Clinical trial NCT03877510
Conditions: Parkinson Disease
Keywords: motor fluctuations IPX203
Sponsor: Impax Laboratories, LLC
Start date: 2019-04-03; Completion date: 2022-03-21
Enrollment: 419 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the long-term safety and clinical utility of IPX203 in the treatment of participants with advanced Parkinson's disease (PD) who have motor fluctuations.

Detailed description:
This is a 9-month, multicenter open-label safety extension study. Participants who have successfully completed Study NCT03670953 \[A Randomized Controlled Study to Compare the Safety and Efficacy of IPX203 with Immediate-Release (IR) Carbidopa-Levodopa (CD-LD) in Parkinson's Disease Patients with Motor Fluctuations\] may have the opportunity to enroll in this open-label study.

Arms: arm 1: All participants received oral administration of extended-release capsules IPX203 dosing regimen that was determined at the end of the IPX203 dose conversion period of Study IPX203-B16-02 (NCT03670953) for nine months of open-label therapy. The dose and dosing frequency was determined by the investigator to achieve the optimal balance of efficacy and safety.
Interventions: intervention 1: IPX203
Intervention descriptions: intervention 1: IPX203 extended release capsules

Protocol documents:
Prot_000.pdf: 
 
Title: Open Label Extension (OLE) Study of the Safety and 
Clinical Utility of IPX203 in PD Patients with Motor Fluctuations 
Date: November 26, 2018 
NCT03877510 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
Page 1 of 112 
IPX203 (CARBIDOPA-LEVODOPA) 
EXTENDED-RELEASE CAPSULES 
IPX203-B16-03 
AN OPEN-LABEL EXTENSION STUDY OF THE 
SAFETY AND CLINICAL UTILITY OF IPX203 IN 
PARKINSON’S DISEASE PATIENTS WITH MOTOR 
FLUCTUATIONS 
SPONSOR 
Impax Laboratories, LLC 
400 Crossing Boulevard, Third Floor 
Bridgewater, NJ 08807-2863 
Original Protocol, 25 April 2018 
Amendment 1, 22 June 2018 
Amendment 2, 26 November 2018 
CONFIDENTIALITY STATEMENT 
All information provided is the property of Impax Laboratories, LLC and may not be divulged, 
published or otherwise disclosed without written consent of Impax.  All information provided to 
the Investigator by the Sponsor, including clinical observations at the investigative site, shall be 
held strictly confidential and confined to the clinical personnel involved in conducting the study, 
under the supervision of the Investigator.  This includes but is not limited to preclinical data, 
protocols, case report forms, and verbal or written communications.  This information may be 
related in confidence to the Institutional Review Board or other committees functioning in a 
similar capacity.  All reports, subject samples, data published or submitted to third parties will be 
identified by a coded number and initials only in order to maintain subject confidentiality. 




Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 3 of 112 
INVESTIGATOR’S AGREEMENT 
 
Protocol No.: 
IPX203-B16-03 
Protocol Title: 
An Open-Label Extension Study of the Safety and Clinical Utility of IPX203 
in Parkinson’s Disease Patients with Motor Fluctuations 
 
 
I have read this protocol and agree to conduct the study as outlined herein, complying with the 
obligations and requirements of clinical investigators and all other requirements of International 
Conference on Harmonization (ICH), Good Clinical Practice (GCP), and the appropriate 
regulatory authority. 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this clinical study.  I will discuss this material with them to 
ensure that they are fully informed regarding the study medication, the conduct of the study, and 
the obligations of confidentiality. 
 
 
_________________________________________ 
___________________ 
Principal Investigator’s signature 
Date 
 
 
_________________________________________ 
Principal Investigator’s printed name 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 4 of 112 
STUDY CONTACT INFORMATION 
Changes in Impax study personnel listed on this page do not require a protocol amendment. 
Role  
Name and Contact Information 
Sponsor 
Impax Laboratories, LLC 
400 Crossing Boulevard, Third Floor 
Bridgewater, NJ 08807-2863 
(732) 595-4600 
Serious Adverse Event 
Reporting 
FAX:  (866) 954-2057 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 5 of 112 
1. 
SYNOPSIS 
Name of Sponsor/Company: Impax Laboratories, LLC (Impax) 
Name of Investigational Product: IPX203 (carbidopa-levodopa) Extended-Release Capsules 
Name of Active Ingredients: carbidopa (CD), levodopa (LD) 
Protocol Title: An Open-Label Extension Study of the Safety and Clinical Utility of IPX203 
in Parkinson’s Disease Patients with Motor Fluctuations 
Protocol No.:  IPX203-B16-03 
Study center(s):  Multicenter 
Phase of Development:  Phase 3 
Objectives:   To evaluate the long-term safety and clinical utility of IPX203 in the treatment 
of subjects with advanced Parkinson’s disease (PD) who have motor fluctuations. 
Methodology:  This is a 9-month, multicenter open-label safety extension study.  Subjects 
who have successfully completed Study IPX203-B16-02 (A Randomized Controlled Study to 
Compare the Safety and Efficacy of IPX203 with Immediate-Release Carbidopa-Levodopa in 
Parkinson’s Disease Patients with Motor Fluctuations) may have the opportunity to enroll in 
this open-label study.  This study will consist of a baseline visit (Visit 1) followed by 3 visits 
(Visits 2 to 4) spaced at approximately 3-month intervals.  For subjects who successfully 
complete Study IPX203-B16-02, the baseline visit (Visit 1) of this study will occur coincident 
with the End of Study (EOS) Visit 7 of the preceding study.  After providing written informed 
consent (and signing Health Insurance Portability and Accountability Act [HIPAA] 
authorization for subjects at United States [US] sites only), confirmation of eligibility and 
baseline procedures will be performed.  Subjects will be initially started on the final IPX203 
dosing regimen that was determined during the IPX203 dose conversion period of Study 
IPX203-B16-02.  Investigators are permitted to adjust the dosing regimen of IPX203 during 
this study to achieve the optimal balance of efficacy and safety and any changes will be 
recorded. 
Subjects may continue to take their non-LD-containing PD concomitant medications 
(including dopamine agonists, amantadine, and selective monoamine oxidase-B (MAO-B) 
inhibitors [safinamide, rasagiline and selegiline]) during the study.  Changes in doses or in 
dosing regimens of all non-CD-LD PD medications and/or the addition of new non-CD-LD 
PD medications will be captured.  Supplemental CD and benserazide, apomorphine, and the 
addition of catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone, opicapone, and 
tolcapone) can be initiated during this study. 
Adverse events (AEs), supine and standing orthostatic vital signs, and concomitant 
medications will be evaluated throughout the course of the study.  Electrocardiograms (ECGs), 
clinical laboratory tests, physical examinations, and the Columbia-Suicide Severity Rating 
Scale (C-SSRS) will also be performed.  The following clinical utility measures will be 
assessed:  Patient Global Impression of Severity (PGI-S), Clinician Global Impression of 
Severity (CGI-S), Treatment Satisfaction Assessment (TSA), Parkinson’s Disease Sleep Scale-


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 6 of 112 
2 (PDSS-2), the 39-item Parkinson’s Disease Questionnaire (PDQ-39), Parkinson Anxiety 
Scale (PAS), Non-Motor Symptom assessment scale (NMSS) for Parkinson’s disease, 
Gastroparesis Cardinal Symptom Index (GCSI), The Movement Disorder Society Unified 
Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I to IV, 12-Item Zarit Burden 
Interview (ZBI-12), and Early Morning Symptoms Questionnaire (EMSQ).  Visit 4 is the end 
of study visit (EOS). 
Number of subjects (planned):  Subjects who successfully complete IPX203-B16-02 will be 
eligible to enroll in this open-label extension (OLE) study; it is estimated that approximately 
300 subjects will enroll. 
Diagnosis and main criteria for inclusion: 
Inclusion Criteria 
• Successfully completed Study IPX203-B16-02. 
• Able to provide written informed consent prior to the conduct of any study-specific 
procedures. 
• Female subjects of childbearing potential must have a negative urine pregnancy test at 
the baseline visit (Visit 1). 
• Agrees to use a medically acceptable method of contraception throughout the study and 
for 6 weeks after completing the study. 
Exclusion Criteria 
• Intends to use any doses of Rytary® or Duopa™ during this study. 
• Plans to use an investigational treatment other than IPX203 during the course of this 
study. 
• Neurosurgical ablation treatment for PD is planned or anticipated during the study 
period.  Implantation of a deep brain stimulator (DBS) for the treatment of PD is 
permitted during this study. 
• Subjects who, in the opinion of the clinical investigator, should not participate in the 
study. 
Investigational product, dosage and mode of administration: IPX203 (carbidopa-levodopa) 
Extended-Release capsules for oral administration, provided in 4 dose strengths: 
• IPX203 35-140 mg CD-LD capsule 
• IPX203 52.5-210 mg CD-LD capsule 
• IPX203 70-280 mg CD-LD capsule 
• IPX203 87.5-350 mg CD-LD capsule 
Reference therapy, dosage and mode of administration: None 
Duration of treatment:  Nine (9) months of open-label therapy with IPX203. 
Criteria for evaluation: 
• Safety: AEs, supine and standing orthostatic vital signs, and concomitant medications 
evaluated throughout the course of the study.  ECGs, clinical laboratory tests, physical 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 7 of 112 
examinations, and the C-SSRS will also be performed. 
• Clinical Utility Measures: PGI-S, CGI-S, TSA, PDSS-2, PDQ-39, PAS, NMSS, GCSI, 
MDS-UPDRS Part I to IV, ZBI-12, and EMSQ will be assessed at every visit. 
Statistical methods:  For MDS-UPDRS, the total score (Parts I+II+III+IV), each of its 
components (Parts I through IV), and Parts II + Part III will be summarized across each of the 
time points in the trial (Baseline/Visit 1, Month 3, Month 6, and Month 9) to allow for 
assessment of the sustainability of the clinical effect of IPX203 over the 9-month study 
duration.  Similarly, the PGI-S, CGI-S, TSA, PDSS-2, PDQ-39, PAS, NMSS, GCSI, ZBI-12, 
and EMSQ will be summarized over time. 
The safety analysis will include all subjects who received at least one dose of study 
medication.  The incidence of treatment-emergent AEs and serious adverse events (SAEs) will 
be summarized.  Additionally, laboratory test data, physical examinations, vital signs, ECGs, 
and C-SSRS will be summarized across each time point in the trial. 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 8 of 112 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
SIGNATURE PAGE .......................................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
STUDY CONTACT INFORMATION ...........................................................................................4 
1. 
SYNOPSIS ...................................................................................................................5 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................8 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................12 
4. 
INTRODUCTION ......................................................................................................14 
5. 
TRIAL OBJECTIVES ................................................................................................18 
6. 
INVESTIGATIONAL PLAN .....................................................................................19 
6.1. 
Overall Study Design ..................................................................................................19 
6.2. 
Number of Subjects ....................................................................................................20 
6.3. 
Treatment Assignment ................................................................................................20 
6.4. 
Dosing and Dose Determination Criteria ...................................................................20 
6.5. 
Dose Adjustment Criteria ...........................................................................................20 
6.6. 
Criteria for Study Termination ...................................................................................20 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................21 
7.1. 
Subject Inclusion Criteria ...........................................................................................21 
7.2. 
Subject Exclusion Criteria ..........................................................................................21 
7.3. 
Subject Withdrawal Criteria .......................................................................................21 
8. 
STUDY PROCEDURES ............................................................................................23 
8.1. 
Visit 1 (Baseline) ........................................................................................................27 
8.2. 
Visit 2 (Month 3) ........................................................................................................27 
8.2.1. 
Prior to Visit 2 ............................................................................................................27 
8.2.2. 
At Visit 2.....................................................................................................................27 
8.3. 
Visit 3 (Month 6) ........................................................................................................28 
8.3.1. 
Prior to Visit 3 ............................................................................................................28 
8.3.2. 
At Visit 3.....................................................................................................................28 
8.4. 
Visit 4 − Study Completion (Month 9) or Early Discontinuation ..............................29 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 9 of 112 
8.4.1. 
Prior to Visit 4 ............................................................................................................29 
8.4.2. 
At Visit 4.....................................................................................................................29 
8.5. 
Early Termination .......................................................................................................30 
8.6. 
Blood Volume .............................................................................................................30 
9. 
TREATMENT OF SUBJECTS ..................................................................................31 
9.1. 
Description of Study Drug ..........................................................................................31 
9.2. 
Concomitant Medications ...........................................................................................31 
9.2.1. 
Permitted PD Medications and Surgical Treatments ..................................................31 
9.2.2. 
Prohibited PD Medications and Surgical Treatments .................................................31 
9.3. 
Treatment Compliance ................................................................................................32 
9.4. 
Randomization and Blinding ......................................................................................32 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................33 
10.1. 
Study Drug ..................................................................................................................33 
10.2. 
Study Drug Packaging and Labeling ..........................................................................33 
10.3. 
Study Drug Storage .....................................................................................................33 
10.4. 
Study Drug Administration.........................................................................................34 
10.5. 
Study Drug Dispensing and Accountability ...............................................................34 
10.6. 
Study Drug Handling and Disposal ............................................................................34 
11. 
ASSESSMENT OF EFFICACY ................................................................................35 
11.1. 
Patient and Investigator Global Assessments .............................................................35 
11.2. 
Treatment Satisfaction Assessment (TSA) .................................................................35 
11.3. 
Parkinson’s Disease Sleep Scale-2 (PDSS-2) .............................................................35 
11.4. 
Parkinson’s Disease Questionnaire-39 (PDQ-39) ......................................................35 
11.5. 
Parkinson Anxiety Scale (PAS) ..................................................................................35 
11.6. 
Non-Motor Symptom Assessment Scale for Parkinson’s Disease (NMSS) ..............35 
11.7. 
Movement Disorders Society Version of Unified Parkinson’s Disease Rating 
Scale (MDS-UPDRS) .................................................................................................36 
11.8. 
12-Item Zarit Burden Interview (ZBI-12) ..................................................................36 
11.9. 
Early Morning Symptom Questionnaire (EMSQ) ......................................................36 
12. 
ASSESSMENT OF SAFETY .....................................................................................37 
12.1. 
Safety Parameters .......................................................................................................37 
12.2. 
Adverse Events ...........................................................................................................37 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 10 of 112 
12.2.1. 
Definition of Adverse Event .......................................................................................37 
12.2.2. 
Recording Adverse Events .........................................................................................37 
12.2.3. 
Follow-up ....................................................................................................................38 
12.2.4. 
Relationship to Study Drug ........................................................................................38 
12.2.5. 
Assessment of Severity ...............................................................................................38 
12.3. 
Serious Adverse Events ..............................................................................................38 
12.3.1. 
Definition of Serious Adverse Event ..........................................................................38 
12.3.2. 
Reporting Serious Adverse Events .............................................................................39 
12.4. 
Pregnancy ...................................................................................................................39 
12.5. 
Other Safety Parameters and Related Information .....................................................40 
13. 
STATISTICS ..............................................................................................................41 
13.1. 
Study Design and Sample Size Estimation .................................................................41 
13.2. 
Demographics and Baseline Characteristics ...............................................................41 
13.3. 
Analysis of Efficacy/Clinical Utility Data ..................................................................41 
13.4. 
Analysis of Dosing Data .............................................................................................42 
13.5. 
Population Analysis and Handling of Dropouts .........................................................42 
13.6. 
Analysis of Safety .......................................................................................................42 
14. 
ADMINISTRATIVE PROCEDURES .......................................................................43 
14.1. 
Guidelines for Good Clinical Practice ........................................................................43 
14.2. 
Institutional Review Board Approval .........................................................................43 
14.3. 
Informed Consent .......................................................................................................43 
14.4. 
Study Monitoring ........................................................................................................43 
14.5. 
Protocol Amendments ................................................................................................43 
14.6. 
Termination of Study ..................................................................................................44 
14.7. 
Case Report Forms .....................................................................................................44 
14.8. 
Investigator’s Final Conduct Report ...........................................................................44 
14.9. 
Records Retention .......................................................................................................44 
15. 
PUBLICATION POLICY ..........................................................................................45 
16. 
LIST OF REFERENCES ............................................................................................46 
17. 
APPENDICES ............................................................................................................48 
APPENDIX A. RECOMMENDATIONS FOR IPX203 DOSING ............................................49 
APPENDIX B. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) ..................50 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 11 of 112 
APPENDIX C. CLINICAL LABORATORY STUDIES ...........................................................54 
APPENDIX D. MOVEMENT DISORDERS SOCIETY VERSION OF THE UNIFIED 
PARKINSON’S DISEASE RATING SCALE (MDS-UPDRS) ................................55 
APPENDIX E. PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) .........................89 
APPENDIX F. CLINICAL GLOBAL IMPRESSION OF SEVERITY (CGI-S) .......................90 
APPENDIX G. 39-ITEM PARKINSON’S DISEASE QUESTIONNAIRE (PDQ-39) .............91 
APPENDIX H. GASTROPARESIS CARDINAL SYMPTOM INDEX (GCSI).......................97 
APPENDIX I. NON-MOTOR SYMPTOM ASSESSMENT SCALE FOR 
PARKINSON’S DISEASE (NMSS) ..........................................................................98 
APPENDIX J. PARKINSON’S DISEASE SLEEP SCALE-2 (PDSS-2) ................................101 
APPENDIX K. PARKINSON ANXIETY SCALE (PAS) .......................................................103 
APPENDIX L. TREATMENT SATISFACTION ASSESSMENT (TSA) ..............................107 
APPENDIX M. 12-ITEM ZARIT BURDEN INTERVIEW (ZBI-12) .....................................108 
APPENDIX N. EARLY MORNING SYMPTOMS QUESTIONNAIRE (EMSQ) .................109 
APPENDIX O. COMPONENTS OF IPX203...........................................................................112 
 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................12 
Table 2: 
Events Schedule for Study IPX203-B16-03 ...............................................................24 
Table 3: 
Study Drugs for Study IPX203-B16-03 .....................................................................31 
 
