Clinical trial NCT04191577
Conditions: Parkinson Disease
Sponsor: Cerevance Beta, Inc.
Start date: 2019-12-02; Completion date: 2021-12-13
Enrollment: 136 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase 2 study, randomized, double-blind, placebo-controlled, multicenter study of oral CVN424 at two dose levels (low-dose and high-dose) in Parkinson's disease (PD) patients with motor fluctuations.

Detailed description:
Approximately 135 male and female subjects with Parkinson's disease, on a stable dosage of levodopa but with an average of ≥ 2 h total OFF time/day and not less than 1 h per day, will be enrolled. Following baseline safety and efficacy assessments, subjects will be randomized to receive once-daily doses of either low-dose CVN424, high-dose CVN424, or matching placebo. All subjects not randomized to placebo will initiate treatment with a low-dose of CVN424 on Day 1; the low-dose arm will continue to receive their low dose each day, while the high-dose arm will increase their daily dosage to the high-dose CVN424 beginning on Day 8 ±2 days and continuing thereafter. Study drug will be self-administered each morning as an oral suspension. Subjects will continue their other PD medications.

Arms: arm 1: Placebo to be administered once daily. arm 2: Low dose of CVN424 to be administered once daily. arm 3: Patients randomized to the high dose will receive low-dose CVN424 once daily from day 1 to day 7, and will then increase their dose to the full high-dose once daily beginning on day 8.
Interventions: intervention 1: CVN424 Low Dose intervention 2: CVN424 High Dose intervention 3: Placebo
Intervention descriptions: intervention 1: CVN424 intervention 2: CVN424 intervention 3: Placebo

Protocol documents:
Prot_SAP_000.pdf: 
CVN424 
 
Study No. CVN424-201 
Page 1 of 73 
Protocol v. 4.0 
14 July 2021 
 
CONFIDENTIAL 
PROTOCOL 
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of CVN424 in 
Parkinson’s Disease Patients with Motor Fluctuations 
 
Short Title: Phase 2 Study of CVN424 
 
Sponsor: 
Cerevance Beta, Inc. 
One Marina Park Drive, Suite 1410 
Boston, MA 02210 
Study Number: 
CVN424-201 
IND Number: 
138119 
EudraCT Number:  
Not Applicable 
Compound: 
 
CVN424 
Version/Date: 
Protocol 4.0 
14 July 2021 
 
 
 
CONFIDENTIAL PROPERTY OF CEREVANCE 
This document is a CONFIDENTIAL communication of Cerevance Beta, Inc. (“Cerevance”). Acceptance of this 
document constitutes the agreement by the recipient that no information contained herein will be published or disclosed 
without written authorization from Cerevance except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered. Furthermore, the information is only meant for review and compliance 
by the recipient, his or her staff, and applicable institutional review committee and regulatory agencies to enable conduct 
of the study. 
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CONFIDENTIAL 
1.0 
ADMINISTRATIVE INFORMATION  
1.1 
Contacts  
 
Contact Type / Role 
Contact 
Serious adverse event and pregnancy reporting 
Worldwide Pharmacovigilance  
Fax: +1-866-387-5539 
Email: drugsafety@worldwide.com 
Medical Monitor  
(carries overall responsibility for the conduct of the study)  
Ralph Campaneria, M.D. 
Senior Medical Director 
Worldwide Clinical Trials 
Mobile: +1-202-281-4062 
Email: ralph.campaneria@worldwide.com   
Responsible Medical Officer  
(medical advice on protocol and compound) 
David H. Margolin, M.D.-Ph.D. 
Senior Vice President  
Cerevance, Inc. 
Mobile: +1-508-250-7378 
Email: david.margolin@cerevance.com  
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CONFIDENTIAL 
1.2 
Approval 
REPRESENTATIVES OF CEREVANCE 
This study will be conducted with the highest respect for the individual participants in accordance 
with the requirements of this clinical study protocol and also in accordance with the following: 
 The ethical principles that have their origin in the Declaration of Helsinki. 
 International Council on Harmonisation (ICH) E6 Good Clinical Practice (GCP) Consolidated 
Guideline. 
 All applicable laws and regulations, including, without limitation, data privacy laws, clinical trial 
disclosure laws, and regulations. 
 
SIGNATURES  
Approved by: 
 
 
 
Signature __________________________________       Date__________________________ 
 
David H. Margolin, MD PhD 
Senior Vice President 
Cerevance, Inc. 
 
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CVN424 
 
Study No. CVN424-201 
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CONFIDENTIAL 
INVESTIGATOR AGREEMENT  
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, and any 
other product information provided by the sponsor. I agree to conduct this study in accordance with 
the requirements of this protocol and also to protect the rights, safety, privacy, and well-being of 
study subjects in accordance with the following: 
 The ethical principles that have their origin in the Declaration of Helsinki 
 International Council on Harmonisation, E6 GCP: Consolidated Guideline 
 All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations 
 Regulatory requirements for reporting serious adverse events (SAEs) defined in Section 9.6 of 
this protocol 
 Terms outlined in the Clinical Study Site Agreement 
 Appendix B – Responsibilities of the Investigator 
 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix C of this protocol. 
Signature of Investigator 
Date 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State/Province) 
Location of Facility (Country) 
 
