or in situ cervical cancer;  
11. Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination 
(MMSE) score of less than 24 during screening; 
12. Hoehn and Yahr Stage 5; 
13. Presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive 
Disorder) or symptom (e.g., hallucinations, agitation, paranoia, suicidal ideation) that, 
in the opinion of the investigator, would  affect the subject’s ability to complete study 
assessments; 
14. Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure 
(at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes 
of the subject standing up, compared to pressures obtained while sitting; 
15. Any of the following laboratory test results at screening:  
 Hemoglobin < 10 g/dL 


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CONFIDENTIAL and PROPRIETARY 
 WBC <3.0 x 109/L 
 Neutrophils <1.5 x 109/L 
 Lymphocytes < 0.5 x 109/L 
 Platelets <100 x 109/L 
 Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 
times the upper limit of normal 
16. Estimated GFR < 50 mL/min/1.73m2 (calculated using Modification of Diet in Renal 
Disease (MDRD)); 
17. Inability to swallow oral capsules, or a history of gastrointestinal malabsorption that 
would preclude the use of oral medication;     
18. If female, is pregnant or lactating;  
19. If a sexually active female, is not surgically sterile or at least 2 years postmenopausal, 
or does not agree to utilize a highly effective hormonal method of contraception (an 
IUD, or vasectomized male partner is also acceptable), in combination with a barrier 
method, from screening through at least 4 weeks after the completion of study 
treatment;  
20. Documented inability to tolerate amantadine or history of suicidal ideation or suicide 
attempt during prior amantadine use; 
21. History of hypersensitivity or allergic reaction to amantadine, rimantidine, or 
memantine, or to any of the excipients used in the study medication capsules (see 
Section 8.7);  
22. Received live attenuated influenza vaccine within 2 weeks prior to enrollment 
(amantadine may interfere with the efficacy of  live attenuated vaccine); 
23. Current treatment with carbonic anhydrase inhibitors, sodium bicarbonate, or urinary 
acidification agents, quinine, quinidine, triamterene, or trimethoprim  (see 
Appendix E); 
24. Current treatment with medications that act primarily by blocking dopamine receptors 
and current treatment with medications that prolong the QT interval and have a 
known risk of torsades de pointes (see Appendix E).  Subjects who are able to 
appropriately discontinue these agents at least 60 days prior to screening will be 
eligible for screening; 
25. Treatment with an investigational drug (other than ADS-5102) or device within 30 
days prior to screening; 
26. Treatment with an investigational biologic within 6 months prior to screening; 
27. Anticipated need for treatment with restricted medication (see Appendix E); 
28. Current or planned participation in another interventional clinical trial. 


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CONFIDENTIAL and PROPRIETARY 
Group 3: Non Adamas LID study subjects – with prior DBS 
Below are the eligibility criteria for subjects who would have been deemed ineligible for 
participation in previous or current Adamas efficacy studies due to having undergone deep 
brain stimulation. 
INCLUSION CRITERIA: 
1. Signed a current IRB/REB/IEC-approved informed consent form; 
2. Male or female subjects between 30 and 85 years of age, inclusive; 
3. Subject has undergone a deep brain stimulation procedure prior to start of this study 
(14 July 2014); 
4. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the 
subject can complete study assessments;   
5. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the 
subject to study visits and assist in completion of study instruments, as needed and 
allowed; 
6. Peak dose dyskinesia during Screening that might benefit from specific dyskinesia 
treatment in the judgment of the subject and clinical investigator OR a history of peak 
dose dyskinesia that is currently being managed by amantadine treatment;  
7. 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; 
8. Parkinson’s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank 
Clinical Diagnostic Criteria (see Appendix C). 
EXCLUSION CRITERIA: 
 
1. History of neurosurgical intervention related to Parkinson’s disease, with the 
exception of deep brain stimulation; 
2. History of other neurological disease that, in the opinion of the investigator, would  
affect motor function or cognition, including, but not limited to Alzheimer’s 
dementia, Huntington’s disease, Lewy body dementia, frontotemporal dementia, 
corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy, 
motor or sensory dysfunction secondary to stroke or brain trauma, or multi-infarct 
dementia with lacunae; 
3. Current sensory impairments (e.g., hearing, vision) that, in the opinion of the 
investigator, would impair the subject’s ability to complete study assessments, or 
presence of untreated angle closure glaucoma; 
4. History of alcohol or substance dependence or abuse within 2 years prior to 
screening; 
5. History of seizures within 2 years prior to screening;  
6. History of stroke or TIA within 2 years prior to screening;  


ADS-5102 for Treatment of LID 
 
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CONFIDENTIAL and PROPRIETARY 
7. History of myocardial infarction, or NYHA Functional Classification of Heart Failure 
Class 3 or 4 within 2 years prior to screening (see Appendix D);  
8. Any clinically significant ECG abnormalities, including any findings of abnormal 
ventricular conduction or rhythm other than isolated PVCs or first degree AV block; 
9. History of cancer within 5 years of screening, with the following exceptions: 
adequately treated non-melanomatous skin cancers, localized bladder cancer, non-
metastatic prostate cancer or in situ cervical cancer;  
10. Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination 
(MMSE) score of less than 24 during screening; 
11. Hoehn and Yahr Stage 5; 
12. Presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive 
Disorder) or symptom (e.g., hallucinations, agitation, paranoia, suicidal ideation) that, 
in the opinion of the investigator, would  affect the subject’s ability to complete study 
assessments; 
13. Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure 
(at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes 
of the subject standing up, compared to pressures obtained while sitting; 
14. Any of the following laboratory test results at screening:  
 Hemoglobin < 10 g/dL 
 WBC <3.0 x 109/L 
 Neutrophils <1.5 x 109/L 
 Lymphocytes < 0.5 x 109/L 
 Platelets <100 x 109/L 
 Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 
times the upper limit of normal 
15. Estimated GFR < 50 mL/min/1.73m2 (calculated using Modification of Diet in Renal 
Disease (MDRD)); 
16. Inability to swallow oral capsules, or a history of gastrointestinal malabsorption that 
would preclude the use of oral medication;     
17. If female, is pregnant or lactating;  
18. If a sexually active female, is not surgically sterile or at least 2 years postmenopausal, 
or does not agree to utilize a highly effective hormonal method of contraception (an 
IUD, or vasectomized male partner is also acceptable), in combination with a barrier 
method, from screening through at least 4 weeks after the completion of study 
treatment; 
19. Documented inability to tolerate amantadine or history of suicidal ideation or suicide 
attempt during prior amantadine use; 


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CONFIDENTIAL and PROPRIETARY 
20. History of hypersensitivity or allergic reaction to amantadine, rimantidine, or 
memantine, or to any of the excipients used in the study medication capsules (see 
Section 8.7);  
21. Received live attenuated influenza vaccine within 2 weeks prior to enrollment 
(amantadine may interfere with the efficacy of  live attenuated vaccine); 
22. Current treatment with carbonic anhydrase inhibitors, sodium bicarbonate, or urinary 
acidification agents, quinine, quinidine, triamterene, or trimethoprim (see 
Appendix E); 
23. Current treatment with medications that act primarily by blocking dopamine receptors 
and current treatment with medications that prolong the QT interval and have a 
known risk of torsades de pointes (see Appendix E).  Subjects who are able to 
appropriately discontinue these agents at least 60 days prior to screening will be 
eligible for screening; 
24. Treatment with an investigational drug (other than ADS-5102) or device within 30 
days prior to screening; 
25. Treatment with an investigational biologic within 6 months prior to screening; 
26. Anticipated need for treatment with restricted medication (see Appendix E); 
27. Current or planned participation in another interventional clinical trial. 
Investigational product, dosage, mode of administration, and dosing regimen:  
Subjects will be allowed to change their PD medications as needed and record updates on the 
Concomitant Medications case report forms.  Use of amantadine (other than provided study 
drug) is not allowed during study participation.  
Treatment 
Week 1 
Weeks 2 – 100 
Week  101 
ADS-5102 
170 mg  
ADS-5102 
(1 x 170 mg capsule) 
340 mg 
ADS-5102 
(2 x 170 mg capsules) 
170 mg 
ADS-5102 
(1 x 170 mg capsule) 
Capsules are to be swallowed intact, and can be taken with any nonalcoholic beverage, and 
with or without food.  Dosing will continue through Week 101. 
Subjects whose estimated GFR falls below 50 mL/min/1.73m2 (but is ≥30 mL/min/1.73m2), 
confirmed by repeat testing, should discontinue study drug after receiving a reduced dose of 
170 mg ADS-5102 for one additional week.  The additional week of dosing at a reduced dose 
will not be needed for subjects who discontinue study drug before Week 4. 
Subjects whose estimated GFR falls below 30 mL/min/1.73m2, confirmed by repeat testing, 
at any time during the study should discontinue study drug (without the additional week of 
dosing at a reduced dose).  
Subjects who discontinue study drug will have an early termination visit that includes 
efficacy assessments and safety follow-up.   


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CONFIDENTIAL and PROPRIETARY 
Duration of treatment: Duration of subject participation will be up to 105 weeks and will 
include a 2-week (maximum) screening period and up to 101 weeks of open-label treatment, 
followed by a safety follow-up visit 2 weeks after completion of treatment. 
Criteria for evaluation: 
Efficacy: 
The following efficacy assessment will be performed during the study: 

Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)
Safety:  
The following safety assessments will be performed during the study: 

AEs

Safety-related study drug discontinuations

Vital signs

Safety laboratory tests


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CONFIDENTIAL and PROPRIETARY 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
APPROVALS: .................................................................................................................................1 
1. 
SYNOPSIS ...................................................................................................................2 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............12 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................17 
4. 
INTRODUCTION ......................................................................................................19 
4.1. 
Product Rationale ........................................................................................................20 
4.2. 
Dose and Dose Regimen Justification ........................................................................20 
4.3. 
Summary Pharmacokinetic Information for Extended Release Amantadine 
Formulations ...............................................................................................................21 
4.3.1. 
Single Dose Studies ....................................................................................................21 
4.3.2. 
Effect of Food on Bioavailability of Amantadine ER ................................................22 
4.3.3. 
Relative Bioavailability of Amantadine ER vs. Amantadine IR at Steady 
State ............................................................................................................................22 
4.4. 
Summary Safety Information for Extended Release Amantadine 
Formulations ...............................................................................................................22 
4.5. 
Rationale for ADS-AMT-PD302 Study Design .........................................................23 
4.6. 
Population to be Studied .............................................................................................23 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................24 
5.1. 
Primary Objective .......................................................................................................24 
5.2. 
Secondary Objectives .................................................................................................24 
5.3. 
Safety Outcome Assessments .....................................................................................24 
5.4. 
Efficacy Outcome Assessments ..................................................................................24 
6. 
INVESTIGATIONAL PLAN .....................................................................................24 
6.1. 
Overall Study Design ..................................................................................................24 
6.2. 
Number of Subjects ....................................................................................................26 
6.3. 
Treatment Assignment ................................................................................................26 
6.4. 
Dose Adjustment Criteria ...........................................................................................26 
6.5. 
Criteria for Study Termination ...................................................................................26 
6.6. 
Duration of Subject Participation ...............................................................................26 
6.7. 
Estimated Study Duration ...........................................................................................26 


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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................27 
7.1. 
Subject Inclusion Criteria ...........................................................................................27 
7.1.1. 
Group 1: Current Adamas LID study subjects ...........................................................27 
7.1.2. 
Group 2: Previous Adamas LID study subjects ..........................................................27 
7.1.3. 
Group 3: Non Adamas LID study subjects – with prior DBS ....................................28 
7.2. 
Subject Exclusion Criteria ..........................................................................................28 
7.2.1. 
Group 1: Current Adamas LID study subjects ...........................................................28 
7.2.2. 
Group 2: Previous Adamas LID study subjects ..........................................................29 
7.2.3. 
Group 3: Non Adamas LID Study Subjects – with prior DBS ...................................31 
7.3. 
Subject Withdrawal Criteria .......................................................................................32 
7.4. 
Subject Enrollment .....................................................................................................33 
7.5. 
Discontinuation of Study Medication .........................................................................33 
8. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................34 
8.1. 
Study Drug ..................................................................................................................34 
8.2. 
Study Drug Packaging and Labeling ..........................................................................35 
8.3. 
Study Drug Storage .....................................................................................................35 
8.4. 
Administration ............................................................................................................35 
8.5. 
Study Drug Accountability .........................................................................................35 
8.6. 
Study Drug Handling and Disposal ............................................................................36 
8.7. 
Prohibited Medications and Restrictions ....................................................................36 
8.8. 
Concomitant Medications ...........................................................................................36 
8.9. 
Treatment Compliance ................................................................................................37 
8.10. 
Randomization and Blinding ......................................................................................37 
9. 
ASSESSMENT OF EFFICACY ................................................................................37 
10. 
ASSESSMENT OF SAFETY .....................................................................................38 
10.1. 
Physical Assessments Relating to Safety ...................................................................38 
10.2. 
Clinical Laboratory Tests ...........................................................................................39 
10.3. 
Demographic/Medical History ...................................................................................41 
10.4. 
Total Blood Volume Collected ...................................................................................41 
11. 
EVALUATIONS BY VISIT ......................................................................................41 
11.1. 
Screening/Day -14 to -1 ..............................................................................................41 
11.2. 
Treatment Period ........................................................................................................42 
11.3. 
Baseline/Day 1/Week 0 ..............................................................................................42 


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11.4. 
Week 4 +/- 1 Day (End of Week 4) ............................................................................43 
11.5. 
Week 8 +/- 1 Day (End of Week 8) ............................................................................43 
11.6. 
Week 16 +/- 3 days (End of Week 16) .......................................................................44 
11.7. 
Week 28 +/- 3 days (End of Week 28) .......................................................................44 
11.8. 
Week 40 +/- 3 days (End of Week 40) .......................................................................45 
11.9. 
Week 52 +/- 3 Days (End of Week 52) ......................................................................45 
11.10. 
Week 64 +/- 3 Days (End of Week 64) ......................................................................46 
11.11. 
Week 76 +/- 3 Days (End of Week 76) ......................................................................46 
11.12. 
Week 88 +/- 3 Days (End of Week 88) ......................................................................47 
11.13. 
Week 100 +/- 3 Days (End of Week 100) ..................................................................47 
11.14. 
Early Termination Visit ..............................................................................................48 
11.15. 
Safety Follow Up Visit ...............................................................................................48 
12. 
ADVERSE AND SERIOUS ADVERSE EVENTS ...................................................48 
12.1. 
Definition of Adverse Events .....................................................................................48 
12.1.1. 
Adverse Event (AE) ....................................................................................................49 
12.1.2. 
Severity of Adverse Events ........................................................................................50 
12.1.3. 
Follow-up of Adverse Events and Serious Adverse Events .......................................50 
12.1.4. 
Serious Adverse Event (SAE) ....................................................................................51 
12.1.4.1. 
Clarification of SAE Definition ..................................................................................51 
12.1.4.2. 
Clarification of Subject Deaths ...................................................................................52 
12.2. 
Relationship to Study Drug ........................................................................................52 
12.3. 
Recording Adverse Events .........................................................................................53 
12.4. 
Reporting Adverse Events ..........................................................................................53 
12.4.1. 
Post-Study Reporting Requirements ...........................................................................53 
12.4.2. 
Investigator Reporting Responsibility ........................................................................54 
12.4.3. 
Pregnancy ...................................................................................................................54 
13. 
STATISTICS ..............................................................................................................55 
13.1. 
Statistical Analyses .....................................................................................................55 
13.1.1. 
Sample Size Determination ........................................................................................55 
13.1.2. 
Analysis Populations ..................................................................................................55 
13.1.2.1. 
Efficacy Populations ...................................................................................................55 
13.1.3. 
Handling of Missing Data ...........................................................................................55 
13.1.4. 
Safety and Tolerability ...............................................................................................55 


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13.1.5. 
Demographics and Baseline Characteristics ...............................................................55 
13.1.6. 
Prior and Concomitant Medications ...........................................................................55 
13.1.7. 
Completion of the Study and Withdrawals .................................................................55 
13.1.8. 
Protocol Deviations ....................................................................................................56 
14. 
STUDY CONDUCT ...................................................................................................57 
14.1. 
Study Monitoring ........................................................................................................57 
14.2. 
Audits and Inspections ................................................................................................57 
14.3. 
Subject Confidentiality ...............................................................................................57 
14.4. 
Case Report Forms .....................................................................................................58 
14.5. 
Retention and Availability of Records .......................................................................58 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................59 
16. 
ETHICS ......................................................................................................................60 
16.1. 
Ethics Review .............................................................................................................60 
16.2. 
Ethical Conduct of the Study ......................................................................................60 
16.3. 
Written Informed Consent ..........................................................................................60 
16.4. 
Changes in the Conduct of the Study or Planned Analyses ........................................61 
16.5. 
Emergency Contact with Investigator ........................................................................61 
17. 
INFORMATION DISCLOSURE AND INVENTIONS ............................................62 
17.1. 
Ownership ...................................................................................................................62 
17.2. 
Confidentiality ............................................................................................................62 
18. 
PUBLICATION POLICY ..........................................................................................63 
19. 
LIST OF REFERENCES ............................................................................................64 
20. 
APPENDICES ............................................................................................................66 
APPENDIX A. SCHEDULE OF EVENTS ...............................................................................67
APPENDIX B. STUDY ENTRY DESIGN SCHEMATIC ........................................................70 
APPENDIX C. UK PARKINSON'S DISEASE SOCIETY (UKPDS) BRAIN BANK 
CLINICAL DIAGNOSTIC CRITERIA ............................................................71 
APPENDIX D. NYHA FUNCTIONAL CLASSIFICATION ....................................................72 
APPENDIX E. PROHIBITED MEDICATIONS .......................................................................73 


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LIST OF TABLES 
Table 1: 
Abbreviations ..............................................................................................................17 
Table 2: 
Clinical Formulation for Study ADS-AMT-PD302 ...................................................34 
Table 3: 
Treatment Schedule for Study ADS-AMT-PD302 .....................................................35 
Table 4: 
Efficacy Assessments .................................................................................................37 
Table 5: 
Physical Assessments Relating to Safety ...................................................................38 
Table 6: 
Clinical Laboratory and Other Assessments ...............................................................39 
LIST OF FIGURES 
Figure 1: 
Pharmacokinetic Modeling of Steady-state Concentrations for ADS-5102 vs 
Approved Doses of Amantadine IR ............................................................................21 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations are used in this study protocol. 
Table 1: 
Abbreviations  
Abbreviation 
Explanation 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BMI 
body mass index 
BP 
blood pressure 
BUN 
blood urea nitrogen 
C 
Concentration 
Cmax 
observed maximum concentration 
Cmin 
observed minimum concentration 
CHF 
congestive heart failure 
CNS 
central nervous system 
CRF 
Case Report Form (paper and/or electronic) 
DBS 
Deep brain stimulation 
dL 
Deciliter 
ECG 
electrocardiogram 
eGFR 
estimated glomerular filtration rate 
ER 
extended release 
ET 
Early Termination 
FDA 
Food and Drug Administration (United States) 
g 
Grams 
GCP 
Good Clinical Practice 
GGT 
-glutamyltransferase 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 


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Table 1: 
Abbreviations (Continued) 
IEC 
Independent Ethics Committee 
IR 
Immediate release 
IRB 
Institutional Review Board 
IUD 
intra-uterine device 
LID 
Levodopa Induced Dyskinesia 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MDRD 
Modification Of Diet In Renal Disease 
MDS-UPDRS 
Movement Disorder Society-Unified Parkinson’s Disease Rating Scale 
MI 
Myocardial Infarction 
MITT 
Modified Intent-To-Treat 
MMSE 
Mini Mental Status Examination 
NF 
National Formulary 
NMDA 
N-Methyl D-Aspartate 
NYHA 
New York Heart Association 
PD 
Parkinson’s Disease 
PI 
Principal Investigator 
PP 
Per Protocol 
PVC 
Premature Ventricular Contractions 
RBC 
Red Blood Cell(s) 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
TIA 
Transient Ischemic Attack 
tmax 
Time Of Observed Maximum Concentration 
UA 
Urinalysis 
UK PDS 
UK Parkinson's Disease Society 
US/USA 
United States (Of America) 
USP 
United States Pharmacopeia 
WBC 
White Blood Cell(s); Leukocyte(s) 
WHO 
World Health Organization 


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4. 
INTRODUCTION 
Parkinson's disease is a chronic, progressive disorder with prominent motor signs including 
tremors, rigidity, bradykinesia and postural instability.  Levodopa is the most commonly 
prescribed and effective drug treatment for symptomatic relief in PD; however, chronic treatment 
with levodopa often results in the emergence of dose-limiting motor side-effects, including 
abnormal involuntary movements known as LID.  With continued levodopa treatment, and as PD 
progresses, LID can become severely disabling and has been associated with a decrease in the 
quality of life (Encarnacion et al., 2008).  There are currently no medications approved for the 
treatment of LID, thus there is a significant unmet medical need for new treatments for this 
condition. 
Dyskinesia can be an adverse effect of all dopaminergic therapies, but mostly related to the use 
of levodopa (Del Sorbo et al., 2008).  LID can be diagnosed by the characteristics of the 
exhibited movement and time to onset relative to daily administration of levodopa.  The most 
common type of LID is referred to as “peak-dose dyskinesia” and usually consists of 
stereotypical choreic or ballistic movements involving the head, trunk, and/or limbs.  Movement 
disorder specialists have developed rating scales to evaluate dyskinesia for purposes of clinical 
diagnosis and clinical trial investigation (Goetz et al., 2008; Colosimo et al., 2010; Goetz et al., 
2013). 
The incidence of LID reported in the literature, including reports of individual studies, varies 
widely (Duvoisin 1974; Parkinson Study Group 1989; Parkinson Study Group 1996; Thanvi et 
al., 2007).  Based on published studies utilizing a Medicare beneficiaries’ database, IMS 
prescribing data, and demographic studies presented in the peer-reviewed literature, we have 
estimated a prevalence of approximately 140,000 Parkinson’s patients with LID.  
The underlying cause of LID is unknown, but the pulsatile administration of levodopa treatment 
and the degree of denervation in the striatum appear to influence its development (Del Sorbo et 
al., 2008).  Other factors that have been associated with a higher incidence and severity of LID 
include early age of onset of PD, longer duration of levodopa treatment, levodopa total exposure, 
female gender, and genetic factors.  The preferential use of dopamine agonists in the treatment of 
early disease and the careful management of pulsatile effects of levodopa therapy can delay but 
not eliminate the development of LID.  
Amantadine IR, which is approved for the treatment of PD, is used off-label by movement 
disorder specialists and other neurologists to treat LID in patients with PD.  A number of 
literature reports suggest amantadine is effective for the treatment of LID (Verhagen et al., 1998; 
Verhagen et al., 1999; Luginger et al., 2000; Snow et al., 2000; Paci et al. 2001; Thomas et al., 
2004; da Silva-Junior et al., 2005; Sawada et al., 2010; Wolf et al., 2010; Goetz et al., 2013). 
Despite amantadine’s reported utility in the treatment of LID, until recently, the drug was not 
extensively studied in well-controlled clinical trials that meet evidence-based clinical or 
regulatory standards of acceptance, nor was the optimal dose for this indication established.  The 
majority of patients with PD tolerate 200 mg/day of the amantadine IR formulation; however, the 
available literature on amantadine for the treatment of LID indicates that higher doses of 
amantadine produce a greater reduction in LID symptoms (Verhagen et al., 1998; Luginger et al., 
2000).  However, the increased frequency of adverse events (AEs) at higher doses, in particular 
central nervous system (CNS) events and sleep disturbances, limits the routine use of amantadine 


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IR at doses of 300 mg/day or higher (Tyrrell et al., 1964; Jackson et al., 1967; Hayden et al., 
1981). 
4.1. 
Product Rationale 
The pharmacologic rationale for a formulation that slows the release of amantadine is based upon 
the nature and timing of amantadine IR CNS side effects relative to dosing as well as 
observations with other CNS active drugs.  Symmetrel (amantadine HCl IR tablet) has a short 
tmax of 2-4 hours (Aoki et al., 1988), and the most commonly reported side effects are CNS 
related, including dizziness (lightheadedness), agitation, hallucinations, and insomnia which can 
occur within a few hours of dosing (Hayden 1981; Jackson et al., 1967).  These side effects may 
explain why amantadine is usually administered in divided doses, despite a 16 hour half-life, 
which would typically support once daily dosing.  Moreover, the CNS effects are particularly 
disruptive late in the day or evening (following a second or third amantadine dose) as the patient 
is trying to sleep (Tyrrell et al., 1964; Jackson et al., 1967). 
In addition to amantadine, there are other CNS active stimulant drugs, such as methylphenidate 
and cocaine that have high blood brain permeability (CNS penetrants), and exhibit a short tmax.  
By modifying the PK profile of these drugs to change the initial release characteristics, the type 
and timing of the CNS effects can be modulated (Volkow et al., 1998; Swanson et al., 2002; 
Spencer et al., 2006).  Hence, the pharmacologic rationale for improved tolerability of an 
extended-release formulation of amantadine is that the reduction in the rate of rise in plasma 
concentration may reduce the CNS adverse effects that can occur shortly after dosing, without 
compromising concentration-dependent efficacy. 
4.2. 
Dose and Dose Regimen Justification 
The proposed dose of amantadine HCl in ADS-5102 is 340 mg, to be taken once nightly at 
bedtime.  The tmax for ADS-5102 is expected to occur at 12 to 14 hours post dose.  ADS-5102 is 
designed to achieve maximal concentrations in the early morning through mid-day, when LID 
tends to be troublesome, and lower concentrations in the evening, potentially reducing the 
negative impact of amantadine on sleep. This pharmacokinetic profile could enable higher daily 
doses to be tolerated with a once-nightly ER preparation than can be tolerated with an IR 
formulation. The once-nightly dosing regimen may also provide enhanced convenience and 
improve compliance.  The labeled dose of Symmetrel for initiating treatment of PD is 100 mg 
given twice daily.  The label also allows for an increase of up to 400 mg daily in divided doses 
for patients whose responses are not optimal with 200 mg daily.  Figure 1 shows 
pharmacokinetic modeling of the steady state exposure for the ADS-5102 formulation compared 
to the approved doses of amantadine IR. Profiles were generated from Adamas clinical data in 
healthy volunteers (NPI-5103-C101). 