 
LIST OF FIGURES 
Figure 1: 
IPX203-B16-03 Study Flow Chart .............................................................................20 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 12 of 112 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
AADC 
aromatic amino acid decarboxylase 
AE 
adverse event 
CD 
carbidopa 
CGI-S 
Clinical Global Impression of Severity 
CR 
controlled release 
CRF 
case report form 
COMT 
catechol-O-methyltransferase 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DBS 
deep brain stimulator or 
deep brain stimulation 
ECG 
electrocardiogram 
EMSQ 
Early Morning Symptoms Questionnaire 
EOS 
end of study 
ER 
extended release 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GCSI 
Gastroparesis Cardinal Symptom Index 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
independent ethics committee 
IR 
immediate release 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 13 of 112 
Abbreviation or Specialist Term 
Explanation 
IRB 
institutional review board 
IWRS 
interactive web response system 
LD 
levodopa 
MAO 
monoamine oxidase inhibitors 
MAO-A 
MAO type A inhibitors 
MAO-B 
MAO type B inhibitors 
MDS-UPDRS 
Movement Disorders Society version of the Unified Parkinson’s 
Disease Rating Scale 
M-EDL 
Motor Aspects of Experiences of Daily Living 
m-MIDI 
Modified-Minnesota Impulsive Disorders Interview 
nM-EDL 
Non-Motor Aspects of Experiences of Daily Living 
NMSS 
Non-Motor Symptom assessment scale for PD 
OLE 
open-label extension 
PAS 
Parkinson Anxiety Scale 
PD 
Parkinson’s disease 
PDQ-39 
39-item Parkinson’s Disease Questionnaire 
PDSS-2 
Parkinson’s Disease Sleep Scale-2 
PGI-S 
Patient Global Impression of Severity 
PK 
pharmacokinetic (adjective)  
pharmacokinetics (singular noun) 
PI 
principal investigator 
SAE 
serious adverse event 
TSA 
Treatment Satisfaction Assessment 
US 
United States 
ZBI-12 
12-Item Zarit Burden Interview 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 14 of 112 
4. 
INTRODUCTION 
Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the extrapyramidal 
nervous system.  Levodopa (LD) used in combination with carbidopa (CD) is considered the 
gold standard for the symptomatic treatment of PD.  LD is a dopamine precursor converted to 
dopamine by aromatic amino acid decarboxylase (AADC).  Carbidopa is an AADC inhibitor that 
does not cross the blood-brain barrier.  When used in combination with LD, CD increases the 
plasma half-life of LD from 50 minutes to 1.5 hours.  Carbidopa inhibits the conversion of LD 
into dopamine in the periphery, thereby reducing the peripheral side-effects caused by dopamine 
and increasing the amount of LD available for transport into the brain.  The administration of CD 
with LD reduces the dose of LD required to produce a dopaminergic response by about 
75 percent (Sinemet prescribing information). 
Due to its proven efficacy, LD is prescribed eventually to most subjects with PD.  However, 
long-term use of LD is associated with certain complications, including “wearing off” or “end-
of-dose effect,” where symptom control decreases and the drug effects wear off sooner.  As the 
disease progresses further, motor complications, namely dyskinesias and motor “On/Off” 
fluctuations, develop in about 50% of the patients after 5 years of treatment (Fahn 1999).  Such 
motor complications can be a significant source of disability and their management is a major 
unmet need in the treatment of PD. 
Mechanisms underlying motor complications involving dyskinesias and “On/Off” fluctuations in 
PD are unclear.  The pulsatile nature of standard orally administered LD is thought to contribute 
to the appearance of motor complications.  Chronic intermittent pulsatile stimulation of the 
dopamine receptors that are under tonic control contributes to the development of dyskinesia in 
PD animal models as compared to animals treated with continuous infusion (Juncos et al 1989, 
Engber et al 1989, Blanchet et al 1995).  In addition, unreliable absorption of LD potentially due 
to erratic gastric empting and variable in vivo dissolution of LD products is thought to contribute 
to the delay or inadequate response after oral dosing with standard CD-LD products (Melamed 
1986, Kurlan et al 1988, Stocchi et al 1994).  These findings suggest that motor complications in 
patients with PD may be less likely to develop with continuous dopaminergic stimulation. 
Intraduodenal infusion of LD has been shown to significantly reduce motor complications and to 
reduce “Off” time.  The findings of infusion studies in PD patients indicate that the maintenance 
of stable plasma LD concentrations and the avoidance of low trough levels are effective in 
reducing “Off” hours, increasing “On” hours without disabling dyskinesia, and reducing the 
severity of dyskinesia versus standard oral LD formulations (Mizuno 2007, Nilsson et al 2001, 
Nyholm et al 2005, Stocchi et al 2005).  These findings provide a strong rationale for the 
development of an extended-release (ER) oral formulation that delivers a constant LD plasma 
concentration in order to optimize relief of PD symptoms, and to minimize “Off” time and 
dyskinesia. 
IPX203 is an investigational product containing CD-LD that is being developed by Impax 
Laboratories, LLC (Impax).  The primary objective of the IPX203 program is to develop an 
extended release product that can attain therapeutic LD plasma concentrations rapidly and 
maintain constant LD plasma concentrations for a longer duration than currently approved 
products with minimal peak-to-trough fluctuations.  IPX203 is designed to be dosed 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 15 of 112 
approximately every 7 to 8 hours, based on the plasma LD concentration time profile observed in 
subjects with advanced PD (Study IPX203-B14-02 and IPX203-B16-01). 
Study IPX203-B14-02 characterized the PK and pharmacodynamics of IPX203 following a 
single dose in subjects with advanced PD versus immediate-release (IR) CD-LD and Rytary®.  
Twenty-six (26) subjects were randomized with 25 subjects completing all 3 treatments.  One 
subject discontinued study early due to subject withdrawal.  Administration of IPX203 yielded 
an initial increase in LD plasma concentrations that was similar to both IR CD-LD and Rytary 
but maintained LD concentrations longer.  IPX203 provided a longer pharmacodynamic duration 
of effect compared with IR CD-LD and Rytary, including “Off” time and “Good on” time based 
on the Assessment of Subject’s Motor State and on several of the MDS-UPDRS Part III 
improvement thresholds.  Of the 26 subjects who received at least one of the 3 treatments, 
9 subjects (34.6%) reported at least one treatment-emergent adverse event (AE).  None of these 
subjects reported a SAE nor did any subjects prematurely discontinue the study because of an 
AE.  Adverse events were reported by more subjects during IR CD-LD (28.0%) and IPX203 
(19.2%) than during Rytary (8.0%) treatment.  None of the reported AEs were classified as 
severe.  Adverse events reported by 2 or more subjects included dizziness (3 subjects), nausea 
(2 subjects), and hypertension (2 subjects).  The numbers of subjects reporting these AEs during 
any single treatment period were small (0 to 2 subjects).  Two subjects reported dizziness during 
IR CD-LD treatment and one subject each during IPX203 and Rytary treatments.  Hypertension 
was reported by a total of 2 subjects, both reporting this AE during IPX203 and IR CD-LD 
treatments and 1 subject during Rytary treatment.  Two subjects reported nausea only during the 
IR CD-LD treatment period.  Of the 9 subjects reporting AEs, 6 (23.1%) subjects reported AEs 
that were assessed as related to treatment, including all of the reports of dizziness, nausea, and 
dyskinesia (1 subject).  Most subjects reported AEs that were assessed as mild in severity, but 
during treatment with IPX203, 2 subjects (7.7%) reported moderate AEs (dyskinesia and 
hypertension), during IR CD-LD treatment 1 subject (4.0%) reported atrial flutter of moderate 
severity, and during Rytary treatment, 1 subject (4.0%) reported dyskinesia of moderate severity. 
The pharmacokinetics and pharmacodynamics of IPX203 were studied in a randomized, open-
label, rater-blinded, multicenter, 2-treatment, 2-period, multiple-dose crossover study (IPX203-
B16-01).  Twenty-eight (N=28) advanced PD subjects were randomized to 1 of 2 dosing 
sequences, with each treatment period lasting 15 days and separated by a 1-week wash-out 
period where subjects return to their usual stable pre-study CD-LD regimen.  The objectives of 
this study are to compare the PK, pharmacodynamics, efficacy, and safety of IPX203 with 
IR CD-LD after single and multiple dosing.  Subjects were permitted to take allowed non-CD-
LD-based PD medications throughout the study if dosing regimens had been stable for at least 
4 weeks.  Subjects were instructed to take their last dose of CD-LD no later than 10:00 PM on 
the evening prior to Day 1 of each treatment period and to withhold dosing for at least 5 hours 
before arriving at the site on Day 15 of each treatment period.  On Day 1 of the IR CD-LD 
treatment period, subjects were started with a single dose of their usual prestudy first morning 
IR CD-LD dose.  On Day 1 of the IPX203 treatment period, subjects were started with a single 
dose of IPX203 based on their usual prestudy first morning IR CD-LD dose using a LD 
conversion of 100 mg IR LD to 360 mg of IPX203 LD.  During the IR CD-LD treatment period, 
the initial dosing regimen of IR CD-LD was the same as the subject’s stable prestudy regimen.  
During the IPX203 treatment period, the IPX203 regimen for subsequent doses for the day was 
determined by identifying the most frequent prestudy IR LD dose in milligrams that the subject 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 16 of 112 
received in the afternoon and evening and administering IPX203 using a LD conversion of 
100 mg IR LD to 270 mg of IPX203 LD.  The protocol recommended that IPX203 be dosed 
approximately every 7 to 8 hours.  During Days 1 through 9 of both treatment periods, 
investigators had the opportunity to adjust each subject’s study medication regimen if necessary 
to optimize efficacy and safety.  Pharmacokinetics and pharmacodynamics (MDS-UPDRS Part 
III and Assessments of Subject’s Motor State) were periodically evaluated on Day 1 and Day 15 of 
each treatment period by qualified clinical staff who were blinded to dosing. 
Data from this multiple-dose study confirmed the PK and pharmacodynamic results observed in 
the single dose study with IPX203: 
• PK data from 27 subjects indicates IPX203 shows a rapid increase in LD 
concentrations followed by extended-release characteristics.  Following IPX203; 
initial increases in LD concentrations were comparable to that from IR CD-LD.  
Bioavailability of LD following IPX203 was ~89% relative to IR CD-LD.  LD 
plasma concentrations were sustained longer after IPX203 treatment than after 
IR CD-LD and support dosing every 8 hours.  No accumulation of LD was evident at 
steady-state following IPX203 or IR CD-LD.  Plasma LD concentrations following 
IPX203 were characterized by lower peak-to-trough fluctuation.  No time-variant or 
time-dependent changes were noted in PK of CD or LD following IPX203. 
• IPX203 demonstrated an onset of effect that was comparable to IR CD-LD in 
MDS-UPDRS Part III scores.  IPX203 prolonged the duration over which 
MDS-UPDRS Part III scores were improved by prespecified threshold changes from 
baseline (≥4, ≥7, and ≥13 units). 
• IPX203 provides a significant decrease in “Off” time and a significant increase in 
“Good on” time compared to IR CD-LD treatment on Day 1 and Day 15 when 
assessed by the Investigator’s Assessment of Subject’s Motor State.  Subjects treated 
with IPX203 did not experience a significant increase in “On” time with troublesome 
dyskinesia compared to IR CD-LD. 
• Subjects achieved significant improvements in “Off” time, “Good on” time, and 
frequency of motor state fluctuations based on the 3-day PD Diaries. 
• Twenty-eight subjects were enrolled in the multiple-dose study and 27 subjects 
completed both treatments.  Safety results were as follows: 
− One subject discontinued during the IPX203 treatment period due to an AE 
(orthostatic hypertension) that was considered possibly related to treatment. 
− A total of 39.3% (11/28) of treated subjects reported at least one treatment 
emergent AE, including 35.7% (10/28) during IPX203 treatment and 7.4% (2/27) 
during IR CD-LD treatment.  Eight subjects reported AEs that were related to 
treatment (8 subjects during IPX203 treatment and 1 during IR CD-LD 
treatment). 
− Two subjects experienced serious adverse events (SAEs).  One subject reported 
increased hypertension of mild severity during IPX203 treatment that was 
considered unrelated to treatment and resolved.  A second subject reported 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 17 of 112 
moderate to severe dehydration, diarrhea, and atrial fibrillation during the 
washout period that were considered unrelated to treatment and resolved. 
− AEs reported in 2 or more subjects included nausea (2), dizziness (2), and 
dyskinesia (5), all of mild or moderate severity, and all during the IPX203 
treatment. 
Study IPX203-B16-02 is a randomized, double-blind, double-dummy, active-control, parallel-
group, multicenter study designed to compare the efficacy, safety and tolerability of IPX203 with 
IR CD-LD in CD-LD-experienced subjects with advanced PD and motor fluctuations following 
13 weeks of therapy. 
Subjects who successfully complete Study IPX203-B16-02 may have the opportunity to enroll in 
this 9-month, open-label safety extension study. 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 18 of 112 
5. 
TRIAL OBJECTIVES 
The objective of this study is to evaluate the long-term safety and clinical utility of IPX203 in 
subjects with advanced Parkinson’s disease (PD) who have motor fluctuations. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 19 of 112 
6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
Subjects who have successfully completed Study IPX203-B16-02 (A Randomized Controlled 
Study to Compare the Safety and Efficacy of IPX203 with Immediate-Release Carbidopa-
Levodopa in Parkinson’s Disease Patients with Motor Fluctuations) may be offered the 
opportunity to enroll in this 9-month, multicenter open-label study (Figure 1).  The study consists 
of a baseline visit (Visit 1) followed by 3 visits (Visits 2 to 4) spaced at approximately 3-month 
intervals.  For subjects who successfully complete Study IPX203-B16-02, the baseline visit 
(Visit 1) of this study will occur coincident with the End of Study (EOS) Visit 7 of the preceding 
study.  After providing written informed consent (and signing Health Insurance Portability and 
Accountability Act [HIPAA] authorization for subjects at United States [US] sites only), 
confirmation of eligibility and baseline procedures will be performed.  Subjects will be initially 
started on the final IPX203 dosing regimen that was determined during the IPX203 dose 
conversion period of Study IPX203-B16-02.  Investigators are permitted to adjust the dosing 
regimen of IPX203 during this study to achieve the optimal balance of efficacy and safety and 
any changes will be recorded. 
Subjects may continue to take their non-LD-containing PD medications (including dopamine 
agonists, amantadine, and selective monoamine oxidase-B (MAO-B) inhibitors [safinamide, 
rasagiline and selegiline]) during the study.  Changes in doses or in dosing regimens of all non-
CD-LD PD medications and/or the addition of new non-CD-LD PD medications will be 
captured.  Supplemental CD and benserazide, apomorphine, and the addition of catechol-O-
methyltransferase (COMT) inhibitors (eg, entacapone, opicapone, and tolcapone) can be initiated 
during the study. 
Adverse events, supine and standing orthostatic vital signs, and concomitant medications will be 
evaluated throughout the course of the study.  Electrocardiograms (ECGs), clinical laboratory 
tests, physical examinations, and the Columbia-Suicide Severity Rating Scale (C-SSRS) will also 
be performed.  The following clinical utility measures will be assessed:  Patient Global 
Impression of Severity (PGI-S), Clinician Global Impression of Severity (CGI-S), Treatment 
Satisfaction Assessment (TSA), Parkinson’s Disease Sleep Scale-2 (PDSS-2), the 39-item 
Parkinson’s Disease Questionnaire (PDQ-39), Parkinson Anxiety Scale (PAS), Non-Motor 
Symptom assessment scale (NMSS) for Parkinson’s disease, Gastroparesis Cardinal Symptom 
Index (GCSI), The Movement Disorder Society Unified Parkinson’s Disease Rating Scale 
(MDS-UPDRS) Parts I to IV, 12-Item Zarit Burden Interview (ZBI-12), and Early Morning 
Symptoms Questionnaire (EMSQ).  Visit 4 is the end of study (EOS). 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 20 of 112 
Figure 1: 
IPX203-B16-03 Study Flow Chart 
 
 
 
 
 
 
 