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CONFIDENTIAL 
TABLE OF CONTENTS 
1.0 
ADMINISTRATIVE INFORMATION ..............................................................................2 
1.1 
Contacts..........................................................................................................................2 
1.2 
Approval ........................................................................................................................3 
2.0 
STUDY SUMMARY...........................................................................................................9 
3.0 
STUDY REFERENCE INFORMATION .........................................................................16 
3.1 
List of Abbreviations ...................................................................................................16 
4.0 
INTRODUCTION .............................................................................................................18 
4.1 
Background ..................................................................................................................18 
4.2 
Rationale for the Proposed Study ................................................................................19 
5.0 
STUDY OBJECTIVES AND ENDPOINTS .....................................................................20 
5.1 
Objectives ....................................................................................................................20 
5.1.1 Primary Objective ..................................................................................................20 
5.1.2 Secondary Objectives.............................................................................................20 
5.1.3 Exploratory Objectives ..........................................................................................20 
5.2 
Endpoints .....................................................................................................................20 
5.2.1 Primary Endpoints .................................................................................................20 
5.2.2 Secondary Endpoints .............................................................................................20 
5.2.3 Additional and Exploratory Endpoints ..................................................................20 
6.0 
STUDY DESIGN AND DESCRIPTION ..........................................................................22 
6.1 
Study Design ................................................................................................................22 
6.1.1 Study Committees ..................................................................................................23 
6.2 
Justification for Study Design, Dose, and Endpoints ..................................................23 
6.3 
Premature Termination or Suspension of Study or Investigational Site ......................25 
6.3.1 Criteria for Premature Termination or Suspension of the Study ...........................25 
6.3.2 Criteria for Premature Termination or Suspension of Investigational Sites ..........25 
6.3.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s)...................................................................25 
7.0 
SUBJECT POPULATION.................................................................................................26 
7.1 
Inclusion Criteria .........................................................................................................26 
7.2 
Exclusion Criteria ........................................................................................................26 
7.3 
Excluded Medications and Dietary Products ...............................................................28 
7.4 
Diet and Fluid Control .................................................................................................28 
7.5 
Criteria for Discontinuation or Withdrawal of a Subject .............................................28 
7.6 
Procedures for Discontinuation or Withdrawal of a Subject .......................................29 
8.0 
CLINICAL TRIAL MATERIAL MANAGEMENT .........................................................30 
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CONFIDENTIAL 
8.1 
Study Medication and Materials ..................................................................................30 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling ......................................30 
8.1.2 Drug Storage ..........................................................................................................30 
8.1.3 Dose and Regimen .................................................................................................30 
8.1.4 Overdose ................................................................................................................31 
8.2 
Investigational Drug Assignment and Dispensing Procedures ....................................31 
8.3 
Randomization Code Creation and Storage .................................................................31 
8.4 
Unblinding Procedure ..................................................................................................31 
8.5 
Accountability and Destruction of Sponsor-Supplied Drugs.......................................32 
9.0 
STUDY PLAN ...................................................................................................................34 
9.1 
Study Procedures .........................................................................................................34 
9.1.1 Informed Consent Procedure .................................................................................34 
9.1.2 Demographics, Medical History, and Medication History Procedure ...................34 
9.1.3 Physical Examination Procedure ...........................................................................34 
9.1.4 Weight, Height, and BMI.......................................................................................35 
9.1.5 Vital Sign Procedure ..............................................................................................35 
9.1.6 Documentation of Concomitant Medications ........................................................35 
9.1.7 Documentation of Concurrent Medical Conditions ...............................................35 
9.1.8 Procedures for Clinical Laboratory Samples .........................................................35 
9.1.9 Contraception and Pregnancy Avoidance Procedure .............................................37 
9.1.10 Pregnancy ...............................................................................................................38 
9.1.11 ECG Procedure ......................................................................................................38 
9.1.12 Pharmacogenomic Sample Collection ...................................................................39 
9.1.13 PK Sample Collection ............................................................................................40 
9.1.14 PK Parameters ........................................................................................................40 
9.1.15 Documentation of Screen Failure ..........................................................................41 
9.1.16 Documentation of Randomization .........................................................................42 
9.2 
Monitoring Subject Treatment Compliance.................................................................42 
9.3 
Schedule of Observations and Procedures ...................................................................42 
9.3.1 Observations and Procedures .................................................................................42 
9.3.2 Early Termination ..................................................................................................45 
9.4 
Biological Sample Retention and Destruction .............................................................45 
9.5 
Definitions....................................................................................................................46 
9.5.1 PTE ........................................................................................................................46 
9.5.2 AE ..........................................................................................................................46 
9.5.3 Additional Points to Consider for PTEs and AEs ..................................................46 
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9.5.4 SAEs ......................................................................................................................48 
9.5.5 Severity of PTEs and AEs......................................................................................49 
9.5.6 Causality of AEs ....................................................................................................49 
9.5.7 Relationship to Study Procedures ..........................................................................49 
9.5.8 Start Date ...............................................................................................................50 
9.5.9 Stop Date ................................................................................................................50 
9.5.10 Frequency ...............................................................................................................50 
9.5.11 Action Concerning Study Medication ...................................................................50 
9.5.12 Outcome .................................................................................................................50 
9.6 
Procedures ....................................................................................................................51 
9.6.1 Collection and Reporting of AEs ...........................................................................51 
9.6.2 Collection and Reporting of SAEs .........................................................................52 
9.6.3 Reporting of Abnormal LFT ..................................................................................52 
9.7 
Follow-up of SAEs ......................................................................................................52 
9.7.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities .....53 
10.0 
STUDY-SPECIFIC COMMITTEES .................................................................................54 
11.0 
DATA HANDLING AND RECORDKEEPING ..............................................................55 
11.1 
CRFs (Electronic) ........................................................................................................55 
11.2 
Record Retention .........................................................................................................55 
12.0 
STATISTICAL METHODS ..............................................................................................57 
12.1 
Statistical and Analytical Plans ....................................................................................57 
12.1.1 Analysis Sets ..........................................................................................................57 
12.1.2 Analysis of Demographics and Other Baseline Characteristics ............................57 
12.1.3 PK Analysis ...........................................................................................................58 
12.1.4 Safety Analysis ......................................................................................................59 
12.1.5 Efficacy Analysis ...................................................................................................59 
12.2 
Interim Analysis and Criteria for Early Termination ...................................................60 
12.3 
Determination of Sample Size .....................................................................................60 
13.0 
QUALITY CONTROL AND QUALITY ASSURANCE .................................................62 
13.1 
Study-Site Monitoring Visits .......................................................................................62 
13.2 
Protocol Deviations ......................................................................................................62 
13.3 
Quality Assurance Audits and Regulatory Agency Inspections ..................................63 
14.0 
ETHICAL ASPECTS OF THE STUDY ...........................................................................64 
14.1 
IRB and/or IEC Approval ............................................................................................64 
14.2 
Subject Information, Informed Consent, and Subject Authorization ..........................64 
14.3 
Subject Confidentiality ................................................................................................66 
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CONFIDENTIAL 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy ..................................66 
14.4.1 Publication and Disclosure ....................................................................................66 
14.4.2 Clinical Trial Registration......................................................................................66 
14.4.3 Clinical Trial Results Disclosure ...........................................................................67 
14.5 
Insurance and Compensation for Injury .......................................................................67 
15.0 
REFERENCES ..................................................................................................................68 
 
LIST OF IN-TEXT TABLES 
Table 1 
Subject Visit Schedule ...........................................................................................23 
Table 2 
Prohibited Medications and Dietary Products .......................................................28 
Table 3 
Planned Study Arms and Dose Levels by Cohort ..................................................31 
Table 4 
Clinical Laboratory Tests .......................................................................................36 
Table 5 
Collection of Blood Plasma Samples for PK Analysis ..........................................40 
Table 6 
Pharmacokinetic Parameters ..................................................................................41 
Table 7 
Medically Significant AE List ...............................................................................49 
Table 8 
Windows for PK Blood Sample Collection ...........................................................62 
 
LIST OF IN-TEXT FIGURES 
Figure 1. Schematic design of study ..............................................................................................22 
 
LIST OF APPENDICES 
Appendix A: Schedule of Study Procedures ...............................................................................69 
Appendix B: Responsibilities of the Investigator ........................................................................72 
Appendix C: Investigator Consent to Use of Personal Information ............................................73 
 
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2.0 
STUDY SUMMARY 
Name of Sponsor(s): 
Cerevance Beta, Inc. 
Compound: 
CVN424 
Title of Protocol: A Phase II, Randomized, Double-Blind, Placebo-
Controlled, Multicenter Study of CVN424 in Parkinson’s Disease 
Patients with Motor Fluctuations 
IND No.: 138119 
EudraCT No.: Not applicable 
Study Number: CVN424-201 
Phase: 2 
Study Design: 
This is a phase 2 study, randomized, double-blind, placebo-controlled, multicenter study of oral CVN424 at two dose levels (low-
dose 50 mg, high-dose 150 mg) in Parkinson’s disease (PD) patients with motor fluctuations. The overall study design is depicted 
and described below: 
 
Approximately 135 male and female subjects with Parkinson’s disease, on a stable dosage of levodopa but with an average of ≥ 2 
h total OFF time/day and not less than 1 h per day, will be enrolled. Following baseline safety and efficacy assessments, subjects 
will be randomized to receive once-daily doses of either low-dose CVN424, high-dose CVN424, or matching placebo. The 
planned low-dose and high-dose levels will be 50 and 150 mg CVN424 per day, respectively. All subjects not randomized to 
placebo will initiate treatment with 50 mg CVN424 on Day 1; the low-dose arm will continue to receive 50 mg per day, while the 
high-dose arm will increase their daily dosage to 150 mg CVN424 beginning on Day 8 ±2 days and continuing thereafter. 
Investigator or their delegate will manage incident AEs according to their medical judgment. Study drug will be self-
administered each morning as an oral suspension. Subjects will continue their other PD medications. 
Subjects will follow the study schedule presented below. Dosing on Day 1, Day 8, and Day 22 visits will be observed at the study 
site by Investigator or their delegate. For Visit Days 8 and 22, dosing of study drug (but not subjects’ other medications) will be 
deferred until after collection of a blood sample for determination of the study drug “trough” concentration. 
Screening a 
Baseline 
& Random-
ization 
Treatment b 
Follow-up c 
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CONFIDENTIAL 
Consent,  
Eligibility 
Patient 
Motor Diary 
at Home 
Study Visit 
Study Visit 
Study Visit 
Study Visit 
Study Visit 
Study Visit 
Final  
Study Visit 
Days  
-28 to -1 
Days  
-2 & -1  
Day 0 
Day 1 d 
Day 8 
±2 days 
Day 15  
±2 days 
Day 22  
±2 days 
Day 27  
±1 day 
Day 35  
±2 days 
(a) 
Screening activities must occur within 28 days of randomization, but may be completed in fewer than 28 days. 
Screening days are nominally called Day -28 to Day -1 but will not necessarily correspond numerically to the calendar 
days prior to the Baseline Visit. By the same convention, the Patient Motor Diary will be recorded at home over 2 
consecutive days during screening, but not necessarily on the 2 days immediately prior to the Baseline visit. 
(b) Study drug supply will be dispensed (as suspension in amber colored bottles) on Day 1 and at subsequent weekly study 
visits. Subjects will return empty and unused bottles to site. Study drug will be self-administered each morning as an 
oral suspension. For Visit Days 8 and 22, dosing of study drug (but not subjects’ other medications) will be deferred 
until after collection of a blood sample for determination of the study drug “trough” concentration. 
(c) 
Subjects who have abnormal, clinically significant (CS) findings at the Final Study Visit may be asked to return to the 
clinic subsequently to ensure appropriate safety follow-up. 
(d) By convention, Day 1 will be the first day of treatment. It will not necessarily occur on the calendar day following the 
baseline and randomization visit. 
 