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Figure 1: 
Pharmacokinetic Modeling of Steady-state Concentrations for ADS-5102 vs 
Approved Doses of Amantadine IR   
 
ADS-5102 administered as 340 mg once-nightly results in a PK profile that provides higher 
exposures than possible with 100 mg bid amantadine IR, and yet remains within those approved 
in the Symmetrel package insert.  As seen in Figure 1, the Cmax of the recommended dose of 
ADS-5102 remains below that of the 200 mg amantadine IR bid. The minimal concentration 
after dosing with ADS-5102 remains above the Cmax from a 100 mg dose of amantadine IR. 
4.3. 
Summary Pharmacokinetic Information for Extended Release 
Amantadine Formulations 
4.3.1. 
Single Dose Studies 
In a single-dose trial, the PK performance of 3 amantadine ER formulations [labeled A, B  
(ADS-5101), and C (ADS-5102)] was studied in healthy volunteers (Study No. NPI-5103-C-
101).  The study demonstrated that all 3 ER amantadine formulations had lower Cmax and longer 
tmax compared to IR amantadine.  Relative bioavailability (based on AUC0-inf) of amantadine 
ER formulations A, B, and C compared to IR amantadine was 85.3%, 94.6%, and 88.5%, 
respectively.  
0
200
400
600
800
1000
1200
1400
0
4
8
12
16
20
24
Plasma Amantadine Concentration (ng/mL)
Time (h)
Amantadine IR 200 mg BID
Amantadine IR 100 mg BID
ADS-5102 340 mg QD
8 PM
8 AM
8 PM


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4.3.2. 
Effect of Food on Bioavailability of Amantadine ER  
Two single-dose crossover studies (study NPI-5101-FE-103 and study ADS-5101-106) 
established the lack of effect of food on pharmacokinetics and one study demonstrated that 
administering the ADS-5101 capsule contents sprinkled on applesauce  
(Study NPI-5101-FE-106) does not affect the bioavailability of amantadine. 
When study medication was administered after a standard meal, absorption of amantadine was 
faster, with slightly higher peak concentration and 1 hour earlier median tmax value as compared 
with the reference fasted treatment.  The 90% CIs of the ratio of the least squares geometric 
mean for Cmax, AUC0-t, and AUC0-∞ fell within the 80.00% to 125.00% interval for each test 
treatment (fed and sprinkled) relative to the reference treatment (fasted condition).  The results 
from these studies support dosing recommendations that amantadine ER can be administered 
with food and can be sprinkled on applesauce. 
Steady state pharmacokinetic data are not available for ADS-5102.  One of the objectives of this 
study is to measure steady state amantadine concentrations at the three dose levels. 
4.3.3. 
Relative Bioavailability of Amantadine ER vs. Amantadine IR at Steady State 
Two multiple dose studies were conducted with similar study designs: NPI-5101-MD-104 which 
studied a daily dose of 200 mg (two 100 mg ADS-5101 capsules administered once daily), and 
ADS-5101-105 which used a dose of 220 mg (two 110 mg ADS-5101 capsules administered 
once daily).  Both studies were 2-treatment, 2-period crossover, single and multiple-dose PK 
studies comparing once-daily ADS 5101 and twice–daily amantadine IR (2 x 100 mg) in healthy 
adults under fasting conditions.  In each trial, a single dose of the reference (2 x 100 mg 
amantadine IR) and test (200 mg or 220 mg ADS-5101) substance was administered, followed 
by 48 hours of plasma sampling to characterize the single dose pharmacokinetic profile.  The 
subjects were then administered 7 days of study drugs (amantadine IR, 100 mg bid or  
ADS-5101, 200 or 220 mg qd), and the steady state pharmacokinetic profile was assessed.  
Following a seven day washout, the subjects were crossed over to the alternate test regimens. 
Similar PK results were observed on Day 1 and on Day 9.  These studies suggest linear kinetics 
over time for both the IR and ER formulations. 
4.4. 
Summary Safety Information for Extended Release Amantadine 
Formulations  
The safety of amantadine ER formulation has been examined in approximately 120 healthy 
subjects in the five single dose Phase 1 studies and 61 patients in one repeated dose Phase 2/3 
efficacy study. 
In the Phase 1 studies in healthy volunteers, the most frequently occurring adverse events 
reported with the ER formulations of amantadine were headache, fatigue, and dizziness, 
occurring in 5-10% of subjects.  The majority of adverse events were categorized as mild. There 
were no serious adverse events in any of the trials to date, and no deaths were reported.  No 
meaningful trends were observed for serum chemistry, hematology, or urinalysis results. 
In the Phase 2/3 safety and efficacy study conducted in 83 patients with PD, most frequently 
reported adverse events were constipation, dizziness, dry mouth and hallucinations.  Most of 


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these AEs were mild to moderate.  Five patients had serious adverse events, and no deaths were 
reported. No meaningful trends were observed for serum chemistry, hematology, or urinalysis 
results. 
In all the amantadine ER studies, the reported adverse events were generally consistent with the 
known safety profile of amantadine. 
For additional information please refer to the Investigator’s Brochure. 
4.5. 
Rationale for ADS-AMT-PD302 Study Design 
This study is designed to further investigate the safety and tolerability profile of ADS-5102 oral 
capsules, an extended release formulation of amantadine, administered at a dose of 340 mg once 
nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with 
Parkinson’s disease (PD).  Additionally, this study will evaluate duration of ADS-5102 effect on 
dyskinesia as assessed by Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Part IV, as 
well as evaluate clinical progression of Parkinson’s disease as assessed by MDS-UPDRS, 
Combined Score, Parts I, II, and III. 
4.6. 
Population to be Studied 
This study will be offered to subjects who are described by one of the following 3 groups:  
 Group 1 (current Adamas LID study subjects): Subjects who are participating in 
Adamas efficacy studies evaluating ADS-5102 in LID and choose to immediately 
transition into ADS-AMT-PD302 without a time gap; 
 Group 2 (previous Adamas LID study subjects): Subjects who have participated in 
previous Adamas efficacy studies evaluating ADS-5102 in LID and will enter ADS-
AMT-PD302 with a time gap; 
 Group 3 (non Adamas LID study subjects with prior DBS): Subjects who would have 
been deemed ineligible for participation in previous Adamas efficacy studies due to 
having undergone deep brain stimulation.  
 
 


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5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Primary Objective 
To evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release 
formulation of amantadine, administered at a dose of 340 mg once nightly at bedtime for the 
treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson’s disease (PD). 
5.2. 
Secondary Objectives 
To evaluate duration of ADS-5102 effect on dyskinesia as assessed by the Unified Parkinson’s 
Disease Rating Scale (MDS-UPDRS), Part IV. 
To evaluate clinical progression of Parkinson’s disease as assessed by MDS-UPDRS, Combined 
Score, Parts I, II, and III. 
5.3. 
Safety Outcome Assessments 
The following safety assessments will be performed during the study: 
 AEs   
 Safety-related study drug discontinuations 
 Vital signs 
 Safety laboratory tests  
5.4. 
Efficacy Outcome Assessments 
The following efficacy assessment will be performed during the study:  
 Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) 
6. 
 INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This study will be offered to subjects who are described by one of the following 3 groups:  
 Group 1 (current Adamas LID study subjects): Subjects who are participating in 
Adamas efficacy studies evaluating ADS-5102 in LID and choose to immediately 
transition into ADS-AMT-PD302 without a time gap; 
 Group 2 (previous Adamas LID study subjects): Subjects who have participated in 
previous Adamas efficacy studies evaluating ADS-5102 in LID and will enter ADS-
AMT-PD302 with a time gap; 
 Group 3 (non Adamas LID study subjects with prior DBS): Subjects who would have 
been deemed ineligible for participation in previous Adamas efficacy studies due to 
having undergone deep brain stimulation.  


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Detailed inclusion/exclusion criteria and a schedule of events are described in this protocol 
Section 7 and Appendix A, respectively, for each of these groups.  
 Current Adamas LID study subjects (Group 1) should have their Screening Visit (Visit 
1), including consent, for the ADS-AMT-PD302 study occur at the same visit as the final 
efficacy visit for the previous Adamas efficacy study, as outlined in the previous 
protocol. Subsequently, they should also have their Baseline Visit (Visit 2) for the ADS-
AMT-PD302 study occurs during the final study visit (not including any safety follow up 
visit) of the previous Adamas efficacy study visit, as outlined in the previous protocol. 
 Previous Adamas LID study subjects (Group 2) and Non Adamas LID study subjects 
with prior DBS (Group 3) will not have overlapping visits with any previous protocol.  
A study design schematic for study entry differences between these groups can be found in 
Appendix B.  
Consented subjects who complete screening (Visit 1) and meet study eligibility criteria will have 
a baseline visit and receive 1 week of 170 mg ADS-5102 (1 capsule) nightly at bedtime, 
followed by 340 mg ADS-5102 (2 capsules) nightly at bedtime for up to 99 additional weeks. 
The final week (Week 101) of dosing will be at the reduced dose of 170 mg ADS-5102(1 
capsule) nightly at bedtime.  
Subjects will be enrolled into the study at Visit 2 (Week 0, Baseline) and return to the clinic after 
4, 8, 16, 28, 40, 52, 64, 76, 88 and 100weeks dosing.  Subjects will receive a telephone reminder 
at the end of Week 1 to increase their dose during Week 2.  At the Week 100 visit, subjects will 
be instructed to reduce their dose for 1 week, taking 1 capsule nightly at bedtime.  The amount of 
available unused drug will be assessed during the Week 100 visit, and if a subject needs an 
additional bottle dispensed to cover 1 week of a reduced dose, they should be provided with a 
new bottle.  
An efficacy assessment using the MDS-UPDRS will be completed at all study visits, beginning 
with the Screening Visit, with the exception of the Baseline/Week 0 visit & Week 4 visit.  A 
safety follow-up visit will occur approximately 2 weeks following the completion of treatment.  
Women of childbearing potential will also have a pregnancy test performed at the early 
termination visit or 2 weeks following the completion of treatment at the safety follow up visit.  
Subjects who discontinue study drug before Week 101 will have an early termination visit that 
includes MDS-UPDRS assessments and safety follow-up.   
Subjects who discontinue study drug after Week 4 should receive a reduced dose of 170 mg 
ADS-5102 for one additional week.  The additional week of dosing at a reduced dose will not be 
needed for subjects who discontinue study drug before Week 4. 
Adverse events (AEs) will be recorded beginning with the first dose of study drug and will 
continue through the safety follow-up visit.  Concomitant medications will be recorded 
throughout the study.   
 


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6.2. 
Number of Subjects 
Up to 250 (all active) will be enrolled at approximately 90 sites worldwide. 
6.3. 
Treatment Assignment 
All enrolled subjects will receive active treatment (ADS-5102). 
6.4. 
Dose Adjustment Criteria 
Subjects who discontinue study drug after Week 4 should receive a reduced dose for one 
additional week before stopping study drug.  The additional week of dosing at a reduced dose 
will not be needed for subjects who discontinue study drug before Week 4. 
Subjects whose estimated GFR falls below 50 mL/min/1.73m2, confirmed by repeat testing,(but 
is ≥ 30 mL/min/1.73m2) should discontinue study drug after receiving a reduced dose of 170 mg 
ADS-5102 for one additional week. The additional week of dosing at a reduced dose will not be 
needed for subjects who discontinue study drug before Week 4. 
Subjects whose estimated GFR falls below 30 mL/min/1.73m2, confirmed by repeat testing, at 
any time during the study should discontinue study drug (without the additional week at a 
reduced dose).  
6.5. 
Criteria for Study Termination 
The Sponsor reserves the right to discontinue the trial at any time; reasons will be provided in the 
event of this happening.  The Principal Investigator reserves the right to discontinue participation 
in the study for safety or other reasons at any time in collaboration with the Sponsor.  The 
Investigator should notify the IRB/REC/IEC in writing of the trial’s completion or early 
termination and provide a copy of the notification to the Sponsor.   
6.6. 
Duration of Subject Participation 
Duration of subject participation will be up to 105 weeks and will include a 2-week (maximum) 
screening period and up to 101 weeks of open-label treatment, followed by a final safety follow-
up visit 2 weeks after completion of treatment. 
6.7. 
Estimated Study Duration 
Approximately 37 months (from enrollment of first subject to last subject completion of last visit 
[LSLV]). 


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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
7.1.1. 
Group 1: Current Adamas LID study subjects 
Below are the inclusion criteria subjects who are continuing directly into ADS-AMT-PD302 
without a time gap between their Adamas LID efficacy study and ADS-AMT-PD302:   
1. Signed a current IRB/REB/IEC-approved informed consent form;
2. Completed study visits per protocol in a previous Adamas efficacy study;
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the
subject can complete study assessments;
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the
subject to study visits and assist in completion of study assessments, as needed and
allowed;
5. History of peak dose dyskinesia that might benefit from specific dyskinesia treatment in
the judgment of the subject and clinical investigator;
6. On a stable regimen of antiparkinson’s medications, including a levodopa preparation
administered not less than three times daily.
7.1.2. 
Group 2: Previous Adamas LID study subjects  
Below are the inclusion criteria for subjects who participated in a previous Adamas efficacy 
study evaluating ADS-5102 in LID and will enter ADS-AMT-PD302 with a time gap: 
1. Signed a current IRB/REB/IEC-approved informed consent form;
2. Completed study visits per protocol in a previous Adamas efficacy study;
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the
subject can complete study assessments;
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the
subject to study visits and assist in completion of study instruments, as needed and
allowed;
5. Peak dose dyskinesia during Screening that might benefit from specific dyskinesia
treatment in the judgment of the subject and clinical investigator OR a history of peak
dose dyskinesia that is currently being managed by amantadine treatment;
6. 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;
7. Parkinson’s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical
Diagnostic Criteria (see Appendix C).


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7.1.3. 
Group 3: Non Adamas LID study subjects – with prior DBS 
Below are the inclusion criteria for subjects who would have been deemed ineligible for 
participation in previous or current Adamas efficacy studies due to having undergone deep brain 
stimulation: 
1. Signed a current IRB/REB/IEC-approved informed consent form;
2. Male or female subjects between 30 and 85 years of age, inclusive;
3. Subject has undergone deep brain stimulation procedure prior to start of this study
(14 July 2014);
4. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the
subject can complete study assessments;
5. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the
subject to study visits and assist in completion of study instruments, as needed and
allowed;
6. Peak dose dyskinesia during Screening that might benefit from specific dyskinesia
treatment in the judgment of the subject and clinical investigator OR a history of peak
dose dyskinesia that is currently being managed by amantadine treatment;
7. 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;
8. Parkinson’s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical
Diagnostic Criteria (see Appendix C).
7.2. 
Subject Exclusion Criteria 
7.2.1. 
Group 1: Current Adamas LID study subjects 
Below are the exclusion criteria subjects who are continuing directly into ADS-AMT-PD302 
without a time gap between their Adamas LID efficacy study and ADS-AMT-PD302:   
1. Discontinued study drug in previous Adamas studies due to intolerable or unacceptable
AEs considered to be related to ADS-5102;
2. Hoehn and Yahr Stage 5;
3. Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure (at
least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes of the
subject standing up, compared to pressures obtained while sitting;
4. Estimated GFR < 50 mL/min/1.73m2 (calculated using Modification of Diet in Renal
Disease (MDRD));
5. If female, is pregnant or lactating;
6. If a sexually active female, is not surgically sterile or at least 2 years postmenopausal, or
does not agree to utilize a highly effective hormonal method of contraception (an IUD, or
vasectomized male partner is also acceptable), in combination with a barrier method,
from screening through at least 4 weeks after the completion of study treatment;


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7. Anticipated need for treatment with restricted medication (reference Appendix E);
8. Planned participation in another interventional clinical trial.
7.2.2. 
Group 2: Previous Adamas LID study subjects  
Below are the exclusion criteria for subjects who participated in a previous Adamas efficacy 
study evaluating ADS-5102 in LID and will enter ADS-AMT-PD302 with a time gap: 
1. Discontinued study drug in previous Adamas studies due to intolerable or unacceptable
AEs considered to be related to ADS-5102;
2. History of neurosurgical intervention related to Parkinson’s disease, with the exception of
deep brain stimulation;
3. History of other neurological disease that, in the opinion of the investigator, would  affect
motor function or cognition, including, but not limited to Alzheimer’s dementia,
Huntington’s disease, Lewy body dementia, frontotemporal dementia, corticobasal
degeneration, progressive supranuclear palsy, multiple system atrophy, motor or sensory
dysfunction secondary to stroke or brain trauma, or multi-infarct dementia with lacunae;
4. Current sensory impairments (e.g., hearing, vision) that, in the opinion of the investigator,
would impair the subject’s ability to complete study assessments, or presence of
untreated angle closure glaucoma;
5. History of alcohol or substance dependence or abuse since completion of participation in
previous Adamas trial;
6. History of seizures since completion of participation in previous Adamas trial;
7. History of stroke or TIA since completion of participation in previous Adamas trial;
8. History of myocardial infarction, or NYHA Functional Classification of Heart Failure
Class 3 or 4 since completion of participation in previous Adamas trial (see Appendix D);
9. Any clinically significant ECG abnormalities, including any findings of abnormal
ventricular conduction or rhythm other than isolated PVCs or first degree AV block;
10. History of cancer since completion of participation in previous Adamas trial, with the
following exceptions: adequately treated non-melanomatous skin cancers, localized
bladder cancer, non-metastatic prostate cancer or in situ cervical cancer;
11. Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination
(MMSE) score of less than 24 during screening;
12. Hoehn and Yahr Stage 5;
13. Presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive
Disorder) or symptom (e.g., hallucinations, agitation, paranoia, suicidal ideation) that, in
the opinion of the investigator, would  affect the subject’s ability to complete study
assessments;
14. Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure
(at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes of
the subject standing up, compared to pressures obtained while sitting;


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15. Any of the following laboratory test results at screening:  
 Hemoglobin < 10 g/dL 
 WBC <3.0 x 109/L 
 Neutrophils <1.5 x 109/L 
 Lymphocytes < 0.5 x 109/L 
 Platelets <100 x 109/L 
 Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 times 
the upper limit of normal; 
16. Estimated GFR < 50 mL/min/1.73m2 (calculated using Modification of Diet in Renal 
Disease (MDRD)); 
17. Inability to swallow oral capsules, or a history of gastrointestinal malabsorption that 
would preclude the use of oral medication;     
18. If female, is pregnant or lactating;  
19. If a sexually active female, is not surgically sterile or at least 2 years postmenopausal, or 
does not agree to utilize a highly effective hormonal method of contraception (an IUD, or 
vasectomized male partner is also acceptable), in combination with a barrier method, 
from screening through at least 4 weeks after the completion of study treatment;  
20. Documented inability to tolerate amantadine, or history of suicidal ideation or suicide 
attempt during prior amantadine use; 
21. History of hypersensitivity or allergic reaction to amantadine, rimantidine, or memantine, 
or to any of the excipients used in the study medication capsules (see Section 8.7);  
22. Received live attenuated influenza vaccine within 2 weeks prior to enrollment 
(amantadine may interfere with the efficacy of live attenuated vaccine); 
23. Current treatment with carbonic anhydrase inhibitors, sodium bicarbonate, or urinary 
acidification agents, quinine, quinidine, triamterene, or trimethoprim (see Appendix E); 
24. Current treatment with medications that act primarily by blocking dopamine receptors 
and current treatment with medications that prolong the QT interval and have a known 
risk of torsades de pointes (see Appendix E).  Subjects who are able to appropriately 
discontinue these agents at least 60 days prior to screening will be eligible for screening; 
25. Treatment with an investigational drug (other than ADS-5102) or device within 30 days 
prior to screening; 
26. Treatment with an investigational biologic within 6 months prior to screening; 
27. Anticipated need for treatment with restricted medication (see Appendix E); 
28. Current or planned participation in another interventional clinical trial. 


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7.2.3. 
Group 3: Non Adamas LID Study Subjects – with prior DBS 
Below are the exclusion criteria for subjects who would have been deemed ineligible for 
participation in previous or current Adamas efficacy studies due to having undergone deep brain 
stimulation: 
1. History of neurosurgical intervention related to Parkinson’s disease, with the exception of
deep brain stimulation;
2. History of other neurological disease that, in the opinion of the investigator, would  affect
motor function or cognition, including, but not limited to Alzheimer’s dementia,
Huntington’s disease, Lewy body dementia, frontotemporal dementia, corticobasal
degeneration, progressive supranuclear palsy, multiple system atrophy, motor or sensory
dysfunction secondary to stroke or brain trauma, or multi-infarct dementia with lacunae;
3. Current sensory impairments (e.g., hearing, vision) that, in the opinion of the investigator,
would impair the subject’s ability to complete study assessments, or presence of
untreated angle closure glaucoma;
4. History of alcohol or substance dependence or abuse within 2 years prior to screening;
5. History of seizures within 2 years prior to screening;
6. History of stroke or TIA within 2 years prior to screening
7. History of myocardial infarction, or NYHA Functional Classification of Heart Failure
Class 3 or 4 within 2 years prior to screening (see Appendix D);
8. Any clinically significant ECG abnormalities, including any findings of abnormal
ventricular conduction or rhythm other than isolated PVCs or first degree AV block;
9. History of cancer within 5 years of screening, with the following exceptions: adequately
treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate
cancer or in situ cervical cancer;
10. Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination
(MMSE) score of less than 24 during screening;
11. Hoehn and Yahr Stage 5;
12. Presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive
Disorder) or symptom (e.g., hallucinations, agitation, paranoia, suicidal ideation) that, in
the opinion of the investigator, would  affect the subject’s ability to complete study
assessments;
13. Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure
(at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes of
the subject standing up, compared to pressures obtained while sitting;
14. Any of the following laboratory test results at screening:

Hemoglobin < 10 g/dL

WBC <3.0 x 109/L

Neutrophils <1.5 x 109/L


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 Lymphocytes < 0.5 x 109/L 
 Platelets <100 x 109/L 
 Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 times 
the upper limit of normal; 
15. Estimated GFR < 50 mL/min/1.73m2 (calculated using Modification of Diet in Renal 
Disease (MDRD)); 
16. Inability to swallow oral capsules, or a history of gastrointestinal malabsorption that 
would preclude the use of oral medication;     
17. If female, is pregnant or lactating;  
18. If a sexually active female, is not surgically sterile or at least 2 years postmenopausal, or 
does not agree to utilize a highly effective hormonal method of contraception (an IUD, or 
vasectomized male partner is also acceptable), in combination with a barrier method, 
from screening through at least 4 weeks after the completion of study treatment;  
19. Documented inability to tolerate amantadine, or history of suicidal ideation or suicide 
attempt during prior amantadine use; 
20. History of hypersensitivity or allergic reaction to amantadine, rimantidine, or memantine, 
or to any of the excipients used in the study medication capsules (see Section 8.7);  
21. Received live attenuated influenza vaccine within 2 weeks prior to enrollment 
(amantadine may interfere with the efficacy of live attenuated vaccine); 
22. Current treatment with carbonic anhydrase inhibitors, sodium bicarbonate, or urinary 
acidification agents, quinine, quinidine, triamterene, or trimethoprim (See Appendix E); 
23. Current treatment with medications that act primarily by blocking dopamine receptors 
and current treatment with medications that prolong the QT interval and have a known 
risk of torsades de pointes (see Appendix E).  Subjects who are able to appropriately 
discontinue these agents at least 60 days prior to screening will be eligible for screening; 
24. Treatment with an investigational drug (other than ADS-5102) or device within 30 days 
prior to screening; 
25. Treatment with an investigational biologic within 6 months prior to screening; 
26. Anticipated need for treatment with restricted medication (see Appendix E); 
27. Current or planned participation in another interventional clinical trial. 
7.3. 
Subject Withdrawal Criteria 
Subjects will be advised that they are free to withdraw from the study at any time. Reasons that 
subjects may be withdrawn from the study include the following: 
 Subject discontinued study medication (see Section 7.5);  
 Subject consent is withdrawn; 
 Sponsor decision, after discussion with the Investigator. 