6.2. 
Number of Subjects 
Subjects who successfully complete IPX203-B16-02 are eligible to enroll in this open-label 
extension (OLE) study; it is estimated that approximately 300 subjects will enroll. 
6.3. 
Treatment Assignment 
All subjects will receive IPX203. 
6.4. 
Dosing and Dose Determination Criteria 
Subjects will start on the IPX203 dosing regimen that was determined at the end of the IPX203 
dose conversion period of Study IPX203-B16-02 (Visit 4 of Study IPX203-B16-02). 
6.5. 
Dose Adjustment Criteria 
Investigators are permitted to adjust the dosing regimen of IPX203 during the study to achieve 
the optimal balance of efficacy and safety; all dosing changes will be recorded. 
Recommendations for dosing IPX203 are provided in Appendix A. 
6.6. 
Criteria for Study Termination 
The Sponsor has the right to terminate this study and remove all study material from the study 
site at any time for medical or administrative reasons.  The Sponsor will endeavor to give 
adequate notice to allow safe withdrawal of subjects from the study. 
Baseline 
Visit 1 
Month 9 
Visit 4 
End of Study 
Month 3 
Visit 2 
IPX203-B16-02 
Completers 
Month 6 
Visit 3 
~
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 21 of 112 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Subjects must meet all of the following inclusion criteria to qualify for enrollment.  Subjects who 
have any of the following exclusion criteria will not be enrolled in the study. 
7.1. 
Subject Inclusion Criteria 
1. Successfully completed Study IPX203-B16-02. 
2. Able to provide written informed consent prior to the conduct of any study-specific 
procedures. 
3. Female subjects of childbearing potential must have a negative urine pregnancy test at the 
baseline visit (Visit 1). 
4. Agrees to use a medically acceptable method of contraception throughout the study and 
for 6 weeks after completing the study.  Medically acceptable methods of contraception 
that may be used by the subject and/or partner include but are not limited to:  abstinence, 
oral contraception, NuvaRing or transdermal systems, diaphragm with vaginal 
spermicide, intrauterine device, condom and partner using vaginal spermicide, surgical 
sterilization (6 months), progestin implant or injection, or postmenopausal female (no 
menstrual period for ˃2 years) or vasectomy (˃6 months). 
7.2. 
Subject Exclusion Criteria 
1. Intends to use any doses of Rytary or Duopa™ during this study. 
2. Plans to use an investigational treatment other than IPX203 during the course of this 
study. 
3. Neurosurgical ablation treatment for PD is planned or anticipated during the study period.  
Implantation of a deep brain stimulator (DBS) for the treatment of PD is permitted during 
this study. 
4. Subjects who, in the opinion of the clinical investigator, should not participate in the 
study. 
7.3. 
Subject Withdrawal Criteria 
Site personnel should make every effort to conduct all protocol-specific procedures to complete 
the study.  A subject may be discontinued from the study due to the following reasons: 
1. Withdrawal by subject 
2. Adverse event 
3. Lack of efficacy 
4. Study terminated by Sponsor 
5. Protocol deviation 
6. Noncompliance with study drug 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 22 of 112 
7. Lost to follow-up 
8. Death 
9. Other 
Subjects who withdraw early from the study will not be replaced.  The reason or reasons for 
discontinuation will be specified and documented. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 23 of 112 
8. 
STUDY PROCEDURES 
The procedures to be performed at each study visit are summarized in Table 2. 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 24 of 112 
Table 2: 
Events Schedule for Study IPX203-B16-03 
 
Visit 1 
Baseline 
9 Months of 
IPX203 Therapy 
Study Drug 
Resupply 
Months 1-2 
Visit 2 
Study Drug 
Resupply 
Months 4-5 
Visit 3 
Study Drug 
Resupply 
Months 7-8 
Visit 4/ 
Early 
Termination 
Study Month 
0 
 
3 
 
6 
 
9 
ICF and HIPAA Authorization 
X 
 
 
 
 
 
 
Check Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
Update Medical History 
X 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
X 
Vital Signs 
X 
 
X 
 
X 
 
X 
Weight 
X 
 
X 
 
X 
 
X 
C-SSRS 
X 
 
X 
 
X 
 
X 
Clinical Laboratory Tests 
X 
 
X 
 
X 
 
X 
Urine Pregnancy Test 
X 
 
 
 
 
 
 
ECG 
X 
 
X 
 
X 
 
X 
MDS-UPDRS Parts I-IV 
X 
 
X 
 
X 
 
X 
PGI-S 
X 
 
X 
 
X 
 
X 
CGI-S 
X 
 
X 
 
X 
 
X 
PDQ-39 
X 
 
X 
 
X 
 
X 
GCSI 
X 
 
 
 
 
 
X 
NMSS 
X 
 
X 
 
X 
 
X 
PDSS-2 
X 
 
X 
 
X 
 
X 
PAS 
X 
 
X 
 
X 
 
X 
TSA 
 
 
X 
 
X 
 
X 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 25 of 112 
 
Visit 1 
Baseline 
9 Months of 
IPX203 Therapy 
Study Drug 
Resupply 
Months 1-2 
Visit 2 
Study Drug 
Resupply 
Months 4-5 
Visit 3 
Study Drug 
Resupply 
Months 7-8 
Visit 4/ 
Early 
Termination 
Study Month 
0 
 
3 
 
6 
 
9 
ZBI-12 
X 
 
X 
 
X 
 
X 
EMSQ 
X 
 
X 
 
X 
 
X 
Contact phone calls 
 
 
X 
 
X 
 
X 
Contact IWRS to dispense study medication 
X 
X 
X 
X 
X 
X 
 
Collect empty medication bottles and any unused 
study drug/Perform study drug accountability 
 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
 