Follow-up assessments will occur approximately 7 days after the final (Day 27 ±1 day) dose. 
 
Study committees: 
None. (Review of incident and cumulative safety data and findings is the responsibility of the Medical Monitor and sponsor’s 
Responsible Medical Officer.) 
 
Safety stopping rules: 
If any of the following occur, the Medical Monitor and Sponsor’s Responsible Medical Officer will review the relevant data, 
including unblinded data if deemed necessary, and decide whether it is safe to suspend dosing or continue dosing at either the 
planned or alternative dose levels or decides to prematurely terminate the study: 
1. 
Four or more subjects receiving CVN424 experience the same type of serious or Medically Significant event deemed 
related to study drug. 
2. 
Three or more subjects receiving CVN424 experience alanine aminotransferase (ALT) and/or aspartate 
aminotransferase (AST) elevations >5 × upper limit of normal (ULN) in the absence of a concomitant bilirubin increase 
(see below). 
3. 
One or more subjects receiving CVN424 experience ALT and/or AST elevations >3 ×ULN in the presence of a total 
bilirubin increase >2 ×ULN or an international normalized ratio (INR) >1.5 without findings of cholestasis or other 
alternate etiology to explain the elevations (i.e., “Hy’s Law cases”). 
4. 
Two or more subjects receiving CVN424 experience ALT and/or AST elevations >3 ×ULN with the appearance of 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
 
Primary Objective: 
To assess the safety and tolerability of CVN424 when administered as daily oral doses for 28 days, adjunctive to levodopa, in 
subjects with Parkinson’s disease and motor fluctuations. 
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Secondary Objectives: 
• To assess potential efficacy of CVN424 adjunctive to levodopa in alleviating symptoms of PD 
• To assess CVN424 multiple-dose PK in blood of PD subjects 
Exploratory Objectives: 
• To explore possible serum/plasma, DNA and/or RNA markers (e.g., drug metabolic enzyme and transporter polymorphisms) 
that may contribute to variability in CVN424 PK, safety or efficacy 
Subject Population:  
Male and female subjects, ages 30 to 80 years old, with idiopathic Parkinson’s disease and motor fluctuations on stable doses of 
levodopa 
Target Number of Subjects: 
45 subjects per arm (total n=135 subjects)  
Number of Sites: 
Approximately 30 in the United States of America 
Dose Level(s): 
Planned dose levels are placebo, 50 mg, and 150 mg CVN424. 
Study drug dispensed as CVN424 suspension (or matching placebo) 
in amber colored bottles suitable for self-administered dosing. 
Route of Administration: 
Oral 
 
Duration of Treatment: 
Daily oral doses for 28 days.  
Period of Evaluation: 
Screening Period: up to 28 days 
Treatment Period: 28 days 
Follow-up Period: approximately 7 days 
Total Duration: Approximately 9 weeks 
Main Criteria for Inclusion: 
1. Male or female adult who is 30 to 80 years of age inclusive at study entry. 
2. Has idiopathic Parkinson’s disease, Hoehn and Yahr stages 2-4, and is on a stable dosage of levodopa. (Stable is defined 
as a dosage unchanged in the 30 days prior to randomization and, in the opinion of the investigator, able to continue the 
current regimen throughout the month-long study without undue inconvenience or harm.) 
3. Experiences an average of at least 2 h total OFF time/day, and at least 1 h each day, per Patient Motor Diary over 2 days 
during Screening assessment. 
4. The subject signs and dates a written informed consent form (ICF) and any required privacy authorization prior to the 
initiation of any study procedures.  
 
Main Criteria for Exclusion: 
1. Has atypical parkinsonism, severe disabling dyskinesia, or severe motor fluctuations that the investigator considers 
likely to interfere with study participation or assessments, or history of implant for Deep Brain Stimulation. 
2. Poor concordance (<75%) of self-report with site rater on in-clinic Screening period Patient Motor Diary. Subjects with 
low concordance may be retested after further instruction, at investigator’s discretion. 
3. Screening period Patient Motor Diary scored at-home over 2 days demonstrates unacceptable quality of the diary, with 
more than 4 errors per day. (Assistance from caregivers is permitted if they also will be providing assistance with home 
Patient Motor Diary entries for Day 15 and 27 efficacy assessments.) Subjects with more than 4 errors per day may be 
retested after further instruction, at investigator’s discretion. 
4. Body mass index (BMI) at Screening <18.0 or >35.0 kg/m2, inclusive.  
5. Subject has evidence of CS neurologic or other disorder or impairment that, in opinion of Investigator, is reasonably 
expected to impact the ability of the subject to participate or to confound the study results.  
6. Subject has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the 
absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption [e.g., bariatric 
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surgery or bowel resection]). 
7. Subject has a history of cancer or other malignancy, with the exception of low-grade cervical intraepithelial neoplasia, 
low-grade (low-risk) prostate cancer, or 5-year cancer-free survivors of basal or squamous cell carcinoma, higher-grade 
cervical intraepithelial neoplasia or prostate cancer. 
8. Has a history of human immunodeficiency virus (HIV) infection. 
9. Subject has a supine blood pressure outside the ranges of 80 to 160 mm Hg for systolic and 50 to 100 mm Hg for 
diastolic, confirmed with up to two repeat tests, at the Screening Visit; or symptomatic orthostatic hypotension, in the 
opinion of the investigator. 
10. Subject has a resting heart rate outside the range 50 to 100 bpm, confirmed with up to two repeat tests, at the Screening 
Visit. 
11. Positive urine result for illegal drugs (except cannabis) at Screening, or history of illegal drug use (except cannabis) or 
alcohol abuse within 1 year prior to the Screening Visit.  
12. Subject has received any investigational compound (defined as a drug that has not been FDA-approved) within 30 days 
prior to the first dose of study medication, or within 5 half-lives of the investigational compound, whichever is greater. 
13. Subject has, within the prior month, ingested any excluded medication, supplements, or food products listed in the 
Excluded Medications and Dietary Products table as listed in Table 2. 
14. Male subjects who do not agree to all the following rules: when sexually active with female partner(s) of childbearing 
potential during the study and for 12 weeks after the last dose of study drug: a) use an acceptable method of birth control 
(condom with spermicide or surgical sterilization) and b) refrain from sexual activity with female partners who do not 
use an acceptable method of birth control. Barrier contraception (condom with spermicide) must be used by all male 
subjects who were not surgically sterilized at least 90 days prior to screening. Male subjects must also agree to refrain 
from sperm donation during the study and until 12 weeks after the last dose of study drug. 
15. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova during the study or for 30 
days after the last dose of study drug. Women of childbearing potential (WOCBP) also must be practicing an adequate 
method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence).  
*Definitions and acceptable methods of contraception are defined in Section 9.1.9, Contraception and Pregnancy 
Avoidance Procedure, and reporting responsibilities are defined in Section 9.1.10, Pregnancy. 
16. Risk of suicide according to the investigator’s clinical judgment or has made a suicide attempt in the previous 3 years. 
17. Subject is a study site employee or an immediate family member of a study site employee. 
 
In addition, subjects may not use any excluded medications, supplement, or food product as listed in Table 2 during the study. 
 
- Safety assessments:  
Safety assessments will include AEs, clinical laboratory results, vital signs and weight, physical examinations, electrocardiogram 
(ECG), Questionnaire for Impulsive-Compulsive Disorders (QUIP), and Beck Depression Inventory. AEs will be collected from 
signing of ICF. AEs with onset or exacerbation up until dosing on Day 1 will be scored as pretreatment events (PTEs), and AEs 
that occur from first dosing until 30 days after the last dose will be captured as a treatment-emergent AE (TEAE). Vital signs will 
be recorded at Screening and at least once at each Study Visit. On Day 1 and Day 8, vital sign assessments will be conducted pre-
dose [within 90 minutes prior to dosing], and at least hourly through 3 h post-dose. Vital signs will include oral temperature, 
blood pressure, respiration rate and heart rate. Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded 15 
minutes apart at baseline. Orthostatic vital signs (non-triplicate) will be recorded pre-dose and at 3 h post-dose on Visit Days 1 
and 8. Heart rate and blood pressure will be measured after at least 5 minutes supine and (when orthostatic vital signs are 
specified) again after 2 minutes standing. Additional monitoring of vital signs and ECGs may continue beyond 3 h post-dose at 
the discretion of Investigator. 
Standard 12-lead ECGs will be recorded in triplicate at Screening and on Visit Days 1, 8, 27, and 35.  
A description of safety assessments is provided in Section 9.1 and the full Schedule of Study Procedures is provided in Appendix 
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A. 
 
