Open-Label Safety Study of ADS-5102 (Amantadine HCl) Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia (LID)
Phase: PHASE3
Conditions: Dyskinesia, Levodopa Induced Dyskinesia (LID), Parkinson's Disease (PD)
Sponsor: Adamas Pharmaceuticals, Inc.

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.
oate U U
/ 7J^-|-V ao tf
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.
l?tuhltr(
Date
ûl
Date
11 fialq 20 ts
Date
U
1A5ûLU "2lf
Date
CONFIDENTIAL and PROPRIETARY

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 2 of 74 
 
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. 
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 3 of 74 
 
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.   
 
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 4 of 74 
 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 5 of 74 
 
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). 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 6 of 74 
 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 7 of 74 
 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 8 of 74 
 
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 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 9 of 74 
 
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; 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 10 of 74 
 
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.   

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 11 of 74 
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

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 12 of 74 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 13 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 14 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 15 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 16 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 17 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 18 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 19 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 20 of 74 
CONFIDENTIAL and PROPRIETARY 
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). 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 21 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 22 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 23 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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.  
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 24 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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.  

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 25 of 74 
 
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 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.   
 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 26 of 74 
CONFIDENTIAL and PROPRIETARY 
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]). 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 27 of 74 
CONFIDENTIAL and PROPRIETARY 
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).

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 28 of 74 
CONFIDENTIAL and PROPRIETARY 
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;

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 29 of 74 
CONFIDENTIAL and PROPRIETARY 
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;

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 30 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 31 of 74 
CONFIDENTIAL and PROPRIETARY 
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

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 32 of 74 
 
CONFIDENTIAL and PROPRIETARY 
 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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 33 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 34 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 35 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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.  

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 36 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 37 of 74 
CONFIDENTIAL and PROPRIETARY 
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) 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 38 of 74 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 39 of 74 
CONFIDENTIAL and PROPRIETARY 
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.   

ADS-5102 for Treatment of LID 
16 July 2015 
Adamas Pharmaceuticals, Inc.
Protocol ADS-AMT-PD302 (Amendment 4) 
Page 40 of 74 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 41 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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; 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 42 of 74 
 
CONFIDENTIAL and PROPRIETARY 
 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;  

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 43 of 74 
 
CONFIDENTIAL and PROPRIETARY 
 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;  

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 44 of 74 
 
CONFIDENTIAL and PROPRIETARY 
 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; 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 45 of 74 
 
CONFIDENTIAL and PROPRIETARY 
 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). 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 46 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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). 
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 47 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 48 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 49 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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).   

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 50 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 51 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 52 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 53 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 54 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 55 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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.  

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 56 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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). 
 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 57 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 58 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 59 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 60 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 61 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 62 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 
 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 63 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 64 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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. 

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 65 of 74 
 
CONFIDENTIAL and PROPRIETARY 
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.  

ADS-5102 for Treatment of LID 
 
16 July 2015  
Adamas Pharmaceuticals, Inc.              Protocol ADS-AMT-PD302 (Amendment 4) 
Page 66 of 74 
 
CONFIDENTIAL and PROPRIETARY 
20. 
APPENDICES