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If a subject is withdrawn from the study, all efforts will be made to complete the early 
termination visit that includes efficacy assessments and safety follow-up. In addition, women of 
childbearing potential will have a pregnancy test performed at the early termination visit. 
All information, including the reason for withdrawal, should be reported on the applicable pages 
of the case report form (CRF). 
For subjects who are lost to follow-up, three documented attempts will be made to contact the 
subject for follow-up information, including reason for discontinuation and follow-up of AEs. 
Subjects who withdraw from the study will not be replaced. 
7.4. 
Subject Enrollment 
All subjects must sign and date an IRB/REB/IEC-approved ICF before any study procedures, 
including screening procedures, are performed.  During screening, the investigator or designee is 
to assess the need and requirements for a caregiver and/or study partner during the course of the 
study, and to assure the commitment of the person(s) so designated.  It is preferable that the 
involved caregiver remains consistent during study participation; however, if circumstances 
require that the involved caregiver changes, he/she must undergo appropriate training prior to 
assisting the subject in completion of study assessments. 
Subjects will be considered enrolled into the study after they have signed the ICF, have met all 
study mandated inclusion/exclusion criteria, and are enrolled at Visit 2 (Week 0, Baseline). 
7.5. 
Discontinuation of Study Medication   
Subjects who discontinue study drug after Week 4 should receive a reduced dose for one 
additional week of ADS-5102 before stopping study drug.  The additional week of dosing at a 
reduced dose will not be needed for subjects who discontinue study drug before Week 4. 
Subjects should discontinue study medication if judged necessary by the investigator or sponsor, 
and reasons may include any of the following: 
 Estimated glomerular filtration rate (eGFR) falls below 50 mL/min/1.73m2, 
confirmed by repeat testing. (see Section 6.4) 
NOTE:  
 Subjects whose eGFR falls below 30 mL/min/1.73m2 while on study should 
discontinue study drug without the additional week at a reduced dose. 
 Need to take a medication that is excluded or that may interfere with study 
measurements 
 Intolerable or unacceptable AEs 
 Positive pregnancy test 
If the subject decides to discontinue study drug, they will have an early termination visit that 
includes efficacy assessments and safety follow-up. 


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8. 
STUDY DRUG MATERIALS AND MANAGEMENT 
8.1. 
Study Drug 
The clinical supplies will include 170 mg ADS-5102 capsules.  
Amantadine hydrochloride is designated generically as amantadine hydrochloride and 
chemically as 1-adamantanamine hydrochloride. 
The clinical formulation is shown in Table 2. 
Table 2: 
Clinical Formulation for Study ADS-AMT-PD302 
ADS-5102 
170 mg 
Formulation 
Extended release coated pellets of amantadine HCl in an oral 
capsule 
Dose Strength 
170 mg amantadine HCl per capsule 
Description 
White to off-white pellets filled in blue/blue colored hard gelatin 
capsule, size 0.  
Excipients 
Microcrystalline cellulose, NF 
Hypromellose, USP 
Copovidone, NF 
Talc, USP 
Ethyl cellulose, NF  
Povidone , USP  
Medium chain triglycerides,  USP 
Magnesium stearate, NF 


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8.2. 
Study Drug Packaging and Labeling 
Bottles containing 60 capsules (30 day supply of study drug) of 170 mg ADS-5102 will be 
provided at each study visit once enrolled. The number of bottles provided will depend on the 
visit. One bottle will be dispensed on Day 1 and Week 4. Two bottles will be dispensed on Week 
8, and three bottles will be dispensed at Week 16, Week 28, Week 40, Week 52, Week 64, Week 
76, and Week 88.  
The amount of available unused drug will be assessed during the Week 100 visit, and if a subject 
needs an additional bottle dispensed to cover 1 week of a reduced dose, they should be provided 
with a new bottle. 
All bottles will be labeled with, at a minimum, the protocol number, route of administration, 
number of capsules to be administered, lot number, storage conditions, Sponsor’s name and 
address, and the applicable investigational drug caution statements and will be compliant with 
the “EU Guidelines for Good Manufacturing Practice Medicinal Products for Human and 
Veterinary Use Annex 13. Investigational Medicinal Products”.  
8.3. 
Study Drug Storage 
All study drugs must be stored at 25oC (77oF) with excursions permitted to 15-30°C (59-86°F) in 
a secured location with access limited to authorized personnel. 
An authorized pharmacist or designated staff member will dispense the study drug. The 
dispensing and administration will be recorded in a drug accountability log. 
8.4. 
Administration 
Table 3: 
Treatment Schedule for Study ADS-AMT-PD302 
Treatment 
Week 1 
Week 2 – Week 100 
Week 101 
ADS-5102 
170 mg ADS-5102 
(1 x 170 mg capsule) 
340 mg ADS-5102 
(2 x 170 mg capsules) 
170 mg ADS-5102 
(1 x 170 mg capsule) 
Each dose will be administered as 1 or 2 oral capsules once nightly at bedtime (if possible, no 
earlier than 9 pm).   
Capsules are to be swallowed intact, and can be taken with any nonalcoholic beverage, and with 
or without food.  Dosing will continue through Week 101. 
8.5. 
Study Drug Accountability 
All study drug supplied is for use only in this clinical study and must not be used for any other 
purpose.  The Investigator is responsible for the study drug accountability, reconciliation and 
record maintenance at the investigational site.  In accordance with all applicable regulatory 
requirements, the Investigator or designated site staff must maintain study drug accountability 
records throughout the course of the study.  This person will document the amount of study drug 
received and the amount supplied and/or administered to and returned by subjects, if applicable.  
Copies of all packing slips for the study drug shipments must be retained.  


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A Study Drug Accountability Record must be kept current and will contain at a minimum the 
following information: 

The identification of the subject to whom the drug was dispensed

The date(s) and quantity of the drug dispensed to the subject

Any product accidentally or deliberately destroyed

Current quantity of total study drug supply
Subjects will be instructed to return all used and unused bottles (with unused capsules) of study 
drug for drug accountability purposes.  All used and unused bottles (with unused capsules) must 
be saved for reconciliation by the Sponsor’s study monitor or an assigned designee. 
During the study, the study drug and all shipment, accountability and dispensing records must be 
available for inspection by the study monitor.  Drug supply reconciliation is required at the end 
of the study by the study monitor.   
8.6. 
Study Drug Handling and Disposal 
After reconciliation, all unused drug supplies will be disposed of according to instructions 
provided by the Sponsor.  Records shall be maintained by the Investigator of any such 
disposition of the study drug, which must show the identification and quantity of each unit 
returned. 
8.7. 
Prohibited Medications and Restrictions 
A list of medications prohibited prior to study entry, as well as during study participation,  
is provided in Appendix E. 
In addition, the following medications are prohibited during study participation: 

Use of amantadine (other than provided study drug) during study participation

Live attenuated influenza vaccine during study participation

While taking study drug, it is recommended as a general safety precaution when
evaluating a CNS-active agent that subjects who wish to consume alcohol should do
so only in moderation
8.8. 
Concomitant Medications 
Information regarding medications taken by the subject within 30 days prior to the Screening 
Visit and throughout the study will be collected and recorded on the Prior/Concomitant 
Medications CRF.  This information will include the name of the medication, dosage information 
(including frequency and route of administration), dates taken, reason for use, and stop date, if 
available. 
All subjects must be on a stable regimen of antiparkinson’s medications for at least 30 days prior 
to screening, including any levodopa preparation dosed at least three times daily.  
Any other current and allowed prescription/non-prescription medications and/or nutritional 
supplements must have been at a stable dose and frequency for at least 30 days prior to 


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screening. (This criterion does not apply to medications that are taken on an as-needed basis 
only).   
8.9. 
Treatment Compliance 
One bottle containing a 30 day supply of study drug will be dispensed on Day 1 and Week 4. 
Two bottles will be dispensed on Week 8, and three bottles will be dispensed at Week 16, Week 
28, Week 40, Week 52, Week 64, Week 76, and Week 88. 
The amount of available unused drug will be assessed during the Week 100 visit, and if a subject 
needs an additional bottle dispensed to cover 1 week of a reduced dose, they should be provided 
with a new bottle. 
Subjects will be instructed to return all used/unused bottles at the next study visit (i.e. Weeks 4, 
8, etc or ET), when the designated study site staff will review the number of returned capsules to 
assess subject compliance. 
8.10. 
Randomization and Blinding 
This is an open label study in which all subjects receive active treatment (340 mg ADS-5102), 
therefore randomization is not necessary. 
9. 
ASSESSMENT OF EFFICACY 
Evaluations relating to efficacy to be performed during the study are described in Table 4. 
Table 4: 
Efficacy Assessments 
Assessment 
Study Visit 
Description 
MDS-UPDRS 
Screening 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52 
Week 64 
Week 76 
Week 88 
Week 100 (or ET) 
The MDS-UPDRS has 4 parts: Part I (non-motor 
experiences of daily living), Part II (motor experiences of 
daily living), Part III (motor examination), and Part IV 
(motor complications) 


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10.
ASSESSMENT OF SAFETY
10.1. 
Physical Assessments Relating to Safety 
Physical assessments relating to safety to be performed during the study are described in Table 5. 
Table 5: 
Physical Assessments Relating to Safety 
Assessment 
Study Visit 
Description 
Complete Physical 
Examination 
Screening 
Week 16 
Week 52  
Week 100 (or ET) 
Physical examination including: skin, head-
neck, eyes-ears-nose-throat, lungs-chest, 
heart, abdomen, extremities, neurological.  
Targeted Physical 
Examination 
Baseline/Day 1 (Week 0) 
Week 4 
Week 8 
Week 28 
Week 40 
Week 64 
Week 76 
Week 88 
Safety Follow Up Visit 
Physical examination including: skin, lungs-
chest, heart, abdomen, extremities.   
Weight and height 
Screening 
Week 4 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52  
Week 64 
Week 76 
Week 88 
Weel 100 (or ET) 
Height will be measured at screening only 
and recorded in centimeters. Weight will be 
recorded in kilograms.  Subjects may be 
weighed in their undergarments, or in light 
clothing (no jackets or shoes).  Measuring 
weight must be done consistently during the 
study, using the same set of weighing scales 
when possible. 


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Table 5: 
Physical Assessments Relating to Safety (Continued) 
Assessment 
Study Visit 
Description 
Vital Signs 
Screening 
Baseline/Day 1 (Week 0) 
Week 4 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52  
Week 64 
Week 76 
Week 88 
Week 100 (or ET) 
Safety Follow Up Visit 
Systolic and diastolic blood pressures, heart 
rate, should be recorded after the subject 
has been seated quietly for at least 5 
minutes.   Body temperature will be 
obtained at screening, Day 1, and at the 
safety follow up visit. Blood pressure, 
respiratory rate and heart rate will be 
measured once each day assessed.   
During screening only, after the seated 
blood pressure has been obtained, the 
measurement will be repeated within 3 
minutes of the subject standing up. This 
procedure may be repeated, if appropriate, 
following hydration.  If repeated, a total of 
two additional pairs of BP assessments 
(sitting/standing) should be obtained, and 
the results of the last attempt should be 
reported. 
ECG (12-lead) 
Screening 
A 12-lead ECG (25 or 50 mm/sec) with a 
10-second rhythm strip will be recorded 
after the subject has rested supine or semi-
recumbent for at least 5 minutes.  ECGs are 
only necessary for Group 2 and Group 3 
study subjects at the Screening Visit.  
10.2. 
Clinical Laboratory Tests 
The clinical laboratory and other tests relating to safety to be performed during the study are 
described in Table 6. 
Table 6: 
Clinical Laboratory and Other Assessments 
Assessment 
Study Visit 
Description 
Hematology 
Screening 
Week 4 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52  
Week 64 
Week 76 
Week 88 
Week 100 (or ET) 
Blood samples (5 mL) will be collected.  Hematology 
parameters include: hemoglobin, hematocrit, mean 
corpuscular volume (MCV), mean corpuscular 
hemoglobin concentration (MCHC), red blood cell 
(RBC) count, white blood cell (WBC) count, WBC 
differential count, platelet count.  Hematology will be 
conducted by a central laboratory.   


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Table 6: 
Clinical Laboratory and Other Assessments (Continued) 
Assessment 
Study Visit 
Description 
Serum Chemistry  Screening 
Week 4 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52 
Week 64 
Week 76 
Week 88 
Week 100 (or ET) 
Blood samples (10 mL) will be collected (fasting is not 
required).  Routine serum chemistry parameters include 
alkaline phosphatase, albumin, blood urea nitrogen, 
calcium, carbon dioxide, chloride, creatininea, γ-
glutamyltransferase, glucose, inorganic phosphorus, 
potassium, alanine aminotransferase, lactate 
dehydrogenase, aspartate aminotransferase, sodium, 
total bilirubin, and total protein. 
Urinalysis 
Screening 
Week 4 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52 
Week 64 
Week 76 
Week 88 
Week 100 (or ET) 
UA will be performed locally using sponsor-supplied 
dipsticks, including specific gravity, pH, protein, 
ketones, glucose, nitrite, leukocytes, blood, 
urobilinogen, and bilirubin. If nitrite, blood, or protein 
tests are positive, a microscopic examination will be 
performed at the central laboratory.   
Serum pregnancy 
test (if 
applicable) 
Screening 
Safety Follow Up Visit 
(or ET) 
Serum pregnancy test will be performed for all female 
subjects of childbearing potential. 
Urine pregnancy 
test (if 
applicable) 
Baseline/Day1/Week 0 
Week 4 
Week 8 
Week 16 
Week 28 
Week 40 
Week 52 
Week 64 
Week 76 
Week 88 
Week 100 
Urine pregnancy test will be performed for all female 
subjects of childbearing potential. 
a Estimated glomerular filtration rate (eGFR) will be calculated by the central laboratory using MDRD 


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10.3. 
Demographic/Medical History 
A complete medical history (including PD history, mental health history, alcohol and drug use) 
will be obtained from the subject at the Screening Visit and recorded on the appropriate CRF.  
The medical history and other enrollment criteria will be reviewed and updated at the 
Baseline/Day 1 (Week 0) visit to determine continued eligibility for the study.   
10.4. 
Total Blood Volume Collected 
The estimated total blood volume collected throughout the study (for clinical laboratory tests) is 
expected to be approximately 165 mL for safety serum chemistry and hematology laboratory 
evaluations. 
11. 
EVALUATIONS BY VISIT 
A schedule of study evaluations is provided in Appendix A. 
11.1. 
Screening/Day -14 to -1 
During screening, potential subjects for the study will be fully informed about the nature of the 
study and possible adverse events (AEs).  Subjects who wish to participate in the study must read 
and understand the consent form and sign the document after the investigator has answered all 
questions to the candidate’s satisfaction.  Further procedures can begin only after the consent 
form has been signed.  
The Screening Visit must be conducted within 14 days prior to Day 1.   
NOTE: If a subject from a previous Adamas LID study wishes to enroll directly in ADS-AMT-
PD302 without a time gap, they should have their Screening Visit (Visit 1), including consent, 
for the ADS-AMT-PD302 study occur during the final efficacy study visit for the previous 
Adamas efficacy study, as outlined in the previous protocol.  
Per the Schedule of Events in Appendix A, if a subject is directly rolling over to the open label 
extension, a number of common assessments between the Adamas efficacy study visit and the 
Screening Visit (ADS-AMT-PD302) only need to be performed once.  
Potential study subjects will be evaluated for entry into the study according to the stated 
inclusion and exclusion criteria.  Individuals who are identified during this screening as not 
eligible for study enrollment need not complete all screening procedures.  The reason for 
ineligible status is to be documented. 
The following procedures will be performed to establish each subject’s qualifications for 
enrollment into the study: 
 The subject is fully informed about the study and gives written informed consent to 
participate in the study; 
 Confirm commitment of caregiver and/or study partner, if applicable; 
 Review inclusion/exclusion criteria and evaluate initial subject eligibility; 
 Record demographic information; 


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 Vital signs (standing blood pressure), assessment of orthostatic hypotension should 
occur at screening visit and apply only to ADS-AMT-PD302; 
 Medical history with an emphasis on the subject’s Parkinson’s disease and movement 
disorders, including dyskinesia and past treatments for these conditions; alcohol and 
drug use, other neurological diseases, psychiatric disorders including Major 
Depressive Disorder or symptom (e.g., hallucinations, agitation, paranoia), history of 
seizures, stroke or TIA; history of MI or CHF; and history of cancer; 
 Record medications currently taken or taken in the previous 30 days for Parkinson’s 
Disease, including dyskinesia and medications currently taken for any condition; 
 ECG (12-lead); NOTE: Only for Group 2 or Group 3 subjects;  
 Mini-Mental Status Examination (MMSE). 
Assessments that could be shared between the previous Adamas LID efficacy study & Screening 
(ADS-AMT-PD302):  
 MDS-UPDRS; 
 Complete physical examination; 
 Obtain subject weight in kilograms and height in centimeters; 
 Vital signs (sitting blood pressure, respiratory rate, heart rate, temperature); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Blood sample for serum pregnancy test in female subjects of childbearing potential. 
11.2. 
Treatment Period 
The treatment period will be a maximum of 101 weeks. 
11.3. 
Baseline/Day 1/Week 0 
NOTE: If a subject from a previous Adamas LID efficacy study wishes to enroll directly in 
ADS-AMT-PD302 without a time gap, they should have their Baseline Visit (Visit 2) for the 
ADS-AMT-PD302 study occur on the same day as the final study visit (not including any safety 
follow up visit) of the previous Adamas efficacy study visit, as outlined in the previous protocol. 
The following procedures will be performed: 
 Review inclusion/exclusion criteria and determine subject eligibility; 
 Medical history with an emphasis on the subject’s Parkinson’s disease and movement 
disorders, including dyskinesia and past treatments for these conditions; other 
neurological diseases, psychiatric disorders including Major Depressive Disorder or 
symptom (e.g., hallucinations, agitation, paranoia), history of seizures, stroke or TIA; 
history of MI or CHF; and history of cancer;  


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 Record medications currently taken for any condition or discontinued since 
Screening; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 Dispense study medication (4-week supply, 1 bottle of 60 capsules); 
 Targeted physical examination; 
 Vital signs (blood pressure, respiratory rate, heart rate and temperature). 
11.4. 
Week 4 +/- 1 Day (End of Week 4)  
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted Physical Exam; 
 Obtain subject weight in kilogram; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis;  
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (4-week supply, 1 bottle of 60 capsules). 
11.5. 
Week 8 +/- 1 Day (End of Week 8) 
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted Physical Exam; 
 Obtain subject weight in kilogram; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis;  


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 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (8-week supply, 2 bottles of 60 capsules). 
11.6. 
Week 16 +/- 3 days (End of Week 16) 
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Complete physical examination; 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 
11.7. 
Week 28 +/- 3 days (End of Week 28) 
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted physical examination; 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 


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 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 
11.8. 
Week 40 +/- 3 days (End of Week 40) 
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted physical examination; 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 
11.9. 
Week 52 +/- 3 Days (End of Week 52)  
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Complete physical examination including body weight (recorded in kilograms); 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 


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11.10. 
Week 64 +/- 3 Days (End of Week 64)  
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted physical examination; 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 
11.11. 
Week 76 +/- 3 Days (End of Week 76)  
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted physical examination; 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 
 
 


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11.12. 
Week 88 +/- 3 Days (End of Week 88)  
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted physical examination; 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication (12-week supply, 3 bottles of 60 capsules). 
11.13. 
Week 100 +/- 3 Days (End of Week 100)  
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Complete physical examination including body weight (recorded in kilograms); 
 Obtain subject weight in kilograms; 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 Urine pregnancy test will be performed for all female subjects of childbearing 
potential; 
 MDS-UPDRS; 
 Collect unused study drug and bottles and evaluate compliance; 
 Dispense study medication, if necessary. 


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11.14. 
Early Termination Visit 
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Complete physical examination including body weight (recorded in kilograms); 
 Vital signs (blood pressure, respiratory rate, heart rate); 
 Blood sample for central laboratory analysis including hematology, serum chemistry 
and eGFR; 
 Urinalysis; 
 MDS-UPDRS; 
 Blood sample for serum pregnancy test in female subjects of childbearing potential; 
 Collect unused study drug and bottles and evaluate compliance. 
11.15. 
Safety Follow Up Visit 
The following procedures will be performed: 
 Assess and record concomitant medications; 
 Assess and record Adverse Events; 
 Targeted Physical Exam; 
 Vital signs (temperature, blood pressure, respiratory rate, heart rate); 
 Blood sample for serum pregnancy test in female subjects of childbearing potential. 
12. 
ADVERSE AND SERIOUS ADVERSE EVENTS 
During the study, the Investigator or study site personnel will be responsible for querying and 
recording adverse events (AEs) and serious adverse events (SAEs), as detailed in this section of 
the protocol.  In this study AEs and SAEs will be reported from the time of study drug 
administration until the last study visit or death, whichever occurs first. 
12.1. 
Definition of Adverse Events 
An adverse event (AE) is any untoward medical occurrence that occurs in conjunction with the 
use of a medicinal product in humans, whether or not considered to have a causal relationship to 
the medicinal product.  An AE can, therefore, be any unfavorable or unintended sign (including a 
clinically significant abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal product, whether or not considered related to the medicinal product. 


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12.1.1. 
Adverse Event (AE) 
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the first date of study drug administration is usually considered to be pre-existing, and should not 
be documented in the CRF as an AE. 
Any AE (i.e., a new event or an exacerbation of a pre-existing condition) with an onset date after 
study drug administration up to and including the designated follow-up safety visit should be 
recorded as an AE on the CRF.  All AEs must be recorded on the AE CRF regardless of the 
severity or relationship to study medication.  It is important that Investigators also report all AEs 
that result in permanent discontinuation of the study drug being studied, whether serious or non-
serious. 
An AE does include: 
 an exacerbation of a pre-existing illness; 
 an increase in frequency or intensity of a pre-existing episodic event or condition; 
 a condition detected or diagnosed after study drug administration even though it may 
have been present prior to the start of the study; 
 persistent disease or symptoms present at baseline which worsen following the start of 
the study. 
An AE does not include: 
 medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion) 
Note:  in this case, the condition that led to the procedure is an AE; 
 pre-existing diseases or conditions present or detected prior to start of study drug 
administration, which do not worsen; 
 the disease or disorder being studied or a sign or symptom associated with that disease 
(i.e., signs or symptoms associated with lack of efficacy will generally be considered to 
reflect underlying disease, rather than AEs); 
 situations where an untoward medical occurrence has not occurred (e.g., hospitalization 
for elective surgery, social, and/or convenience admissions); 
 overdose of either study drug or concomitant medication without any signs or symptoms. 
(Dosing details will be recorded on the appropriate eCRF(s)). 
The Investigator should attempt to establish a diagnosis of the event based on the signs, 
symptoms and/or other clinical information.  In such cases, the diagnosis should be documented 
as the AE (and SAE if serious) and not the individual signs/symptoms. 
All AEs must be fully and completely documented on the AE page of the CRF and in the 
subject’s medical notes.  The following attributes must be assigned: description of AE, dates and 
times of onset and resolution (or whether ongoing), severity (Section 12.1.2), causality to study 
drug (Section 12.2), whether an SAE or not (Section 12.1.4), and action taken (i.e., no action 
taken; study medication interrupted; study medication discontinued; other).   


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In the event that a subject is withdrawn from the study because of an AE, it must be recorded on 
the CRF.  The subject should be followed and treated by the investigator until the AE has 
resolved or a new chronic baseline has been established. 
The investigator must report all directly observed AEs and all spontaneously reported AEs.  At 
each visit the investigator will ask the subject a nonspecific question (e.g., “Have you noticed 
anything different since your last visit?”) to assess whether any AEs have occurred since the last 
report or visit.  AEs will be identified and documented on the AE page of the CRF in appropriate 
medical terminology. 
12.1.2. 
Severity of Adverse Events 
The severity of each AE/SAE should be classified into one of three defined categories as 
follows: 
 Mild:  the AE is easily tolerated by the subject, causes minimal discomfort, and does not 
interfere in a significant manner with the subject’s normal functioning level or activities;  
 Moderate:  the AE is sufficiently uncomfortable to interfere with normal everyday 
activities, but is not hazardous to health;  
 Severe:  the AE produces significant impairment of functioning or incapacitation and is a 
definite hazard to the subject’s health. 
These three categories are based on the investigator’s clinical judgment, which in turn depends 
on consideration of various factors such as the subject’s reports, the physician’s observations, 
and the physician’s prior experience.  The severity of the AE should be recorded in the 
appropriate section on the AE page of the CRF.   
The evaluation of severity must be distinguished from the evaluation of “seriousness” (see 
Section 12.1.4).  A severe event might not meet the criteria for seriousness and a serious event 
might be evaluated as mild or moderate.  For example, a subject might have a severe headache 
that does not require hospitalization and is consequently not serious; or a subject might have a 
mild myocardial infarction that requires hospitalization and is therefore serious. 
12.1.3. 
Follow-up of Adverse Events and Serious Adverse Events 
All AEs and SAEs must be followed until resolution (or return to baseline status), or until the 
condition stabilizes or is otherwise explained, or until the subject dies or is lost to follow-up.  
The Investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as may be indicated to elucidate as completely as practical the nature and/or 
causality of the AE/SAE.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
The sponsor may request that the Investigator perform or arrange for the conduct of 
supplemental measurements and/or evaluations.  If a subject dies during participation in the 
study or during a recognized follow-up period, the Investigator should provide the Sponsor with 
a copy of any post-mortem findings, including histopathology. 
 