- Efficacy assessments: 
Efficacy assessments will include Patient Motor Diary (Hauser diary), Unified Parkinson’s Disease Rating Scale (UPDRS), 
Epworth Sleepiness Scale, Clinical Global Impression (CGI), and Patient Global Impression (PGI). 
 
- Determination of CVN424 concentration in plasma:  
Plasma samples will be collected for the determination of concentrations of CVN424 as described in Section 9.1.13, PK Sample 
Collection. 
PK parameters of CVN424 will be derived from the concentration-time data for evaluable subjects. The following PK parameters 
will be determined from concentrations of CVN424 in plasma: Cmin at steady state (trough level on Day 22), Cmax on Day 22, 
time to reach Cmax on Day 22 (tmax), AUC from time 0 to 6 h (AUC6), terminal elimination rate constant (λz), terminal elimination 
half-life (t1/2z), apparent clearance (CL/F), and apparent volume of distribution (Vz/F).  
- Pharmacogenomics: 
One whole blood sample will be collected at Baseline for pharmacogenomic analysis; this will only be collected once per subject. 
A whole blood sample will be collected at pre-dose and 3 h post-dose on Day 1 for ribonucleic acid (RNA) pharmacogenomic 
analysis. The samples will be stored for no longer than 15 years after completion of the CVN424 study and/or until the drug 
development of CVN424 is no longer actively pursued by Cerevance or its collaborators. No samples will be stored for longer 
than permitted by the applicable law and samples will be destroyed upon notification from Cerevance. “Stored samples” in this 
context are defined as samples that are double coded (the samples are stripped of all personal identifying information but a key 
links the samples to the clinical data collected from the sample donor) and are used in the analysis of investigational drug or 
related drug. 
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; every subject must sign the ICF in 
order to participate in this study. DNA samples can be used to identify markers (e.g., potential metabolites, or drug metabolic 
enzyme and transporter polymorphisms) that may contribute to variability in CVN424 PK, pharmacodynamics, or safety. Also, 
since pharmacogenomics is an evolving science, many genes and their functions are not yet fully understood. Future data may 
suggest a role of some of these genes in drug response, which may lead to additional hypothesis-generating exploratory research 
and diagnostic development on stored samples. 
 
Endpoints: 
The primary endpoint of this study will be:  
 
Percentage of subjects with TEAE related to study drug 
The secondary endpoints will include:  
 
Percentages of subjects with abnormal and clinically significant (CS) safety laboratory test results, ECG test results, or 
vital sign measurements at least once post-dose 
 
Change from baseline in 2-day average OFF time at Day 27 as recorded in the Patient Motor Diary over the two days 
prior to each visit 
Additional and Exploratory endpoints will include: 
 
Change from baseline in UPDRS Part I at Day 27 
 
Change from baseline in UPDRS Part II at Day 27 
 
Change from baseline in UPDRS Part III at Day 27  
 
Change from baseline in UPDRS Part IV question 32 at Day 27 
 
Change from baseline in UPDRS Part IV question 33 at Day 27 
 
Change from baseline in CGI and PGI at Day 27 
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 
Change from baseline in Epworth Sleepiness Scale at Day 27 
 
Change from baseline in 2-day average ON time without troublesome dyskinesia at Day 27 
 
Change from baseline in efficacy measures at Days 15 and 27 
 
Plasma PK parameters 
 
Possible characterization of plasma metabolites, or metabolic enzyme and transporter polymorphisms. 
Statistical Considerations: 
Safety: 
Safety will be assessed among all subjects who receive at least one dose of study drug, classified according to the treatment 
actually received. AEs will be presented in listings, and TEAEs will be summarized as number of distinct events and the number 
and percentage of subjects experiencing a given class of AE as defined by the Medical Dictionary for Regulatory Activities 
(MedDRA) System Organ Class and Preferred Term. Individual results of laboratory tests (e.g., hematology, chemistry, 
urinalysis, and endocrine) will be listed and observed values and change from baseline will be summarized. Individual results of 
vital signs and weight will be listed and observed values and changes from baseline will be summarized. Individual results of 
quantitative ECG parameters from the 12-lead safety ECGs will be listed and observed values and changes from baseline will be 
summarized. All summaries will be performed by placebo, by CVN424 dose level, and for CVN424 overall. Subgroup analyses 
will assess the influence of selected demographic and disease-related characteristics. Physical exam findings will be presented in 
data listings. 
 
Efficacy: 
Efficacy will be assessed among all subjects who were eligible, randomized, and received at least one dose of study drug, 
classified according to the treatment actually received. Secondary tests of efficacy will assess subjects who were eligible, 
randomized, and judged compliant with treatment and follow-up as classified prior to breaking the blind. Serial assessments of 
average daily hours of OFF time as recorded in the Patient Motor Diary over the two days prior to each visit will be using mixed 
model for repeated measures (MMRM). The model will include fixed terms for treatment, visit, treatment x visit interaction and 
baseline measurement with subject-level unstructured covariance among repeated measurements. Other covariance structures 
may be used in case the model do not converge using unstructured covariance structure. Additional covariates may be included 
based on review prior to breaking the blind. The primary estimand of efficacy for each active dose vs. placebo will be the 
treatment-dependent difference in change from baseline to Day 27 and will be tested using linear contrasts of least-square means. 
Each comparison will test for significance at one-tailed p < 0.1 to control the overall type 1 error rate at 20% based on Dunnett’s 
method for comparing two treatments to the same control. Additional contrasts will be used to test for a dose-dependent effect of 
treatment and to estimate dosage-dependent differences in change from baseline at all other visits. Additional and exploratory 
efficacy endpoints will be analyzed in the same model and using the same estimands. Subgroup analyses will assess the influence 
of selected demographic and disease-related characteristics. 
 