X 
 
X 
 
X 
Concomitant Medications 
X 
 
X 
 
X 
 
X 
a Visit 1 is expected to occur on the same day as the End-of-Study Visit (Visit 7) of Study IPX203-B16-02 but not later than 1 week.  After the subject provides 
consent for this study, carry over and record information from procedures at the End-of-Study Visit of IPX203-B16-02 as the Baseline data for this study. 
b Subjects enrolled at sites in the United States (US) must sign HIPAA authorization prior to the conduct of any study-specific procedures. 
c Record vital signs (blood pressure, heart rate, respiratory rate, and temperature [Visit 1 and Study Exit only]) after subject has been resting supine for at least 
5 minutes, then record orthostatic blood pressure and heart rate after subject has been standing for approximately 2 minutes. 
d See Appendix B. 
e See Appendix C. 
f This test will be performed at Visit 1 of this study. 
g See Appendix D. 
h See Appendix E. 
i See Appendix F. 
j See Appendix G. 
k See Appendix H. 
l See Appendix I. 
m See Appendix J. 
n See Appendix K. 
o See Appendix L. 
p See Appendix M. 
q See Appendix N. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 26 of 112 
r 
Contact phone calls for Visits 2 through 4: 
•  Following Visit 1, contact subjects weekly for the first month and then approximately monthly thereafter between visits to review the subject’s medication 
dosing regimen. 
•  Instruct subjects to call the study site before making any changes to their IPX203 dosing regimen. 
•  Update and record concomitant medications and IPX203 dose adjustments. 
•  Contact subjects 1 day prior to Visits 2 to 4 to remind them to bring back any unused medication and empty medication bottles. 
CGI-S = Clinical Global Impression of Severity Scale; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EMSQ = Early Morning 
Symptoms Questionnaire; GCSI = Gastroparesis Cardinal Symptom Index; HIPAA = Health Insurance Portability and Accountability Act; ICF = informed 
consent form; IWRS = interactive web response system; PAS = Parkinson Anxiety Scale; PD = Parkinson’s disease; PDQ-39 = 39-Item Parkinson’s Disease 
Questionnaire; PDSS-2 = Parkinson’s Disease Sleep Scale-2; PGI-S = Patient Global Impression of Severity Scale; MDS-UPDRS = MDS version of Unified 
Parkinson’s Disease Rating Scale; NMSS = Non-Motor Symptom assessment scale for PD; TSA = Treatment Satisfaction Assessment; ZBI-12 = 12-Item Zarit 
Burden Interview. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 27 of 112 
8.1. 
Visit 1 (Baseline) 
Visit 1 is expected to occur on the same day as the End-of-Study Visit (Visit 7) of Study 
IPX203-B16-02.  After the subject provides consent for this study, carry over and record 
information from procedures at the End-of-Study Visit of IPX203-B16-02 as the baseline data 
for this study. 
After the subject has signed the informed consent (and HIPAA authorization for subjects at US 
sites), complete the following procedures and assessments: 
• Review and record study entry criteria (Section 7). 
• Update the subject’s medical history. 
• Perform urine pregnancy test for females of childbearing potential. 
• Complete the 12-Item Zarit Burden Interview (ZBI-12) (Appendix M). 
• Administer the Early Morning Symptoms Questionnaire (EMSQ) (Appendix N). 
• Contact the interactive web response system (IWRS) to dispense study drug. 
• Instruct the subject on dosing. 
• After Visit 1, contact subjects weekly for the first month and then approximately 
monthly thereafter to discuss the subject’s dosing regimen.  Record the subject’s 
current IPX203 dose regimen. 
• Instruct subjects to call the study site before making any changes to their IPX203 
dosing regimen. 
• Subjects may return for study drug resupply approximately every 1 to 2 months as 
needed. 
8.2. 
Visit 2 (Month 3) 
8.2.1. 
Prior to Visit 2 
Call the subjects prior to Visit 2 and remind them to bring any unused study medication and 
empty medication bottles to Visit 2. 
8.2.2. 
At Visit 2 
• Collect unused study drug and empty bottles. 
• Review study drug accountability. 
• Update IPX203 regimen (dose, frequency, number of capsules) and concomitant 
medications. 
• Assess vital signs after subject is supine for at least 5 minutes (blood pressure, heart 
rate, temperature and respiratory rate) and then assess orthostatic blood pressure and 
heart rate after subject is standing for approximately 2 minutes. 
• Record AEs. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 28 of 112 
• Weigh the subject. 
• Perform a 12-lead ECG. 
• Administer C-SSRS (Appendix B) 
• Collect blood and urine samples for clinical laboratory studies (Appendix C). 
• Administer MDS-UPDRS Parts I through IV (Appendix D). 
• Determine PGI-S and CGI-S scores (Appendix E and Appendix F, respectively). 
• Complete PDQ-39 (Appendix G). 
• Perform NMSS (Appendix I). 
• Complete the PDSS-2 (Appendix J). 
• Complete PAS (Appendix K). 
• Complete TSA (Appendix L). 
• Complete the ZBI-12 (Appendix M). 
• Administer the EMSQ (Appendix N). 
• Contact IWRS and enter study drug dispensing information. 
• Dispense study drug and provide dosing instructions. 
• Subjects may return for study drug resupply approximately every 1 to 2 months as 
needed. 
• Instruct subjects to call the study site before making any changes to their IPX203 
dosing regimen. 
• Call subjects approximately monthly to discuss IPX203 dosing.  Record the subject’s 
current IPX203 dose regimen. 
8.3. 
Visit 3 (Month 6) 
8.3.1. 
Prior to Visit 3 
Call the subjects prior to Visit 3 and remind them to bring any unused study medication and 
empty medication bottles to Visit 3. 
8.3.2. 
At Visit 3 
• Collect unused study drug and empty bottles. 
• Review study drug accountability. 
• Update IPX203 regimen (dose, frequency, number of capsules) and other concomitant 
medications. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 29 of 112 
• Assess vital signs after subject is supine for at least 5 minutes (blood pressure, heart 
rate, temperature and respiratory rate) and then assess orthostatic blood pressure and 
heart rate after subject is standing for approximately 2 minutes. 
• Record AEs. 
• Weigh the subject. 
• Perform a 12-lead ECG. 
• Administer C-SSRS (Appendix B). 
• Collect blood and urine samples for clinical laboratory studies (Appendix C). 
• Administer MDS-UPDRS Parts I through IV (Appendix D). 
• Determine PGI-S and CGI-S scores (Appendix E and Appendix F, respectively) 
• Complete PDQ-39 (Appendix G). 
• Perform NMSS (Appendix I). 
• Complete the PDSS-2 (Appendix J). 
• Complete PAS (Appendix K). 
• Complete TSA (Appendix L). 
• Complete the ZBI-12 (Appendix M). 
• Administer the EMSQ (Appendix N). 
• Contact IWRS and enter study drug dispensing information. 
• Dispense study drug and provide dosing instructions. 
• Subjects may return for study drug resupply approximately every 1 to 2 months as 
needed. 
• Instruct subjects to call the study site before making any changes to their IPX203 
dosing regimen. 
• Call subjects approximately monthly to discuss IPX203 dosing.  Record the subject’s 
current IPX203 dose regimen. 
8.4. 
Visit 4 − Study Completion (Month 9) or Early Discontinuation 
8.4.1. 
Prior to Visit 4 
Call the subjects prior to Visit 4 and remind them to bring any unused study medication and 
empty medication bottles to the visit. 
8.4.2. 
At Visit 4 
• Collect unused study drug and empty bottles. 
• Review study drug accountability. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 30 of 112 
• Update IPX203 regimen (dose, frequency, number of capsules) and other concomitant 
medications. 
• Assess vital signs after subject is supine for at least 5 minutes (blood pressure, heart 
rate, temperature and respiratory rate) and then assess orthostatic blood pressure and 
heart rate after subject is standing for approximately 2 minutes. 
• Record AEs. 
• Weigh the subject. 
• Perform physical exam including weight. 
• Perform a 12-lead ECG. 
• Administer C-SSRS (Appendix B). 
• Collect blood and urine samples for clinical laboratory studies (Appendix C). 
• Administer MDS-UPDRS Parts I through IV (Appendix D). 
• Determine PGI-S and CGI-S scores (Appendix E and Appendix F, respectively). 
• Complete PDQ-39 (Appendix G). 
• Complete GCSI (Appendix H). 
• Perform NMSS (Appendix I). 
• Complete the PDSS-2 (Appendix J). 
• Complete PAS (Appendix K). 
• Complete the TSA (Appendix L). 
• Complete the ZBI-12 (Appendix M). 
• Administer the EMSQ (Appendix N). 
• Contact IWRS to report subject disposition. 
8.5. 
Early Termination 
Subjects who withdraw early should complete Study Exit procedures described in Section 8.4. 
8.6. 
Blood Volume 
Safety blood draws:  Approximately 20 mL of blood will be drawn at each study visit for a 
combined total of 80 mL. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 31 of 112 
9. 
TREATMENT OF SUBJECTS 
9.1. 
Description of Study Drug 
Study drugs will be provided by Impax for this study: 
IPX203 (carbidopa-levodopa) Extended-Release Capsules, in four strengths, containing 
35-140 mg, 52.5-210 mg, 70-280 mg, and 87.5-350 mg of CD-LD, for oral administration. 
Table 3: 
Study Drugs for Study IPX203-B16-03 
Investigational Product 
Dosage Form and Strength 
(mg CD-LD) 
Manufacturer 
IPX203 (carbidopa-levodopa) 
Extended-Release Capsules 
35-140 mg capsule 
52.5-210 mg capsule 
70-280 mg capsule 
87.5-350 mg capsule 
Impax Laboratories, LLC 
9.2. 
Concomitant Medications 
9.2.1. 
Permitted PD Medications and Surgical Treatments 
Concomitant therapy with amantadine, selective monoamine oxidase (MAO) type B inhibitors 
(eg, safinamide, selegiline, rasagiline), anticholinergic PD medications (eg, benztropine, 
trihexyphenidyl), hypnotics (including low doses of quetiapine ≤ 25 mg per day), dopamine 
agonists, including apomorphine, supplemental CD, and COMT inhibitors are allowed provided 
the doses and regimens (and any adjustments) are recorded on the concomitant medication form.  
Implantation of a deep brain stimulator (DBS) for the treatment of PD is permitted during this 
study provided the stimulation settings are recorded. 
Although apomorphine, supplemental CD, COMT inhibitors, and DBS were not permitted in 
Study IPX203-B16-02, these treatments may be initiated during the current study. 
All concomitant medications taken during this study will be recorded. 
9.2.2. 
Prohibited PD Medications and Surgical Treatments 
Prohibited treatments during the study include the following: 
• Any doses of Rytary and Duopa during this study. 
• Nonselective MAO inhibitors or selective MAO type A inhibitors (MAO-A). 
• Neurosurgical ablation treatment procedures for PD. 
• Investigational agents other than IPX203. 
• Dopamine antagonists with the exception of low doses (≤ 25 mg) of quetiapine for 
sleep. 
A subject who reports the use of any prohibited medications will be discontinued. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 32 of 112 
9.3. 
Treatment Compliance 
Study drug accountability and reconciliation will be performed by the site staff and the study 
monitor. 
9.4. 
Randomization and Blinding 
This is a nonrandomized open-label study. 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 33 of 112 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Study Drug 
The study drug is IPX203 (carbidopa-levodopa) Extended-Release capsules for oral 
administration, provided in 4 dose strengths: 
• IPX203 35-140 mg CD-LD capsule 
• IPX203 52.5-210 mg CD-LD capsule 
• IPX203 70-280 mg CD-LD capsule 
• IPX203 87.5-350 mg CD-LD capsule. 
IPX203 will be supplied by Impax. 
10.2. 
Study Drug Packaging and Labeling 
Impax or designee will provide study medications in bottles with appropriate labeling affixed. 
Labels on the study medication may include the following information: 
• Name, address, and phone number of the Sponsor. 
• Pharmaceutical dosage form/route of administration, quantity of dosage units, the 
name/identifier, and strength/potency. 
• Batch and/or code number to identify the contents and packaging operation. 
• Trial reference code (protocol number). 
• Trial subject identification number and where relevant, the visit number. 
• Name of Investigator. 
• Directions for use: Take capsule(s) orally with water as directed. 
• For clinical trial use only. 
• Storage information:  Store at room temperature between 15-30°C (59-86°F). 
• Protect from light and moisture. 
• Period of use (use-by date, expiry date or retest date as applicable), in month/year 
format and in a manner that avoids any ambiguity. 
• Keep out of reach of children. 
• Caution statement:  Caution: New Drug—Limited by Federal (or United States) law 
to investigational use. 
10.3. 
Study Drug Storage 
The study medications should be stored at 25°C (77°F), with excursions permitted to 15°C to 
30°C (59°F to 86°F).  They should be stored in a tightly closed container, protected from light 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 34 of 112 
and moisture.  Storage temperature excursions below 15°C (59°F) or above 30°C (86°F) should 
be reported to Product Development at Impax or its designee. 
10.4. 
Study Drug Administration 
Subjects will be instructed to take their medications with approximately 240 mL of room-
temperature water.  The capsules should not be crushed or chewed. 
10.5. 
Study Drug Dispensing and Accountability 
The Investigator must ensure that all study medication received at the study site is inventoried 
and accounted for, and that dispensed study medication is recorded in the subject’s source 
documents, the CRF, and the study medication inventory log.  Site personnel must not relabel or 
reassign study medication to other subjects or to individuals not enrolled in the study.  The study 
monitor verifies medication accountability during monitoring visits. 
10.6. 
Study Drug Handling and Disposal 
The Investigator must retain and properly store all partially used and unused study medication 
until authorized by Impax regarding disposition. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 35 of 112 
11. 
ASSESSMENT OF EFFICACY 
To allow for assessment of the sustainability of the clinical effect of IPX203 over the 9-month 
study duration, the following clinical utility measures will be assessed at every visit: PGI-S, 
CGI-S, TSA, PDSS-2, PDQ-39, PAS, NMSS, MDS-UPDRS Parts I to IV, ZBI-12 and EMSQ. 
11.1. 
Patient and Investigator Global Assessments 
• Patient Global Impression of Severity (PGI-S) (Appendix E):  The subject will 
determine the severity of the disease on a 7-point scale ranging from “Normal, not at 
all ill” (1) to “Extremely severely ill” (7) at the time of the assessment. 
• Clinical Global Impression of Severity (CGI-S) (Appendix F):  The clinician will 
determine the severity of the disease on a 7-point scale ranging from “Normal, not at 
all ill” (1) to “Among the most extremely ill of subjects” (7) at the time of the 
assessment. 
11.2. 
Treatment Satisfaction Assessment (TSA) 
The TSA is a single-question, self-reported questionnaire (Appendix L).  The subject will 
determine his/her treatment satisfaction using a 7-point scale ranging from “Very much 
dissatisfied” (1) to “Very much satisfied” (7) at the time of the assessment. 
11.3. 
Parkinson’s Disease Sleep Scale-2 (PDSS-2) 
The PDSS-2 is 15-item self-reported questionnaire (Appendix J).  Three domains are defined:  
disturbed sleep (Questions 1-3, 8, 14), motor symptoms at night (Questions 4-6, 12, 13), PD 
symptoms at night (Questions 7, 9-11, 15). 
11.4. 
Parkinson’s Disease Questionnaire-39 (PDQ-39) 
The PDQ-39 is a self-reported questionnaire (Appendix G).  Using the 39 items, 8 domains are 
defined:  mobility (Questions 1-10), activities of daily living (ADL) (Questions 11-16), 
emotional well-being (Questions 17-22), stigma (Questions 23-26), social support (Questions 
27-29), cognition (Questions 30-33), communication (Questions 34-36) and bodily discomfort 
(Questions 37-39). 
11.5. 
Parkinson Anxiety Scale (PAS) 
The PAS is a 12-item subject- or observer-rated questionnaire with 3 domains:  persistent anxiety 
(Questions A.1-A.5), episodic anxiety (Questions B.1-B.4) and avoidance anxiety (Questions 
C.1-C.3) (Appendix K). 
11.6. 
Non-Motor Symptom Assessment Scale for Parkinson’s Disease 
(NMSS) 
The NMSS is a 30-item, investigator-rated questionnaire (Appendix I).  The NMSS contains 
9 domains: cardiovascular (Questions 1, 2), sleep/fatigue (Questions 3-6), mood/cognition 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 36 of 112 
(Questions 7-12), perceptual problems (Questions 13-15), attention/memory (Questions 16-18), 
gastrointestinal (Questions 19-21), urinary (Questions 22-24), sexual function (Questions 25, 
26), and miscellaneous (Questions 27-30). 
11.7. 
Movement Disorders Society Version of Unified Parkinson’s Disease 
Rating Scale (MDS-UPDRS) 
The MDS-UPDRS has 4 parts (Appendix D): 
• Part I:  Non-Motor Aspects of Experiences of Daily Living (nM-EDL) has 
2 components.  Component IA contains a number of behaviors assessed by the 
investigator with all pertinent information from the subjects and caregivers.  
Component IB is completed by the subject with or without help from the caregiver 
but independent of the investigator.  These sections can be reviewed by the rater to 
ensure all questions are answered clearly and the rater can help explain any 
ambiguities. 
• Part II:  Motor Aspects of Experiences of Daily Living (M-EDL) is a self-
administered questionnaire but can be reviewed by the investigator to ensure 
completeness and clarity. 
• Part III:  Motor Examination assesses the motor signs of PD and has instructions for 
the rater to give to or to demonstrate to the subject.  It is completed by the rater. 
• Part IV:  Motor Complications integrates subject-derived information with the rater’s 
clinical observations and judgements and is completed by the rater.  It contains 
instructions for the rater and instructions to be read to the subject. 
11.8. 
12-Item Zarit Burden Interview (ZBI-12) 
The Zarit Burden Interview (ZBI) is used to assess the perceived burden of family caregivers 
who provide assistance to patients with long-term progressive neurological disorders, including 
PD.  The ZBI-22 consists of 22 items with five ordered frequency-related response categories 
scored 0 (never) to 4 (nearly always), except for the final item, which has 5 ordered intensity-
related response categories (0 = not at all; 4 = extremely).  All 22 items are used to calculate a 
total score that can range between 0 and 88 (88 = more burden).  A total score of 21 has been 
suggested as a burden cut point.  The ZBI-12 is a 12-item short form of the ZBI-22 and has been 
shown to be reliable and valid and to produce results that are similar to the longer version 
(Hagell et al 2017, Bédard et al 2001) (Appendix M) while minimizing respondent time and 
burden.  The ZBI-12 should be completed by the same caregiver during each visit. 
11.9. 
Early Morning Symptom Questionnaire (EMSQ) 
The EMSQ is a 3-question, subject-rated questionnaire (Appendix N) that is used to assess 
whether a subject is experiencing any of 10 early morning PD symptoms by answering questions 
about prevalence (Question 1), severity (Question 2), and response to the first morning dose of 
PD medications (Question 3).  Study site staff will complete this questionnaire by questioning 
subjects during each study visit. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 37 of 112 
12. 
ASSESSMENT OF SAFETY 
12.1. 
Safety Parameters 
Safety will be assessed by the following parameters: 
• Electrocardiograms (ECGs), clinical laboratory tests, physical examinations, the 
Columbia-Suicide Severity Rating Scale (C-SSRS), and vital signs, including supine 
and standing orthostatic blood pressure and heart rate. 
• Adverse events and concomitant medications will be evaluated throughout the course 
of the study. 
• The Gastroparesis Cardinal Symptom Index (GCSI) at Screening, and Visit 4 (Exit) 
only. 
12.2. 
Adverse Events 
12.2.1. 
Definition of Adverse Event 
An adverse event (adverse experience) is any untoward medical occurrence in a patient or 
clinical trial subject administered a medicinal product and which does not necessarily have to 
have a causal relationship with this treatment.  An adverse event can therefore be any 
unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. 
All AEs and any clinically significant physical examination findings, 12-lead ECG 
abnormalities, or clinical laboratory measurements occurring during the study that were not 
present prior to administration of study medication and that continue at Study Exit should be 
followed and evaluated with additional tests, if necessary, until the AEs are medically stable or 
resolved.  Follow-up on these AEs should be recorded on the source documents and reported to 
Impax. 
12.2.2. 
Recording Adverse Events 
Elicit information about AEs with nonselective questions such as:  “Have you experienced any 
changes in your health status since your last visit?”  Encourage subjects to report AEs at onset. 
Record information for any AE that emerges from the time the subject signs the ICF until Study 
Exit. 
Monitor each subject closely for the development of AEs and record all such events on the AE 
page of the CRF.  Whenever possible, group signs and symptoms that constitutes a single 
diagnosis.  For example, cough, rhinitis, and sneezing might be grouped as upper respiratory 
infection. 
For each AE, record the onset date, severity, seriousness, relationship to study medication, date 
of resolution (or continuing), action taken, and outcome in the CRF.  The Investigator is to make 
a causality assessment (relationship to study medication) for every AE. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 38 of 112 
12.2.3. 
Follow-up 
The Investigator must follow each AE until resolved or medically stable. 
12.2.4. 
Relationship to Study Drug 
The Investigator documents his/her opinion of the relationship of the AE to the study medication 
as follows: 
• Not Related—the experience can be readily explained by the subject’s underlying 
medical condition or concomitant medications and no relationship exists between the 
study medication and the experience. 
• Unlikely Related—the temporal relationship between the AE and the administration 
of the study medication is uncertain and it is likely that the AE can be explained by 
the subject’s medical condition or other therapies. 
• Possibly Related—there is some logical temporal relationship between the AE and 
the administration of the study medication and the experience is unlikely to be 
explained by the subject’s medical condition or other therapies. 
• Related—the temporal relationship is compelling between the administration of the 
study medication and the AE cannot be explained by the subject’s medical condition 
or other therapies. 
12.2.5. 
Assessment of Severity 
Grade each AE for severity and note in the description of the AE.  Determine the severity 
category of mild, moderate, or severe, as defined below, and enter the information on the AE 
page of the CRF. 
• Mild—causing no limitation of usual activities 
• Moderate—causing some limitation of usual activities 
• Severe—causing inability to carry out usual activities 
12.3. 
Serious Adverse Events 
12.3.1. 
Definition of Serious Adverse Event 
A serious adverse event (SAE) is any AE occurring at any dose that results in any of the 
following outcomes, regardless of relationship to the study medication: 
• Death 
• A life-threatening adverse drug experience 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 39 of 112 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
12.3.2. 
Reporting Serious Adverse Events 
Any SAE that occurs from the time the subject signs an ICF until 30 days after taking the final 
dose of study medication must be reported by the investigative staff to the Sponsor or the 
Sponsor’s representative within 24 hours of knowledge of the event (see Study Contact 
Information). 
An SAE form must be completed and sent to the Sponsor and/or the Sponsor’s representative.  
All SAEs must also be recorded on the AE page of the CRF.  Additionally, all SAEs must be 
reported to the institutional review board (IRB) per the IRB’s requirements. 
Those SAEs that are considered both serious and unexpected and related to the study drug are 
subject to expedited reporting.  An “unexpected AE” is any AE where the nature or severity is 
not consistent with the current investigator brochure (IB) or if an IB is not required or available, 
the specificity or severity is not consistent with the provided risk information. 
Unexpected fatal or life-threatening SAEs related to the study drug must be reported by the 
Sponsor to the appropriate regulatory authority in an expedited manner (ie, first report within 
7 days of first knowledge by the Sponsor).  The Sponsor will provide a final written report to that 
authority within 15 days of initial receipt of information on the event.  The Sponsor or the 
Sponsor’s representative will also inform all participating Investigators of the SAE. 
Unexpected SAEs that are not fatal or life-threatening must be reported by the Sponsor to the 
appropriate regulatory authority as soon as possible but no later than 15 calendar days after first 
knowledge of the SAE by the Sponsor.  The Sponsor or the Sponsor’s representative also 
informs all participating Investigators of the SAE. 
Subjects withdrawn from the study due to any SAE will be followed until the SAE is resolved or 
medically stable.  Record all SAEs, regardless of severity and whether or not related to the study 
medication, on the appropriate page of the CRF. 
The Investigator must determine whether the seriousness of the event warrants removal of the 
subject from the study.  He/she should, in any case, institute appropriate diagnostic and 
therapeutic measures and keep the subject under observation for as long as is medically 
indicated, or refer the subject to appropriate health professionals. 
12.4. 
Pregnancy 
Any pregnancy that occurs from the time the subject signs an ICF until 30 days after taking the 
final dose of study medication must be reported within 24 hours to the Sponsor or the Sponsor’s 
representative and the subject should be terminated from the study.  All pregnancies will be 
followed through to delivery of the infant.  If the subject experiences a termination of the 
pregnancy, it should be reported as defined in Section 12.3.2. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 40 of 112 
12.5. 
Other Safety Parameters and Related Information 
Additional safety parameters (laboratory tests, 12-lead ECGs, physical examinations, and vital 
signs), the C-SSRS, the GCSI, and concomitant medications are collected as shown in the 
Schedule of Assessments in Section 8 and evaluated over the course of the study.  Clinical 
laboratory assessments are listed in Appendix C. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 41 of 112 
13. 
STATISTICS 
13.1. 
Study Design and Sample Size Estimation 
This study is an open-label study in PD subjects.  All subjects who successfully complete 
IPX203-B16-02 are eligible to enroll in this study; it is estimated that approximately 300 subjects 
will be enrolled. 
13.2. 
Demographics and Baseline Characteristics 
Prestudy subject demographics and baseline characteristics will be summarized to describe the 
subject population. 
13.3. 
Analysis of Efficacy/Clinical Utility Data 
The MDS-UPDRS Parts I to IV, PGI-S, CGI-S, PDQ-39, PDSS-2, PAS, NMSS, ZBI-12, and 
EMSQ will be assessed at every visit.  The TSA will be assessed at every visit postbaseline.  
These data, along with the IPX203 dose and frequency information, will help characterize the 
clinical utility of IPX203.  These measures will be analyzed as follows: 
MDS-UPDRS – The Total MDS-UPDRS and each of its components (Parts I through IV), and 
Parts II and III combined, as well as the changes from Baseline in these scores, will be 
summarized across each of the time points in the trial (Baseline/Visit 1, Month 3, Month 6, 
Month 9) to allow for clinical assessment of the continuing effect of IPX203 and of switching to 
IPX203 for those who were randomized to IR CD-LD.  For example, subjects randomized to 
IR CD-LD in Study IPX203-B16-02, will be examined for clinical improvement when switching 
to and following on IPX203 treatment.  Subjects randomized to IPX203 in Study IPX203-B16-
02 will be examined for maintaining clinical effect on IPX203. 
PGI-S – Subjects’ global impression of the severity of their PD and its treatment with IPX203 
will be summarized at Months 3, 6, and 9 to assess the overall impact of IPX203 treatment over 
time.  The mean changes from Baseline/Visit 1 in PGI-S as well as the frequencies and 
percentages of each component of the PGI-S will be summarized over time.  The proportion of 
subjects with a PGI-S ≥ 4 and PGI-S ≥ 5 will also be summarized over time. 
CGI-S – Clinicians’ global impression of the severity of the subject’s PD and its treatment with 
IPX203 will be summarized at Months 3, 6, and 9 to assess the overall impact of IPX203 
treatment over time.  The mean changes from Baseline/Visit 1 in CGI-S as well as the 
frequencies and percentages of each component of the CGI-S will be summarized over time.  
The proportion of subjects with a CGI-S ≥ 4 and CGI-S ≥ 5 will also be summarized over time. 
PDQ-39 – The PDQ-39 and its domains will be assessed in the same manner as the 
MDS-UPDRS. 
PAS – The PAS and its subscales (persistent anxiety, episodic anxiety, and avoidance behavior) 
will be assessed in the same manner as the MDS-UPDRS. 
NMSS – The NMSS and individual domain will be assessed in the same manner as the 
MDS-UPDRS. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 42 of 112 
PDSS-2 – The PDSS-2 (the total score and each component) will be summarized across all visits. 
TSA – The TSA will be summarized across all visits. 
ZBI-12 – The ZBI-12 will be summarized across all visits. 
EMSQ – The proportions of subjects with each of the early morning symptoms, the severity of 
each symptom, and whether the symptom improves after Parkinson’s medication will be 
summarized across all visits.  The change from baseline in total severity score will also be 
summarized across all visits. 
13.4. 
Analysis of Dosing Data 
Frequency of daily dosing and total daily dose of IPX203 at each visit after the baseline visit 
(Visit 1) will be summarized and compared against the baseline/Visit 1 daily dosing frequency.  
Percentages of subjects who require up-titration and down-titration, as well as the number of 
titration steps, will be summarized. 
13.5. 
Population Analysis and Handling of Dropouts 
Assessments will be made on available data with no adjustments for dropouts. 
13.6. 
Analysis of Safety 
The safety analysis will include all subjects who received at least one dose of study medication.  
Adverse events, supine and standing orthostatic vital signs, concomitant medications, 
electrocardiograms (ECGs), clinical laboratory tests, physical examinations, and the Columbia-
Suicide Severity Rating Scale (C-SSRS) will be evaluated throughout the course of the study. 
Adverse events will be collected and summarized both for the time in the open-label extension 
trial and the time of overall IPX203 exposure.  For summary and reporting purposes, “unlikely 
related,” “possibly related,” and “related” will be combined and will be counted as “related.” 
Vital signs and ECGs will be summarized across the entire IPX203 exposure including 
information from the open-label extension and the prior IPX203-B16-02 study into which the 
subjects were enrolled. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 43 of 112 
14. 
ADMINISTRATIVE PROCEDURES 
14.1. 
Guidelines for Good Clinical Practice 
This study will be conducted in accordance with principles of Good Clinical Practice (GCP) as 
promulgated by the ICH.  Good Clinical Practice is an international ethical and scientific quality 
standard for designing, conducting, recording, and reporting trials that involve the participation 
of human subjects.  Compliance with this standard provides public assurance that the rights, 
safety, and well-being of human subjects are protected under current ethical principles, and that 
the clinical trial data are credible.  Current GCP standards may be found in ICH Guidance E6 
(Good Clinical Practice:  Consolidated Guidance).  This guidance describes the principles of 
GCP and the obligations of the institutional review board (IRB), the Investigator and the Sponsor 
in conducting this study in accordance with those principles. 
14.2. 
Institutional Review Board Approval 
The review of this protocol by an IRB and the performance of all aspects of the study, including 
the methods used for obtaining informed consent, must be in accordance with principles 
enunciated in the ICH and GCP Guidelines and by the appropriate regulatory authorities. 
The Investigator is responsible for preparing documents for submission to the relevant IRB and 
obtaining written approval for this study.  Institutional Review Board approval must be obtained 
prior to the initiation of the study.  The Investigator’s continued participation in the study is 
contingent on renewing approval with the IRB at least annually. 
14.3. 
Informed Consent 
Site personnel should prepare an Informed Consent Form (ICF) incorporating the necessary 
elements of consent.  The ICF is to be approved by Impax prior to submission to the IRB.  The 
Investigator or his/her staff must explain the nature of the investigation and the risks involved to 
each subject prior to screening, and obtain a signed ICF.  The subject should also be informed 
that he/she is free to voluntarily withdraw from the study at any time. 
14.4. 
Study Monitoring 
Impax representatives or designees will conduct site visits to the investigational facilities for the 
purpose of monitoring the study.  The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relevant to study conduct.  The Investigator must permit access to 
such records if a regulatory or compliance audit is required. 
14.5. 
Protocol Amendments 
All amendments to the protocol must be documented in writing, reviewed and approved by the 
Sponsor and Investigator, and submitted to the IRB for approval prior to implementation.  If the 
protocol amendment substantially alters the study design or potential risk to the subject, a new 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 44 of 112 
written ICF for continued participation in the study must be obtained from each subject affected 
by the change. 
14.6. 
Termination of Study 
The Sponsor has the right to terminate this study and remove all study material from the site at 
any time for medical or administrative reasons.  In this event, the Sponsor will endeavor to give 
adequate notice to allow safe withdrawal of subjects from the study. 
14.7. 
Case Report Forms 
Site personnel should collect and record data for the study as source documents, and transfer the 
data into the CRF. 
The Investigator must ensure that complete data for the clinical study are collected and 
accurately documented in the appropriate sections of the CRF and adequately supported by the 
appropriate source documentation.  In addition, it is the Investigator’s responsibility to provide 
signatures where requested indicating concurrence with data in the CRF. 
14.8. 
Investigator’s Final Conduct Report 
At the completion of the study, the Investigator must provide Impax a copy of the final conduct 
report that was submitted to their IRB, including a review of AEs. 
14.9. 
Records Retention 
International Conference on Harmonization, GCP, and US FDA guidelines require that essential 
documents be retained until at least 2 years after the last approval of a marketing application and 
until there are no pending or contemplated marketing applications, or at least 2 years have 
elapsed since the formal discontinuation of clinical development of the investigational product. 
However, the essential documents should be retained for a longer period if required by the 
applicable regulatory requirements or by an agreement with the Sponsor.  Records should never 
be destroyed without written approval from the Sponsor. 
If an Investigator leaves the institution, he/she must transfer responsibilities for record retention 
to another individual willing to accept them.  The Investigator must notify the Sponsor in writing 
of the transfer of study documents before the transfer of the study documents. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 45 of 112 
15. 
PUBLICATION POLICY 
Study results may not be published without prior written approval from Impax. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 46 of 112 
16. 
LIST OF REFERENCES 
Bédard M, Molloy DW, Squire L, Dubois S, Lever JA, O'Donnell M. The Zarit Burden 
Interview: a new short version and screening version. Gerontologist. 2001;41(5):652-7. 
Blanchet PJ, Calon F, Martel JC, et al. Continuous administration decreases and pulsatile 
administration increases behavioral sensitivity to a novel dopamine D2 agonist (U-91356A) in 
MPTP-exposed monkeys. J Pharmacol Exp Ther. 1995;272:854-859. 
Engber TM, Susel Z, Juncos JL, Chase TN. Continuous and intermittent levodopa differentially 
affect rotation induced by D-1 and D-2 dopamine agonists. European Journal of Pharmacology. 
1989;168:291-298. 
Fahn S. Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs Later L 
DOPA. Arch Neurol. 1999 May;56(5):529-35. 
Food and Drug Administration 2003.  Guidance for Industry.  Bioavailability and 
Bioequivalence Studies for Orally Administered Drug Products — General Considerations.  U.S. 
Department of Health and Human Services.  Food and Drug Administration. Center for Drug 
Evaluation and Research (CDER). March 2003. 
Hagell P, Alvariza A, Westergren A, Årestedt K. Assessment of burden among family caregivers 
of people with Parkinson's disease using the Zarit Burden Interview. J Pain Symptom Manage. 
2017;53(2):272-278. 
Juncos JL, Engber TM, Raisman R, et al. Continuous and intermittent levodopa differentially 
affect basal ganglia function. Ann Neurol. 1989;25:473-478. 
Kurlan R, Rothfield KP, Woodward WR, Nutt JG, Miller C, Lichter D, et al. Erratic gastric 
emptying of levodopa may cause “random” fluctuations of parkinsonian mobility. Neurology. 
1988;38(3):419-21. 
Melamed E, Bitton V, Zelig O. Delayed onset of responses to single doses of L-dopa in 
parkinsonian fluctuators on long-term L-dopa therapy. Clin Neuropharmacol. 1986;9(2):182-8. 
Mizuno Y. Where do we stand in the treatment of Parkinson's disease? Neurology. 2007;254:13-
18. 
Nilsson D, Nyholm D, Aquilonius S-M. Duodenal levodopa infusion in Parkinson's disease--
long-term experience. Acta Neurologica Scandinavica. 2001;104:343-348. 
Nyholm D, Nilsson Remahl AI, Dizdar N, et al. Duodenal levodopa infusion monotherapy vs 
oral polypharmacy in advanced Parkinson disease. Neurology. 2005;64:216-223. 
Sinemet (Carbidopa-Levodopa) Tablets Prescribing Information. Whitehouse Station, NJ: 
Manufactured by Merck & Co., Inc.; Marketed by Bristol-Myers Squibb Company; 2013. 
Stocchi F, Quinn NP, Barbato L, Patsalos PN, O’Connel MT, Ruggieri S, et al. Comparison 
between a fast and a slow release preparation of levodopa and a combination of the two:  a 
clinical and pharmacokinetic study. Clinical Neuropharmacol. 1994;17(1):38-44. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 47 of 112 
Stocchi F, Vacca L, et al. Intermittent vs continuous levodopa administration in patients with 
advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005:62(6):905-
910. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 48 of 112 
17. 
APPENDICES 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 49 of 112 
APPENDIX A. RECOMMENDATIONS FOR IPX203 DOSING 
Subjects will be initially started on the final IPX203 dosing regimen that was determined during 
the IPX203 dose conversion period of Study IPX203-B16-02.  Investigators are permitted to 
adjust the dosing regimen of IPX203 during this study to achieve the optimal balance of efficacy 
and safety and any dosing changes will be recorded at the study visit. 
1. It is recommended that the subject takes IPX203 doses approximately every 8 hours apart 
(for example, a subject may take IPX203 at 6 AM, 2 PM, and 10 PM) with the exception 
that subjects who converted from a total daily dose of less than 125-500 mg IR CD-LD may 
take IPX203 every 12 hours.  Some subjects may benefit from a shorter or longer dosing 
interval.  The dosing interval may vary but should not be more frequent than every 
6 hours. 
2. The Investigator (or his/her staff) is advised to be in telephone contact with the subject, 
especially during the initial weeks of this study, to assess the need for dosage adjustment 
with the goal of minimizing “Off” time without causing troublesome dyskinesia or other 
dopaminergic side effects.  Calls to the subject can be reduced when the subject reaches 
an acceptable stable dosing regimen. 
3. If dose adjustment is necessary, consider the following options recognizing that the 
number of capsules at each dose may be varied to achieve an optimal response. 
a. If turning “On” is slow following the first morning dose, consider taking the morning 
IPX203 dose in the fasted state and/or increasing the dose by one capsule (35-140 mg 
IPX203 CD-LD). 
b. If turning “On” is slow later in the day or to reduce “end-of-dose” “Off” time, 
consider increasing the dose by one capsule (35-140 mg IPX203 CD-LD) before 
reducing the dosing interval. 
c. In case of troublesome dyskinesias, consider reducing the dose by one capsule 
(35-140 mg IPX203 CD-LD) prior to increasing the dosing interval. 
4. Initially, all subjects will be dispensed 2 capsule dosage strengths, one of which will be 
the 35-140 mg IPX203 CD-LD capsules.  Following dose regimen stabilization, up to 
2 capsule dosage strengths may be dispensed from those available (35-140 mg, 52.5-210 
mg, 70-280 mg, and 87.5-350 mg IPX203 CD-LD) 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 50 of 112 
APPENDIX B. COLUMBIA-SUICIDE SEVERITY RATING SCALE 
(C-SSRS) 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 51 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
   