 


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12.1.4. 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is any AE occurring at any dose that: 
 results in death; 
 is life-threatening (subject is at immediate risk of death at the time of the event); 
 requires inpatient hospitalization or results in prolongation of existing hospitalization; 
 results in persistent or significant disability/incapacity; 
 is a congenital anomaly/birth defect in the offspring of a subject who received study drug; 
 is a significant or important medical event, i.e., an event that, based upon appropriate 
medical judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the above mentioned criteria (examples of such events are 
intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse). 
When a causality assessment is provided for an SAE, it is important to include a rationale for the 
assessment, so that a better understanding of the reported event can be compiled.  The rationale 
should be accompanied by all available supporting evidence, including relevant laboratory tests, 
histopathology evaluations, and the results of other diagnostic procedures.  The Investigator’s 
rationale with supporting evidence is valuable when the Sponsor performs a cumulative analysis 
of similar events. 
A Suspected Unexpected Serious Adverse Reaction (SUSAR) is any serious adverse event that is 
considered related to the investigational product, and that is also unexpected.  SUSARs qualify 
for expedited reporting to applicable Health Authorities, Eudravigilance, and IRB/REB/IECs. 
12.1.4.1. Clarification of SAE Definition 
“Occurring at any dose” does not imply that the subject is receiving study drug at the time of the 
event.  Dosing may have been interrupted temporarily prior to the onset of the SAE, but may 
have contributed to the event. 
“Life-threatening” means that the subject was at immediate risk of death from the event as it 
occurred.  This does not include an event that might have led to death, had it occurred with 
greater severity. 
Complications that occur during hospitalizations are AEs.  If a complication prolongs 
hospitalization, it is an SAE. 
“Inpatient hospitalization” does not imply that the subject must have had an overnight stay in the 
hospital.  If the subject was admitted to the hospital for less than a day for the purpose of 
treatment or observation, the definition of “Inpatient hospitalization” is met.  Brief treatment in 
an outpatient clinic or Emergency department does not constitute “inpatient hospitalization.” 
The term “severe” is often used to describe the intensity (severity) of a specific event (see 
Section 12.1.2); the event itself, however, may be of relatively minor medical significance (such 
as severe headache).  This is not the same as “serious,” which is based on event outcome or 


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action criteria usually associated with events that pose a threat to a subject’s life or functioning.  
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. 
An SAE is considered “unexpected” if it is not listed in the Investigator’s Brochure or is not 
listed at the specificity or severity that has been observed. It is the responsibility of the Sponsor 
to make this determination. 
12.1.4.2. Clarification of Subject Deaths 
All subject deaths (regardless of relationship to study drug) should be reported within 24 hours 
for subjects while on study protocol up to and including the safety follow-up visit.  This should 
be recorded on the subject CRF and the SAE form.  
Death is an outcome of an AE and not an AE in itself.  All reports of subject death should 
include an AE term for the cause of the death unless the protocol provides other specific 
instructions (e.g., mortality related to underlying disease is an efficacy endpoint).  For all reports 
in which an AE term is not provided (other than “Death”), follow-up for the cause of death will 
be required.  Only in the rare occurrence that no verbatim description of an AE can be obtained 
from the investigative site, then “Death – Unknown Cause” will be used as the event term. 
12.2. 
Relationship to Study Drug 
The relationship or association of the AE/SAE to study drug will be characterized as “related” 
or “not related”.  An AE/SAE will be considered to be not related to the use of the study drug 
if any of the following criteria are met: 
 An unreasonable temporal relationship between administration of the product and the 
onset on the AE (e.g., the event occurred either before, or too long after administration of 
the product for it to be considered product-related); 
 A causal relationship between the product and the AE is biologically implausible  
(e.g., death as a passenger in an automobile accident); 
 A clearly more likely alternative explanation for the AE is present (e.g., typical adverse 
reaction to a concomitant drug). 
Adverse events will be considered “related” to the use of the study drug if none of the  
“not related” criteria are met. 
The Investigator will use clinical judgment to determine the relationship of the AE/SAE to study 
drug.  An AE/SAE may be related to the study drug, other concomitant medications, intercurrent 
illness, a procedure performed in the course of the study, or another reason.  Among the potential 
etiologies, the investigator should make a determination based on the most likely causal 
relationship.  Alternative causes, such as the natural history of any underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the study 
drug should be considered.  The Investigator will also take into account the Investigator’s 
Brochure (or Prescribing Information, if applicable) in the causality assessment.   
There may be situations when an SAE has occurred and the Investigator has minimal information 
to include in the initial report to the Sponsor.  However, it is very important that the Investigator 
always makes an assessment of causality prior to transmission of the SAE report to the Sponsor, 
as the causality assessment is one of the criteria used when determining regulatory reporting 


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requirements.  The Investigator may change the causality assessment in light of follow-up 
information, by amending the SAE report accordingly.   
12.3. 
Recording Adverse Events 
Out of range clinical laboratory findings (e.g., clinical chemistry, hematology) or findings on 
other assessments (e.g., electrocardiogram, X rays, vital signs) per se are not reported as AEs.  
However, if the out of range finding that is deemed clinically significant or is associated with 
signs and/or symptoms must be recorded as an AE (and additionally as an SAE if it meets the 
criteria of being serious; see Section 12.1.4), as described above. 
The Investigator should exercise medical and scientific judgment in deciding whether an out of 
range clinical laboratory finding or finding on other assessment is clinically significant.  Usually, 
the abnormality should be associated with a clinically evident sign or symptom, or be likely to 
result in an evident sign or symptom in the near term, in order to be considered clinically 
significant.  A clinically significant laboratory abnormality in the absence of clinical symptoms 
may jeopardize the subject and may require intervention to prevent immediate consequences.  
For example, a markedly low serum glucose concentration may not be accompanied by coma or 
convulsions, yet be of a magnitude to require glucose administration to prevent such sequelae. 
12.4. 
Reporting Adverse Events 
The Sponsor has requirements for reporting SAEs to both the local regulatory authority, other 
regulatory agencies, and Eudravigilance about the safety of a drug under clinical investigation.  
The Sponsor or designee must be notified within 24 hours once the Investigator determines that 
an AE meets the protocol definition of an SAE.  The procedures for reporting serious adverse 
events are as follows: 
 Complete the “Serious Adverse Event Report”; 
 Contact the pharmacovigilance staff member identified on the SAE Report Form and 
report the Serious Adverse Event within 24 hours of the Investigator’s knowledge of the 
event; 
 For fatal or life-threatening events, also fax copies of hospital case reports, autopsy 
reports, and other documents when requested and applicable. 
The Sponsor or designee may request additional information from the Investigator to ensure the 
timely completion of accurate safety reports. 
Any fatal or life-threatening events should also be reported immediately by telephone to the 
Sponsor’s designee. 
The Investigator, or responsible person according to local requirements, must comply with the 
applicable local regulatory requirements concerning the reporting of SAEs to all applicable 
regulatory authorities and IRB/REB/IECs. 
12.4.1. 
Post-Study Reporting Requirements 
All SAEs, regardless of cause or relationship, which occur from the time of study drug 
administration up to and including the safety follow-up visit, must be reported to the Sponsor or 
designee.  If the Investigator learns at any time after a subject has been discharged from the study 


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of an untoward medical occurrence that would have qualified as an SAE during the study, and 
such event is reasonably related to previous study drug exposure, the Investigator should 
promptly notify the Sponsor or designee. 
12.4.2. 
Investigator Reporting Responsibility 
When an investigative site receives an initial or follow-up notification of an SAE or other safety 
information (e.g., revised Investigator’s Brochure) from the Sponsor, the responsible person, 
according to local requirements, must submit this information to the local IRB/REB/IEC and 
keep a copy in their files. 
12.4.3. 
Pregnancy 
A pregnancy is not an AE.  If a subject becomes pregnant while enrolled in the study following 
administration of study drug, the Sponsor or designee must be notified within 24 hours of the 
Investigator learning of the pregnancy.  Administration of study drug will be discontinued 
immediately and the subject will be followed through the outcome of the pregnancy.  The 
Investigator will be required to complete a Pregnancy Information Form and fax the information 
to the Sponsor or designee. 
 
 


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13. 
STATISTICS 
13.1. 
Statistical Analyses 
13.1.1. 
Sample Size Determination 
It is expected that a study size of up to 250 subjects and duration of treatment up to 101 weeks 
will support the goal of 100 subjects completing one year of treatment.  
13.1.2. 
Analysis Populations 
13.1.2.1. Efficacy Populations 
The efficacy analysis population will include all enrolled subjects who receive at least one dose 
of study drug and provide at least one post-enrollment MDS-UPDRS assessment.  
MDS-UPDRS data will be summarized across study visits and include all available data.  The 
baseline MDS-UPDRS scores will be from each subject’s Screening Visit.  
13.1.3. 
Handling of Missing Data 
Observed data will be summarized.  There will be no imputation of missing data.  
13.1.4. 
Safety and Tolerability 
The safety analysis population will include all enrolled subjects who receive at least one dose of 
study drug.  Safety data will be summarized from the time of first dose and include all available 
safety data.  No formal statistical testing will be done. 
All AE data will be listed and will be summarized by system organ class, preferred term, and 
analysis group, as well as for all analysis groups combined.  Quantitative safety variables (e.g., 
vital signs and clinical laboratory tests) will be summarized at each visit by analysis group, as 
well as for all analysis groups combined. 
13.1.5. 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics (age at screening, gender, weight, height, BMI, race, 
ethnicity, medical history, physical examination) will be listed for individual subjects and will be 
summarized by analysis group, as well as for all analysis groups combined.  Demographic data 
and key baseline characteristics will be summarized for the Efficacy and Safety populations. 
13.1.6. 
Prior and Concomitant Medications 
All prior and concomitant medications will be assigned a generic name and a drug class based on 
the World Health Organization (WHO) Dictionary.  Prior and concomitant medications will be 
listed and summarized by analysis group, as well as for all analysis groups combined. 
13.1.7. 
Completion of the Study and Withdrawals 
Withdrawals and the reason for withdrawal will be tabulated.  


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13.1.8. 
Protocol Deviations 
Significant protocol deviations will be listed and categorized (for example, deviations related to 
entry criteria, dosing, prohibited concomitant medications, other). 
 
 


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14. 
STUDY CONDUCT 
14.1. 
Study Monitoring 
Sponsor representatives and regulatory authority inspectors are responsible for contacting and 
visiting the Investigator for the purpose of inspecting the facilities and, upon request, inspecting 
the various records of the study (e.g., CRFs and other pertinent data), provided that subject 
confidentiality is respected. 
The study monitor is responsible for inspecting the CRFs at regular intervals throughout the 
study to verify the following:  adherence to the protocol; completeness, accuracy, and 
consistency of the data; and adherence to local regulations on the conduct of clinical research.  
The monitor should have access to subject medical records and other study-related records 
needed to verify the entries on the CRFs.  The investigator must agree to cooperate with the 
monitor to ensure that any problems detected in the course of these monitoring visits are 
resolved. 
In accordance with International Committee on Harmonisation (ICH) Good Clinical Practice 
(GCP) and the Sponsor audit plans, this study may be selected for an audit.  Inspection of site 
facilities (e.g., pharmacy, drug storage areas, laboratories, etc.) and review of study-related 
records may occur in order to evaluate the trial conduct and compliance with the protocol, ICH 
GCP, and applicable regulatory requirements.  The investigator is to notify the Sponsor 
immediately if contacted by a regulatory agency for audit of documents related to this study. 
14.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an Independent Ethics 
Committee or an Institutional Review Board may visit the site to perform audits or inspections, 
including source data verification.  The purpose of a the Sponsor audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analyzed, and 
accurately reported according to the protocol, Good Clinical Practice guidelines of the 
International Conference on Harmonization, and any applicable regulatory requirements.  The 
investigator should contact the Sponsor immediately if contacted by a regulatory agency about 
an inspection. 
14.3. 
Subject Confidentiality 
The Investigator must ensure that each subject’s anonymity is maintained. Subjects will be 
identified by a unique Subject Identification Number.  Study related documents should be kept in 
strict confidence by the Investigator in compliance with applicable regulations and ICH GCP 
Guidelines.  The Investigator and Institution must permit authorized representatives of regulatory 
agencies, and the IRB/REB/IEC direct access to review the subject’s original medical records for 
verification of study-related procedures and data.  Direct access includes examining, analyzing, 
verifying, and reproducing any records and reports that are needed for the evaluation of the 
study.  The Investigator is obligated to inform the subject in the ICF that the above named 
representatives may review study-related records from subjects. 


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14.4. 
Case Report Forms 
Electronic Case Report Forms (CRFs) will be completed for each enrolled subject.  The 
participants of the study will not be identified by name on any study documents to be collected 
by the Sponsor or designee.  The PI is required to review and sign-off on all eCRFs.  The sign off 
is done by an electronic signature within the EDC system.  Also, a CD of all site specific subject 
data (including PI approval, audit history, and discrepancies) will be sent to each site that has 
subject data in the system for archival purposes.   
14.5. 
Retention and Availability of Records 
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor, and Regulatory Agency inspectors upon request.  A file for each 
subject must be maintained that includes the signed ICF and the Investigator’s copies of all 
source documentation related to that subject.  The Investigator must ensure the reliability and 
availability of source documents from which the information on the CRF was derived. 
Investigators are required to maintain all study documentation, including copies of CRFs, 
Informed Consent Forms, and adequate records for the receipt and disposition of all study 
medications, for a period of 2 years following the FDA or other regulatory approval date of the 
drug, or until 2 years after the drug investigational program is discontinued, unless a longer 
period is required by applicable law or regulation.  The Investigator must not discard any records 
unless given authorization by the Sponsor. 
Subject identity information will be maintained for 15 years unless applicable law or regulation 
requires a longer period. 


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
the Sponsor may conduct a quality assurance audit.  Please see Section 14.2 for more details 
regarding the audit process. 


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16. 
ETHICS 
16.1. 
Ethics Review 
The Principal Investigator must obtain IRB/REB/IEC approval for the investigation.  Initial 
IRB/REB/IEC approval, and all materials approved by the IRB for this study including the 
patient consent form and recruitment materials must be maintained by the Investigator and made 
available for inspection. 
This study will be conducted in accordance with the US Code of Federal Regulations governing 
the protection of human subjects (21 CFR 50), Institutional Review Boards (IRB), Research 
Ethics Boards (REB) or Independent Ethics Committees (IEC) (21 CFR 56), the obligations of 
clinical investigators (21 CFR 312), and ICH GCP guidelines. 
The Sponsor expects the Principal Investigator to comply with local IRB/REB/IEC requirements.  
The Investigator will also comply with current standards of GCP, particularly in reference to the 
safety and rights of the subjects.  Investigators are encouraged to discuss any ethical issues that 
arise prior to or during the conduct of the study with the Sponsor. 
The Principal Investigator at the site is responsible for obtaining IRB/REB/IEC approval for the 
final protocol, Sponsor-approved ICF, and any advertisements to recruit subjects.  Written 
approval of these documents must be obtained from the IRB/REB/IEC before any subject is 
enrolled at a site. 
The Principal Investigator is also responsible for the following interactions with the 
IRB/REB/IEC: 
 Obtaining IRB/REB/IEC approval for any protocol amendments and ICF revisions before 
implementing the changes; 
 Providing the IRB/REB/IEC with any required information before or during the study; 
 Submitting progress reports to the IRB/REB/IEC, as required, during the conduct of the 
study; requesting re-review and approval of the study, as needed; providing copies of all 
IRB/REB/IEC re-approvals and relevant communication to the Sponsor; 
 Notifying the IRB/REB/IEC of all serious and unexpected adverse events related to the 
study medication reported by the Sponsor, as required. 
16.2. 
Ethical Conduct of the Study 
This study will be conducted in compliance with GCP according to ICH guidelines (Topic E6: 
Guideline for Good Clinical Practice), the US Code of Federal Regulations (21 CFR), and local 
ethical and legal requirements that are consistent with the most current version of the Declaration 
of Helsinki. 
16.3. 
Written Informed Consent 
The Sponsor must review the draft ICF prior to submission to the IRB/REB/IEC for approval.  
An IRB/REB/IEC-approved copy of the ICF will be forwarded to the Sponsor or designee. 


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Written informed consent will be obtained from all study subjects prior to any tests or 
evaluations.  The contents and process of obtaining informed consent will be in accordance with 
all applicable regulatory requirements.   
The ICF documents the study-specific information the Investigator provides to the subject and 
the subject’s agreement to participate.  Among other things, the Investigator or designee will 
fully explain in layman’s terms the nature of the study, along with the aims, methods, potential 
risks, and any discomfort that participation may entail, as well as insurance and other procedures 
for compensation in case of injury.  It will be explained that the study is for research purposes 
only and may not provide any therapeutic benefit to the individual.  The Investigator must also 
explain to the volunteers that they are completely free to refuse to enter the study or to withdraw 
from it at any time without prejudice.  Each subject will acknowledge receipt of this information 
by giving written informed consent for participation in the study.   
Each subject must sign and date the ICF before any study-related procedures are performed.  
When a protocol amendment (see Section 16.4) substantially alters the study design or the 
potential risks or burden to subjects, the ICF will be amended and approved by the 
IRB/REB/IEC, and all active subjects will again provide informed consent.  The original and any 
amended signed and dated ICF(s) must be retained in the subject’s file at the study site and a 
copy must be given to the subject. 
The Informed Consent must comply with all applicable US Code of Federal Regulations  
(21 CFR 50), and ICH Good Clinical Practice guidelines.  It should also include any additional 
information required by local laws relating to institutional review.  A statement that subject 
medical records must be available for investigations into SAEs must be included in the ICF.  It 
should also include any additional information required by local laws relating to institutional 
review. 
16.4. 
Changes in the Conduct of the Study or Planned Analyses 
Only the Sponsor may modify the protocol.  Any change in study conduct considered necessary 
by the investigator will be made only after consultation with the Sponsor, who will then issue a 
formal protocol amendment to implement the change.  The only exception is when the 
Investigator considers that a subject’s safety is compromised without immediate action.  The 
Investigator should inform the Sponsor and the IRB/REB/IEC within one working day after the 
emergency occurred.  With the exception of minor administrative or typographical changes, all 
amendments must be reviewed and approved by the IRB/REB/IEC in accordance with 
IRB/REB/IEC requirements.  Amendments that have an impact on subject risk or the study 
objectives, or require revision of the ICF, must receive approval from the IRB/REB/IEC prior to 
their implementation.  The Investigator must send a copy of the approval letter for protocol 
amendments and changes to the ICF from the IRB/REB/IEC to the Sponsor. 
16.5. 
Emergency Contact with Investigator 
Suitable arrangements will be made for subjects to make contact with the Principal Investigator 
or a medically qualified Sub-Investigator in the event of an emergency during the study. 


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17. 
INFORMATION DISCLOSURE AND INVENTIONS 
17.1. 
Ownership 
All information provided by Adamas Pharmaceuticals, Inc. and all data and information 
generated by the site as part of the study (other than a subject’s medical records) are the sole 
property of Adamas Pharmaceuticals, Inc. 
All rights, title and interests in any inventions, know-how or other intellectual or industrial 
property rights, which are conceived or reduced to practice by site staff during the course of or as 
a result of the study are the sole property of Adamas Pharmaceuticals, Inc. and are hereby 
assigned to Adamas Pharmaceuticals, Inc. 
If a written contract for the conduct of the study is executed between Adamas Pharmaceuticals, 
Inc. and a study site and includes ownership provisions that are inconsistent with this section of 
the protocol that contract’s ownership provisions shall apply rather than this statement. 
17.2. 
Confidentiality 
All information provided by Adamas Pharmaceuticals, Inc. and all data and information 
generated by the site as part of the study, other than a subject’s medical records, will be kept 
confidential by the Investigator and other site staff.  The Investigator or other site personnel will 
not use this information and data for any purpose other than conducting the study.  These 
restrictions do not apply to: 
 Information that becomes publicly available through no fault of the Investigator or 
site staff; 
 Information that it is necessary to disclose in confidence to an IRB/REB/IEC solely 
for the evaluation of the study; 
 Information that it is necessary to disclose in order to provide appropriate medical 
care to a study subject; 
 Study results that may be published as described in Section 18.  
If a written contract for the conduct of the study, which includes confidentiality provisions 
inconsistent with this statement is executed, that contract’s confidentiality provisions shall apply 
rather than this statement. 
 


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18. 
PUBLICATION POLICY 
Adamas intends to work with its investigators to rapidly publish the results of this study.  No 
publication of the results shall take place without Adamas Pharmaceuticals, Inc.’s express 
consent.  Prior to submitting for any publication, presentation, use for instructional purposes or 
otherwise disclosing the study results generated by the site (collectively, a “Publication”), the 
Investigator shall provide Adamas Pharmaceuticals, Inc. with a copy of the proposed Publication 
and allow Adamas Pharmaceuticals, Inc. a period of at least thirty (30) days [or for abstracts, at 
least five (5) working days] to review the proposed Publication.  Proposed publications shall not 
include Adamas Pharmaceuticals, Inc.’s confidential information.  
At Adamas Pharmaceuticals, Inc.’s request, the submission or other disclosure of a proposed 
Publication will be delayed a sufficient time to allow Adamas Pharmaceuticals, Inc. to seek 
patent or similar protection of any inventions, know how or other intellectual or industrial 
property rights disclosed in the proposed Publication. 
If a written contract for the conduct of the study is executed, which includes publication 
provisions inconsistent with this statement that contract’s publication provisions shall apply 
rather than this statement. 


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19. 
LIST OF REFERENCES 
Aoki F, Sitar D. Clinical pharmacokinetics of amantadine hydrochloride. Clinical 
Pharmacokinetics. 1988; 14(1): 35-51. 
Colosimo C, Martinez-Martin P, Fabbrini G, Hauser R, Merello M, Miyasaki J, Poewe W, 
Sampaio C, Rascol O, Stebbins G, Schrag A, Goetz C. Task force report on scales to assess 
dyskinesia in Parkinson's disease: Critique and recommendations. Movement Disorder. 2010; 
25(9): 1131-1142. 
da Silva-Junior F, Braga-Neto P, Sueli Monti F, de Bruin V. Amantadine reduces the duration of 
levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. 
Parkinsonism & Related Disorders. 2005; 11(7): 449-452. 
Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management. J Neurol. 2008; 
255 Suppl 4: 32-41. 
Duvoisin, R.  Hyperkinetic reactions with L-DOPA.  In: Yahr, MD, ed.  Current Concepts in the 
Treatment of Parkinsonism.  New York, NY: Raven Press; 1974: 203-210. 
Encarnacion E, Hauser R. Levodopa-induced dyskinesias in Parkinson's disease: etiology, impact 
on quality of life, and treatments. European Neurology. 2008; 60(2): 57-66. 
Goetz C, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins G, Stern M, Tilley B, 
dodel r, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang A, Lees A, Leurgans S, LeWitt 
P, Nyenhuis D, Olanow C, Rascol O, Schrag A, Teresi J, val Hilten J, LaPelle N. Movement 
Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-
UPDRS): Process, format, and clinimetric testing plan. Movement Disorder. 2007; 22(1): 41-47. 
Hayden F, Gwaltney J, Van De Castle R, Adams K, Giordani B. Comparative toxicity of 
amantadine hydrochloride and rmantadine hydrochloride in healthy adults. Antimicrobial Agents 
Chemotherapy. 1981; 19(2): 226-233. 
Jackson G, Stanley E, Lee Muldoon R. Chemoprophylaxis of viral respiratory diseases. Bulletin 
Pan Am Health Org. 1967; 147: 595-603. 
Luginger E, Wenning G, Bosch S, Poewe W. Beneficial effects of amantadine on L-dopa-
induced dyskinesias in Parkinson's disease. Movement Disorders. 2000; 15(5): 873-878. 
Paci C, Thomas A, Onofrj M. Amantadine for dyskinesia in patients affected by severe 
Parkinson's disease. Neurological Sciences. 2001; 22(1): 75-76. 
Parkinson's Study Group. DATATOP: A Multicenter Controlled Clinical Trial in Early 
Parkinson's Disease. Arch Neurol. 1989; 46: 1052-1060. 
Parkinson's Study Group. Impact of Deprenyl and Tocopherol Treatment on Parkinson's Disease 
in DATATOP Patients Requiring Levodopa. Ann Neurol. 1996; 39:37-45. 
Sawada H, Oeda T, Kuno S, Nomoto M, Yamamoto K, Yamamoto M, Hisanaga K, Kawamura 
T. Amantadine for Dyskinesia in Parkinson's Disease: A Randomized Controlled Trial. PLOS 
ONE. 2010; 5(2):1-7. 


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Snow B, Macdonald L, Mcauley D, Wallis W. The effect of amantadine on levodopa-induced 
dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study. Clinical 
Neuropharmacology. 2000; 23(2): 82-85. 
Spencer T, Biederman J, Ciccone P, Madras B, Dougherty D, Bonab A, Livni E, Parasrampuira 
D, Fischman A. PET study examining pharmacokinetics, detection and likeability, and dopamine 
transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry. 
2006; 163(3): 387-395. 
Swanson T, Volkow N. Pharmacokinetic and pharmacodynamic properties of stimulants: 
implications for the design of new treatments for ADHD. Behav Brain Res. 2002; 130(1-2):  
73-78. 
Thanvi B, Lo N, Robinson T. Levodopa-induced dyskinesia in Parkinson's disease: clinical 
features, pathogenesis, prevention and treatment. PostGradMed Journal. 2007; 83:384-388. 
Thomas A, Iacono D, Luciano A, Armellino K, Di Iorio A, Onofrj M. Duration of amantadine 
benefit on dyskinesia of severe Parkinson's disease. Journal of Neurology, Neurosurgery and 
Psychiatry. 2004; 75(1): 141-143. 
Tyrrell D, Bynoe M, Hoorn B. Studies on the antiviral activity of 1-adamantanamine. British 
Journal of Experimental Pathology. 1964; 46(4): 370-375. 
Verhagen-Metman L, del Dotto P, Blanchet P, van den Munckhof P, Chase T.  Blockade of 
glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's 
disease. Amino Acids. 1998; 14(1-3): 75-82. 
Verhagen-Metman, Del Dotto P, Van Den Muckhof, Fang J, Mouradian M, Chase T. 
Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. 
Neurology. 1998; 50(5): 1323-1326. 
Verhagen-Metman, Del Dotto P, LePoole K, Konitsiotis S, Fang J, Chase T. Amantadine for 
levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol. 1999; 56(11): 1383-1386. 
Volkow N, Wang G, Fowler J, Gatley S, Logan J, Ding Y, Hitzemann R, Pappas N. Dopamine 
transporter occupancies in the human brain induced by therapeutic doses of oral 
methylphenidate. Am J Psychiatry. 1998; 155(10): 1325-1331. 
Wolf E, Seppi K, Katzenschlager R, Hochschorner G, Ransmayr G, Schwingenschuh P, Ott E, 
Kloiber I, Haubenberger D, Auff E, Poewe W. Long-term antidyskinetic efficacy of amantadine 
in Parkinson's disease. Movement Disorder. 2010; 25(10): 1357-1363.  