PK Measures: 
Concentrations of CVN424 in plasma will be summarized by dose level and by gender (if possible) over each scheduled 
sampling time using descriptive statistics. Individual plasma concentration data versus time will be presented in a data listing.  
PK parameters of CVN424 will be summarized by dose and by gender (if possible) using descriptive statistics.  
Sample Size Justification:  
The safety and tolerability of single- and repeated (7 daily) administration of CVN424, including doses higher than in the present 
study, were previously demonstrated in a study with 64 healthy volunteers (NCT03657030). The target sample size of 45 subjects 
per treatment arm (total N=135) is considered to be sufficient for the preliminary evaluation of CVN424 safety, tolerability and 
efficacy in a PD population. The study will have 90% power to detect at least one instance of any TEAE with an expected 
incidence of 0.10 per participant exposed at a given dosage of CVN424.  
When the true effect of both dosages is zero, the study will have an 80% probability of declaring neither dosage of CVN424 
significantly better than placebo at reducing OFF time based on the one-tailed p < 0.1 criterion, allowing 20% non-evaluable 
(e.g., loss to follow-up, incomplete data) and assuming a standard deviation (SD) of 3 h for the change in OFF time from baseline 
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to 27 days. When the true effect of a dosage is a reduction in average OFF time of at least 1.5 h, the study will have an 80% 
probability of declaring at least one dosage of CVN424 significant based on the one-tailed p < 0.1 criterion. By this construction, 
the study has 80% power to detect whether CVN424 does not reduce OFF time and 80% power to detect whether CVN424 at one 
or both of the two dosages tested reduces OFF time by at least 1.5 h. 
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3.0 
STUDY REFERENCE INFORMATION 
3.1 
List of Abbreviations 
λz 
terminal elimination rate constant 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANOVA 
analysis of variance 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
AUC6 
area under the plasma concentration-time curve from time 0 to 6 hours  
AUC∞ 
area under the plasma concentration-time curve from time 0 to infinity 
AUCt 
area under the plasma concentration-time curve from time 0 to the last quantifiable 
concentration  
BCRP 
breast cancer resistance protein 
BMI 
body mass index 
CGI 
Clinical Global Impression Scale 
CL/F 
apparent clearance 
cm 
centimeter 
Cmax 
maximum observed plasma concentration 
CNS 
central nervous system 
CS 
clinically significant 
D2 
dopamine receptor, type 2 
EC50 
half maximal effective concentration 
ECG 
electrocardiogram 
eCRF 
electronic case report form  
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
γ-glutamyl transferase 
GPR 
G-protein coupled receptor 
h 
hour(s) 
hCG 
human chorionic gonadotropin 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
IEC 
independent ethics committee 
INR 
international normalized ratio 
IRB 
institutional review board 
K2EDTA 
dipotassium ethylenediamine tetraacetic acid 
LFT 
liver function test 
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m 
meter 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MSN 
medium spiny neuron 
N 
number 
NCS 
not clinically significant 
ng 
nanogram 
Occ50 
50% receptor occupancy 
Occ90 
90% receptor occupancy 
PD 
Parkinson’s disease 
PGI 
Patient Global Impression Scale 
Pgp 
P-glycoprotein 1 
PK 
pharmacokinetic 
PTE 
pretreatment event 
QD 
once daily 
OATP 
organic-anion-transporting polypeptide 
QTcB 
QT interval with Bazett’s correction method 
QTcF 
QT interval with Fridericia’s correction method 
QUIP 
Questionnaire for Impulsive-Compulsive Disorders 
RNA 
ribonucleic acid 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SUSARs 
suspected unexpected serious adverse reactions 
t1/2z 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to reach Cmax 
ULN 
upper limit of normal 
UPDRS 
Unified Parkinson’s Disease Rating Scale 
Vz/F 
apparent volume of distribution 
WOCBP 
women of childbearing potential 
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4.0 
INTRODUCTION 
4.1 
Background 
Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the central nervous system 
(CNS) caused by the gradual loss of the dopaminergic neurons of the substantia nigra pars compacta 
that project to the striatum (Wichmann, 2011). PD afflicts >1 million individuals in the United States 
of America and >10 million worldwide (APDA.org, accessed 26 Jan 2018), causing cardinal 
symptoms of tremor, bradykinesia, and postural instability. The financial burden of PD is significant. 
GPR6 is an orphan G-protein coupled receptor that is selectively expressed in the brain, and is a 
nondopaminergic target for the treatment of PD. In the brain, GPR6 is predominantly localized to 
striatopallidal medium spiny neurons (MSNs) that also express dopamine D2 receptors (Lein et al. 
2007; also Cerevance data on file). GPR6 is a constitutively active Gs- coupled receptor that 
functionally opposes the Gi-coupled D2 receptor in indirect MSNs. Pharmacological intervention to 
inhibit the GPR6 pathway using an inverse agonist is predicted to exert antiparkinsonian effects by 
reducing overactivity of striatopallidal output neurons in the indirect pathway without activating the 
dopamine D1-receptor expressing MSNs of the direct (striatonigral) pathway.  
CVN424 is a potent and selective inverse agonist of GPR6. The efficacy of CVN424 has not 
previously been studied in humans, but has been demonstrated in various animal models of PD. It 
was dose-dependently effective as monotherapy in reversing immobility in rats with bilateral 6-
OHDA lesions. It dose-dependently blocked D2 antagonist induced (indirect pathway dependent) 
catalepsy in rats. Safety studies of CVN424 conducted in rodents, dogs, and monkeys have 
demonstrated minimal toxicity, with the primary dose-limiting effect of body weight loss or reduced 
body weight gain. All toxicity findings demonstrated dose-dependency and reversibility of effects.  
A first-in-humans safety study of CVN424 in 64 healthy volunteers has been completed 
(NCT03657030); the study findings are summarized in the Investigator’s Brochure. In brief, 
CVN424 was safe and well tolerated when administered to healthy subjects as a single oral dose of 
between 1 mg and 225 mg, or when administered as 7 daily oral doses of between 25 mg and 150 
mg. Study drug-related adverse events (AEs) were reported by 2 of 40 subjects (5.0%) overall in the 
single-dose cohorts (feeling hot; headache). Study drug-related AEs were reported by 2 of 24 
subjects (8.3%) overall in the multiple-dose cohorts (dysphagia; chills). With one exception, all AEs 
were mild in severity; dysphagia of moderate severity led to treatment discontinuation in one subject 
after their third daily dose (75 mg). There were no severe or serious AEs, and all AEs had resolved 
by the end of the study. Administration of the first dose of CVN424 was associated with an elevation 
in group mean and median body temperature. These changes were detectable at 1 h post-dose (the 
earliest scheduled post-dose assessment), increased further by 6 h post-dose, and spontaneously 
returned to baseline by 24 h post-dose. The increases tended to be larger at higher doses but did not 
appear to be strictly dose-proportional. A trend of increase in heart rate while standing was also 
observed with a similar time course and relationship to dosage. These trends were not considered 
clinically significant, and no individual vital sign measurement was reported as an AE. In the 
multiple-dose cohorts, elevations in body temperature and heart rate were observed only after the 
first dose of CVN424, not following subsequent doses. No other trends in vital sign measurements 
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were noted. No treatment-related trends were observed in the clinical laboratory results or 12-lead 
electrocardiogram (ECG) measurements.  
In the healthy volunteer study, CVN424 in suspension was rapidly absorbed after oral administration 
in the fasted state; peak plasma concentration was usually attained between 1 and 3 h post-dose 
(median 1.5 h). When CVN424 was administered after a meal, the peak plasma concentration was 
delayed and decreased while total exposure was minimally increased compared to the same dose 
level administered under fasted conditions. With repeated once-daily dosing, trough plasma 
concentrations usually reached a steady-state level by Day 4, with a terminal elimination half-life of 
approximately 33 h. Accordingly, CVN424 PK is appropriate for once-daily oral dosing, with or 
without food. 
CVN424 is expected to be a pharmacological treatment for PD subjects, as monotherapy or 
adjunctive to dopaminergic therapy, to elicit sustained improvement of motor activity with a reduced 
risk of troublesome dyskinesia compared with dopaminergic therapies. As a novel, first in class, 
non-dopaminergic drug for the symptomatic treatment of PD, CVN424 may become a significant 
addition to neurologists’ clinical armamentarium. 
4.2 
Rationale for the Proposed Study 
Although available medications and implanted deep brain stimulation can often treat the motoric 
symptoms of PD, many patients with PD have motor fluctuations despite treatment and may not 
experience improvement in non-motor symptoms. Moreover, current treatments are fraught with 
side-effects (e.g., drug induced dyskinesia), and their efficacy diminishes as the disease progresses. 
Therefore, novel therapies are needed to improve the quality of life for patients with PD. The 
efficacy of CVN424 in animal models of PD supports its investigational use in PD patients.  
A safety and pharmacokinetic (PK) study previously performed in 64 healthy volunteers supports the 
selected dose levels of CVN424 in this study. Section 6.2 outlines the justification for the planned 
dosages. This will be the first study conducted with CVN424 in patients with PD, and will examine 
the safety, tolerability, efficacy, and plasma PK of the compound in PD patients. 
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5.0 
STUDY OBJECTIVES AND ENDPOINTS 
5.1 
Objectives 
5.1.1 Primary Objective 
To assess the safety and tolerability of CVN424 when administered as daily oral doses for 28 days, 
adjunctive to levodopa, in subjects with Parkinson’s disease and motor fluctuations. 
5.1.2 Secondary Objectives  
 To assess potential efficacy of CVN424 adjunctive to levodopa in alleviating symptoms of 
PD 
 To assess CVN424 multiple-dose PK in blood of PD subjects 
5.1.3 Exploratory Objectives 
 To explore possible serum/plasma, DNA and/or ribonucleic acid (RNA) markers (e.g., drug 
metabolic enzyme and transporter polymorphisms) that may contribute to variability in 
CVN424 PK, pharmacodynamics, safety or efficacy 
5.2 
Endpoints 
5.2.1 Primary Endpoints 
The primary endpoint of this study will be:  
 Percentage of subjects with treatment-emergent adverse events (TEAE) related to study drug 
5.2.2 Secondary Endpoints 
The secondary endpoints will include:  
 Percentages of subjects with abnormal and clinically significant (CS) safety laboratory test 
results, ECG test results, or vital sign measurements at least once post-dose 
 Change from baseline in 2-day average OFF time at Day 27 as recorded in the Patient Motor 
Diary  
5.2.3 Additional and Exploratory Endpoints 
Additional and Exploratory endpoints will include: 
 Change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS) Part I at Day 27 
 Change from baseline in UPDRS Part II at Day 27 
 Change from baseline in UPDRS Part III at Day 27  
 Change from baseline in UPDRS Part IV question 32 at Day 27 
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 Change from baseline in UPDRS Part IV question 33 at Day 27 
Change from baseline in Clinical Global Impression Scale (CGI) and Patient Global Impression 
(PGI) at Day 27 
 Change from baseline in Epworth Sleepiness Scale at Day 27 
 Change from baseline in 2-day average ON time without troublesome dyskinesia at Day 27 
as recorded in the Patient Motor Diary 
 Change from baseline in efficacy measures at Days 15 and 27 
 Plasma PK parameters 
 Possible characterization of plasma metabolites, or metabolic enzyme and transporter 
polymorphisms via pharmacogenomic analyses 
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6.0 
STUDY DESIGN AND DESCRIPTION 
6.1 
Study Design 
This is a phase 2, randomized, double-blind, placebo-controlled, multicenter study of two dose levels 
of oral CVN424 (low-dose 50 mg, high-dose 150 mg) in Parkinson’s disease (PD) patients with 
motor fluctuations. The overall study design is depicted in Figure 1. 
Figure 1. Schematic design of study  
  