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 52 of 112 
 
 
 
  
  
 
 
 
 
  
 
 
  
 
  
   
 
 
 
 
   
  
  
  
  
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
  
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
  
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 53 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
  
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
   
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
   
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
  
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
  
 
  
 
  
 
 
 
 
 
  
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 54 of 112 
APPENDIX C. CLINICAL LABORATORY STUDIES 
 
HEMATOLOGY 
hemoglobin 
hematocrit 
red blood cell count 
white blood cell count 
% neutrophils 
% lymphocytes 
% monocytes 
% basophils 
% eosinophils 
absolute neutrophils 
absolute lymphocytes 
absolute monocytes 
absolute basophils 
absolute eosinophils 
platelet count 
CHEMISTRY 
sodium 
potassium 
chloride 
carbon dioxide 
blood urea nitrogen (BUN) 
creatinine 
glucose 
calcium 
phosphorous 
albumin 
total protein 
uric acid 
total bilirubin 
direct bilirubin 
indirect bilirubin 
alkaline phosphatase 
alanine aminotransferase 
(ALT, SGPT) 
aspartate aminotransferase 
(AST, SGOT) 
creatine phosphokinase 
lactate dehydrogenase 
URINALYSIS 
pH 
specific gravity 
blood 
glucose 
ketones 
microscopic exam (RBC 
and WBC, only when 
indicated) 
leukocyte esterase 
protein
 
PREGNANCY TEST 
Urine pregnancy test (to be completed on site) for female subjects of childbearing potential. 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 55 of 112 
APPENDIX D. MOVEMENT DISORDERS SOCIETY VERSION OF THE 
UNIFIED PARKINSON’S DISEASE RATING SCALE 
(MDS-UPDRS) 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 56 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 57 of 112 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 58 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 59 of 112 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
  
 
  
   
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 60 of 112 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 61 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
  
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 62 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 63 of 112 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 64 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 65 of 112 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 66 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 67 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 68 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 69 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 70 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 71 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 72 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 73 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
  
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
  
  
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 74 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 75 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 76 of 112 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 77 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 78 of 112 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 79 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 80 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 81 of 112 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
  
 
 
  
  
 
  
 
  
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 82 of 112 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
  
 
 
 
 
  
 
  
 
 
  
  
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
   
  
 
 
 
 
 
 
 
  
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
  
  
 
 
 
 
  
 
 
  
  
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 83 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 84 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 85 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 86 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 87 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 88 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 89 of 112 
APPENDIX E. PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) 
 
The subject will independently rate the following question of Patient Global Impression of 
Severity (PGI-S) based on his/her overall impression of the study medication at Visit 2 
(Month 3), Visit 3 (Month 6), and Visit 4 (Month 9) or early discontinuation. 
 
Patient Global Impression of Severity Scale 
 
Severity of Illness 
 
Considering the severity of your Parkinson’s disease, how severe is your condition at this time? 
 
 
Severity Score: 
 
 1 
 2 
 3 
 4 
 5 
 6 
 7 
Normal, 
not at all ill 
Borderline 
ill 
Mildly 
ill 
Moderately 
ill 
Markedly 
ill 
Severely 
ill 
 
Extremely 
severely ill 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 90 of 112 
APPENDIX F. CLINICAL GLOBAL IMPRESSION OF SEVERITY 
(CGI-S) 
 
The Investigator will independently rate the following question of Clinical Global Impression of 
Severity (CGI-S) based on his/her overall impression of the study medication at Visit 2 
(Month 3), Visit 3 (Month 6), and Visit 4 (Month 9) or early discontinuation. 
 
Clinical Global Impression of Severity Scale 
 
Severity of Illness 
 
Considering your total clinical experience with this particular population,  
how ill is the patient at this time? 
 
 
Severity Score: 
 
 1 
 2 
 3 
 4 
 5 
 6 
 7 
Normal, 
not at all ill 
Borderline 
ill 
Mildly 
ill 
Moderately 
ill 
Markedly 
ill 
Severely 
ill 
 
Among the 
most 
extremely ill 
of subjects 
 
 
 
 
 
 
 
Guy W. ECDEU assessment manual for psychopharmacology publication; ADM, 76-338. 
Washington DC, US. Department of health, education and welfare, 1976. 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 91 of 112 
APPENDIX G. 39-ITEM PARKINSON’S DISEASE QUESTIONNAIRE 
(PDQ-39) 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 92 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 93 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 94 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 95 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 96 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 97 of 112 
APPENDIX H. GASTROPARESIS CARDINAL SYMPTOM INDEX 
(GCSI) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
   
 
 
 
 
 
  
  
 
 
 
 
   
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 98 of 112 
APPENDIX I. NON-MOTOR SYMPTOM ASSESSMENT SCALE FOR 
PARKINSON’S DISEASE (NMSS) 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 99 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
   
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
  
   
 
 
 
 
 
 
  
 
 
 
 
   
 
   
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 100 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 101 of 112 
APPENDIX J. PARKINSON’S DISEASE SLEEP SCALE-2 (PDSS-2) 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 102 of 112 
 
 
Trenkwalder C, Kohnen R, Högl B, Metta V, Sixel-Döring F, Frauscher B, Hülsmann J, Martinez-Martin P, 
Chaudhuri KR. Parkinson’s disease sleep scale--validation of the revised version PDSS-2. Mov Disord. 
2011;26(4):644-52 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
  
 
 
    
  
 
 
  
  
  
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
 
  
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 103 of 112 
APPENDIX K. PARKINSON ANXIETY SCALE (PAS) 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 104 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 105 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 106 of 112 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 107 of 112 
APPENDIX L. TREATMENT SATISFACTION ASSESSMENT (TSA) 
 
The subject independently answers the following question of treatment satisfaction based on 
his/her overall impression of the study medication at Visits 2, 3, and 4. 
 