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20. 
APPENDICES 
 
 

SAP_001.pdf: 
Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
 
 
 
 
Adamas Pharmaceuticals, Inc. 
 
Integrated Summary of Safety for ADS-5102 
 
13Nov2015 
 
Final Statistical Analysis Plan 
 
Version 1.0 
 
 
 
Prepared by: 
 
PPD On Behalf of 
Adamas Pharmaceuticals, Inc. 
1900 Powell Street, Suite 750 
Emeryville, CA 94608 
 
 




Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
Table of Contents 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................... 5 
1 
INTRODUCTION............................................................................................................. 6 
2 
SUBMISSION OBJECTIVES ......................................................................................... 6 
2.1 
SAFETY SUMMARY ............................................................................................................. 6 
3 
STUDIES TO BE INCLUDED ........................................................................................ 6 
4 
PLANNED ANALYSES ................................................................................................... 7 
5 
ANALYSIS SETS.............................................................................................................. 8 
5.1 
SAFETY ............................................................................................................................... 8 
6 
GENERAL CONSIDERATIONS FOR STATISTICAL ANALYSES ........................ 8 
7 
DATA HANDLING CONVENTIONS ........................................................................... 9 
7.1 
DERIVED AND TRANSFORMED DATA .................................................................................. 9 
7.2 
TREATMENT ASSIGNMENTS AND ANALYSIS GROUPS ......................................................... 9 
7.3 
SUBJECT IDENTIFICATION ................................................................................................... 9 
7.4 
CODING DICTIONARIES ....................................................................................................... 9 
7.5 
SUBGROUP DEFINITIONS ................................................................................................... 10 
7.6 
DEFINITIONS OF BASELINE, ANALYSIS DAY 1, AND STUDY DAY 1 ................................... 10 
7.7 
CALCULATIONS USING DATES .......................................................................................... 11 
8 
SUMMARY POPULATION.......................................................................................... 11 
8.1 
DISPOSITION OF SUBJECTS ................................................................................................ 11 
8.2 
PROTOCOL DEVIATIONS ................................................................................................... 12 
8.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ........................................................... 12 
8.4 
MEDICAL HISTORY ........................................................................................................... 12 
8.5 
PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 13 
8.6 
PARKINSON’S DISEASE-RELATED BASELINE CHARACTERISTICS ...................................... 14 
8.7 
PHYSICAL EXAMINATION ................................................................................................. 14 


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Date Issued: 13Nov2015 
 
8.8 
TREATMENT COMPLIANCE ................................................................................................ 14 
9 
SAFETY ANALYSIS...................................................................................................... 14 
9.1 
STUDY DRUG EXPOSURE .................................................................................................. 14 
9.2 
ADVERSE EVENTS ............................................................................................................. 14 
9.2.1 
Incidence of Adverse Events ..................................................................................... 15 
9.2.2 
Causality of Adverse Events due to Study Drug ....................................................... 15 
9.2.3 
Intensity of Adverse Events ....................................................................................... 15 
9.2.4 
Serious Adverse Events ............................................................................................. 16 
9.2.5 
Adverse Events Leading to Treatment Discontinuation............................................ 16 
9.2.6 
Adverse Events Leading to Study Drug Dose Reduction .......................................... 16 
9.2.7 
Adverse Events Leading to Death ............................................................................. 16 
9.2.8 
Adverse Events of Special Interest ............................................................................ 16 
9.3 
CLINICAL LABORATORY EVALUATIONS ........................................................................... 17 
9.4 
VITAL SIGN MEASUREMENTS ........................................................................................... 18 
10 
REFERENCES ................................................................................................................ 19 
11 
APPENDICES ................................................................................................................. 20 
11.1 
STUDY DESIGN SCHEMATIC FOR ADS-PAR-AM201 .................................................... 21 
11.2 
STUDY DESIGN SCHEMATIC FOR ADS-AMT-PD301 .................................................... 22 
11.3 
STUDY DESIGN SCHEMATIC FOR ADS-AMT-PD302 .................................................... 23 
 
 


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Date Issued: 13Nov2015 
 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
CGI-C 
Clinician’s Global Impression of Change 
CI 
Confidence Interval 
CNS 
Central Nervous System 
CSR 
Clinical Study Report 
DBS 
Deep Brain Stimulation 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerular Filtration Rate 
EOS 
End–of–study 
ET 
Early Termination 
HEENT 
Head, eyes, ears, nose, and throat   
ICH 
International Conference on Harmonisation 
LS 
Least Square 
LID 
Levodopa–Induced Dyskinesia 
LOCF 
Last Observation Carried Forward 
IR 
Immediate Release 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MDS-UPDRS 
Movement Disorder Society–Unified Parkinson’s Disease Rating Scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
MITT 
Modified Intent–To–Treat 
MMSE 
Mini-Mental Status Examination 
PD 
Parkinson’s Disease 
PP 
Per Protocol 
PT 
Preferred Term 
RBC 
Red Blood Cell(s) 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SE  
Standard Error 
SOC 
System Organ Class 
UDysRS 
Unified Dyskinesia Rating Scale 
WBC 
White Blood Cell(s); leukocyte(s) 
WHO 
World Health Organization 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
1 Introduction 
This analysis plan describes the integrated summary of safety to support the regulatory submission 
of ADS-5102, an extended release formulation of amantadine HCl. The proposed nightly dose of 
ADS-5102 is 170 mg during the first week of dosing, and 340 mg thereafter, each dose to be taken 
once nightly at bedtime. Three studies (ADS-PAR-AM201, ADS-AMT-PD301, and ADS-AMT-
PD302) will be included. 
2 Submission Objectives 
2.1 
Safety Summary 
Safety and demographic data from: 
 ADS-PAR-AM201 
 ADS-AMT-PD301 
 ADS-AMT-PD302 
will be integrated for purposes of further characterizing the safety of ADS-5102. See Section 
5.1 for a detailed description of the Safety population.  
3 Studies to be included 
The following studies will form the basis of the submission: 
 ADS-PAR-AM201, a phase II/III, multi-center, randomized, double-blind, placebo-
controlled, 4-arm parallel group study of ADS-5102 in subjects with PD who have LID. 
83 subjects were randomized in a 1:1:1:1 ratio to one of four treatments (Placebo, 260 mg 
ADS–5102, 340 mg ADS–5102, or 420 mg ADS–5102). Subjects who were assigned to 
Placebo or 260 mg ADS–5102 received the same nightly dose throughout the entire 8–
week dosing period. Subjects who were assigned 340 mg ADS–5102 or 420 mg 
ADS–5102 received, in double-blind fashion, escalating doses of ADS-5102 as indicated 
in Table 1: 
Table 1: ADS-PAR-AM201 Dose Escalation 
Treatment 
Dosing Days 1–7 
(Week 1) 
Dosing Days 8–14 
(Week 2) 
Dosing Days 15–56 
(Weeks 3–8) 
Placebo 
Placebo 
Placebo 
Placebo 
260 mg ADS–5102 260 mg ADS–5102 260 mg ADS–5102 260 mg ADS–5102 
340 mg ADS–5102 260 mg ADS–5102 340 mg ADS–5102 340 mg ADS–5102 
420 mg ADS–5102 260 mg ADS–5102 340 mg ADS–5102 420 mg ADS–5102 
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
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Date Issued: 13Nov2015 
 
The primary objective of the study was to evaluate the efficacy of each of three dose levels 
of ADS–5102 oral capsules dosed once nightly for the treatment of LID in subjects with 
PD. The secondary objectives of the study was to evaluate the potential efficacy of each of 
three dose levels of ADS–5102 for the treatment of PD–related fatigue, to evaluate the 
safety and tolerability of each of three dose levels of ADS–5102 in this study population, 
to select an appropriate dose level of ADS–5102 dosed once nightly for future trials, and 
to measure steady–state amantadine concentrations at each of three dose levels of ADS–
5102 dosed once nightly. 
 ADS-AMT-PD301, a phase III, multi-center, randomized, double-blind, placebo-
controlled, 2-arm, parallel group study of ADS-5102 in subjects with PD who have LID. 
126 subjects were randomized in a 1:1 ratio to placebo or active (340 mg ADS-5102). 
Study medications were administered as 2 capsules once nightly at bedtime (if possible, no 
earlier than 9 pm) for 25 weeks. The primary objective of the study was to evaluate the 
efficacy of ADS-5102 oral capsules, an extended release formulation of amantadine, at a 
dose level of 340 mg, dosed once nightly at bedtime, for the treatment of levodopa induced 
dyskinesia (LID) in subjects with Parkinson’s disease (PD). The secondary objective was 
to evaluate the safety and tolerability of ADS-5102 in this study population. 
 ADS-AMT-PD302, a phase III, multi-center, open-label study of ADS-5102. Up to 250  
subjects will be enrolled with each belonging to one of the following three groups: 
1. Group 1 (current Adamas LID study subjects): Subjects who are participating in 
Adamas efficacy studies evaluating ADS-5102 in LID and choose to immediately 
transition into ADS-AMT-PD302 without a time gap 
2. Group 2 (previous Adamas LID study subjects): Subjects who have previously 
participated in Adamas efficacy studies evaluating ADS-5102 in LID and will enter 
ADS-AMT-PD302 after a time gap 
3. Group 3 (non Adamas LID study subjects with prior DBS): Subjects who would 
have been deemed ineligible for participation in previous or current Adamas 
efficacy studies due to having undergone deep brain stimulation 
The primary objective of the study is to evaluate the safety and tolerability of ADS-5102 
oral capsules, an extended release formulation of amantadine, administered at a dose of 
340 mg once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in 
subjects with Parkinson’s disease (PD). The secondary objectives of the study are to 
evaluate duration of ADS-5102 effect on dyskinesia as assessed by the Unified Parkinson’s 
Disease Rating Scale (MDS-UPDRS), Part IV and to evaluate clinical progression of 
Parkinson’s disease as assessed by MDS-UPDRS, Combined Score, Parts I, II, and III. 
4 Planned Analyses 
Analyses will be performed after database locks for ADS-PAR-AM201 and ADS-AMT-PD301, 
and database freeze for ADS-AMT-PD302.  


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
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Date Issued: 13Nov2015 
 
5 Analysis Sets 
5.1 
Safety 
The Safety population will include all subjects who received at least one dose of study drug. It 
will be used for all safety analyses. 
6 General Considerations for Statistical Analyses 
Analysis Dataset Model (ADaM) datasets will be in accordance with the Clinical Data 
Interchange Standards Consortium (CDISC) standards and will be derived from the individual 
study data tabulation model (SDTM) and ADaM datasets for each study.   
All tables, listings, figures and any other supportive SAS output will include in the footer 
explanatory notes that will indicate, at a minimum, the programming source (i.e., name, file 
path of the SAS program that generates the output), and run date. 
Continuous data will be described using descriptive statistics as follows: number of 
observations (n), mean, median, standard deviation, minimum, and maximum, unless 
otherwise specified.  All minimum and maximum values will be displayed with the same 
number of decimal places relative to the raw data, the mean and median will be displayed with 
one additional decimal place, and the standard deviation will be displayed with two additional 
decimal places.  
Categorical data will be summarized by the number and percentage of subjects in each 
category. The denominator of all percentages will be the number of subjects in the population 
of interest, unless otherwise stated. When count data are presented, the percent will be 
suppressed when the count is zero in order to draw attention to the non-zero counts. A row 
denoted “Missing” will be included in count tabulations where necessary to account for 
dropouts and missing values. Non-zero percentages will be rounded to one decimal place, 
except 100% will be displayed without any decimal places.  
In summary tables for categorical data, all categories will be presented if they are specified on 
the Case Report Form (CRF), or if categories are ordered intervals (e.g., age groups), regardless 
of whether data were present in each category, unless otherwise specified. For other categorical 
data (e.g., AEs and medications), only categories with non-zero frequencies will be presented. 
Data will be displayed in all listings sorted by subject, study ID, and treatment. All summaries 
will be presented by treatment/analysis group, unless otherwise specified. 
When no data are available for a table or appendix, an empty page with the title will be 
produced with suitable text (e.g., “There are no observations for this table/appendix.”).  


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
7 Data Handling Conventions 
7.1 
Derived and Transformed Data 
Details on derivations and transformations for each individual study are specified in the study 
SAPs. The study teams have worked closely to ensure consistent algorithms were implemented 
across studies.  Modifications to study algorithms are not planned for data integration.  In the 
rare instance where modifications to specific algorithms are necessary to facilitate 
programming, documentation will be provided in the data definition tables and reviewer’s 
guide. 
7.2 
Treatment Assignments and Analysis Groups 
Treatment will be assigned using the treatment assignments from the individual studies.  
Integrated listings will display the treatment received at the time the data was collected. 
The following treatment/analysis groups will be included in summary tables, in the order 
shown: 
 Placebo 
 340 mg ADS-5102 
 ≥ 340 mg ADS-5102 
 ADS-5102 
 
Individual summaries for 260 mg ADS-5102 and 420 mg ADS-5102 will not be included, but 
are available in the study results for ADS-PAR-AM201. 
Since subjects may have received more than one treatment or ADS-5102 dose-level, they may 
be counted multiple times in summary tables, but will appear at most once in each 
treatment/analysis group and at most once in the overall column (where displayed). 
7.3 
Subject Identification  
The Unique Subject Identifier (USUBJID) is unique for all subjects for every study in which 
they participated and is used to identify subjects in the analysis database. A truncated version 
of this identifier will be displayed in data listings. Since this identifier was not displayed in the 
individual study results, a listing will be provided displaying this value along with the subject 
identifier displayed in the individual study results.  
7.4 
Coding Dictionaries 
Integrated concomitant medication data will be recoded using World Health Organization 
(WHO) Drug Dictionary dated March, 2014. 


Adamas Pharmaceuticals, Inc.  
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Date Issued: 13Nov2015 
 
Integrated adverse event data will be recoded using Medical Dictionary for Regulatory 
Activities (MedDRA®) version 17.0. 
7.5 
Subgroup Definitions 
The following subgroups will be explored for key safety analyses: 
 Gender 
 Age (<65, ≥65, ≥65 to <75, ≥75) 
 Race (white, non-white) 
 Baseline renal function (estimated GRF <60 or estimated GFR ≥60) 
 Weight (< or ≥ median) 
 Baseline MAO-B inhibitor medications (Yes, No) 
 Baseline Dopamine Agonist medications (Yes, No) 
 Baseline levodopa dose (< or ≥ median) 
 Time since PD diagnosis in years (< or ≥ median) 
 Age at PD diagnosis (< or ≥ median) 
 Prior Deep Brain Stimulation (Yes, No) 
 Geographic Region (European Union vs North American) 
For subgroups categorizations based on median values, a value for each treatment/analysis 
group will be calculated and subjects will be categorized separately for each treatment/analysis 
group in which they are included. 
7.6 
Definitions of Baseline, Analysis Day 1, and Study Day 1 
The baseline assessment will be the last available assessment prior to the first dose of study 
medication for a particular treatment. For subjects receiving multiple treatments, baseline 
assessments will be defined for each treatment assignment. For subjects receiving 340 mg 
ADS-5102 in more than one study, the following logic will be applied to assign the baseline 
value: 
 For subjects continuing into ADS-AMT-PD302 with no gap in treatment prior to 
enrollment, the baseline assessment will be the last available assessment prior to the 
first dose of 340 mg ADS-5102 in any study. 
 For subjects continuing in ADS-AMT-PD302 with a gap in treatment prior to 
enrollment, the baseline assessment will be the last available assessment prior to the 
first dose of 340 mg ADS-5102 in ADS-AMT-PD302. Assessments from the first study 
in which the subject enrolled will not be considered for assignment as baseline. 
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
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Date Issued: 13Nov2015 
 
An overall baseline value will be determined and used in summaries were overall values are 
calculated and displayed. This value will be assigned following the same logic outlined previously, 
but study treatment will not be considered in the selection of this value. 
Analysis Day 1 is defined as the date of the baseline visit. Subjects should be dispensed the study 
drug at the baseline visit and presumably take the first dose at bedtime on the same day.  No Day 
0 is defined. Negative study days indicate observations were obtained prior to treatment. 
Study Day 1 is defined as the date of the first dose of study drug for the individual study in which 
the subject participated.  
7.7 
Calculations Using Dates 
The following conventions will be used to calculate analysis day for reporting purposes: 
 Analysis Day = date of measurement – analysis day 1 +1, if date of measurement is on 
or after analysis day 1.  
 Analysis Day = date of measurement – analysis day 1, if date of measurement is prior 
to analysis day 1.  
Study day will be presented in applicable listings where the calculated analysis day of the 
measurement is negative due to the definition of baseline for rollover subjects with treatment 
gaps prior to enrollment in the open-label extension. The following conventions will be used 
to calculate study day for reporting purposes: 
 Study Day = date of measurement – study day 1 +1, if date of measurement is on or 
after study day 1.  
 Study Day = date of measurement – study day 1, if date of measurement is prior to 
study day 1.  
8 Summary Population 
8.1 
Disposition of Subjects 
Disposition data from each study will be integrated, listed, and summarized for the Safety 
population. 
A frequency table by treatment/analysis group and overall will include the number and 
percentage of subjects along with last available completion status.  
A separate table will show the number (%) of subjects who withdrew and the primary reason 
for withdrawal, by treatment/analysis group and overall. The primary reasons of withdrawal 
reported by subjects will be presented in this table. The number (%) of subjects who 
discontinued study drug and the reason for early discontinuation will be summarized in a 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
separate table. Subjects may contribute more than one event to the summary table since it is 
possible for a subject to discontinue from more than one study. A footnote indicating the 
number of subjects with multiple study discontinuations will be included in the summary table.  
The time to discontinuation of study drug will be analyzed. The time to discontinuation is 
defined as the number of days from the Analysis Day 1 date to the last dose of study drug for 
a particular treatment. Subjects will be censored if no early study drug discontinuation 
occurred. The median duration and the associated 95% confidence interval for each treatment 
group will be estimated using the Kaplan-Meier method (log-log transformation). Kaplan-
Meier estimates of the survival function will be calculated and displayed graphically. 
8.2 
Protocol Deviations 
Protocol deviations data will not be integrated. Summaries are available in the individual study 
results. 
8.3 
Demographic and Baseline Characteristics 
Demographic and baseline characteristic data will be integrated, listed, and summarized for 
the Safety population. 
The following demographic information will be summarized by treatment/analysis group and 
overall. 
 Age (years), calculated as (informed consent date – birthdate +1)/365.25 
 Age Categories (<65, >=65) 
 Sex (male/female) 
 Race (White, Black, American Indian/Alaska Native, Native Hawaiian or Other Pacific 
Islander, Asian, Other) 
 Ethnicity (Hispanic or Latino, Non-Hispanic/Non-Latino) 
 Height (cm) 
 Body Weight (kg) 
 Body mass index (BMI) 
 eGFR provided by the central lab using subject data and MDRD-NKDEP equation  
8.4 
Medical History 
General medical history data will not be integrated. Summaries are provided in the individual 
study results.  
Parkinson’s disease history data including the following will be integrated, listed, and 
summarized for the Safety population by treatment/analysis group and overall. 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
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Date Issued: 13Nov2015 
 
 Age (years) at PD diagnosis 
 Time since PD diagnosis in years 
 Age (years) at start of levodopa treatment 
 Duration of levodopa treatment in years 
 Duration of levodopa-induced dyskinesia in years 
 Baseline Levodopa dose 
For the duration of Parkinson’s disease, if only the month and year of diagnosis is available, 
the 15th day of the indicated month is assumed, and when only the year of diagnosis is 
available, July 1 of the indicated year is assumed. A similar algorithm is used for age at PD 
diagnosis, age at start of levodopa treatment, duration of levodopa treatment, and duration of 
levodopa–induced dyskinesia. Fractional years of duration will be used for the analyses. 
8.5 
Prior and Concomitant Medications 
Prior medications are defined as medications with a stop date occurring before the first dose 
date.  Concomitant medications are defined as medications with a stop date occurring on or 
after the first dose date, or listed as ongoing.  Medications with start and stop dates (or ongoing) 
which bracket the first dose date will be summarized as both prior and concomitant 
medications. 
All non-study drugs (including prescribed and over the counter medications) taken are 
collected on the CRFs for the individual studies.  
Prior and concomitant medication data will be integrated, listed, and summarized by 
Anatomical Therapeutic Chemical (ATC) Level and preferred term (PT) by treatment/analysis 
group for the Safety population.  At each level of summarization, a subject is counted once if 
he/she reported one or more medications at that level. The PD prior and concomitant 
medications will be presented separately.  
For the purpose of classifying medications as prior and/or concomitant in summaries, 
incomplete medication start and stop dates will be imputed as detailed below: 
 If year and month are present and day is missing then set start day to last day of month, 
and set end day to the later of (first day of month, start day)  
 If year and day are present and month is missing then set start month to December, and 
set end month to the later of (January, start month) 
 If year is present and month and day are missing then set start month and day to 
December 31st, and set end month and day to the later of (January 1st, start month and 
day)  
 Completely missing dates will not be imputed 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
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Date Issued: 13Nov2015 
 
If start date is completely missing and end date is after the first dose, then the medication will 
be classified as both prior and concomitant. If the end date is missing, then the medication will 
be classified as ongoing. Medications for which the start and end dates are missing will be 
classified as prior and concomitant. 
8.6 
Parkinson’s Disease-Related Baseline Characteristics 
Parkinson disease related baseline characteristic data will be integrated, listed, and summarized 
for the Safety population.  
 MDS-UPDRS: Part I, Part II, Part III, Combined (Parts I, II, and III), Part IV, Part IV 
item 4.1, Part IV, item 4.2 
 MMSE score 
 Hoehn and Yahr Stage 
8.7 
Physical Examination 
Physical examination data will not be integrated. Summaries are available in the individual 
study results. 
8.8 
Treatment Compliance 
Treatment compliance data will not be integrated. Summaries are provided in the individual 
study results. 
9  Safety Analysis 
Safety endpoints will be summarized using integrated data by treatment/analysis group from the 
time of first dose and include all available safety data. No formal statistical testing is planned. 
9.1 
Study Drug Exposure 
Study drug exposure data will be integrated, listed, and summarized for the Safety population. 
Duration of exposure will be summarized by treatment/analysis group and is defined as: 
Duration of exposure (Days) = (Date of Last Dose – Analysis Day 1) + 1.  
9.2 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence that occurs in conjunction with the 
use of a medicinal product in humans, whether or not considered to have a causal relationship 
to the medicinal product. An AE can, therefore, be any unfavorable or unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
temporally associated with the use of a medicinal product, whether or not considered related 
to the medicinal product. 
Adverse event data will be integrated, listed, and summarized for the Safety population. Events 
will be presented according to MedDRA® system organ class (SOC) and preferred term (PT). 
Summaries will be ordered alphabetically by SOC and PT, and by decreasing frequency of 
preferred term among all treatment/analysis groups regardless of whether a “total” column is 
presented. 
Partial (Incomplete) AE onset and end dates will be listed as such. All AEs collected on the 
AE eCRF page will be considered treatment–emergent.  
Most commonly reported (at least 2% of either active or placebo treatments) AEs will be 
presented by preferred term, and summarized by treatment/analysis group.   
For each summary, at each of the SOC and PT levels, a subject will be counted once if he/she 
reported one or more AEs.  Percentages will be calculated out of the number of subjects in the 
Safety population.   
9.2.1 Incidence of Adverse Events 
Adverse events will be summarized by treatment/analysis group, SOC and PT.   
9.2.2 Causality of Adverse Events due to Study Drug 
The investigator will use clinical judgment to assess the causality of each AE/Serious 
Adverse Event (SAE) due to study drug based on pre-defined criteria. Adverse events will 
be summarized by this causality. 
In the statistical analyses, if a subject experiences multiple occurrences of the same SOC 
or PT, only the related occurrence (if any exists) will be summarized. If the causality due 
to the study drug is missing, it will be considered “related”. The imputed values for 
causality due to study drug will be used for the incidence summary while actual values will 
be listed. 
9.2.3 Intensity of Adverse Events 
Adverse events will be summarized by treatment/analysis group and intensity.  In this 
summary, if a subject reported multiple occurrences of the same AE, only the most intense 
AE will be presented.  AEs with missing intensity will not be included in the summary 
table, but will be presented in the data listing with a missing intensity. 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
9.2.4 Serious Adverse Events 
The seriousness of an AE should be assessed by the investigator independently from the 
intensity of the AE.  A SAE is any AE occurring at any dose that: 
 results in death; 
 is life-threatening (subject is at immediate risk of death at the time of the event); 
 requires inpatient hospitalization or results in prolongation of existing 
hospitalization; 
 results in persistent or significant disability/incapacity; 
 is a congenital anomaly/birth defect in the offspring of a subject who received study 
drug; or 
 is a significant or important medical event, i.e., an event that, based upon 
appropriate medical judgment, may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the above mentioned criteria. 
SAEs will be summarized by treatment/analysis group and listed. 
9.2.5 Adverse Events Leading to Treatment Discontinuation 
Any AEs collected with an investigational product action taken of “Study drug 
discontinued” will be summarized by treatment/analysis group. 
9.2.6 Adverse Events Leading to Study Drug Dose Reduction 
Adverse events leading to a study drug dose reduction will be summarized by 
treatment/analysis group. Events leading to study drug dose reductions will be identified as 
events having an investigational product action taken response of “Other” with a “Specify” 
value indicating a study drug dose reduction.  
9.2.7 Adverse Events Leading to Death  
Any AEs leading to death will be listed. 
9.2.8 Adverse Events of Special Interest 
Adverse events of special interest are grouped into three event categories: Neuropsychiatric 
(CNS), Falls, and Hallucinations. The CNS category combines the following SOCs: 
Nervous system disorder and Psychiatric disorder. The Falls category combines all PTs 
that contain the term “Fall” or “Falls”. The Hallucinations category combines all PTs that 
contain the term “Hallucination”. 
Event incidence will be summarized treatment/analysis group. 