Approximately 135 subjects with Parkinson’s disease will be enrolled. Following baseline safety and 
efficacy assessments, subjects will be randomized in a 1:1:1 ratio into one of 3 study arms to receive 
low-dose CVN424, high-dose CVN424 or matching placebo. The planned low-dose and high-dose 
levels will be 50 and 150 mg CVN424 per day, respectively, as shown in Table 3.  
Subjects not randomized to placebo will initiate treatment with 50 mg CVN424 on Day 1. 
Thereafter, the low-dose arm will continue to receive 50 mg per day, while the high-dose cohort will 
increase their dosage to 150 mg CVN424 per day beginning on Day 8 ±2 days and continuing 
thereafter. This step-wise increase is intended to limit the changes that the first dose of CVN424 may 
elicit in vital signs (notably, increased temperature and heart rate, which were dose-dependent and 
not clinically significant in a healthy volunteer study). Investigator or their delegate will manage 
incident AEs according to their medical judgment.  
Study drug supply will be dispensed (as suspension in amber colored bottles) on Day 1 and at 
subsequent weekly study visits. Study drug will be self-administered each morning on an outpatient 
basis as an oral suspension. Dosing on Day 1, Day 8 and Day 22 visits will be observed at the study 
site by Investigator or their delegate. For Visit Days 8 and 22, dosing of study drug (but not subjects’ 
other medications) will be deferred until after collection of a blood sample for determination of the 
study drug “trough” concentration.  
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Following dosing on days 1 and 8, subjects will remain on site until at least 3 h after dosing for 
safety and PK assessments. Investigator or their delegate will manage any incident AEs. 
The study visit schedule is summarized in Table 1. Follow-up assessments will occur approximately 
7 days after the final (Day 27 or 28) dose. A summary of activities scheduled at each study visit is 
included in Section 9.3. A Schedule of Study Procedures is listed in Appendix A. 
Table 1 
Subject Visit Schedule 
Screening a 
Baseline 
& Random-
ization 
Treatment b 
Follow-up c 
Consent,  
Eligibility 
Patient 
Motor Diary 
at Home 
Study Visit Study Visit Study Visit Study Visit Study Visit Study Visit 
Final  
Study Visit 
Days  
-28 to -1 
Days  
-2 & -1  
Day 0 
Day 1 d 
Day 8 
±2 days 
Day 15  
±2 days 
Day 22  
±2 days 
Day 27  
±1 day 
Day 35  
±2 days 
(a) 
Screening activities must occur within 28 days of randomization but may be completed in fewer than 28 days. 
Screening days are nominally called Day -28 to Day -1,but will not necessarily correspond numerically to the 
calendar days prior to the Baseline Visit. By the same convention, the Patient Motor Diary will be recorded at 
home over 2 consecutive days during screening, but not necessarily on the 2 days immediately prior to the 
Baseline visit. 
(b) Study drug supply will be dispensed (as suspension in amber colored bottles) on Day 1 and at subsequent 
weekly study visits. Subjects will return empty and unused bottles to site. Study drug will be self-administered 
each morning as an oral suspension. For Visit Days 8 and 22, dosing of study drug (but not subjects’ other 
medications) will be deferred until after collection of a blood sample for determination of the study drug 
“trough” concentration. 
(c) 
Subjects who have abnormal, clinically significant (CS) findings at the Final Study Visit may be asked to return 
to the clinic subsequently to ensure appropriate safety follow-up. 
(d) By convention, Day 1 will be the first day of treatment. It will not necessarily occur on the calendar day 
following the baseline and randomization visit. 
6.1.1 Study Committees  
None.  
Review of incident and cumulative safety data and findings during study is the responsibility of the 
Medical Monitor and sponsor’s Responsible Medical Officer. 
6.2 
Justification for Study Design, Dose, and Endpoints 
The study is double-blind and placebo-controlled to avoid subjective bias in the assessment of the 
safety, tolerability, and efficacy of CVN424.  
The selected dose levels are predicted to achieve potentially therapeutic concentrations of drug 
exposure. The lower dose (50 mg per day) may attain CNS exposure at the low end of the 
therapeutic range, while the higher dose (150 mg per day) is expected to provide a high level of 
GPR6 occupancy in brain tissue even at its steady-state nadir plasma concentration.  
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CVN424 is a potent inverse agonist of GPR6 (half maximal effective concentration [EC50] = 8.5 nM 
to 27 nM) in mice, rats, dogs, and humans. The minimum target for a potentially therapeutic drug 
exposure in plasma and CSF was informed by (i) plasma concentrations yielding half maximal 
effectiveness (EC50) in rodent models of PD; (ii) plasma concentrations yielding 50% receptor 
occupancy (Occ50) in mouse brain; and (iii) estimation of the ratio of CVN424 concentration in brain 
(mice) or CSF (monkeys) versus unbound in plasma; and (iv) the similar % binding of CVN424 to 
plasma proteins in rodents and humans (approximately 2%), which implies a similar proportion 
across these species of unbound drug in plasma available to enter the CNS. CVN424 has high 
cellular membrane permeability and is not a substrate for various transporter proteins (P-
glycoprotein 1 [Pgp], breast cancer resistance protein [BCRP], or organic-anion-transporting 
polypeptide [OATP]), so CNS penetration in humans is expected to be similar to that in nonhuman 
species.  
The EC50 for influencing motor function in unlesioned rodents ranged from 4 to 13 ng/mL in plasma 
with predicted CNS receptor occupancy (RO) between 39 to 76%. Supporting this prediction, direct 
measurement showed that brain Occ50 was achieved at plasma concentrations of 6.0±0.9 ng/mL to 
7.4 ± 0.9 ng/mL. However, correcting motor impairments in 6-OHDA lesioned rats required 10-fold 
higher plasma concentrations, likely corresponding to approximately CNS Occ90.  
Assuming Parkinson’s disease subjects will require a CNS exposure closer to that of 6-OHDA 
lesioned rats than to that of unlesioned rats, the minimum plasma level for a potentially therapeutic 
level of drug exposure is predicted to be between approximately 50 ng/mL and 150 ng/mL, 
corresponding to CSF drug concentrations between 1 ng/mL and 3 ng/mL. Based on observations in 
the phase 1 study, the low-dose in the present study (50 mg) is expected to yield a steady-state 
trough plasma drug concentration of approximately 150 ng/mL, corresponding to the minimum 
potentially therapeutic drug exposure. The high-dose (150 mg) will achieve a higher plasma level, 
and higher CNS RO, to maximize the likelihood of detecting an efficacy signal. 
Importantly, the planned low- and high-dose levels of CVN424 are both within the dose range that 
has been previously shown to be safe and well-tolerated in healthy volunteers. 
In the phase 1 multiple-dosing cohorts, the trough plasma concentration (Cmin) of CVN424 typically 
reached steady state by day 4, so trough sample collection on Visit Days 8 and 22 in the present 
study will adequately measure steady state trough concentrations. The terminal elimination half-life 
of CVN424 is approximately 33 h. Therefore, with dosing ending on Day 28, sample collection on 
Day 35 (i.e., washout over approximately 5 half-lives) will be adequate to document substantial 
elimination of CVN424.  
AEs, physical exams, vital signs and weight, ECG findings, and clinical laboratory results are used 
as safety assessments to determine dose tolerability and dose limiting effects of CVN424. The 
efficacy of CVN424 in symptomatic treatment of PD will be explored using scales and methods that 
are standard in studies of this indication. The plasma PK parameters will further elucidate the 
pharmacology of CVN424 in the intended subject population.  
Samples collected for serum/plasma, DNA and/or RNA analysis will be used to evaluate markers 
(e.g., DNA polymorphisms; RNA expression profile) that may contribute to variability in CVN424 
PK, pharmacodynamics, efficacy or safety. 
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6.3 
Premature Termination or Suspension of Study or Investigational Site 
6.3.1 Criteria for Premature Termination or Suspension of the Study 
The study will be completed as planned unless new information or other evaluation regarding the 