Treatment Satisfaction Assessment: 
In general, how satisfied are you with your current Parkinson’s disease medication? 
 1 
 2 
 3 
 4 
 5 
 6 
 7 
Very much 
dissatisfied 
Very 
dissatisfied 
Somewhat 
dissatisfied 
Neither 
satisfied nor 
dissatisfied 
Somewhat 
satisfied 
Very 
satisfied 
Very much 
satisfied 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 108 of 112 
APPENDIX M. 12-ITEM ZARIT BURDEN INTERVIEW (ZBI-12) 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 109 of 112 
APPENDIX N. EARLY MORNING SYMPTOMS QUESTIONNAIRE 
(EMSQ) 
 
Questions:  
1. Over the past week, when you awakened in the morning for the day from your night-time 
sleep, on how many days did you experience each of the following symptoms? 
a. Tremor 
  0 
  1-3 
  4-7 
b. Stiffness 
  0 
  1-3 
  4-7 
c. Slowness 
  0 
  1-3 
  4-7 
d. Walking/Turning 
  0 
  1-3 
  4-7 
e. Loss of Balance 
  0 
  1-3 
  4-7 
f. Urinary Control 
  0 
  1-3 
  4-7 
g. Anxious Feelings 
  0 
  1-3 
  4-7 
h. Too Much Saliva 
  0 
  1-3 
  4-7 
i. Depressed or Sad Feelings 
  0 
  1-3 
  4-7 
j. Bodily Discomfort or Pain 
  0 
  1-3 
  4-7 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 110 of 112 
 
2. If you experienced any symptom in the question (Q.1) above on at least one day over the 
past week, indicate for this symptom (or for these symptoms) the severity to which this 
symptom impaired your morning activities and social interactions using the severity 
definitions below: 
a. Tremor 
 Mild 
 Moderate 
 Severe 
b. Stiffness 
 Mild 
 Moderate 
 Severe 
c. Slowness 
 Mild 
 Moderate 
 Severe 
d. Walking/Turning 
 Mild 
 Moderate 
 Severe 
e. Loss of Balance 
 Mild 
 Moderate 
 Severe 
f. Urinary Control 
 Mild 
 Moderate 
 Severe 
g. Anxious Feelings 
 Mild 
 Moderate 
 Severe 
h. Too Much Saliva 
 Mild 
 Moderate 
 Severe 
i. Depressed or Sad Feelings 
 Mild 
 Moderate 
 Severe 
j. Bodily Discomfort or Pain 
 Mild 
 Moderate 
 Severe 
 
Severity Definitions: 
Mild:  Causes mild impact on one or more early morning functions but I am usually able to 
perform most morning activities and participate in most social interactions. 
Moderate:  Impacts one or more early morning functions to the point that I am usually not able 
to perform some morning activities and/or participate in some social interactions. 
Severe:  Impacts one or more early morning functions to the point that I am usually not able to 
perform most morning activities and/or participate in most social interactions. 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 111 of 112 
 
3. Which of the early morning symptoms (if any) that you identified above and assessed 
severity in Q.2 above improved after taking a first morning dose of your Parkinson’s 
medication(s)?  For each symptom, indicate “YES” improved or “NO” did not improve.  If 
you did not experience the symptom (ie, answered 0 in Q.1 above), indicate “Did not 
experience”. 
a. Tremor 
  Yes 
  No 
  Did not experience 
b. Stiffness 
  Yes 
  No 
  Did not experience 
c. Slowness 
  Yes 
  No 
  Did not experience 
d. Walking/Turning 
  Yes 
  No 
  Did not experience 
e. Loss of Balance 
  Yes 
  No 
  Did not experience 
f. Urinary Control 
  Yes 
  No 
  Did not experience 
g. Anxious Feelings 
  Yes 
  No 
  Did not experience 
h. Too Much Saliva 
  Yes 
  No 
  Did not experience 
i. Depressed or Sad Feelings 
  Yes 
  No 
  Did not experience 
j. Bodily Discomfort or Pain 
  Yes 
  No 
  Did not experience 
 
 
 


Protocol No. IPX203-B16-03 
CONFIDENTIAL 
Amendment 2: 26 November 2018 
Impax Laboratories, LLC 
 
Page 112 of 112 
APPENDIX O. COMPONENTS OF IPX203 
 
Active ingredients:  carbidopa and levodopa 
 
Inactive ingredients:  The excipients in the IPX203 investigational formulations include the 
following: microcrystalline cellulose, mannitol, amino methacrylate copolymer, sodium lauryl 
sulfate, methacrylic acid copolymer Type A, copovidone, cellulose acetate, croscarmellose 
sodium, talc, triethyl citrate, povidone, magnesium stearate.  All these excipients are United 
States Pharmacopeia and National Formulary.  The investigational formulations will be enclosed 
in hard gelatin capsules. 
 

SAP_001.pdf: 
 
SAP Title: An Open-Label Extension Study of the Safety and 
Clinical Utility of IPX203 in Parkinson’s Disease 
Patients with Motor Fluctuations 
Date: December 7, 2021 
NCT03877510 
 


Impax Laboratories, LLC - IPX203-B16-03 – Clinical Study Report 
1 
16.1.9       Documentation of Statistical Methods 
This appendix contains the following document: 
Statistical Analysis Plan Final dated December 07, 2021 


IPX203–B16-03 
Statistical Analysis Plan 
Impax Laboratories, Inc 
CONFIDENTIAL 
Page 1 of 43 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
 
Study Title: 
An Open-Label Extension Study of the Safety and 
Clinical Utility of IPX203 in Parkinson’s Disease 
Patients with Motor Fluctuations 
Name of Test Drug: 
IPX203 
Protocol Number: 
IPX203-B16-03 
Protocol Version (Date): 
Original Protocol, 25 April 2018 
Amendment 1, 22 June 2018 
Amendment 2, 26 November 2018 
Analysis Type: 
Final 
Analysis Plan Version: 
Final 
Analysis Plan Date: 
07Dec2021 
Analysis Plan Author: 
 
 
 
 
 
SPONSOR 
Impax Laboratories, LLC 
400 Crossing Boulevard, Third Floor 
Bridgewater, NJ 08807-2863 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


IPX203–B16-03 
Statistical Analysis Plan 
Impax Laboratories, Inc 
CONFIDENTIAL 
Page 2 of 43 
 
 
 
SIGNATURE PAGE 
 
 
 
 
 
 


IPX203–B16-03 
Statistical Analysis Plan 
Impax Laboratories, Inc 
CONFIDENTIAL 
Page 3 of 43 
 
 
TABLE OF CONTENTS 
1 
INTRODUCTION 
7 
1.1 
Study Objectives 
7 
1.2 
Study Design 
7 
1.3 
Sample Size and Power 
8 
2 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS 
8 
2.1 
Definitions of Baseline 
9 
2.2 
Analysis Sets 
9 
2.2.1 
Safety Analysis Set 
9 
2.2.2 
Intent-to-Treat Analysis Set 
9 
2.3 
Visit Windows 
9 
2.4 
Early Termination Visits 
10 
3 
SUBJECT DISPOSITION AND BASELINE CHARACTERISTICS 
10 
3.1 
Subject Enrollment and Disposition 
10 
3.2 
Demographics and Baseline Characteristics 
10 
3.3 
Study Drug Exposure 
11 
3.4 
Protocol Deviations 
12 
3.5 
Medical History 
12 
4 
CLINICAL UTILITY ANALYSES 
12 
4.1 
Imputation of missing data 
12 
4.1.1 
Missing Data for MDS-UPDRS 
13 
4.2 
Analysis of the Clinical Utility Endpoints 
13 
4.2.1 
MDS-UPDRS 
13 
4.2.2 
PGI-S and CGI-S 
13 
4.2.3 
PDQ-39 total score and individual domain scores 
14 
4.2.4 
PAS total score and individual domains 
14 
4.2.5 
NMSS total score and individual domains 
14 
4.2.6 
PDSS-2 total score and individual domains 
14 
4.2.7 
TSA 
15 
4.2.8 
ZBI-12 
15 
4.2.9 
EMSQ 
15 
5 
SAFETY ANALYSES 
16 
5.1 
Adverse Events 
16 
5.2 
Laboratory Evaluations 
18 


IPX203–B16-03 
Statistical Analysis Plan 
Impax Laboratories, Inc 
CONFIDENTIAL 
Page 4 of 43 
 
 
5.3 
Vital Signs 
19 
5.4 
Electrocardiogram 
19 
5.5 
Physical Examination 
20 
5.6 
C-SSRS 
21 
5.7 
GCSI 
21 
5.8 
Concomitant Medications 
21 
6 
COVID-19 considerations for analyses 
22 
7 Changes From Protocol-Specified Analyses 
23 
8 
REFERENCES 
24 
9 
APPENDICES 
25 
9.1 
Schedule of events 
25 
 
 


IPX203–B16-03 
Statistical Analysis Plan 
Impax Laboratories, Inc 
CONFIDENTIAL 
Page 5 of 43 
 
 
 
LIST OF ABBREVIATIONS 
 
Abbreviation 
Explanation 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Transaminase 
ATC 
Anatomic-therapeutic-chemical 
BMI 
Body Mass Index 
CD-LD 
Carbidopa-Levodopa 
CGI-S 
Clinical Global Impression of Severity 
CR 
Controlled Release 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
eCRF 
Electronic Case Report Form 
EMSQ 
Early Morning Symptoms Questionnaire 
EOS 
End of Study 
GCSI 
Gastroparesis Cardinal Symptom Index 
HIPAA 
Health Insurance Portability and Accountability Act 
IR 
Immediate Release 
ISS 
Integrated Summary of Safety 
ITT 
Intent-to-Treat 
LD 
Levodopa 
LLC 
Limited Liability Company 
MAO-B 
Monoamine oxidase B 
MDS-UPDRS 
Movement Disorder Society version of the Unified Parkinson’s 
Disease Rating Scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
NCS 
Not Clinically Significant 
NMSS 
Non-Motor Symptom Assessment Scale 
PAS 
Parkinson Anxiety Scale 
PD 
Parkinson Disease 
PDQ-39 
Parkinson’s Disease Questionnaire-39 
PDSS-2 
Parkinson’s Disease Sleep Scale-2 
PGI-S 
Patient Global Impression of Severity 
PT 
Preferred Term 
RBC 
Red Blood Cells 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TLFs 
Tables, Listings and Figures 
TSA 
Treatment Satisfaction Assessment  
US 
United States 
WBC 
White Blood Cells 


IPX203–B16-03 
Statistical Analysis Plan 
Impax Laboratories, Inc 
CONFIDENTIAL 
Page 6 of 43 
 
 
WHO 
World Health Organization 
ZBI-12 
12-Item Zarit Burden Interview (ZBI-12) 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 7 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
1 INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, listings, and figures (TLFs) in the clinical study report 
(CSR) for Study IPX203-B16-03. This SAP is based on the study protocol amendment 2 
dated 26November2018. The SAP will be finalized before database lock. Any changes made 
after the finalization of the SAP will be documented in the CSR. 
1.1 
Study Objectives 
The objective of this study is to evaluate the long-term safety and clinical utility of IPX203 in the 
treatment of subjects with advanced Parkinson’s disease (PD) who have motor fluctuations. 
1.2 
Study Design 
Subjects who have successfully completed Study IPX203-B16-02 (A Randomized Controlled 
Study to Compare the Safety and Efficacy of IPX203 with Immediate-Release Carbidopa-
Levodopa in Parkinson’s Disease Patients with Motor Fluctuations) may be offered the 
opportunity to enroll in this 9-month, multicenter open-label study. The study consists of a 
baseline visit (Visit 1) followed by 3 visits (Visits 2 to 4) spaced at approximately 3-month 
intervals. For subjects who successfully complete Study IPX203-B16-02, the baseline visit (Visit 
1) of this study will occur coincident with the End of Study (EOS) Visit 7 of the preceding study, 
(with an allowed window of + 7 days). After providing written informed consent (and signing 
Health Insurance Portability and Accountability Act [HIPAA] authorization for subjects at 
United States [US] sites only), confirmation of eligibility and baseline procedures will be 
performed. Subjects will be initially started on the final IPX203 dosing regimen that was 
determined during the IPX203 dose conversion period of Study IPX203-B16-02. Investigators 
are permitted to adjust the dosing regimen of IPX203 during this study to achieve the optimal 
balance of efficacy and safety and any changes will be recorded. 
Subjects may continue to take their non-LD-containing PD concomitant medications (including 
dopamine agonists, amantadine, and selective monoamine oxidase-B (MAO-B) inhibitors 
[safinamide, rasagiline and selegiline]) during the study. Changes in doses or in dosing regimens 
of all non-CD-LD PD medications and/or the addition of new non-CD-LD PD medications will 
be captured. Supplemental CD and benserazide, apomorphine, and the addition of catechol-O-
methyltransferase (COMT) inhibitors (eg, entacapone, opicapone, and tolcapone) can be initiated 
during the study. 
Adverse events, supine and standing orthostatic vital signs, and concomitant medications will be 
evaluated throughout the course of the study. Electrocardiograms (ECGs), clinical laboratory 
tests, physical examinations, and the Columbia-Suicide Severity Rating Scale (C-SSRS) will also 
be performed. The following clinical utility measures will be assessed: Patient Global Impression 
of Severity (PGI-S), Clinician Global Impression of Severity (CGI-S), Treatment Satisfaction 
Assessment (TSA), Parkinson’s Disease Sleep Scale-2 (PDSS-2), the 39-item Parkinson’s 
Disease Questionnaire (PDQ-39), Parkinson Anxiety Scale (PAS), Non-Motor Symptom 
assessment scale (NMSS) for Parkinson’s disease, Gastroparesis Cardinal Symptom Index 
(GCSI), The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-
UPDRS) Parts I to IV, 12-Item Zarit Burden Interview (ZBI-12), and Early Morning Symptoms 
Questionnaire (EMSQ). Visit 4 is the end of study (EOS). 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 8 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
Figure 1 Study Flowchart 
 
1.3 
Sample Size and Power 
This study is an open-label study in PD subjects. All subjects who successfully complete 
IPX203-B16-02 are eligible to enroll in this study; it was originally estimated that approximately 
300 subjects would be enrolled, but a larger number could be enrolled. 
 
2 GENERAL CONSIDERATIONS FOR DATA ANALYSIS 
The database will be locked and final analysis of the data will be performed after all 
subjects have completed the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized. The statistical 
analyses will be performed by Quartesian LLC, with approval of the Sponsor, using SAS 
Version 9.4 (or higher).  
All tables, figures and listings will be produced in landscape format.  
Subjects will be assigned to treatment group defined by the treatment the subject received 
in the double-blind phase of the previous study IPX203-B16-02 (IPX203 or IR CD-LD). 
In general, all data will be listed by subject and visit/time point where appropriate. 
The summary tables will be stratified by, or have columns corresponding to, 
treatment groups. Total group will also be presented. 
The total number of subjects in the treatment group (N) under the stated population 
will be displayed in the header of summary tables. 
Data will be summarized using descriptive statistics for continuous variables. 
Unless otherwise specified, descriptive statistics will include number of subjects, 
mean, standard deviation, minimum, median and maximum. Number of subjects 
with missing values will also be displayed, but only if non-zero. The minimum and 
maximum statistics will be presented to the same number of decimal places as the 
original data. The mean and median will be presented to one more decimal place 
than the original data. The standard deviation will be presented to two more 
decimal places than the original data. 
In summary tables of categorical variables, counts and percentages will be 
displayed. The count [n] indicates the actual number of subjects in a particular 
category, which should always be less than or equal to the total number of subjects 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 9 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
in the respective study group with known (non-missing) category [M]. Percentage 
will be obtained by: % = n/M*100. Unless otherwise specified, all percentages will 
be expressed to one decimal place. 
In by-visit summaries, only data collected on scheduled visits/timepoints will be 
summarized. Data from unscheduled assessments will be included in listings and 
may be used in determination of baseline if applicable. 
Relative days will be calculated relative to date of the first open-label study drug 
dose in the study IPX203-B16-03. Relative days will be calculated as follows only 
when the full assessment date is known (i.e., partial dates will have missing relative 
days). 
For assessment on or after the day of first study drug dose: 
Relative Day = Date of Assessment – Date of First Study Drug Dose +1. 
For assessment before the day of first study drug dose: 
Relative Day = Date of Assessment – Date of First Study Drug Dose. 
All dates will be displayed in DDMMMYYYY format. 
2.1 
Definitions of Baseline 
Baseline is defined as the last assessment obtained prior to the first dose of the open-label 
drug in the study IPX203-B16-03. 
The study eCRF does not explicitly capture when the subject took the first open-label study 
drug dose. It will be assumed that this dose is taken on the day of Visit 1 after all study 
assessments. 
2.2 
Analysis Sets 
Analysis sets define the subjects to be included in an analysis. Analysis sets and their 
definitions are provided in this section. The analysis set will be identified and included as a 
subtitle of each table, listing, and figure. 
2.2.1 Safety Analysis Set 
The Safety Analysis set will include all subjects who were treated with the open-label study drug 
in the study. 
The study eCRF does not explicitly capture if a subject took the open-label study drug. It will be 
assumed that a subject took the open-label study drug if and only if study drug was dispensed to 
the subject at one of the study visits. 
2.2.2 Intent-to-Treat Analysis Set 
The Intent-to-treat Analysis Set (ITT) will include all subjects who were treated with the open-
label study drug in the study and have at least one post-baseline clinical utility assessment. 
2.3 
Visit Windows 
Generally data will be analyzed by nominal visit when the data was collected. However, if a 
subject does not have a particular data point for a certain scheduled visit, but instead has it for an 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 10 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
unscheduled visit that occurred within +/-14 days window of the planned date of the scheduled 
visit, then the data from the unscheduled visit will be used in place of the missing scheduled 
visit. This will apply to both the clinical utility and safety data. 
2.4 
Early Termination Visits 
Early termination visits and Visits 4 are collected in the study database as a single Visit/ET visit. 
For the purposes of by-visit summaries two separate visits will be presented: 
 Visit 4 (identified as Visit 4/ET from the study database for subjects who completed the 
study) 
 Visit 4/ET (i.e. all visits collected as Visit 4/ET in the study database) 
3 SUBJECT DISPOSITION AND BASELINE CHARACTERISTICS 
3.1 
Subject Enrollment and Disposition 
The number of subjects that were enrolled, number and percentage of subjects who were 
included in the Safety and ITT analysis sets, completed the study and prematurely 
discontinued from the study (with the breakdown by the primary reason for discontinuation) 
will be presented by treatment group and overall. Percentages will be based on the number of 
enrolled subjects in each treatment group, except percentages for the reasons for 
discontinuation, which will be based on the number of subjects who discontinued early. 
In the summary of reasons for discontinuation a separate line will be provided for 
discontinuations related to the COVID-19 pandemic. 
An overall summary of the number of subjects in each analysis set by site will be created. 
All disposition information will be listed. Also a listing of enrollment details will provide the 
date of informed consent and inclusion/exclusion criteria not met, if any. 
3.2 
Demographics and Baseline Characteristics 
Demographic characteristics will include: 
 
age at the date of informed consent 
 
sex 
 
race 
 
ethnicity 
Baseline physical characteristics will include: 
 
height at study IPX203-B16-02 screening 
 
weight at baseline 
 
BMI at baseline (note that height will not be collected during study IPX203-
B16-03.  Height will be taken from the previous study and BMI will be 
calculated using that height measurement and this study baseline weight) 
Baseline disease characteristics include 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 11 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
 