Adamas Pharmaceuticals, Inc.  
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Date Issued: 13Nov2015 
 
Time to onset will be analyzed and is defined as the number of days from the first dose of 
study drug to the onset of the first AE in the category. Subjects will be censored at the latest 
date known not to have had such AE. The median time to event and the associated 95% 
confidence interval for the Placebo and 340 mg ADS-5102 treatment groups will be 
estimated using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function 
will be calculated and displayed graphically. 
9.3 
Clinical Laboratory Evaluations 
Clinical laboratory data for liver and renal function parameters will be integrated, listed, and 
summarized for the Safety population. Summaries for all other parameters are available in the 
individual study reports.  
Laboratory assessments for these parameters were performed by a central laboratory. All 
summaries will be based on the SI units provided by the central lab. 
Maximum on-treatment values will be summarized for the liver function parameters and 
minimum on-treatment values will be summarized for the renal function parameters. For both 
groups, the change from baseline to the maximum/minimum value will be presented. 
All clinical laboratory measures will be classified as Low, Normal, or High, or 
Normal/Abnormal according to the normal ranges. These categorical data will be summarized 
in shift tables comparing the results at the baseline visit with the most abnormal results over 
the treatment period.  
Liver function parameters include: 
 Bilirubin 
 Alkaline phosphatase 
 -glutamyltransferase 
 Alanine aminotransferase 
 Aspartate aminotransferase 
Renal function parameters include: 
 Blood urea nitrogen 
 Creatinine 
 Estimated GFR – MDRD-NKDEP 
 Estimated GFR – Cockcroft-Gault 
Estimated GRF – Cockcroft-Gault values are not reported in the individual study databases 
and will be calculated as follows: 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
eCreatinine Clearance (ml/min/1.73 m2) =  
[1.73 x (140 – age) x wt (kg) x (0.85 if female) / Serum creatinine (mg/dL) x 72 x Body Surface Area; 
Creatinine in mg/dL is rounded to 1 decimal place prior to applying the Cockcroft-Gault 
equation. 
The equation to calculate Body surface area is described as following: 
Body Surface Area(m2) = [weight (kg) × height (cm)/3600]1/2 
9.4 
Vital Sign Measurements 
Vital sign measures for systolic blood pressure, diastolic blood pressure, and heart rate will be 
integrated and listed for the Safety population. All other measurements will not be integrated. 
Summary tables are available in the individual study results.  
Minimum and maximum on-study values and change from baseline will be presented by 
treatment/analysis group for sitting systolic blood pressure, sitting diastolic blood pressure, 
and heart rate.  
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
10 References 
Aoki F, Sitar D. Clinical pharmacokinetics of amantadine hydrochloride. Clinical 
Pharmacokinetics. 1988; 14(1): 35-51. 
 
Colosimo C, Martinez-Martin P, Fabbrini G, Hauser R, Merello M, Miyasaki J, Poewe W, 
Sampaio C, Rascol O, Stebbins G, Schrag A, Goetz C. Task force report on scales to assess 
dyskinesia in Parkinson's disease: Critique and recommendations. Movement Disorders. 2010; 
25(9): 1131-1142. 
 
Dmitrienko A, D'Agostino R. Traditional multiplicity adjustment methods in clinical trials. 
Statistics in Medicine. 2013; 32(29):5172-218 
 
Encarnacion E, Hauser R. Levodopa-induced dyskinesias in Parkinson's disease: etiology, impact 
on quality of life, and treatments. European Neurology. 2008; 60(2): 57-66. 
 
Goetz C, Nutt J, Stebbins G. The Unified Dyskinesia Rating Scale: Presentation and Clinimetric 
Profile. Movement Disorders. 2008; 23(16): 2398-2403. 
 
Goetz, C. G., et al. (2013). "Which Dyskinesia Scale Best Detects Treatment Response?" 
Movement Disorders 28(3): 341-346 
 
Hayden F, Gwaltney J, Van De Castle R, Adams K, Giordani B. Comparative toxicity of 
amantadine hydrochloride and rmantadine hydrochloride in healthy adults. Antimicrobial Agents 
Chemotherapy. 1981; 19(2): 226-233. 
 
Jackson G, Stanley E, Lee Muldoon R. Chemoprophylaxis of viral respiratory diseases. Bulletin 
Pan Am Health Org. 1967; 147: 595-603. 
 
Luginger E, Wenning G, Bosch S, Poewe W. Beneficial effects of amantadine on L-dopainduced 
dyskinesias in Parkinson's disease. Movement Disorders. 2000; 15(5): 873-878. 
 
Stokes, M. E., Davis, C. S., and Koch, G. G. (2000), Categorical Data Using the SAS System, 
Second Edition, Cary, NC: SAS Institute Inc. 
 
Verhagen-Metman, Del Dotto P, Van Den Muckhof, Fang J, Mouradian M, Chase T. Amantadine 
as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Neurology. 1998; 50(5): 
1323-1326. 
 
Westfall P, Krishen A. Optimally weighted, fixed sequence and gatekeeper multiple testing 
procedures. J. Statistical Planning and Inference. 2001; 99: 25-40. 
 
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
11 Appendices 
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
11.1 Study Design Schematic for ADS-PAR-AM201 
 
 
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
11.2 Study Design Schematic for ADS-AMT-PD301 
 
 
 


Adamas Pharmaceuticals, Inc.  
Statistical Analysis Plan, Version 1.0 
Integrated Summary of Safety for ADS-5102 
Date Issued: 13Nov2015 
 
11.3 Study Design Schematic for ADS-AMT-PD302 
 
No Time 
Gap 
Previous Adamas LID efficacy study 
Week 4 through Week 101 
Final 
efficacy 
visit
Screen 
Baseli
ne 
Final 
visit 
Previous Adamas LID efficacy study 
Time 
Gap 
Screen 
Baseli
ne 
Week 4 through Week 101 
Week 103 
Safety 
Follow Up
Week 103 
Safety 
Follow Up


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Table 1.1.1 Study Withdrawal and Reason for Withdrawal  Safety Population 
Table 1.1.2 Study Drug Discontinuation and Reason for Discontinuation Safety Population 
Table 1.1.3 Kaplan-Meier Analysis of Time to Study Drug Discontinuation Safety Population 
Table 1.2 Demographics and Baseline Characteristics Safety Population 
Table 1.3.1 Parkinson’s Disease History Safety Population 
Table 1.3.2 Parkinson’s Disease Related Baseline Characteristics Safety Population 
Table 1.4.1 Prior PD Medications  Safety Population 
Table 1.4.2 Prior Non-PD Medications  Safety Population 
Table 1.4.3 Concomitant PD Medications Safety Population 
Table 1.4.4 Concomitant Non-PD Medications  Safety Population 
Table 1.5 Study Drug Duration of Exposure  Safety Population 
Table 1.6.1.1 Overview of Adverse Events Safety Population 
Table 1.6.1.2 Overview of Adverse Events by Gender Safety Population 
Table 1.6.1.3 Overview of Adverse Events by Age Safety Population 
Table 1.6.1.4 Overview of Adverse Events by Race Safety Population 
Table 1.6.1.5 Overview of Adverse Events by Baseline Renal Function Safety Population 
Table 1.6.1.6 Overview of Adverse Events by Weight Safety Population 
Table 1.6.1.7 Overview of Adverse Events by Baseline MAO-B Inhibitor Medications Safety Population 
Table 1.6.1.8 Overview of Adverse Events by Baseline Dopamine Agonist Medications Safety Population 
Table 1.6.1.9 Overview of Adverse Events by Baseline Baseline Levodopa Dose Safety Population 
Table 1.6.1.10 Overview of Adverse Events by Time Since PD Diagnosis in Years Safety Population 
Table 1.6.1.11 Overview of Adverse Events by Age at PD Diagnosis Safety Population 
Table 1.6.1.12 Overview of Adverse Events by Prior Deep Brain Stimulation Safety Population 
Table 1.6.1.13 Overview of Adverse Events by Geographic Region Safety Population 
Table 1.6.2.1 Adverse Events, by System Organ Class and Preferred Term Safety Population 
Table 1.6.2.2 Adverse Events, by System Organ Class, Preferred Term by Gender Safety Population 
Table 1.6.2.3 Adverse Events, by System Organ Class, Preferred Term by Age Safety Population 
Table 1.6.2.4 Adverse Events, by System Organ Class, Preferred Term by Race Safety Population 
Table 1.6.2.5 Adverse Events, by System Organ Class, Preferred Term by Baseline Renal Function Safety 
Population 
Table 1.6.2.6 Adverse Events, by System Organ Class, Preferred Term by Weight Safety Population 
Table 1.6.2.7 Adverse Events, by System Organ Class, Preferred Term by Baseline MAO-B Inhibitor Medications 
Safety Population 
Table 1.6.2.8 Adverse Events, by System Organ Class, Preferred Term by Baseline Dopamine Agonist 
Medications Safety Population 
Table 1.6.2.9 Adverse Events, by System Organ Class, Preferred Term by Baseline Levodopa Dose Safety 
Population 
Table 1.6.2.10 Adverse Events, by System Organ Class, Preferred Term by Time since PD Diagnosis in Years 
Safety Population 
Table 1.6.2.11 Adverse Events, by System Organ Class, Preferred Term by Age at PD Diagnosis Safety 
Population 


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Table 1.6.2.12 Adverse Events, by System Organ Class, Preferred Term by Prior Deep Brain Stimulation Safety 
Population 
Table 1.6.2.13 Adverse Events, by System Organ Class, Preferred Term by Geographic Region Safety Population 
Table 1.6.3 Most Common Adverse Events (at least 2% of subjects) Safety Population 
Table 1.6.4 Study-Drug Related Adverse Events, by System Organ Class and Preferred Term Safety Population 
Table 1.6.5 Adverse Events by Highest Intensity, System Organ Class and Preferred Term Safety Population 
Table 1.6.6 Listing of Serious Adverse Events Safety Population 
Table 1.6.7 Adverse Events Leading to Study Drug Discontinuation, by System Organ Class and Preferred Term  
Safety Population 
Table 1.6.8 Adverse Events Leading to Study Drug Dose Reduction, by System Organ Class and Preferred Term  
Safety Population 
Table 1.6.9 Listing of Adverse Events Leading to Death Safety Population 
Table 1.6.10.1 Incidence of AE (Neuropsychiatric) Safety Population 
Table 1.6.10.2 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) Safety Population 
Table 1.6.10.3 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Gender Safety Population 
Table 1.6.10.4 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age Safety Population 
Table 1.6.10.5 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Race Safety Population 
Table 1.6.10.6 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Renal Function 
Safety Population 
Table 1.6.10.7 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Weight Safety Population 
Table 1.6.10.8 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline MAO-B Inhibitor 
Medications Safety Population 
Table 1.6.10.9 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Dopamine Agonist 
Medications Safety Population 
Table 1.6.10.10 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Levodopa Dose 
Safety Population 
Table 1.6.10.11 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) Time since PD Diagnosis in 
Years Safety Population 
Table 1.6.10.12 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age at PD Diagnosis 
Safety Population 
Table 1.6.10.13 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Prior Deep Brain 
Stimulation Safety Population 
Table 1.6.10.14 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Geographic Region Safety 
Population 
Table 1.6.11.1 Incidence of AE (Falls) Safety Population 
Table 1.6.11.2 Kaplan-Meier Analysis of Time to Onset of AE (Falls) Safety Population 
Table 1.6.11.3 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Gender Safety Population 
Table 1.6.11.4 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age Safety Population 
Table 1.6.11.5 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Race Safety Population 
Table 1.6.11.6 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Renal Function Safety 
Population 


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Table 1.6.11.7 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Weight Safety Population 
Table 1.6.11.8 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline MAO-B Inhibitor Medications 
Safety Population 
Table 1.6.11.9 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Dopamine Agonist 
Medications Safety Population 
Table 1.6.11.10 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Levodopa Dose Safety 
Population 
Table 1.6.11.11 Kaplan-Meier Analysis of Time to Onset of AE (Falls) Time since PD Diagnosis in Years 
Safety Population 
Table 1.6.11.12 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age at PD Diagnosis Safety 
Population 
Table 1.6.11.13 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Prior Deep Brain Stimulation Safety 
Population 
Table 1.6.11.14 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Geographic Region Safety Population 
Table 1.6.12.1 Incidence of AE (Hallucinations) Safety Population 
1.6.12.2 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) Safety Population 
1.6.12.3 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Gender Safety Population 
1.6.12.4 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age Safety Population 
1.6.12.5 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Race Safety Population 
1.6.12.6 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Renal Function Safety 
Population 
1.6.12.7 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Weight Safety Population 
1.6.12.8 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline MAO-B Inhibitor 
Medications Safety Population 
1.6.12.9 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Dopamine Agonist 
Medications Safety Population 
1.6.12.10 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Levodopa Dose Safety 
Population 
1.6.12.11 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) Time since PD Diagnosis in Years 
Safety Population 
1.6.12.12 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age at PD Diagnosis Safety 
Population 
1.6.12.13 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Prior Deep Brain Stimulation 
Safety Population 
1.6.12.14 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Geographic Region Safety 
Population 
Table 1.7.1.1 Liver Function Tests Safety Population 
Table 1.7.1.2 Liver Function Tests - Shifts from Baseline to Worst On-Study Value Safety Population 
Table 1.7.2.1 Renal Function Tests Safety Population 
Table 1.7.2.2 Renal Function Tests - Shifts from Baseline to Worst On-Study Value Safety Population 
Table 1.8 Vital Signs Safety Population 


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Table 1.1.1 
Study Withdrawal and Reason for Withdrawal  
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
Subjects who withdrew from any study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    ADS-PAR-AM201 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    ADS-AMT-PD301 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    ADS-AMT-PD302 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Primary reason for withdrawal 
 
 
 
 
 
  Subject discontinued study drug 
    and wished to withdraw1 
 
 
 
 
 
  Subject unwilling to proceed 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Subject consent was withdrawn 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Subject lost to follow up 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Sponsor’s decision 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Note: Percentages are based on the number of subjects in the Safety Population in each treatment/analysis 
group. If a subject withdrew from more than one study, both events will be counted. 
1Subjects who discontinued study drug were encouraged to complete all study assessments. 
Source Data: Listing 2.1.2 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.1.2 
Study Drug Discontinuation and Reason for Discontinuation 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
Subjects who discontinued study drug 
    from any study1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    ADS-PAR-AM201 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    ADS-AMT-PD301 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    ADS-AMT-PD302 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Primary reason for study drug 
    discontinuation  
 
 
 
 
 
  Estimated glomerular filtration 
    rate (eGFR) decreased to less 
    than 50 mL/min/1.73m2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Estimated glomerular filtration 
    rate decreased to less than 30 
    mL/min/1.73m2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Adverse Events 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Positive pregnancy test 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Subject unwilling to proceed 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Subject consent was withdrawn 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Subject lost to follow up 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Sponsor’s decision 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Note: Percentages are based on the number of subjects in the Safety Population in each treatment group. If 
a subject withdrew from more than one study, both events will be counted. 
1Subjects who discontinued study drug early were encouraged to complete all study assessments. 
Source Data: Listing 2.1.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
 
Table 1.1.3 
Kaplan-Meier Analysis of Time to Study Drug Discontinuation 
Safety Population 
 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Time to study drug discontinuation (Days) 
 
 
 
 
 
  Event n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  10th percentile (days) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  25th percentile (days) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  50th percentile (days) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  75th percentile (days) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  90th percentile (days) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min – Max 
xx.x – xx.x 
xx.x – xx.x xx.x – xx.x xx.x – xx.x xx.x – xx.x 
 
 
 
 
 
 
Median (days) 
 
 
 
 
 
  Estimate 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  95% CI 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
 
 
 
 
Note: Percentages are calculated out of the number of subjects in each treatment/analysis group. “+” in MIN 
– MAX means censored value. The time to discontinuation is defined as the number of days from 
Analysis Day 1 to the last dose of study drug. Subjects will be censored if no study drug early 
discontinuation occurred. NE = Non-estimable. 
Source Data: Listing 2.1.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Some percentiles will be non-estimable. When this occurs, use “NE1” 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
 
Table 1.2 
Demographics and Baseline Characteristics 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Age (yrs) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Age categories (yrs) n (%) 
 
 
 
 
 
  <65 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥65 
 
 
 
 
 
  ≥65 to <75 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥75 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Sex n (%) 
 
 
 
 
 
  Female 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Male 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Race n (%) 
 
 
 
 
 
  White 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Non-White 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Black or African American 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Asian 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  American Indian or Alaska Native 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Native Hawaiian or other Pacific Islander 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Note: Percentages are based on the number of subjects in the Safety Population in each treatment group. 
Source Data: Listing 2.2  
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
Table 1.2 
Demographics and Baseline Characteristics 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Ethnicity n (%) 
 
 
 
 
 
  Hispanic or Latino 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Not Hispanic or Latino 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Height (cm) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Weight (kg) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
  < median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥ median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Body Mass Index (kg/m2) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Note: Percentages are based on the number of subjects in the Safety Population in each treatment group. 
Source Data: Listing 2.2  
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.2 
Demographics and Baseline Characteristics 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Estimated GFR – MDRD (mL/min/1.73m2) 
xx 
xx 
xx 
xx 
xx 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
  <60 n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥60 n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Baseline MAO-B inhibitor medications n (%) 
 
 
 
 
 
  Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Baseline Dopamine Agonist medications n (%) 
 
 
 
 
 
  Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Prior deep brain stimulation n (%) 
 
 
 
 
 
  Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Geographic Region n (%) 
 
 
 
 
 
  Eurpean Union 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  North America 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Note: Percentages are based on the number of subjects in the Safety Population in each treatment group. 
Source Data: Listing 2.2  
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.3.1 
Parkinson’s Disease History 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Time since PD diagnosis (yrs)  
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
  < median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥ median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Age at PD diagnosis (yrs) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
  < median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥ median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Age at start of levodopa treatment (yrs) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Note: Durations calculated using diagnosis/start/onset dates.  
Source Data: Listing 2.3.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.3.1 
Parkinson’s Disease History 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Duration of levodopa treatment (yrs) 
 
 
 
 
 
  N 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Duration of levodopa–induced dyskinesia 
 
 
 
 
 
  N 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Baseline levodopa (any preparation) dose (mg)  
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
  < median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ≥ median n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Note: Durations calculated using diagnosis/start/onset dates.  
Source Data: Listing 2.3.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.3.2 
Parkinson’s Disease Related Baseline Characteristics 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
MDS-UPDRS: Part I 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
MDS-UPDRS: Part II 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
MDS-UPDRS: Part III 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
MDS-UPDRS: Combined (Part I, II, and III) 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Source Data: Listings 2.3.2, 2.3.3  
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.3.2 
Parkinson’s Disease Related Baseline Characteristics 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
MDS-UPDRS: Part IV 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
MDS-UPDRS: Part IV, Item 4.1 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
MDS-UPDRS: Part IV, Item 4.2 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
MMSE 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Source Data: Listings 2.3.2, 2.3.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.3.2 
Parkinson’s Disease Related Baseline Characteristics 
Safety Population 
 
 
 
 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
 
ADS-5102 
 
All 
 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Hoehn and Yahr Stage 
 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Source Data: Listings 2.3.2, 2.3.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.4.1 
Prior PD Medications  
Safety Population 
 
 
 
ATC LEVEL 1 
  ATC LEVEL 2 
    PD Medication Class 
      Preferred Term Combined 
        PREFERRED TERM 
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
 
ADS-5102 
(N=xx) 
n (%) 
 
All 
(N=xx) 
n (%) 
 
 
 
 
 
 
Number (%) of subjects with any prior PD 
medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
ATC LEVEL 1  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ATC LEVEL 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PD Medication Class  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
      Preferred Term Combined 1  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
      Preferred Term Combined 2  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
Note: Subjects may have more than one medication per ATC level category and preferred term.  At each level 
of subject summarization, a subject is counted once if the subject reported one or more medications.   
      Prior medications were coded with the WHO Drug dictionary dated March, 2014. PD medications are 
medications indicated by the investigator as prescribed for PD and are classified as Anti-Parkinson 
Drugs. 
Source Data: Listing 2.4 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Medications will be sorted in descending order by ATC level 1 category based on the total of all treatment groups.  
Within each ATC level category, preferred terms will be sorted in alphabetical order. 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.4.2 
Prior Non-PD Medications  
Safety Population 
 
 
ATC LEVEL 1 
  ATC LEVEL 2 
    PREFERRED TERM 
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
ADS-5102 
(N=xx) 
n (%) 
 
All 
(N=xx) 
n (%) 
 
 
 
 
 
 
Number (%) of subjects with any Non-PD 
prior medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
ATC LEVEL 1 #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ATC LEVEL 2 #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
Note: Subjects may have more than one medication per ATC level category and preferred term.  At each level 
of subject summarization, a subject is counted once if the subject reported one or more medications.   
      Prior medications were coded with the WHO Drug dictionary dated March, 2014. Non-PD medications are 
medications indicated by the investigator as prescribed for non-PD related treatment. Anti-Parkinson 
Drugs may be listed if taken for a non-PD indication. 
Source Data: Listing 2.4 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.4.3 
Concomitant PD Medications 
Safety Population 
 
ATC LEVEL 1 
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
ADS-5102 
(N=xx) 
n (%) 
All 
(N=xx) 
n (%) 
  ATC LEVEL 2 
    PD Medication Class  
      Preferred Term Combined  
        PREFERRED TERM 
 
 
 
 
 
 
Number (%) of subjects with any concomitant 
PD medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
ATC LEVEL 1  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ATC LEVEL 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PD Medication Class  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
      Preferred Term Combined 1  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
      Preferred Term Combined 2  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        PREFERRED TERM #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
Note: Subjects may have more than one medication per ATC level category and preferred term.  At each 
level of subject summarization, a subject is counted once if the subject reported one or more 
medications. Concomitant medications were coded with the WHO Drug dictionary dated March, 2014. PD 
medications are medications indicated by the investigator as prescribed for PD and are classified 
as Anti-Parkinson Drugs. 
Source Data: Listing 2.4 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.4.4 
Concomitant Non-PD Medications  
Safety Population 
 
ATC LEVEL 1 
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
ADS-5102 
(N=xx) 
n (%) 
All 
(N=xx) 
n (%) 
  ATC LEVEL 2 
    PREFERRED TERM 
 
 
 
 
 
 
Number (%) of subjects with any Non-PD 
concomitant medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
ATC LEVEL 1 #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ATC LEVEL 2 #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PREFERRED TERM #4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
Note: Subjects may have more than one medication per ATC level category and preferred term.  At each level 
of subject summarization, a subject is counted once if the subject reported one or more medications.   
      Concomitant medications were coded with the WHO Drug dictionary dated March, 2014. Non-PD medications 
are medications indicated by the investigator as prescribed for non-PD related treatment. Anti-
Parkinson Drugs may be listed if taken for a non-PD indication. 
Source Data: Listing 2.4 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
 
Table 1.5 
Study Drug Duration of Exposure  
Safety Population 
 
 
 
 
Placebo 
(N=xx) 
340mg  
ADS-5102 
(N=xx) 
≥340mg  
ADS-5102 
(N=xx) 
ADS-5102 
(N=xx) 
 
 
 
 
 
 
Study drug duration of exposure (days) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x 
xx.x 
xx.x 
xx.x 
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Note: Treatment duration is defined as (Last dose date – First dose date) + 1. For subjects with a gap in treatment 
prior to enrolling in ADS-AMT-PD302, only data from ADS-AMT-PD302 is used.  
Source Data: Listing 2.1.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.1.1 
Overview of Adverse Events 
Safety Population 
 
 
 
 
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
ADS-5102 
(N=xx) 
n (%) 
 
 
 
 
 
Number (%) of subjects with any: 
 
 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Serious AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Study drug related serious AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Number (%) of subjects who permanently discontinued  
 study drug due to any: 
 
 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Number (%) of subjects with any AEs by highest intensity 
 
 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Number (%) of subjects with any study drug related AEs by  
 highest intensity 
 
 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each treatment group. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.1.2 
Overview of Adverse Events by Gender 
Safety Population 
Treatment: Placebo 
 
Female 
(N=xx) 
n (%) 
Male 
(N=xx) 
n (%) 
 
 
 
 
 