safety of the study medication indicates an adverse change in the risk profile for the compound, such 
that Sponsor or an Institutional Review Board (IRB) or Ethics Committee considers the risk is no 
longer acceptable for subjects participating in the study. 
If any of the following occur, the Medical Monitor and Sponsor’s Responsible Medical Officer will 
review the relevant data, including unblinded data if deemed necessary, and decide whether it is safe 
to suspend dosing or continue dosing at either the planned or alternative dose levels or decides to 
prematurely terminate the study: 
1. Four or more subjects receiving CVN424 experience the same type of serious or Medically 
Significant event deemed related to study drug. 
2. Three or more subjects receiving CVN424 experience alanine aminotransferase (ALT) and/or 
aspartate aminotransferase (AST) elevations >5 × upper limit of normal (ULN) in the 
absence of a concomitant bilirubin increase. 
3. One or more subjects receiving CVN424 experience ALT and/or AST elevations >3 ×ULN 
in the presence of a total bilirubin increase >2 ×ULN or an international normalized ratio 
(INR) >1.5 without findings of cholestasis or other alternate etiology to explain the 
elevations (i.e., “Hy’s Law cases”). 
4. Two or more subjects receiving CVN424 experience ALT and/or AST elevations >3 ×ULN 
with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, 
fever, rash and/or eosinophilia (>5%). 
In addition, the study may be terminated at the discretion of the Sponsor. 
6.3.2 Criteria for Premature Termination or Suspension of Investigational Sites 
A study site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant violation of Good Clinical Practice (GCP), protocol, or contractual agreement, is 
unable to ensure adequate performance of the study, or as otherwise permitted by the contractual 
agreement. 
6.3.3 Procedures for Premature Termination or Suspension of the Study or the Participation 
of Investigational Site(s) 
In the event that the sponsor, an IRB/independent ethics committee (IEC), or regulatory authority 
elects to terminate or suspend the study or the participation of an investigational site, a study-specific 
procedure for early termination or suspension will be provided by the sponsor; the procedure will be 
followed by applicable investigational sites during the course of termination or study suspension. 
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7.0 
SUBJECT POPULATION 
Screening for eligible subjects will be performed within 28 days prior to randomization. Subjects 
may be re-screened if their reason for failing screening is thought to be resolved. 
7.1 
Inclusion Criteria 
Subject eligibility is determined according to the following criteria prior to entry into the study: 
1. Male or female adult who is 30 to 80 years of age inclusive at study entry. 
2. Has idiopathic Parkinson’s disease, Hoehn and Yahr stages 2-4, and is on a stable dosage of 
levodopa. (Stable is defined as a dosage unchanged in the 30 days prior to randomization 
and, in the opinion of the investigator, able to continue the current regimen throughout the 
month-long study without undue inconvenience or harm.) 
3. Experiences an average of at least 2 h total OFF time/day, and at least 1 h each day, per 
Patient Motor Diary over 2 days during the Screening assessment. 
4. The subject signs and dates a written informed consent form (ICF) and any required privacy 
authorization prior to the initiation of any study procedures.  
7.2 
Exclusion Criteria 
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. Has atypical parkinsonism, severe disabling dyskinesia, or severe motor fluctuations that the 
investigator considers likely to interfere with study participation or assessments, or history of 
implant for Deep Brain Stimulation. 
2. Poor concordance (<75%) of self-report with site rater on in-clinic Screening period Patient 
Motor Diary. Subjects with low concordance may be retested after further instruction, at 
investigator’s discretion. 
3. Screening period Patient Motor Diary scored at-home over 48 h demonstrates unacceptable 
quality of the diary, with more than 4 errors per day. (Assistance from caregivers is permitted 
if they also will be providing assistance with home Patient Motor Diary entries for Day 15 
and 27 efficacy assessments.) Subject with more than 4 errors per day may be retested after 
further instruction, at investigator’s discretion. 
4. Body mass index (BMI) at Screening <18.0 or >35.0 kg/m2, inclusive.  
5. Subject has evidence of clinically significant (CS) neurologic or other disorder or impairment 
that, in opinion of Investigator, is reasonably expected to impact the ability of the subject to 
participate or to confound the study results.  
6. Subject has current or recent (within 6 months) gastrointestinal disease that would be 
expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical 
intervention known to impact absorption [e.g., bariatric surgery or bowel resection]. 
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7. Subject has a history of cancer or other malignancy, with the exception of low-grade cervical 
intraepithelial neoplasia, low-grade (low-risk) prostate cancer, or 5-year cancer-free 
survivors of basal or squamous cell carcinoma or higher-grade cervical intraepithelial 
neoplasia or prostate cancer. 
8. Has a history of human immunodeficiency virus (HIV) infection. 
9. Subject has a supine blood pressure outside the ranges of 80 to 160 mm Hg for systolic and 
50 to 100 mm Hg for diastolic, confirmed with up to two repeat tests, at the Screening Visit; 
or symptomatic orthostatic hypotension, in the opinion of the investigator. 
10. Subject has a resting heart rate outside the range 50 to 100 bpm, confirmed with up to two 
repeat tests, at the Screening Visit. 
11. Positive urine result for illegal drugs (except cannabis) at Screening, or history of illegal drug 
use (except cannabis) or alcohol abuse within 1 year prior to the Screening Visit.  
12. Subject has received any investigational compound (defined as a drug that has not been 
FDA-approved) within 30 days prior to the first dose of study medication, or within 5 half-
lives of the investigational compound, whichever is greater. 
13. Subject has, within the prior month, ingested any excluded medication, supplements, or food 
products listed in the Excluded Medications and Dietary Products table as listed in Table 2: 
Excluded Medications and Dietary Products. 
14. Male subjects who do not agree to all the following rules: when sexually active with female 
partner(s) of childbearing potential during the study and for 12 weeks after the last dose of 
study drug: a) use an acceptable method of birth control (condom with spermicide or surgical 
sterilization) and b) refrain from sexual activity with female partners who do not use an 
acceptable method of birth control. Barrier contraception (condom with spermicide) must be 
used by all male subjects who were not surgically sterilized at least 90 days prior to 
screening. Male subjects must also agree to refrain from sperm donation during the study and 
until 12 weeks after the last dose of study drug. 
15. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova 
during the study or for 30 days after the last dose of study drug. WOCBP also must be 
practicing an adequate method of birth control (e.g., oral or parenteral contraceptives, 
intrauterine device, barrier, abstinence).  
*Definitions and acceptable methods of contraception are defined in Section 9.1.9, 
Contraception and Pregnancy Avoidance Procedure, and reporting responsibilities are 
defined in Section 9.1.10, Pregnancy. 
16. Risk of suicide according to the investigator’s clinical judgment or has made a suicide 
attempt in the previous 3 years. 
17. Subject is a study site employee or an immediate family member of a study site employee.  
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7.3 
Excluded Medications and Dietary Products 
Use of the agents in Table 2 (prescription or nonprescription) is prohibited from the time points 
specified until completion of all study activities. 
Table 2 
Prohibited Medications and Dietary Products 
Within 28 days prior to randomization 
Nutraceuticals (e.g., St. John’s wort, ginseng, kava, ginkgo biloba, Chinese herbs, and melatonin) 
Known strong inhibitors/inducers of cytochrome P-450 3A4/5, including rifampin, clarithromycin, ketoconazole, itraconazole  
 