MDS-UPDRS Parts I, II, III, and IV total scores at baseline 
 
Hoehn and Yahr stage 
 
Age of onset of PD as continuous variable and categorized as < 65or ≥ 65 
years. 
Descriptive statistics will be presented for continuous variables. Frequency counts and 
percentage will be presented for categorical variables. Height will be reported in centimeters, 
weight in kilograms and BMI in kg/m2. 
Age will be derived from Informed Consent Date and Date of Birth as the number of whole years 
between those two dates. 
These analyses will be performed for the Safety and ITT analysis sets. The summaries will be 
presented for the two treatment group and total. 
All demographic parameters and baseline characteristics will be presented in the by-subject 
listings. 
3.3 
Study Drug Exposure 
Overall summary of study drug exposure will include descriptive summary by treatment group of 
the following parameters: 
 Average total daily dose of IPX203 – defined as the total IPX203 dose taken over the 
course of the study divided by the treatment duration in days 
 Average daily dosing frequency – defined as the total number of administrations over the 
course of the study divided by the treatment duration in days 
 Treatment duration – defined as [the date of last dose] – [the date of first dose] + 1. 
IPX203 dosing regimen will be recorded at each visit. Frequency of daily dose administration 
(number of administrations per day), total daily dose of IPX203 (in mg) and most frequently 
used dose (mg) and their changes from the starting (Visit 1) regimen will be summarized by visit 
and treatment group. If more than one dose is used most frequently, the higher dose will be 
selected as the most frequent dose. 
Total daily dose will also by summarized categorically, categorized as < 400, 400 to < 1000, 
1000 to < 1400, 1400 to < 1800, 1800 to <= 2400, and >2400 mg. 
Changes in total daily dose and daily dosing frequency will be analyzed for the following time 
periods: Visit 1 to Visit 2, Visit 2 to Visit 3, Visit 3 to Visit 4, Visit 1 to Visit 3 and Visit 1 to 
Visit 4. For each period subjects will be categorized into one of the following categories: 
 No change in total daily dose 
 Total daily dose modified, but returned to the same level (e.g. an increase followed by a 
decrease by the same value) 
 Total daily dose increased during the period 
 Total daily dose decreased during the period 
Separately subjects’ changes in daily dosing frequency will be categorized in a similar way. 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 12 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
Number and percentage of subjects in each of these categories will be presented for each time 
period. 
Similar comparison of both total daily dose and daily dosing frequency will be made for the 
subject’s stable IPX203 regimen in study IPX203-B16-03 vs. the starting (Visit 1) regimen in 
this study. 
For subjects who changed their total dose or number of daily doses the number of steps during 
the time period will be categorized as 1, 2, 3, 4 or >4 and also be summarized.  
For each time period Visit 1 to Visit 2, Visit 2 to Visit 3,Visit 3 to Visit 4, Visit 1 to Visit 3 and 
Visit 1 to Visit 4 the number and percentage of subjects with no change on their treatment 
regimen and with any change in their regimen will be provided. Number of changes will be 
summarized descriptively for each time period. Regimen changes include changes in dosing 
frequency or the dose taken at any administration and will be derived from the IPX203 Dose 
Adjustment Log CRF. 
These summaries will be done on the Safety analysis set. 
3.4 
Protocol Deviations 
Protocol deviations, such as subjects who did not meet eligibility criteria at study entry and 
those occurring after subjects entered the study, are documented during routine monitoring 
and throughout the study. The process for the management of protocol deviations is defined in 
the Protocol Deviation and Non-compliance Management Plan. Details of protocol deviations 
for each study site are documented and reviewed regularly, and will be provided by the 
Clinical Operations Group to the Statistics and Data Management Group prior to database 
finalization. These protocol deviations will be listed. Deviations related to COVID-19 will be 
identified in the listing. 
3.5 
Medical History 
Medical history changes since the study IPX203-B16-02 screening will be recorded at Visit 
1. Adverse Events that were recorded in study IPX203-B16-02 that have a stop date prior to 
or equal to Visit 1 Date of study IPX203-B16-03, will be recorded as medical history in this 
study. For the purposes of analysis medical history collected at IPX203-B16-02 screening 
will be pooled with the new entries collected at Visit 1 of study IPX203-B16-03 and 
resolved adverse events from study IPX203-B16-02. 
Medical history will be summarized by MedDRA System Organ Class and Preferred Term. 
Each subject will be counted once within each applicable Preferred Term and System 
Organ Class. This summary will be performed for the Safety analysis set by treatment 
group, as well as for all subjects overall.  
All medical history information will be listed. 
4 CLINICAL UTILITY ANALYSES 
4.1 
Imputation of missing data 
Generally, missing data will not be imputed and data will be summarized as observed. 
Imputations will be performed for partially missing MDS-UPDRS responses as detailed in the 
following section. 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 13 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
4.1.1 Missing Data for MDS-UPDRS 
For all endpoints based in MDS-UPDRS questionnaire the following imputation of missing 
responses will be used. 
If component questions are missing for a particular part of the MDS-UPDRS questionnaire, the 
missing items are assigned the average value for other items in that part as follows: 
 
For Part I (13 questions): up to 1 missing question will be imputed using the 
average value of the remaining 12 questions. 
 
For Part II (13 questions): up to 2 missing questions will be imputed using the 
average value of the remaining 11 questions. 
 
For Part III (33 questions): up to 7 missing questions will be imputed using 
the average value of the remaining 26 questions. 
 
For Part IV (6 questions): no imputation is done. 
If more component questions are missing than above for a particular part of the MDS-UPDRS 
questionnaire, the entire questionnaire and the affected part will not be included in the analysis 
for that particular assessment.  
4.2 
Analysis of the Clinical Utility Endpoints 
Analysis of the clinical utility endpoints will be performed on the ITT population. 
4.2.1 MDS-UPDRS 
MDS-UPDRS will be administered at all scheduled visits 1-4. 
The Total MDS-UPDRS and each of its components (Parts I through IV), and Parts II and III 
combined, as well as the changes from baseline in these scores, will be summarized by visit and 
treatment group, as well as for both treatment groups combined. Summary of study entry 
baseline of study IPX203-B16-02 will also be included. 
4.2.2 PGI-S and CGI-S 
The patients will rate the severity of their disease on a 7-point PGI-S scale ranging from “1: 
Normal, not at all ill” to “7: Extremely severely ill” at every visit. 
Similarly, clinician’s global impression of severity will be rated on a 7-point CGI-S scale 
ranging from “1: Normal, not at all ill” to “7: Among the most extremely ill of subjects” at every 
visit. 
PGI-S and CGI-S scores as well as their changes from baseline will be summarized descriptively 
by visit and treatment group, as well as for both treatment groups combined. Summary of study 
entry baseline of study IPX203-B16-02 will also be included. 
Number and percentage of subjects with each score will also be summarized by visit and 
treatment group. Additionally number of subjects having PGI-S >= 4, CGI-S >= 4 or PGI-S >= 
5, CGI-S >= 5 will be tabulated. Summary of study entry baseline of study IPX203-B16-02 will 
also be included. 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 14 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
4.2.3 PDQ-39 total score and individual domain scores 
Parkinson’s Disease Questionnaire-39 (PDQ-39) is a self-reported questionnaire. Using the 39 
items, 8 domains are defined: mobility (Questions 1-10), activities of daily living (ADL) 
(Questions 11-16), emotional well-being (Questions 17-22), stigma (Questions 23-26), social 
support (Questions 27-29), cognition (Questions 30-33), communication (Questions 34-36) and 
bodily discomfort (Questions 37-39). 
PDQ-39 will be administered at all scheduled visits 1-4.  
Total scores will be calculated for the entire questionnaire and each domain. If at least one 
question is not answered then the total score and the affected domain score will not be 
calculated. 
All scores and their changes from baseline will be summarized descriptively by visit and 
treatment group, as well as both treatment group combined. Summary of study entry baseline of 
study IPX203-B16-02 will also be included. 
4.2.4 PAS total score and individual domains 
Parkinson Anxiety Scale (PAS) is a 12-item patient or observer rated questionnaire with 3 
domains: persistent anxiety (Questions A.1-A.5), episodic anxiety (Questions B.1-B.4) and 
avoidance anxiety (Questions C.1-C.3). 
PAS will be administered at all scheduled visits 1-4. 
Total scores will be calculated for the entire questionnaire and each domain. If at least one 
question is not answered then the total score and the affected domain score will not be 
calculated. 
All scores and their changes from baseline will be summarized descriptively by visit and 
treatment group, as well as both treatment group combined. Summary of study entry baseline of 
study IPX203-B16-02 will also be included. 
4.2.5 NMSS total score and individual domains 
Non-Motor Symptom assessment scale for Parkinson’s Disease (NMSS) is a 30-item investigator 
rated questionnaire. The NMSS contains 9 domains: cardiovascular (Questions 1, 2), 
sleep/fatigue (Questions 3-6), mood/cognition (Questions 7-12), perceptual problems (Questions 
13-15), attention/memory (Questions 16-18), gastrointestinal (Questions 19-21), urinary 
(Questions 22-24), sexual function (Questions 25, 26), and miscellaneous (Questions 27-30). 
NMSS will be administered at all scheduled visits 1-4. 
Total scores will be calculated for the entire questionnaire and each domain. If at least one 
question is not answered then the total score and the affected domain score will not be 
calculated. 
All scores and their changes from baseline will be summarized descriptively by visit and 
treatment group, as well as both treatment group combined. Summary of study entry baseline of 
study IPX203-B16-02 will also be included. 
4.2.6 PDSS-2 total score and individual domains 
Parkinson’s Disease Sleep Scale-2 (PDSS-2) is 15-item self-reported questionnaire. Three 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 15 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
domains are defined: disturbed sleep (Questions 1-3, 8, 14), motor symptoms at night (Questions 
4-6, 12, 13), PD symptoms at night (Questions 7, 9-11, 15). 
PDSS-2 will be administered at all scheduled visits 1-4. 
Total scores will be calculated for the entire questionnaire and each domain. Additionally sum of 
questions 9, 10, 11, 12, and 13 will be calculated. If at least one question is not answered then the 
total score and the affected domain score will not be calculated. 
All scores and their changes from baseline will be summarized descriptively by visit and 
treatment group, as well as both treatment group combined. Summary of study entry baseline of 
study IPX203-B16-02 will also be included. 
4.2.7 TSA 
Treatment Satisfaction Assessment will be administered at visits 2-4. The subjects will rate their 
satisfaction with their PD treatment on a 7-point scale ranging from “1: Very much dissatisfied” 
to “7: Very much satisfied”. 
TSA scores will be summarized descriptively by visit and treatment group, as well as for both 
treatment groups combined. 
Number and percentage of subjects with each score will also be summarized by visit and 
treatment group. Also, the number and percentage of subjects with scores 5-7 (satisfied) vs. 
scores 1-4 (dissatisfied or neutral) will be tabulated. 
4.2.8 ZBI-12 
The 12-Item Zarit Burden Interview (ZBI-12) is used to assess the perceived burden of 
caregivers who provide assistance to patients with long-term progressive neurological disorders, 
including PD. The questionnaire consist of 12 questions, each answered on a scale from “0: 
Never” to “4: Nearly always”.  
The ZBI-12 should be completed by the same caregiver during each scheduled visit. 
Total score will be calculated by summing up the responses to all questions. If at least one 
question is not answered then the total score will not be calculated. 
The total score and its change from baseline will be summarized descriptively by visit and 
treatment group, as well as for both treatment group combined. 
Additionally the total score will be classified as follows: 
 0-10: no to mild burden 
 >10-20: mild to moderate burden 
 >20: high burden 
Number and percentage of subjects at each category will be tabulated by visit and treatment 
group. 
4.2.9 EMSQ 
The EMSQ is a 3-question, subject-rated questionnaire that is used to assess whether a subject is 
experiencing any of 10 early morning PD symptoms by answering questions about prevalence 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 16 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
(Question 1), severity (Question 2), and response to the first morning dose of PD medications 
(Question 3). Study site staff will complete this questionnaire by questioning subjects during 
each scheduled visit. 
For each symptom, number and percentage of subjects with each frequency and severity will be 
tabulated by visit and treatment group, as well as for both treatment groups combined. Whether 
the symptom improves after taking the first morning dose of the study drug will be similarly 
summarized. Summary of study entry baseline of study IPX203-B16-02 will also be included. 
Total severity score will be calculated as the sum of severities across all 10 symptoms (None = 0, 
Mild = 1, Moderate = 2, Severe = 3). If the severity score is missing for at least one symptom, 
then the total severity score will not be calculated. The total severity score and its change from 
baseline will be summarized descriptively by visit and treatment group, as well as for both 
treatment group combined. Summary of study entry baseline of study IPX203-B16-02 will also 
be included. 
5 SAFETY ANALYSES 
Safety analyses will be performed on the Safety Analysis Set. 
No imputation will be performed for missing safety data. In by-visit summaries, if a subject does 
not have a value collected at a given visit, this subject will not be summarized at that visit.  
5.1 
Adverse Events 
Adverse Events will be coded using the Medical Dictionary of Regulatory Activities (MedDRA) 
version 22.0 AE coding system for purposes of summarization. 
Only Treatment Emergent Adverse Events (TEAE) will be used for the summary analysis, unless 
otherwise specified. An AE will be considered as treatment-emergent if the date of onset is on or 
after the date of the first open-label study drug administration in the study IPX203-B16-03 and 
no later than 1 day after the last study drug dose in the study. AEs with unknown start dates will 
be counted as treatment-emergent unless the AE resolution date is prior to the first open-label 
study drug administration date. If the AE start date is partially missing, the AE will be 
considered treatment-emergent, unless the month and year (when available) rule out the 
possibility that the event occurred post start of the open-label study drug and no later than 1 day 
after the last study drug dose. 
A TEAE is defined as treatment-related if it is recorded as “possibly related” or “related” to the 
study medication on the eCRF. AEs recorded as “not related” or “unlikely related” will be 
considered not related. In case the relatedness was not assessed, the most conservative result 
(related) will be chosen for the analysis.  
In summaries of TEAEs a subject experiencing the same AE (with the same preferred term) 
multiple times will only be counted once for that preferred term. Similarly, if a subject 
experiences multiple AEs within the same system organ class, that subject will be counted only 
once in that system organ class. When summarizing AEs by severity, only the most severe 
occurrence within the preferred term or system organ class will be used. Similarly, when 
summarizing AEs by relationship to study drug, only the most related occurrence within the 
preferred term or system organ class will be selected for displays in summary tables. 
An overall summary will include, by treatment group and overall, the number and percentage of 
subjects reporting at least 1 TEAE in the following categories: 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 17 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
 Any TEAE 
 Treatment-related TEAE 
 Serious TEAE 
 TEAE leading to discontinuation of the study drug 
 TEAE leading to death. 
The following TEAE frequency tables will be prepared summarizing the overall number of 
TEAEs, the number and percentage of subjects reporting at least one TEAE by MedDRA System 
Organ Class (SOC) and preferred term (PT), by treatment group and overall: 
 All TEAEs 
 Serious TEAEs 
 Treatment-related TEAEs 
 AEs leading to discontinuation of the study medication 
 TEAEs in subjects with COVID-19 
 TEAEs by severity 
 TEAEs by relationship to study drug. 
TEAEs will also be presented by SOC, PT, treatment group and one of the following subgroups 
of AEs: 
 Total daily dose on the day of AE onset, categorized as < 400, 400 to < 1000, 1000 to < 
1400, 1400 to < 1800, 1800 to <= 2400, and >2400 mg 
 Daily dosing frequency on the day of AE onset (2, 3, 4, etc. times a day) 
 Time to first onset, defined as the study day of the first onset of AE of the given SOC or 
PT for the subject, categorized as <= 7 days, >7 to 30 days, >30 to 90 days, >90 to 180 
days, and >180 days. 
 Time period. In this analysis each AE will be assigned to all (possibly several) time 
periods as in the previous paragraph during which the AE was active (i.e. after onset and 
prior to resolution). 
TEAEs will also be presented by SOC, PT, treatment group and one of the following subgroups 
of subjects: 
 Age: < 65, ≥ 65 years old at Visit 1 
 Sex: Males, Females 
 Race: Caucasians, non-Caucasians 
 Region: North America or Europe 
 PD duration at Visit 1: <8 years or ≥8 years 
 Concomitant medications: the following non-exclusive subgroups will be defined for 
subjects taking concomitant medications of the following categories: 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 18 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
o Amantadine 
o selective MAOB inhibitors 
o anticholinergic PD medications 
o dopamine agonists 
o others 
Additional summaries of non-treatment-emergent AEs that started in the previous study IPX203-
B16-02 will be provided: 
 AEs that started in study IPX203-B16-02 and resolved in the current study vs. those that 
did not resolve, by SOC, PT and treatment at the onset of AE (IPX203 or IR CD-LD and 
both treatments together) 
  AEs that started in study IPX203-B16-02 and ended in the current study vs. are ongoing 
at the end of the current study by SOC, PT and treatment at the onset of AE (IPX203 or 
IR CD-LD and both treatments together) 
For this analysis AE will be defined as resolved if its outcome is recorded as 
“Recovered/Resolved” or “Recovered/Resolved with Sequelae” in the eCRF. All other AEs will 
be considered not resolved. 
The summaries by SOC and PT will be ordered alphabetically by SOC and PT. 
Additionally number and percentage of subjects with TEAE will be presented by preferred term 
only in the descending order of total frequency.  
All information pertaining to adverse events noted during the study will be listed by subject, 
detailing verbatim, preferred term, system organ class, start date, stop date, severity, outcome, 
action taken and causal relationship to the study drug.  
5.2 
Laboratory Evaluations 
The following laboratory tests will be performed at all scheduled visits 1-4: 
HEMATOLOGY: hemoglobin, hematocrit, red blood cell count, white blood cell count, % 
neutrophils, % lymphocytes, % monocytes, % basophils, % eosinophils, absolute neutrophils, 
absolute lymphocytes, absolute monocytes, absolute basophils, absolute eosinophils, platelet 
count 
CHEMISTRY: sodium, potassium, chloride, carbon dioxide, blood urea nitrogen (BUN), 
creatinine, glucose, calcium, phosphorus, albumin, total protein, uric acid, total bilirubin, direct 
bilirubin, indirect bilirubin, alkaline phosphatase, alanine aminotransferase, (ALT, SGPT), 
aspartate aminotransferase (AST, SGOT), creatine phosphokinase, lactate dehydrogenase 
URINALYSIS: pH, specific gravity, blood, glucose, ketones, microscopic exam (RBC and 
WBC, only when indicated), leukocyte esterase, protein 
Urine pregnancy test will be performed at Visit 1 only. 
For hematology, chemistry and urinalysis actual values and changes from baseline will be 
summarized descriptively by visit and treatment group, as well as both treatment group 
combined. 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 19 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
Additionally, numeric hematology, chemistry and urinalysis results will be classified as Low 
(below the reference range), Normal (within the reference range) or High (above the reference 
range). Categorical urinalysis results will be classified as Normal or Abnormal. Shifts among 
these categories between baseline and last available post-baseline assessment will be provided. 
All results will be listed. 
Additionally, subject listings will be provided for the following occurrences during the trial:  
1. Liver enzyme (ALT or AST) values ≥ 2.5 times the upper limit of normal; 
2. Serum creatinine level ≥ 1.75 times the upper limit of normal. 
For subjects/tests that meet the above criteria at least once during the study, results from all 
available visits will be shown. 
5.3 
Vital Signs 
Vital signs will be collected at all scheduled visits. Blood pressure, heart rate and respiratory rate 
will be collected at all visits, temperature at Visits 1 and 4 only.  Blood pressure and heart rate 
will be recorded at two positions: supine and standing.  
Weight will also be measured at all scheduled visits. 
Vital signs (including weight) and their changes from baseline will be summarized descriptively 
by visit, position and treatment group, as well as for both treatment groups combined. 
Vital signs will also be classified as follows: 
 Systolic blood pressure: < 90 mmHg, 90 to < 140 mmHg, and ≥ 140 mmHg. 
 Diastolic blood pressure:  < 60 mmHg, 60 to < 90 mmHg, and ≥ 90 mmHg. 
 Heart rate: < 60 beats/min, 60 to < 100 beats/min, and ≥ 100 beats/min. 
 Respiratory rate: < 9 breaths/min, 9 to < 20 breaths/min, ≥ 20 breaths/min. 
 Body temperature < 36.5ºC, 36.5ºC to < 37.5ºC, 37.5ºC to< 38.5ºC, and ≥ 38.5 ºC 
Subjects will be summarized with counts and percentages by these categories. 
Orthostatic hypotension is defined as a systolic blood pressure decrease of ≥ 20 mmHg or a 
diastolic blood pressure decrease of ≥ 10 mmHg within 3 minutes of standing.  
Number and percentage of subjects with orthostatic hypotension will be presented by treatment 
group and visit, as well as at least once after baseline. 
All vital signs will be listed. 
5.4 
Electrocardiogram 
ECG will be performed at all scheduled visits 1-4. The following parameters will be recorded: 
Ventricular Rate (beats/min), PR Interval (msec), QRS Duration (msec), QT Interval (msec), RR 
Interval (msec), Rhythm Assessment (Normal Sinus Rhythm VR 60-100 bpm, Sinus Bradycardia 
VR less than 60 bpm, Sinus Tachycardia VR greater than 100 bpm or Other) and Overall 
Interpretation (Normal, Abnormal Not Clinically Significant (NCS) or Abnormal Clinically 
Significant (CS)). 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 20 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
QT Interval corrected using Fridericia’s formula (QTcF) will be calculated as follows: 
𝑄𝑇𝑐𝐹=
𝑄𝑇
√( 𝑅𝑅
1000)
3
 