 
Number (%) of subjects with any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
  Serious AEs 
xx (xx.x) 
xx (xx.x) 
  Study drug related serious AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects who permanently discontinued  
 study drug due to any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any AEs by highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any study drug related AEs by  
 highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each treatment group. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.1.2 
Overview of Adverse Events by Gender 
Safety Population 
Treatment: 340 mg ADS-5102 
 
Female 
(N=xx) 
n (%) 
Male 
(N=xx) 
n (%) 
 
 
 
 
 
 
Number (%) of subjects with any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
  Serious AEs 
xx (xx.x) 
xx (xx.x) 
  Study drug related serious AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects who permanently discontinued  
 study drug due to any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any AEs by highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any study drug related AEs by  
 highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each treatment group. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.1.2 
Overview of Adverse Events by Gender 
Safety Population 
Treatment: ≥340mg ADS-5102 
 
Female 
(N=xx) 
n (%) 
Male 
(N=xx) 
n (%) 
 
 
 
 
 
 
Number (%) of subjects with any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
  Serious AEs 
xx (xx.x) 
xx (xx.x) 
  Study drug related serious AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects who permanently discontinued  
 study drug due to any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any AEs by highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any study drug related AEs by  
 highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each treatment group. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.1.2 
Overview of Adverse Events by Gender 
Safety Population 
Treatment: ADS-5102 
 
Female 
(N=xx) 
n (%) 
Male 
(N=xx) 
n (%) 
 
 
 
 
 
 
Number (%) of subjects with any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
  Serious AEs 
xx (xx.x) 
xx (xx.x) 
  Study drug related serious AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects who permanently discontinued  
 study drug due to any 
 
 
  AEs  
xx (xx.x) 
xx (xx.x) 
  Study drug related AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any AEs by highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number (%) of subjects with any study drug related AEs by  
 highest intensity 
 
 
  Mild  
xx (xx.x) 
xx (xx.x) 
  Moderate 
xx (xx.x) 
xx (xx.x) 
  Severe 
xx (xx.x) 
xx (xx.x) 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.1.3 
Overview of Adverse Events by Age 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. <65 
2. ≥65 
3. ≥65 to <75 
4. ≥75 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.1.4 
Overview of Adverse Events by Race 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. White 
2. Non-White 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.1.5 
Overview of Adverse Events by Baseline Renal Function 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. Estimated GFR <60 
2. Estimated GFR ≥60 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.1.6 
Overview of Adverse Events by Weight 
Safety Population 
Repeat of 1.6.1.2 
Columns: 
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.1.7 
Overview of Adverse Events by Baseline MAO-B Inhibitor Medications 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. Yes 
2. No 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.1.8 
Overview of Adverse Events by Baseline Dopamine Agonist Medications 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.1.9 
Overview of Adverse Events by Baseline Baseline Levodopa Dose 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
3. < median 
4. ≥ median 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
Table 1.6.1.10 
Overview of Adverse Events by Time Since PD Diagnosis in Years 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.1.11 
Overview of Adverse Events by Age at PD Diagnosis 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.1.12 
Overview of Adverse Events by Prior Deep Brain Stimulation 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. Yes 
2. No 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.1.13 
Overview of Adverse Events by Geographic Region 
Safety Population 
Repeat of 1.6.1.2 
 
Columns:  
1. European Union 
2. North America 
 
 
Note: A subject is counted once for each type of event. Percentages are calculated out of the number of 
subjects in each subgroup category for the given treatment. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.2.1 
Adverse Events, by System Organ Class and Preferred Term 
Safety Population 
 
 
 
System Organ Class 
  Preferred Term 
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
ADS-5102 
(N=xx) 
n (%) 
 
 
 
 
 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
… 
 
 
 
 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.2.2 
Adverse Events, by System Organ Class, Preferred Term by Gender 
Safety Population 
 
Treatment: Placebo 
System Organ Class  
  Preferred Term  
Female 
Male 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
 
 
 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
… 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Sort by descending total frequency for the treatment/analysis group displayed. 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.2.2 
Adverse Events, by System Organ Class, Preferred Term by Gender 
Safety Population 
 
Treatment: 340mg ADS-5102 
System Organ Class  
  Preferred Term  
Female 
Male 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
 
 
 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
… 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Sort by descending total frequency for the treatment/analysis group displayed. 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.2.2 
Adverse Events, by System Organ Class, Preferred Term by Gender 
Safety Population 
 
Treatment: ≥340mg ADS-5102 
System Organ Class  
  Preferred Term  
Female 
Male 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
 
 
 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
… 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Sort by descending total frequency for the treatment/analysis group displayed. 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.2.2 
Adverse Events, by System Organ Class, Preferred Term by Gender 
Safety Population 
 
Treatment: ADS-5102 
System Organ Class  
  Preferred Term  
Female 
Male 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
 
 
 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
 
 
 
… 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Sort by descending total frequency for the treatment/analysis group displayed. 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.2.3 
Adverse Events, by System Organ Class, Preferred Term by Age 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. <65 
2. ≥65 
3. ≥65 to <75 
4. ≥75 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.2.4 
Adverse Events, by System Organ Class, Preferred Term by Race 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. White 
2. Non-White 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.2.5 
Adverse Events, by System Organ Class, Preferred Term by Baseline Renal Function 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. Estimated GFR <60 
2. Estimated GFR ≥60 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.2.6 
Adverse Events, by System Organ Class, Preferred Term by Weight 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.2.7 
Adverse Events, by System Organ Class, Preferred Term by Baseline MAO-B Inhibitor Medications 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. Yes 
2. No 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.2.8 
Adverse Events, by System Organ Class, Preferred Term by Baseline Dopamine Agonist Medications 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. Yes 
2. No 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.2.9 
Adverse Events, by System Organ Class, Preferred Term by Baseline Levodopa Dose 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.2.10 
Adverse Events, by System Organ Class, Preferred Term by Time since PD Diagnosis in Years 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
3. < median 
4. ≥ median 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.2.11 
Adverse Events, by System Organ Class, Preferred Term by Age at PD Diagnosis 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. < median 
2. ≥ median 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.2.12 
Adverse Events, by System Organ Class, Preferred Term by Prior Deep Brain Stimulation 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. Yes 
2. No 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.2.13 
Adverse Events, by System Organ Class, Preferred Term by Geographic Region 
Safety Population 
Repeat of 1.6.2.2 
 
Columns:  
1. European Union 
2. North America 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are    
calculated out of the number of subjects in each subgroup category for the given treatment/analysis group. 
AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.3 
Most Common Adverse Events (at least 2% of subjects) 
Safety Population 
 
 
 
Preferred Term  
Placebo 
(N=xx) 
n (%) 
340mg  
ADS-5102 
(N=xx) 
n (%) 
≥340mg  
ADS-5102 
(N=xx) 
n (%) 
ADS-5102 
(N=xx) 
n (%) 
 
 
 
 
 
Number (%) of subjects with any  
    AEs experienced by ≥2% of subjects 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Preferred Term 4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Preferred Term 5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Preferred Term 6 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
Note: A subject is counted once within each preferred term. Percentages are calculated out of the number of 
subjects in the active treatment/analysis group. AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Sort by descending frequency in ADS-5102 treatment group 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
 
Table 1.6.4 
Study-Drug Related Adverse Events, by System Organ Class and Preferred Term 
Safety Population 
 
Same display as 1.6.2.1 
 
Note: A subject is counted once within each preferred term. Percentages are calculated out of the number of 
subjects in each treatment/analysis group. AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.5 
Adverse Events by Highest Intensity, System Organ Class and Preferred Term 
Safety Population 
Treatment: Placebo 
 
System Organ Class 
  Preferred Term  
(N=xx) 
n (%) 
Mild 
Moderate 
Severe 
Total 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.5 
Adverse Events by Highest Intensity, System Organ Class and Preferred Term 
Safety Population 
Treatment: 340mg ADS-5102 
 
System Organ Class 
  Preferred Term  
(N=xx) 
n (%) 
Mild 
Moderate 
Severe 
Total 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.5 
Adverse Events by Highest Intensity, System Organ Class and Preferred Term 
Safety Population 
Treatment: ≥340mg ADS-5102 
 
System Organ Class 
  Preferred Term  
(N=xx) 
n (%) 
Mild 
Moderate 
Severe 
Total 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.5 
Adverse Events by Highest Intensity, System Organ Class and Preferred Term 
Safety Population 
Treatment: ADS-5102 
 
System Organ Class 
  Preferred Term  
(N=xx) 
n (%) 
Mild 
Moderate 
Severe 
Total 
Number (%) of subjects with any AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.6 
Listing of Serious Adverse Events 
Safety Population 
 
 
 
Subject 
Identifier 
Study 
Identifier Treatment 
System Organ Class/  
  Preferred Term/  
    VERBATIM TERM 
Start Date (Day)/ 
Stop Date (Day)/ 
Duration (Days)1 
Intensity/ 
Causality/ 
Outcome/ 
Action Taken 
XXXXX-XX-XXX XXXXX 
420mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXXX 
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Mild/ 
Not Related/ 
Recovered/Resolved/ 
Dose not changed 
 
 
 
 
 
 
XXXXX-XX-XXX XXXXX 
340mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Moderate/ 
Related/ 
Recovered/Resolved with sequelae/ 
Drug Interrupted 
 
 
 
 
 
 
XXXXX-XX-XXX XXXXX 
340mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Severe/ 
Not Related/ 
Unknown/ 
Drug Withdrawn 
 
 
 
 
 
 
XXXXX-XX-XXX XXXXX 
260mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Mild/ 
Related/ 
Not Recovered/Not resolved/ 
Other 
 
 
 
 
 
 
XXXXX-XX-XXX XXXXX 
340mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Severe/ 
Not Related/ 
Fatal/ 
Dose not changed 
 
 
 
 
 
 
1Duration (Days) = Stop date — Start date + 1.  
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.7 
Adverse Events Leading to Study Drug Discontinuation, by System Organ Class and Preferred Term  
Safety Population 
 
Same display as 1.6.2.1 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
 
 
 
Table 1.6.8 
Adverse Events Leading to Study Drug Dose Reduction, by System Organ Class and Preferred Term  
Safety Population 
 
Same display as 1.6.2.1 
 
Note: A subject is counted once within each preferred term and system organ class. Percentages are 
calculated out of the number of subjects in each treatment/analysis group. AEs are coded using MedDRA 
Version 17.0. 
Source Data: Listing 2.6.3 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.9 
Listing of Adverse Events Leading to Death 
Safety Population 
 
Same display as 1.6.6, with outcome “Death”. 
 
 
 
 
1Dur = Duration (Days = Stop date — Start date + 1).  
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.10.1 
Incidence of AE (Neuropsychiatric) 
Safety Population 
 
 
System Organ Class 
  Preferred Term 
Placebo 
340mg  
ADS-5102 
≥340mg  
ADS-5102 
ADS-5102 
Number of AE (Neuropsychiatric) events 
xx 
xx 
xx 
xx 
 
 
 
 
 
System Organ Class 1 
xx 
xx 
xx 
xx 
  Preferred Term 1 
xx 
xx 
xx 
xx 
  Preferred Term 2 
xx 
xx 
xx 
xx 
  Preferred Term 3 
xx 
xx 
xx 
xx 
… 
xx 
xx 
xx 
xx 
 
xx 
xx 
xx 
xx 
System Organ Class 2 
xx 
xx 
xx 
xx 
  Preferred Term 1 
xx 
xx 
xx 
xx 
  Preferred Term 2 
xx 
xx 
xx 
xx 
  Preferred Term 3 
xx 
xx 
xx 
xx 
 
 
 
 
 
Note: The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder 
and Psychiatric disorder. AEs are coded using MedDRA Version 17.0. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.2 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) 
Safety Population 
 
 
Placebo 
340 mg ADS-5102 
 
(N=xx) 
(N=xx) 
 
 
 
Days to onset of first AE: Neuropsychiatric 
 
 
  Event n(%) 
xx (xx.x) 
xx (xx.x) 
  10th percentile (days) 
xx.x 
xx.x 
  25th percentile (days) 
xx.x 
xx.x 
  50th percentile (days) 
xx.x 
xx.x 
  75th percentile (days) 
xx.x 
xx.x 
  90th percentile (days) 
xx.x 
xx.x 
  Min – Max 
xx.x – xx.x 
xx.x – xx.x 
 
 
 
Median (days) 
 
 
  Estimate 
xx.x 
xx.x 
  95% CI 
x.xx, x.xx 
x.xx, x.xx 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Some percentiles will be non-estimable. When this occurs, use “NE1” 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.10.3 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Gender 
Safety Population 
Gender: Female 
 
Placebo 
340 mg ADS-5102 
 
(N=xx) 
(N=xx) 
 
 
 
Days to onset of first AE: Neuropsychiatric 
 
 
  Event n(%) 
xx (xx.x) 
xx (xx.x) 
  10th percentile (days) 
xx.x 
xx.x 
  25th percentile (days) 
xx.x 
xx.x 
  50th percentile (days) 
xx.x 
xx.x 
  75th percentile (days) 
xx.x 
xx.x 
  90th percentile (days) 
xx.x 
xx.x 
  Min – Max 
xx.x – xx.x 
xx.x – xx.x 
 
 
 
Median (days) 
 
 
  Estimate 
xx.x 
xx.x 
  95% CI 
x.xx, x.xx 
x.xx, x.xx 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Some percentiles will be non-estimable. When this occurs, use “NE1” 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.3 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Gender 
Safety Population 
Gender: Male 
 
Placebo 
340 mg ADS-5102 
 
(N=xx) 
(N=xx) 
 
 
 
Days to onset of first AE: Neuropsychiatric 
 
 
  Event n(%) 
xx (xx.x) 
xx (xx.x) 
  10th percentile (days) 
xx.x 
xx.x 
  25th percentile (days) 
xx.x 
xx.x 
  50th percentile (days) 
xx.x 
xx.x 
  75th percentile (days) 
xx.x 
xx.x 
  90th percentile (days) 
xx.x 
xx.x 
  Min – Max 
xx.x – xx.x 
xx.x – xx.x 
 
 
 
Median (days) 
 
 
  Estimate 
xx.x 
xx.x 
  95% CI 
x.xx, x.xx 
x.xx, x.xx 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Some percentiles will be non-estimable. When this occurs, use “NE1” 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.4 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age 
Safety Population 
Repeat of 1.6.10.3 
 
Age:  
1. <65 
2. ≥65 
3. ≥65 to <75 
4. ≥75 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.10.5 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Race 
Safety Population 
Repeat of 1.6.10.3 
 
Race:  
1. White 
2. Non-White 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
Table 1.6.10.6 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Renal Function 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Renal Function:  
1. Estimated GFR <60 
2. Estimated GFR ≥60 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.10.7 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Weight 
Safety Population 
Repeat of 1.6.10.3 
 
Weight:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.8 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline MAO-B Inhibitor Medications 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline MAO-B Inhibitors:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.10.9 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Dopamine Agonist Medications 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Dopamine Agonist Medications:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.10 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Levodopa Dose 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Levodopa Dose:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.10.11 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) Time since PD Diagnosis in Years 
Safety Population 
Repeat of 1.6.10.3 
 
Time since PD Diagnosis in Years:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.12 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age at PD Diagnosis 
Safety Population 
Repeat of 1.6.10.3 
 
Age at PD Diagnosis:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.10.13 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Prior Deep Brain Stimulation 
Safety Population 
Repeat of 1.6.10.3 
 
Prior Deep Brain Stimulation:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.10.14 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Geographic Region 
Safety Population 
Repeat of 1.6.10.3 
 
Geographic Region:  
1. European Union 
2. North America 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Neuropsychiatric category combines the following System of Organs: Nervous system disorder and 
Psychiatric disorder. Subjects will be censored at their last contact date if no AE 
(Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.1 
Incidence of AE (Falls) 
Safety Population 
 
Repeat of 1.6.10.1 
 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.11.2 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) 
Safety Population 
Repeat of 1.6.10.2 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Some percentiles will be non-estimable. When this occurs, use “NE1” 
 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.3 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Gender 
Safety Population 
Repeat of 1.6.10.3 
 
Gender:  
1. Female 
2. Male 
 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.11.4 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age 
Safety Population 
Repeat of 1.6.10.3 
Age:  
1. <65 
2. ≥65 
3. ≥65 to <75 
4. ≥75 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.5 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Race 
Safety Population 
Repeat of 1.6.10.3 
 
Race:  
1. White 
2. Non-White 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
Table 1.6.11.6 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Renal Function 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Renal Function:  
1. Estimated GFR <60 
2. Estimated GFR ≥60 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.7 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Weight 
Safety Population 
Repeat of 1.6.10.3 
 
Weight:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.11.8 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline MAO-B Inhibitor Medications 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline MAO-B Inhibitors:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.9 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Dopamine Agonist Medications 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Dopamine Agonist Medications:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Table 1.6.11.10 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Levodopa Dose 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Levodopa Dose:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.11 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) Time since PD Diagnosis in Years 
Safety Population 
Repeat of 1.6.10.3 
 
Time since PD Diagnosis in Years:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
Table 1.6.11.12 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age at PD Diagnosis 
Safety Population 
Repeat of 1.6.10.3 
 
Age at PD Diagnosis:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred.] 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.11.13 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Prior Deep Brain Stimulation 
Safety Population 
Repeat of 1.6.10.3 
 
Prior Deep Brain Stimulation:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
Table 1.6.11.14 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Geographic Region 
Safety Population 
Repeat of 1.6.10.3 
 
Geographic Region:  
1. European Union 
2. North America 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Falls category combines all Preferred Terms that contain the terms “Fall” or “Falls”. Subjects 
will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.6.12.1 
Incidence of AE (Hallucinations) 
Safety Population 
 
Repeat of 1.6.10.1 
 
 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
1.6.12.2 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) 
Safety Population 
Repeat of 1.6.10.2 
 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Programming Note: Some percentiles will be non-estimable. When this occurs, use “NE1” 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
1.6.12.3 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Gender 
Safety Population 
Repeat of 1.6.10.3 
 
Gender:  
1. Female 
2. Male 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
1.6.12.4 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age 
Safety Population 
Repeat of 1.6.10.3 
 
Age:  
1. <65 
2. ≥65 
3. ≥65 to <75 
4. ≥75 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
1.6.12.5 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Race 
Safety Population 
Repeat of 1.6.10.3 
 
Race:  
1. White 
2. Non-White 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
1.6.12.6 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Renal Function 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Renal Function:  
1. Estimated GFR <60 
2. Estimated GFR ≥60 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
1.6.12.7 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Weight 
Safety Population 
Repeat of 1.6.10.3 
 
Weight:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
1.6.12.8 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline MAO-B Inhibitor Medications 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline MAO-B Inhibitors:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
1.6.12.9 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Dopamine Agonist Medications 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Dopamine Agonist Medications:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
1.6.12.10 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Levodopa Dose 
Safety Population 
Repeat of 1.6.10.3 
 
Baseline Levodopa Dose:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
1.6.12.11 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) Time since PD Diagnosis in Years 
Safety Population 
Repeat of 1.6.10.3 
 
Time since PD Diagnosis in Years:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
1.6.12.12 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age at PD Diagnosis 
Safety Population 
Repeat of 1.6.10.3 
 
Age at PD Diagnosis:  
1. < median 
2. ≥ median 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 
1.6.12.13 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Prior Deep Brain Stimulation 
Safety Population 
Repeat of 1.6.10.3 
 
Prior Deep Brain Stimulation:  
1. Yes 
2. No 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
1.6.12.14 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Geographic Region 
Safety Population 
Repeat of 1.6.10.3 
 
Geographic Region:  
1. European Union 
2. North America 
Note: Percentages are calculated out of the number of subjects in each treatment group. “+” in MIN – MAX 
means censored value. AEs are coded using MedDRA Version 17.0. NE = Non-estimable. 
Note: The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. 
Subjects will be censored at their last contact date if no AE (Hallucinations) occurred. 
Source Data: Listing 2.6.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.7.1.1 
Liver Function Tests 
Safety Population 
Parameter: XXXXX (units) 
 
Placebo 
(N=xx) 
340mg  
ADS-5102 
(N=xx) 
≥340mg  
ADS-5102 
(N=xx) 
ADS-5102 
(N=xx) 
 
 
 
 
 
Baseline 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Maximum 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Change From Baseline1 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Note: Baseline is defined as last available value prior to ther first dose of study medication for a 
particular treatment.  
1Change from baseline: post-baseline value – baseline value.  For the change from baseline, only subjects 
with a value at both the baseline visit and the specific post-baseline visit are included. 
Source Data: Listing 2.7.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Parameters: Bilirubin, Alkaline phosphatase, -glutamyltransferase, Alanine aminotransferase, Aspartate aminotransferase 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
Table 1.7.1.2 
Liver Function Tests - Shifts from Baseline to Worst On-Study Value 
Safety Population 
Parameter: XXXXXXXXXXXX (unit) 
 
 
Baseline 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Missing 
n (%) 
Placebo (N = XXX) 
 
 
 
 
  Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
340mg ADS-5102 (N = XXX) 
 
 
 
 
  Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
≥340mg ADS-5102 (N = XXX) 
 
 
 
 
  Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
ADS-5102 (N = XXX) 
 
 
 
 
  Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note: Baseline is defined as last available value prior to ther first dose of study medication for a 
particular treatment. The worst value is defined as the maximum on-study value. High = Higher than the 
upper limit of the normal range, Low = Lower than the lower limit of the normal range, Normal = within the 
lower and upper limits of the normal range. Percentages are based on the number of subjects in each 
treatment/analysis group. 
Source Data: Listing 2.7.1 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
Page x of y 
ADS-5102 Integrated Summary of Safety 
 
 Table 1.7.2.1 
Renal Function Tests 
Safety Population 
Repeat of 1.7.1.1 
 
 
 
 
 
 
Note: Baseline is defined as last available value prior to ther first dose of study medication for a 
particular treatment.  
1Change from baseline: post-baseline value – baseline value.  For the change from baseline, only subjects 
with a value at both the baseline visit and the specific post-baseline visit are included. 
Source Data: Listing 2.7.2 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Parameters: Blood Urea Nitrogen, Creatinine, Estimated GFR – MDRD, Estimated GFR – Cockcroft-Gault 
 
 
Table 1.7.2.2 
Renal Function Tests - Shifts from Baseline to Worst On-Study Value 
Safety Population 
 
Repeat of 1.7.1.2 
 
 
 
 
 
 
 
Note: Baseline is defined as last available value prior to ther first dose of study medication for a 
particular treatment. The worst value is defined as the minimum on-study value. High = Higher than the 
upper limit of the normal range, Low = Lower than the lower limit of the normal range, Normal = within the 
lower and upper limits of the normal range. Percentages are based on the number of subjects in each 
treatment/analysis group. 
Source Data: Listing 2.7.2 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


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Table 1.8 
Vital Signs 
Safety Population 
Parameter: XXXXX (units) 
 
Placebo 
(N=xx) 
340mg  
ADS-5102 
(N=xx) 
≥340mg  
ADS-5102 
(N=xx) 
ADS-5102 
(N=xx) 
 
 
 
 
 
Baseline 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Minimum 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Maximum 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Note: Baseline is defined as last available value prior to ther first dose of study medication for a 
particular treatment. For the change from baseline, only subjects with a value at both the baseline visit 
and the specific post-baseline visit are included. 
Source Data: Listing 2.8 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Parameters: Sitting Systolic BP, Sitting Diastolic DP, Heart Rate 


Adamas Pharmaceuticals, Inc. 
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Table 1.8 
Vital Signs 
Safety Population 
Parameter: XXXXX (units) 
 
Placebo 
(N=xx) 
340mg  
ADS-5102 
(N=xx) 
≥340mg  
ADS-5102 
(N=xx) 
ADS-5102 
(N=xx) 
 
 
 
 
 
Change from Baseline 
(Minimum) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Change from Baseline 
(Maximum) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  Mean 
xx.x  
xx.x  
xx.x  
xx.x  
  SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.x 
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Note: Baseline is defined as last available value prior to ther first dose of study medication for a 
particular treatment. For the change from baseline, only subjects with a value at both the baseline visit 
and the specific post-baseline visit are included. 
Source Data: Listing 2.8 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
Parameters: Sitting Systolic BP, Sitting Diastolic DP, Heart Rate 
 


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Listing 2.1.1 Subject Identification Lookup Table Safety Population 
Listing 2.1.2 Study Withdrawal and Reason for Withdrawal Safety Population 
Listing 2.1.3 Study Drug Discontinuation and Reason for Discontinuation Safety Population 
Listing 2.2 Demographics and Other Baseline Characteristics Safety Population 
Listing 2.3.1 Parkinson's Disease History Safety Population 
Listing 2.3.2 Parkinson's Disease-Related Baseline Characteristics (Part I) Safety Population 
Listing 2.3.3 Parkinson's Disease-Related Baseline Characteristics (Part II) Safety Population 
Listing 2.4 Prior and Concomitant Medications Safety Population 
Listing 2.6.1 Adverse Events  Safety Population 
Listing 2.6.2 Adverse Events Leading to Study Drug Dose Reduction Safety Population 
Listing 2.6.3 Adverse Events Leading to Study Drug Discontinuation Safety Population 
Listing 2.7.1 Laboratory Results – Liver Function Tests Safety Population 
Listing 2.7.2 Laboratory Results – Renal Function Tests Safety Population 
Listing 2.8 Vital Sign Results Safety Population 
 