Ventricular rate and ECG intervals will be summarized descriptively with their changes from 
baseline by visit and treatment group as well as for both treatment groups combined. 
Rhythm assessment and overall interpretation will be summarized categorically by visit and 
treatment group, as well as both treatment group combined. 
Shifts in overall interpretation from baseline to the last available post-baseline assessment will be 
tabulated. 
Additionally, ECG parameters will be classified as follows: 
Parameter 
Categories of value 
Categories of change from 
baseline 
Ventricular rate 
< 60 beats/min, 60 to 100 
beats/min, and > 100 
beats/min 
< -10 beats/min, -10 to < 0 
beats/min, 0 to < 10 
beats/min, and ≥ 10 
beats/min. 
PR Interval 
< 120 msec, 120 to 200 msec, 
and > 200 msec 
< -1 msec, -1 to 5 msec, and ≥ 
5 msec 
QRS Interval 
< 60 msec, 60 to 100 msec, 
and > 100 msec 
< 0 msec, 0 to < 3 msec, and 
≥ 3 msec 
QT Interval 
< 200 msec, 200 to 430 msec, 
>430 to 450 msec, > 450 to 
500 msec, and > 500 msec 
< 30 msec, 30 to < 60 msec, 
and ≥ 60 msec 
RR Interval 
< 600 msec, 600 to 1000 
msec, and > 1000 msec 
< -33 msec, - 33 to < 12 
msec, and ≥ 12 msec 
QTcF Interval 
< 200 msec, 200 to 430 msec, 
> 430 to 450 msec, > 450 to 
500 msec, and > 500 msec 
< 30 msec, 30 to < 60 msec, 
and ≥ 60 msec 
Subjects will be summarized by number and percentage in each of the categories above by visit 
and treatment group, as well as both treatment group combined. 
All results will be listed. 
5.5 
Physical Examination 
Physical examination will be performed at Visit 1 and 4. The following body systems will be 
examined: Gastrointestinal; Reproductive/Breast; Cardiovascular; Endocrine; General 
Appearance; Head, Eyes, Ears, Nose, Throat; Musculoskeletal; Neurologic; Peripheral Vascular; 
Psychiatric; Genitourinary/Renal; Respiratory; Dermatologic. Each system will be classified as 
Normal, Abnormal Not Clinically Significant (NCS) or Abnormal Clinically Significant (CS). 
Number and percentage of subjects with each assessment result will be tabulated by body 
system, visit and treatment group, as well as both treatment group combined. 
All results will be listed. 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 21 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
5.6 
C-SSRS 
Columba Suicide Severity Rating Scale (“Since Last Visit” version) will be administered at each 
scheduled visit.  
Suicidal ideation will be defined as “yes” answer to any one of the five suicidal ideation 
questions (Question 1-5) on the C-SSRS. 
Suicidal behavior will be defined as “yes” answer to any one of the 5 suicidal behavior questions 
(Actual attempt, Interrupted attempt, Preparatory Acts or Behavior, Suicidal behavior, 
Completed suicide) on the C-SSRS. 
Number and percentage of subjects with any suicidal ideation and/or any suicidal behavior will 
be presented by visit and treatment group, as well as for both treatment groups combined. 
Time from baseline to the first appearance of suicidal ideation or suicidal behavior will be 
summarized descriptively for those subjects who develop suicidal ideation or suicidal behavior 
during the study (i.e. do not have suicidal ideation or suicidal behavior at baseline, but report it 
during the study). 
All results will be listed. 
5.7 
GCSI 
Gastroparesis Cardinal Symptom Index (GCSI) questionnaire will be administered at Visits 1 
and 4. GCSI contains 3 subscales: post-prandial fullness/early satiety (questions 4-7), 
nausea/vomiting (questions 1-3) and bloating (questions 8-9).  
Total scores will be calculated for the entire questionnaire and each subscale. If at least one 
question is not answered then the total score and the affected subscale score will not be 
calculated. 
Individual question scores, total score and subscale total scores as well as their changes from 
baseline will be summarized descriptively by visit and treatment group as well as for both 
treatment groups combined. 
All results will be listed. 
5.8 
Concomitant Medications 
Concomitant medications are defined as medications taken while a subject took the open-
label study drug, i.e. medications with stop date on or after the date of the first 
administration of the open-label study drug or those that are ongoing. 
Concomitant medications will be coded using WHO Drug Dictionary version March 2019.  
Use of concomitant medications will be summarized by ATC class (the highest available 
level), preferred name and treatment group, as well as for both treatment groups combined. 
A subject reporting the same medication more than once will be counted only once for that 
medication name; similarly, a subject reporting several medications in an ATC class will be 
counted once for that class. The summary will be ordered alphabetically by ATC class and 
preferred name. 
Concomitant medications will also be grouped into various anti-PD medication classes: 
 Amantadine 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 22 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
 selective MAO-B inhibitors 
 anticholinergic PD medications 
 dopamine agonists 
 others 
as well as antidepressants, sleep aids, and others. 
Frequencies and percentages of subjects taking these classes of medications as well as each 
medication preferred name under the class will be summarized by treatment group as well as for 
both treatment groups combined.  
All concomitant medications will be listed. 
6 COVID-19 considerations for analyses 
As the study will be partly conducted during the COVID-19 pandemic, a number of visits can be 
delayed, canceled or conducted remotely. To account for these circumstances the following 
changes were implemented in analysis: 
1. 
All measurements for the following scales that were done remotely due to 
COVID-19 will be included in the analysis as if they were done at a face-to-
face visit: 
 C-SSRS (Columbia Suicide Severity Rating Scale) 
 NMSS (Non-Motor Symptom Assessment Scale for Parkinson’s Disease 
 PAS (Parkinson Anxiety Scale) 
 PDQ-39 (39-item Parkinson Disease Questionnaire 
 PDSS-2 (Parkinson’s Disease Sleep Scale-2) 
 PGI-S (Patient Global Impression of Severity) 
 GCSI (Gastroparesis Cardinal Symptom Index) 
 TSA (treatment Satisfaction Assessment) 
 ZBI-12 (12-item Zarit Burden Interview) 
 EMSQ (Early Morning Symptoms Questionnaire) 
 MDS-UPDRS parts I, II, and IV 
2. 
Remote measurements, due to COVID-19, of the following scales will be 
excluded from all analyses: 
 MDS-UPDRS Part III 
 CGI-S (Clinical Global Impression of Severity) 
3. 
Samples for laboratory tests and ECG that were done outside of regular visits, 
due to COVID-19, will be included in the analysis and mapped to the closest 
protocol defined visit (section 2.3). 
4. 
Subjects who discontinued for reasons related to COVID-19 pandemic will be 
summarized separately in the disposition tables (section x) 
5. 
Adverse events in subjects with COVID-19 will be summarized separately 
(section 5.1) 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 23 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
6. 
Protocol deviations related to COVID-19 will be identified in the listing 
(section 3.4) 
 
7 Changes From Protocol-Specified Analyses 
The protocol envisioned summarizing AEs, vital signs and ECG across the entire IPX203 
exposure including information from the open-label extension and the prior IPX203-B16-02 
study into which the subjects were enrolled. It was decided to postpone such analyses until an 
Integrated Summary of Safety (ISS) is prepared. Such analyses will not be done as part of this 
SAP. 
Changes related to the COVID-19 pandemic are summarized in section 6. 
There are no other deviations from the protocol-specified safety analyses.


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 24 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
8 REFERENCES 
Study protocol: An Open-Label Extension Study of the Safety and Clinical Utility of IPX203 
in Parkinson’s Disease Patients with Motor Fluctuations, Amendment 1, June 22, 2018. 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 25 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
9 APPENDICES 
9.1 
Schedule of events 
Table 1 Schedule of Events 
 
Visit 1 
Baseline 
9 Months of IPX203 Therapy 
Study 
Drug 
Resupply 
Months 1-
2 
Visit 
2 
Study 
Drug 
Resupply 
Months 4-
5  
Visit 
3 
Study 
Drug 
Resupply 
Months 7-
8 
Visit 4/ 
Early 
Termination 
Study Month  
0 
 
3 
6 
9 
ICF and HIPAA 
Authorization b  
X 
 
 
 
 
 
 
Check Inclusion/Exclusion 
Criteria  
X 
 
 
 
 
 
 
Update Medical History  
X 
 
 
 
 
 
Physical Examination  
X 
 
 
 
 
 
X 
Vital Signs c  
X 
 
X 
 
X 
 
X 
Weight  
X 
 
X 
 
X 
 
X 
C-SSRS d  
X 
 
X 
 
X 
 
X 
Clinical Laboratory Tests e  
X 
 
X 
 
X 
 
X 
Urine Pregnancy Test  
Xf 
 
 
 
 
 
ECG  
X 
 
X 
 
X 
 
X 
MDS-UPDRS Parts I-IV g  
X 
 
X 
 
X 
 
X 
PGI-S h  
X 
 
X 
 
X 
 
X 
CGI-S i  
X 
 
X 
 
X 
 
X 
PDQ-39j  
X 
 
X 
 
X 
 
X 
GCSI k  
X 
 
 
 
 
 
X 
NMSS l  
X 
 
X 
 
X 
 
X 
PDSS-2m  
X 
 
X 
 
X 
 
X 
PAS n  
X 
 
X 
 
X 
 
X 
TSA o  
 
 
X 
 
X 
 
X 
ZBI-12 p  
X 
 
X 
 
X 
 
X 
EMSQ q  
X 
 
X 
 
X 
 
X 
Contact phone calls r  
 
 
X 
 
X 
 
X 
Contact IWRS to dispense 
study medication  
X 
X 
X 
X 
X 
X 
 
Collect empty medication 
bottles and any unused 
study drug/Perform study 
drug accountability  
 
X 
X 
X 
X 
X 
X 
Adverse Events  
X 
 
X 
 
X 
 
X 
Concomitant Medications  
X 
 
X 
 
X 
 
X 
a Visit 1 is expected to occur on the same day as the End-of-Study Visit (Visit 7) of Study IPX203-B16-02 
but not later than 1 week. After the subject provides consent for this study, carry over and record 
information from procedures at the End-of-Study Visit of IPX203-B16-02 as the Baseline data for this 
study. 
b Subjects enrolled at sites in the United States (US) must sign HIPAA authorization prior to the conduct of 
any study-specific procedures. 
c Record vital signs (blood pressure, heart rate, respiratory rate, and temperature [Visit 1 and Study Exit 


Impax Laboratories, Inc 
CONFIDENTIAL 
Page 26 of 43 
IPX203–B16-03 
Statistical Analysis Plan 
 
 
only]) after subject has been resting supine for at least 5 minutes, then record orthostatic blood pressure 
and heart rate after subject has been standing for approximately 2 minutes. 
d See Appendix B of the protocol. 
e See Appendix C of the protocol. 
f This test will be performed at Visit 1 of this study. 
g See Appendix D of the protocol. 
h See Appendix E of the protocol. 
i See Appendix F of the protocol. 
j See Appendix G of the protocol. 
k See Appendix H of the protocol. 
l See Appendix I of the protocol. 
m See Appendix J of the protocol. 
n See Appendix K of the protocol. 
o See Appendix L of the protocol. 
p See Appendix M of the protocol. 
q See Appendix N of the protocol. 
r Contact phone calls for Visits 2 through 4: 
• 
Following Visit 1, contact subjects weekly for the first month and then monthly thereafter between 
visits to review the subject’s medication dosing regimen. 
• 
Instruct subjects to call the study site before making any changes to their IPX203 dosing regimen. 
• 
Update and record concomitant medications and IPX203 dose adjustments. 
• 
Contact subjects 1 day prior to Visits 2 to 4 to remind them to bring back any unused medication and 
empty medication bottles. 
CGI-S = Clinical Global Impression of Severity Scale; C-SSRS = Columbia-Suicide Severity Rating Scale; 
ECG = electrocardiogram; EMSQ = Early Morning Symptoms Questionnaire; GCSI = Gastroparesis 
Cardinal Symptom Index; HIPAA = Health Insurance Portability and Accountability Act; ICF = informed 
consent form; IWRS = interactive web response system; PAS = Parkinson Anxiety Scale; PD = 
Parkinson’s disease; PDQ-39 = 39-Item Parkinson’s Disease Questionnaire; PDSS-2 = Parkinson’s Disease 
Sleep Scale-2; PGI-S = Patient Global Impression of Severity Scale; MDS-UPDRS = MDS version of 
Unified Parkinson’s Disease Rating Scale; NMSS = Non-Motor Symptom Assessment Scale; TSA = 
Treatment Satisfaction Assessment; ZBI-12 = 12-Item Zarit Burden Interview