 
 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
 
Listing 2.1.1 
Subject Identification Lookup Table 
Safety Population 
 
Subject 
Identifier 
Unique Subject Identifier 
Study 
Identifier 
Study 
Subject 
Identifier 
XXXXX-XX-XXX 
ADS-XXX-XXXXX-XX-XXX 
AM201 
XXX 
 
 
 
 
 
ADS-XXX-XXXXX-XX-XXX 
PD302 
XX-X-XXX 
 
 
 
 
XXXXX-XX-XXX 
ADSXXXXXXXX-XX-X-XXX 
PD301 
XX-X-XXX 
 
 
 
 
XXXXX-XX-XXX 
ADSXXXXXXXX-XX-X-XXX 
PD302 
XX-X-XXX 
 
 
 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.1.2 
Study Withdrawal and Reason for Withdrawal 
Safety Population 
 
Subject 
Identifier 
Study 
Identifier 
Treatment 
First Dose Date/ 
Last Dose Date/ 
Subject  
Completed 
Study 
Reason for Not Completing Study 
XXXXX-XX-XXX 
XXXXX 
Placebo 
DDMMMYYYY/ 
DDMMMYYYY 
Y 
 
XXXXX 
340mg ADS-5102 
DDMMMYYYY/ 
DDMMMYYYY 
N 
INTOLERABLE OR UNACCEPTABLE AES 
 
XXXXX-XX-XXX 
XXXXX 
260mg ADS-5102 
DDMMMYYYY/ 
DDMMMYYYY 
Y 
 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 
DDMMMYYYY/ 
DDMMMYYYY 
N 
NON-COMPLIANCE WITH STUDY DRUG 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.1.3 
Study Drug Discontinuation and Reason for Discontinuation 
Safety Population 
 
Subject 
Identifier 
Study 
Identifier Treatment 
First Dose Date/ 
Last Dose Date/ 
Treatment Duration (Days)1 
Subject  
Completed 
Treatment Reason for Not Completing Treatment 
XXXXX-XX-XXX 
XXXXX 
Placebo 
DDMMMYYYY/ 
DDMMMYYYY/ 
XX 
Y 
 
 
 
 
 
 
 
 
XXXXX 
340mg ADS-5102 DDMMMYYYY/ 
DDMMMYYYY/ 
XX 
N 
INTOLERABLE OR UNACCEPTABLE AES 
 
 
 
 
 
 
XXXXX-XX-X-XXX XXXXX 
260mg ADS-5102 DDMMMYYYY/ 
DDMMMYYYY/ 
XX 
Y 
 
 
 
 
 
 
 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 DDMMMYYYY/ 
DDMMMYYYY/ 
XX 
N 
NON-COMPLIANCE WITH STUDY DRUG 
 
 
 
 
 
 
1 Treatment duration is defined as (Last dose date – First dose date) + 1.  
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
 
Listing 2.2 
Demographics and Other Baseline Characteristics 
Safety Population 
 
Subject 
Identifier 
Study 
Identifier Treatment 
Age(yrs)/ 
Sex1/ 
Race2/ 
Ethnicity3 
Country/ 
Geographic Region 
Height(cm)/ 
Weight(kg)/ 
BMI(kg/m2) 
Baseline 
Estimated 
GFR 
(mL/min/1.73m2) 
Baseline 
MAO-B 
Inhibitor/
Baseline 
Dopamine 
Agonist Prior DBS
XXXXX-XX-X-XXX XXXXX 
Placebo 
50/  
M/ 
W/ 
HL 
Canada/ 
North America 
xxx.x/ 
xxx.x/ 
xx.x 
xx.x 
Y/N 
Y 
XXXXX 
340mg ADS-5102 51/  
M/ 
W/ 
HL 
Canada/ 
North America 
xxx.x/ 
xxx.x/ 
xx.x 
xx.x 
Y/N 
Y 
XXXXX-XX-XXX 
XXXXX 
260mg ADS-5102 60/  
F/ 
O/ 
NHL 
Austria/ 
European Union 
xxx.x/ 
xxx.x/ 
xx.x 
xx.x 
Y/Y 
N 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 65/  
M/ 
PI/ 
NHL 
United States/ 
North America 
xxx.x/ 
xxx.x/ 
xx.x 
xx.x 
N/N 
N 
 
 
 
Note: BMI = Body mass index, DBS = Deep Brain Stimulation 
1 F = Female, M = Male 
2 AI = American Indian or Alaska Native, AS = Asian, B = Black or African American, PI = Native Hawaiian or Other 
Pacific Islander, W = White, O = Other 
3 HL = Hispanic or Latino, NHL = Not Hispanic or Latino 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm  


Adamas Pharmaceuticals, Inc. 
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Listing 2.3.1 
Parkinson's Disease History 
Safety Population 
 
Subject 
Identifier 
Study 
Identifier 
Treatment 
Age at PD 
Diagnosis 
(yrs.) 
Time  
Since PD 
Diagnosis  
(yrs.)1 
Age at  
Start of  
Levodopa 
Treatment 
(yrs.) 
Duration 
of 
Levodopa  
Treatment 
(yrs.)1 
Duration  
of LID 
(yrs.)1 
Baseline 
Levodopa 
Dose 
(mg)2 
XXXXX-XX-X-XXX 
XXXXX 
Placebo 
xx 
x 
x 
x.x 
x.x 
xx.x 
 
XXXXX 
340mg ADS-5102 
xx 
x 
x 
x.x 
x.x 
xx.x 
XXXXX-XX-XXX 
XXXXX 
260mg ADS-5102 
xx 
x 
x 
x.x 
x.x 
xx.x 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 
xx 
x 
x 
x.x 
x.x 
xx.x 
 
 
 
 
 
 
 
 
 
Note: PD = Parkinson’s disease, LID = Levodopa-induced dyskinesia, # indicates an imputed date. 
1Time since Parkinson’s disease diagnosis = (Analysis Day 1 – Date of diagnosis of Parkinson’s disease)/ 365.25. When 
only the month and year of diagnosis are available, the 15th day of the indicated month is assumed, and when only the 
year of diagnosis is available, July 1 of the indicated year is assumed. A similar algorithm is used for duration of 
levodopa treatment, and duration of levodopa–induced dyskinesia. 
2 Baseline total levodopa dosage is defined as the levodopa medication (any preparation) with last start date prior to 
first dose of study medication.   
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.3.2 
Parkinson's Disease-Related Baseline Characteristics (Part I) 
Safety Population 
 
Subject 
Identifier 
Study 
Identifier 
Treatment 
MDS-UPDRS 
Part I 
MDS-UPDRS 
Part II 
MDS-UPDRS Part 
III 
MDS-UPDRS 
Combined 
MDS-UPDRS 
Part IV 
XXXXX-XX-X-XXX 
XXXXX 
Placebo 
xx 
x 
x 
x.x 
x.x 
 
XXXXX 
340mg ADS-5102 
xx 
x 
x 
x.x 
x.x 
XXXXX-XX-XXX 
XXXXX 
260mg ADS-5102 
xx 
x 
x 
x.x 
x.x 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 
xx 
x 
x 
x.x 
x.x 
 
 
 
 
 
 
 
 
 
Note: PD = Parkinson’s disease, LID = Levodopa-induced dyskinesia, # indicates an imputed date. 
1Time since Parkinson’s disease diagnosis = (Analysis Day 1 – Date of diagnosis of Parkinson’s disease)/ 365.25. When 
only the month and year of diagnosis are available, the 15th day of the indicated month is assumed, and when only the 
year of diagnosis is available, July 1 of the indicated year is assumed. A similar algorithm is used for duration of 
levodopa treatment, and duration of levodopa–induced dyskinesia. 
2 Baseline total levodopa dosage is defined as the levodopa medication (any preparation) with last start date prior to 
first dose of study medication.   
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
Listing 2.3.3 
Parkinson's Disease-Related Baseline Characteristics (Part II) 
Safety Population 
 
Subject 
Identifier 
Study 
Identifier 
Treatment 
MDS-UPDRS 
Part IV 
Item 4.1 
MDS-UPDRS 
Part IV 
Item 4.2 
MMSE 
Score 
Hoehn and 
Yahr Stage 
XXXXX-XX-X-XXX 
XXXXX 
Placebo 
xx 
x 
x 
x.x 
 
XXXXX 
340mg ADS-5102 
xx 
x 
x 
x.x 
XXXXX-XX-XXX 
XXXXX 
260mg ADS-5102 
xx 
x 
x 
x.x 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 
xx 
x 
x 
x.x 
 
 
 
 
 
 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.4 
Prior and Concomitant Medications 
Safety Population 
 
 
 
Subject 
Identifier 
Study 
Identifier 
Treatment 
ATC TERM/ 
  PREFFERED TERM/ 
    MEDICATION REPORTED 
Indication 
Start Date/ 
Stop Date/ 
Flag1 
 
Dose/ 
Unit/ 
Route/ 
Frequency 
XXXXX-XX-X-XXX 
XXXXX 
Placebo 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXXX 
XXXXXXXXXX 
DDMMMYYYY/ 
Ongoing/ 
P 
XXXXX/ 
XXXXXX/ 
XXXXXX/ 
XXXXXX 
 
 
 
 
 
 
 
XXXXX-XX-XXX 
XXXXX 
340mg ADS-5102 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXXX 
XXXXXXXXXX 
DDMMMYYYY/ 
DDMMMYYYY/ 
P/C 
XXXXX/ 
XXXXXX/ 
XXXXXX/ 
XXXXXX 
 
 
 
 
 
 
 
Note: Freq = Frequency 
Prior medications are defined as medications taken within the 30 days that started and stopped prior to Analysis Day 1 
(first day of study drug administration).  
1P=Prior medication, C=Concomitant medication 
Prior and concomitant medications were coded with the WHO Drug dictionary dated MAR 2014.  
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.6.1 
Adverse Events  
Safety Population 
 
 
 
Subject 
Identifier 
Study 
Identifier Treatment 
System Organ Class/  
  Preferred Term/  
    VERBATIM TERM 
Start Date (Day)/ 
Stop Date (Day)/ 
Duration (Days)1 
Serious/ 
Intensity/ 
Causality/ 
Outcome/ 
Action Taken 
XXXXX-XX-X-XXX XXXXX 
Placebo 
XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXXX 
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Yes/ 
Mild/ 
Not Related/ 
Recovered/Resolved/ 
Dose not changed 
 
 
 
 
 
 
XXXXX-XX-XXX 
XXXXX 
340mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
No/ 
Moderate/ 
Related/ 
Recovered/Resolved with sequelae/ 
Drug Interrupted 
 
 
 
 
 
 
XXXXX-XX-XXX 
XXXXX 
260mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Yes/ 
Severe/ 
Not Related/ 
Unknown/ 
Drug Withdrawn 
 
 
 
 
 
 
XXXXX-XX-XXX 
XXXXX 
420mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
No/ 
Mild/ 
Related/ 
Not Recovered/Not resolved/ 
Other 
 
 
 
 
 
 
XXXXX-XX-XXX 
XXXXX 
340mg ADS-5102 XXXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
DDMMMYYYY (xx)/ 
XX 
Yes/ 
Severe/ 
Not Related/ 
Fatal/ 
Dose not changed 
 
 
 
 
 
 
 
 
 
 
 
 
1Duration (Days = Stop date — Start date + 1). 
Adverse events are coded using MedDRA Version 17.0. 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.6.2 
Adverse Events Leading to Study Drug Dose Reduction 
Safety Population 
 
 
 
 
Same layout as X.X 
 
 
 
 
1Duration (Days = Stop date — Start date + 1). 
Adverse events are coded using MedDRA Version 17.0. 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 
 
 
Listing 2.6.3 
Adverse Events Leading to Study Drug Discontinuation 
Safety Population 
 
 
 
 
Same layout as X.X 
 
 
 
 
1Duration (Days = Stop date — Start date + 1). 
Adverse events are coded using MedDRA Version 17.0. 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.7.1 
Laboratory Results – Liver Function Tests 
Safety Population 
 
 
 
Subject 
Identifier 
Study 
Identifier 
Treatment 
Sample Date 
Laboratory Test 
Result 
Units Flag 
Normal Range 
XXXXX-XX-X-XXX 
XXXXX 
260mg ADS-5102 
DDMMMYYYY  
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
 
XXX.X-XXX.X 
  
 
 
 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
 
XXX.X-XXX.X 
 
 
 
DDMMMYYYY 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX  L* 
XXX.X-XXX.X 
 
 
 
 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
 
XXX.X-XXX.X 
 
 
 
 
 
 
 
 
 
 
XXXXX 
340mg ADS-5102 
DDMMMYYYY 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
H 
XXX.X-XXX.X 
 
 
 
 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
H 
XXX.X-XXX.X 
 
 
 
DDMMMYYYY 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
 
XXX.X-XXX.X 
 
 
 
 
XXXXXXXXXXXXXXX 
XXX.X 
XXXXX 
 
XXX.X-XXX.X 
 
 
 
 
 
 
 
 
 
 
 
Note: H = Above Normal Range, L = Below Normal Range, N = Normal, * indicates minimum value 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY  hh:mm 
 
 
 
 
 
Listing 2.7.2 
Laboratory Results – Renal Function Tests 
Safety Population 
 
 
 
Same as X.X 
 
 
 
Note: H = Above Normal Range, L = Below Normal Range, N = Normal, * indicates maximum value 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 


Adamas Pharmaceuticals, Inc. 
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Listing 2.8 
Vital Sign Results 
Safety Population 
 
 
 
 
 
Subject 
Identifier 
 
 
 
Treatment 
Test Date 
Blood Pressure(mmHg) 
 
Heart 
Rate 
(bpm) 
 
 
Height 
(cm) 
 
 
Weight 
(kg) 
Study 
Identifier 
Sitting 
Systolic/Diastolic 
Standing 
Systolic/Diastolic 
XXXXX-XX-X-XXX 
XXXXX 
260mg ADS-5102 
DDMMMYYYY 
xx/xx 
xx/xx 
xxx 
xxx.x 
xx.x 
 
 
 
DDMMMYYYY 
xx/xx 
 
xxx 
 
 
 
 
340mg ADS-5102 
DDMMMYYYY 
xx/xx 
xx/xx 
xxx 
xxx.x 
xx.x 
 
 
 
 
 
 
 
 
 
Heart Rate (bpm=beats/minute) 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMMMYYYY hh:mm 
 
 


Adamas Pharmaceuticals, Inc. 
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Figure 3.1 Kaplan-Meier Analysis of Time to Study Drug Discontinuation Safety Population 
Figure 3.6.1.1 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) Safety Population 
Figure 3.6.1.2 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Gender Safety Population 
Figure 3.6.1.3 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age Safety Population 
Figure 3.6.1.4 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Race Safety Population 
Figure 3.6.1.5 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Renal Function Safety Population 
Figure 3.6.1.6 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Weight Safety Population 
Figure 3.6.1.7 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline MAO-B Inhibitor Medications Safety 
Population 
Figure 3.6.1.8 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Dopamine Agonist Medications Safety 
Population 
Figure 13.6.1.9 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Levodopa Dose Safety Population 
Figure 13.6.1.10 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Time since PD Diagnosis in Years Safety Population 
Figure 13.6.1.11 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age at PD Diagnosis Safety Population 
Figure 13.6.1.12 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Prior Deep Brain Stimulation Safety Population 
Figure 13.6.1.13 Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Geographic Region Safety Population 
Figure 3.6.2.1 Kaplan-Meier Analysis of Time to Onset of AE (Falls) Safety Population 
Figure 3.6.2.2 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Gender Safety Population 
Figure 3.6.2.3 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age Safety Population 
Figure 3.6.2.4 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Race Safety Population 
Figure 3.6.2.5 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Renal Function Safety Population 
Figure 3.6.2.6 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Weight Safety Population 
Figure 3.6.2.7 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline MAO-B Inhibitor Medications Safety Population 
Figure 3.6.2.8 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Dopamine Agonist Medications Safety Population 


Adamas Pharmaceuticals, Inc. 
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Figure 3.6.2.9 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Levodopa Dose Safety Population 
Figure 3.6.2.10 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Time since PD Diagnosis in Years Safety Population 
Figure 3.6.2.11 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age at PD Diagnosis Safety Population 
Figure 3.6.2.12 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Prior Deep Brain Stimulation Safety Population 
Figure 3.6.2.13 Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Geographic Region Safety Population 
Figure 3.6.3.1 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) Safety Population 
Figure 3.6.3.2 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Gender Safety Population 
Figure 3.6.3.3 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age Safety Population 
Figure 3.6.3.4 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Race Safety Population 
Figure 3.6.3.5 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Renal Function Safety Population 
Figure 3.6.3.6 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Weight Safety Population 
Figure 3.6.3.7 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline MAO-B Inhibitor Medications Safety Population 
Figure 3.6.3.8 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Dopamine Agonist Medications Safety 
Population 
Figure 3.6.3.9 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Levodopa Dose Safety Population 
Figure 3.6.3.10 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Time since PD Diagnosis in Years Safety Population 
Figure 3.6.3.11 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age at PD Diagnosis Safety Population 
Figure 3.6.3.12 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Prior Deep Brain Stimulation Safety Population 
Figure 3.6.3.13 Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Geographic Region Safety Population 
 


Adamas Pharmaceuticals, Inc. 
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Figure 3.1 
Kaplan-Meier Analysis of Time to Study Drug Discontinuation 
Safety Population  
 
 
Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored if study drug was not 
discontinued at or before the last contact. 
Source Data: Listing 2.1.3, Table 1.1.3 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
Programming note: All treatment/analysis groups will be presented.  


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
  
Figure 3.6.1.1 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) 
Safety Population  
 
 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.2 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
Programming note: Only Placebo and 340mg ADS-5102 will be presented.  


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
Figure 3.6.1.2 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Gender 
Safety Population  
 
                    Gender: Female 
 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.3 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   


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Figure 3.6.1.2 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Gender 
Safety Population 
 
          Gender: Male 
 
 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.3 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   


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Figure 3.6.1.3 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age 
Safety Population  
 
Repeat of 3.6.1.2 
 
Age:  
1. 
<65 
2. 
≥65 
3. 
≥65 to <75 
4. 
≥75 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.4 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
Figure 3.6.1.4 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Race 
Safety Population  
 
Repeat of 3.6.1.2 
 
Race:  
1. 
White 
2. 
Non-White 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.5 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 


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Figure 3.6.1.5 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Renal Function 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Renal Function:  
1. 
Estimated GFR <60 
2. 
Estimated GFR ≥60 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.6 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
Figure 3.6.1.6 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Weight 
Safety Population  
 
Repeat of 3.6.1.2 
 
Weight:  
1. 
< median 
2. 
≥ median 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.7 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.1.7 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline MAO-B Inhibitor Medications 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline MAO-B Inhibitors:  
1. 
Yes 
2. 
No 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.8 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 3.6.1.8 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Dopamine Agonist Medications 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Dopamine Agonist Medications:  
1. 
Yes 
2. 
No 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.9 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 13.6.1.9 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Baseline Levodopa Dose 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Levodopa Dose:  
1. 
< median 
2. 
≥ median 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.10 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 13.6.1.10 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Time since PD Diagnosis in Years 
Safety Population  
 
Repeat of 3.6.1.2 
 
Time since PD Diagnosis in Years:  
1. 
< median 
2. 
≥ median 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.11 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 13.6.1.11 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Age at PD Diagnosis 
Safety Population  
 
Repeat of 3.6.1.2 
 
Age at PD Diagnosis:  
1. 
< median 
2. 
≥ median 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.12 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 13.6.1.12 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Prior Deep Brain Stimulation 
Safety Population  
 
Repeat of 3.6.1.2 
 
Prior Deep Brain Stimulation:  
1. 
Yes 
2. 
No 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.13 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 13.6.1.13 
Kaplan-Meier Analysis of Time to Onset of AE (Neuropsychiatric) by Geographic Region 
Safety Population  
 
Repeat of 3.6.1.2 
 
Geographic Region:  
1. 
European Union 
2. 
North America 
The Neuropsychiatric category combines the following System Organ Classes: Nervous system disorder and Psychiatric 
disorder. Analysis Day is the number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact 
date if no AE (Neuropsychiatric) occurred. 
Source Data: Listing 2.6.1, Table 1.6.10.14 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM 


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 Figure 3.6.2.1 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) 
Safety Population  
 
Repeat of 3.6.1.1 
 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.2 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
 
 
 
Figure 3.6.2.2 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Gender 
Safety Population  
 
Repeat of 3.6.1.2 
 
Gender:  
1. 
Female 
2. 
Male 
 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.3 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   


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Figure 3.6.2.3 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age 
Safety Population  
 
Repeat of 3.6.1.2 
 
Age:  
1. 
<65 
2. 
≥65 
3. 
≥65 to <75 
4. 
≥75 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.4 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
Figure 3.6.2.4 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Race 
Safety Population  
 
Repeat of 3.6.1.2 
 
Race:  
1. 
White 
2. 
Non-White 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.5 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 


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Figure 3.6.2.5 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Renal Function 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Renal Function:  
1. 
Estimated GFR <60 
2. 
Estimated GFR ≥60 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.6 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
 
Figure 3.6.2.6 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Weight 
Safety Population  
 
Repeat of 3.6.1.2 
 
Weight:  
1. 
> median 
2. 
≥ median 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.7 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.2.7 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline MAO-B Inhibitor Medications 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline MAO-B Inhibitors:  
1. 
Yes 
2. 
No 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.8 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 
 Figure 3.6.2.8 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Dopamine Agonist Medications 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Dopamine Agonist Medications:  
1. 
Yes 
2. 
No 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.9 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.2.9 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Baseline Levodopa Dose 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Levodopa Dose:  
1. 
< median 
2. 
≥ median 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.10 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 3.6.2.10 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Time since PD Diagnosis in Years 
Safety Population  
 
Repeat of 3.6.1.2 
 
Time since PD Diagnosis in Years:  
1. 
< median 
2. 
≥ median 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.11 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.2.11 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Age at PD Diagnosis 
Safety Population  
 
Repeat of 3.6.1.2 
 
Age at PD Diagnosis:  
1. 
< median 
2. 
≥ median 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.12 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 3.6.2.12 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Prior Deep Brain Stimulation 
Safety Population  
 
Repeat of 3.6.1.2 
 
Prior Deep Brain Stimulation:  
1. 
Yes 
2. 
No 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.13 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.2.13 
Kaplan-Meier Analysis of Time to Onset of AE (Falls) by Geographic Region 
Safety Population  
 
Repeat of 3.6.1.2 
 
Geographic Region:  
1. 
European Union 
2. 
North America 
The Falls category combines all Preferred Terms that contain the term “Fall” or “Falls”. Analysis Day is the number of 
days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Falls) occurred. 
Source Data: Listing 2.6.1, Table 1.6.11.14 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 


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Figure 3.6.3.1 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) 
Safety Population  
 
Repeat of 3.6.1.1 
 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.2 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
 
 
 
Figure 3.6.3.2 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Gender 
Safety Population  
 
Repeat of 3.6.1.2 
 
Gender:  
1. 
Female 
2. 
Male 
 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.3 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   


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Figure 3.6.3.3 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age 
Safety Population  
 
Repeat of 3.6.1.2 
 
Age:  
1. 
<65 
2. 
≥65 
3. 
≥65 to <75 
4. 
≥75 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.4 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
Figure 3.6.3.4 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Race 
Safety Population  
 
Repeat of 3.6.1.2 
 
Race:  
1. 
White 
2. 
Non-White 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.5 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
Figure 3.6.3.5 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Renal Function 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Renal Function:  
1. 
Estimated GFR <60 
2. 
Estimated GFR ≥60 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.6 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM   
 
Figure 3.6.3.6 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Weight 
Safety Population  
 
Repeat of 3.6.1.2 
 
Weight:  
1. 
< median 
2. 
≥ median 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.7 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


Adamas Pharmaceuticals, Inc. 
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ADS-5102 Integrated Summary of Safety 
 
 
Figure 3.6.3.7 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline MAO-B Inhibitor Medications 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline MAO-B Inhibitors:  
1. 
Yes 
2. 
No 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.8 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 3.6.3.8 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Dopamine Agonist Medications 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Dopamine Agonist Medications:  
1. 
Yes 
2. 
No 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.9 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


Adamas Pharmaceuticals, Inc. 
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Figure 3.6.3.9 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Baseline Levodopa Dose 
Safety Population  
 
Repeat of 3.6.1.2 
 
Baseline Levodopa Dose:  
1. 
< median 
2. 
≥ median 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.10 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 3.6.3.10 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Time since PD Diagnosis in Years 
Safety Population  
 
Repeat of 3.6.1.2 
 
Time since PD Diagnosis in Years:  
1. 
< median 
2. 
≥ median 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.11 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.3.11 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Age at PD Diagnosis 
Safety Population  
 
Repeat of 3.6.1.2 
 
Age at PD Diagnosis:  
1. 
< median 
2. 
≥ median 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.12 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  
 Figure 3.6.3.12 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Prior Deep Brain Stimulation 
Safety Population  
 
Repeat of 3.6.1.2 
 
Prior Deep Brain Stimulation:  
1. 
Yes 
2. 
No 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.13 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM  


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Figure 3.6.3.13 
Kaplan-Meier Analysis of Time to Onset of AE (Hallucinations) by Geographic Region 
Safety Population  
 
Repeat of 3.6.1.2 
 
Geographic Region:  
1. 
European Union 
2. 
North America 
The Hallucinations category combines all Preferred Terms that contain the term “Hallucination”. Analysis Day is the 
number of days since Analysis Day 1 + 1. Subjects will be censored at their last contact date if no AE (Hallucinations) 
occurred. 
Source Data: Listing 2.6.1, Table 1.6.12.14 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY HH:MM