The following medications are not prohibited prior to or during the study, but should only be used if 
medically necessary because they may (theoretically) diminish CVN424 bioavailability:  
 Proton pump inhibitors (e.g., omeprazole, pantoprazole, lansoprazole)  
 Histamine H2-receptor antagonists (e.g., cimetidine, ranitidine, famotidine, nizatidine) 
 Antacids taken within 4 hours of dosing. 
All concomitant medications, including proton pump inhibitors and H2-receptor antagonists, will be 
documented. Subjects will be instructed not to take any new medications without first consulting 
with the Investigator or their delegate. 
7.4 
Diet and Fluid Control  
CVN424 suspension (10 mL) will be administered with approximately 120-240 mL (one-half to one 
cup) of water. Diet and fluid intake are not otherwise specified by protocol and may be consumed ad 
libitum per subject’s routine. 
7.5 
Criteria for Discontinuation or Withdrawal of a Subject 
The following represent criteria that require discontinuation of study drug and/or withdrawal from 
the study. The primary reason for discontinuation or withdrawal of the subject from the study or 
study medication should be recorded in the electronic case report form (eCRF). For screen failure 
subjects, refer to Section 9.1.15. 
1. The subject has experienced a pretreatment event (PTE) or AE that requires early termination 
because continued participation imposes an unacceptable risk to the subject’s health or the 
subject is unwilling to continue because of the PTE or AE. 
2. Liver Function Test (LFT) abnormalities meeting prespecified criteria. 
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests, until a subject’s laboratory profile has returned to 
normal/baseline status, see Section 9.1.8), if the following circumstances occur at any time 
during study medication treatment: 
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– ALT or AST >8 × ULN, or 
– ALT or AST >5 × ULN and persists for more than 2 weeks, or 
– ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or INR 
>1.5, or 
– ALT or AST >3 × ULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
3. Lost to follow-up. The subject did not return to the clinic and attempts to contact the subject 
were unsuccessful. Attempts to contact the subject must be documented. 
4. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF. 
Note: Attempts should be made to determine the underlying reason for the withdrawal and, 
where possible, the primary underlying reason should be recorded (e.g., withdrawal due to an 
AE; withdrawal due to relocation). 
5. The sponsor, IRB, IEC, or regulatory agency terminates the study. 
Additionally, the Investigator should consider discontinuation of study drug and/or 
withdrawal from the study for subjects with a major protocol deviation, including violation of 
protocol entry criteria, such that continuation on study poses an unacceptable risk to the 
subject’s health or to the study’s scientific objectives.  
7.6 
Procedures for Discontinuation or Withdrawal of a Subject 
The investigator must discontinue a subject’s study participation at any time during the study when 
the subject meets the study discontinuation criteria described in Section 7.5. In addition, a subject 
may discontinue his or her participation without giving a reason at any time during the study. Should 
a subject’s participation be discontinued, the primary criterion for termination must be recorded by 
the Investigator. In addition, efforts should be made to perform all procedures scheduled for the 
Early Termination Visit. Discontinued or withdrawn subjects may be replaced at Sponsor’s 
discretion. 
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8.0 
CLINICAL TRIAL MATERIAL MANAGEMENT 
This section contains information regarding all medication and materials provided directly by the 
sponsor, and/or sourced by other means, that are required by the study protocol, including important 
sections describing the management of clinical trial material. 
8.1 
Study Medication and Materials 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling 
In this protocol, the terms “study medication”, “study drug”, and “investigational drug” refer to 
CVN424 and/or matching placebo. Study drug will be supplied to sites in bottles with contents and 
label individualized per randomization assignment.  
8.1.1.1 Investigational Drug 
CVN424 and Matching Placebo 
CVN424 drug substance is manufactured at Aptuit or Pharmaron.  
The oral suspension drug products will be compounded by an accredited compounding pharmacy, 
e.g. Infuserve America Inc. 
CVN424 oral suspension is prepared by suspending CVN424 drug substance in 2% Methocel, E15 
Premium LV Hydroxypropyl Methylcellulose (HPMC)/0.5% Tween 80 vehicle. The placebo does 
not contain CVN424 drug substance, and is comprised of the same suspending liquid plus calcium 
carbonate, an insoluble excipient safe to humans (it is the main ingredient in the antacid brand, 
Tums®) and included to match the appearance of the active drug suspension. CVN424 oral 
suspension is supplied to the clinical sites in bottles with contents and label individualized per 
randomization assignment. 
8.1.2 Drug Storage 
All study medication stored at the investigative site must be kept in an appropriate, limited-access, 
secure place until it is used or returned to the sponsor or designee for destruction. All study 
medication must be stored under the conditions specified on the label and remain in the original 
container until dispensed. A daily temperature log of the drug storage area must be maintained every 
working day. 
CVN424 oral suspension and matching placebo must be stored at 2°C-8°C (35.6°F-46.4°F); storage 
in subject’s home refrigerator is permitted for their individual weekly drug supply. CVN424 oral 
suspension is stable for 2 weeks under refrigeration, and at room temperature for up to 24 h.  
8.1.3 Dose and Regimen 
Prior to treatment initiation, the investigator or investigator’s designee will instruct each subject (and 
their home caregiver, where applicable) on dosing procedures, and observe the subject in a practice 
(i.e., unblinded placebo) self-administration to confirm the subject can properly self-administer the 
study drug at home. 
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The planned study arms and dose levels are provided in Table 3.  
Table 3 
Planned Study Arms and Dose Levels by Cohort 
Study Arm 
Planned Treatment* 
No. of Subjects 
Low-dose 
CVN424 50 mg per day 
40 
High-dose 
CVN424 150 mg per day 
40 
Placebo 
Placebo 
40 
* Dose (active or placebo) is in 10 mL of suspension. 
8.1.4 Overdose 
An overdose is defined as a known deliberate or accidental administration of investigational drug, to 
or by a study subject, at a dose above that which is assigned to that individual subject according to 
the study protocol. 
All cases of overdose (with or without associated AEs) will be documented on an Overdose page of 
the eCRF, in order to capture this important safety information consistently in the database. Cases of 
overdose without manifested signs or symptoms are not considered AEs. AEs associated with an 
overdose will be documented on AE eCRF(s) according to Section 9.5, PTEs and AEs. 
Serious adverse events (SAEs) associated with overdose should be reported according to the 
procedure outlined in Section 9.6.2, Collection and Reporting of SAEs. 
In the event of an overdose, supportive measures should be employed as needed, e.g., administration 
of supportive therapy as dictated by the subject’s clinical status, removal of unabsorbed material 
from the gastrointestinal tract and initiation of additional clinical monitoring.  
8.2 
Investigational Drug Assignment and Dispensing Procedures 
Study drug will be dispensed to subjects as a suspension in properly labeled, capped amber colored 
bottles. The suspension must be stored refrigerated (2-8°C) until use. If properly refrigerated, the 
suspension is stable for up to 14 days. At room temperature, the suspension is stable for up to 24 h. 
Study drug may settle. Shake well before using to ensure complete resuspension.  
8.3 
Randomization Code Creation and Storage  
Randomization assignments will be generated using an online interactive response system. All 
randomization information will be stored in a secured area, accessible only by authorized personnel.  
8.4 
Unblinding Procedure 
The investigational drug blind shall not be broken by the investigator unless information concerning 
the investigational drug is necessary for the medical treatment of the subject. All study assessments 
and causality assessment should be performed, if possible, prior to unblinding. After unblinding, no 
change should be made to any previously recorded assessment of the subject. 
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For unblinding a subject, requests can be initiated by contacting the Medical Monitor.  
The sponsor must be notified as soon as possible if the investigational drug blind is broken. The 
date, time, and reason the blind is broken must be recorded in the source documents and the same 
information (except the time) must be recorded on the eCRF. 
If an unblinded AE assessment raises concern for potential risks to this or other study subjects, the 
Sponsor in consultation with the Investigator and the Medical/Safety monitor will review available 
unblinded data and will decide whether it is appropriate for the subject to discontinue study 
treatment and/or withdraw from study, and whether changes to study design are necessary to protect 
the safety of other subjects. 
The randomization schedule for all subjects will be released for analysis after the database is locked.  
8.5 
Accountability and Destruction of Sponsor-Supplied Drugs 
The investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to subjects enrolled in the study. To document appropriate 
use of study medication, the investigator must maintain records of all study medication delivery to 
the site, site inventory, use by each subject, and return to the sponsor or designee. 
Upon receipt of study medication, the investigator or designee must verify the contents of the 
shipments against the packing list, ensure the quantity is correct, and the medication is received 
within the labeled storage conditions. If quantity and conditions are acceptable, investigator or 
designee should acknowledge the receipt of the shipment per instructions provided on the form. If 
there are discrepancies between the packing list versus the actual product received, the sponsor must 
be contacted to resolve the issue. The packing list should be filed in the investigator’s essential 
document file. The investigator must maintain 100% accountability for all study medication received 
and dispensed during his or her entire participation in the study. Proper drug accountability includes, 
but is not limited to: 
 Continuously monitoring expiration dates 
 Frequently verifying that actual inventory matches documented inventory 
 Verifying that all containers used are documented accurately on the log 
 Verifying that required fields are completed accurately and legibly 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
The investigator or designee must record the current inventory of all study medication on a sponsor-
approved drug accountability log. The following information will be recorded at a minimum: 
protocol number and title, name of investigator, site identifier and number, description of study 
medication, expiry date, and amount dispensed, including the initials of the person dispensing and 
receiving the study medication. (For participating subjects receiving study medication, their ID 
number should substitute for initials.) The log should include all required information as a separate 
entry for each subject to whom study medication is dispensed. 
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Subjects will return their bottles of study medication, whether empty or unused, at weekly study 
visits. The investigator or designee must record the number of empty and unused bottles returned. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee will 
perform clinical study material accountability and reconciliation before clinical study materials are 
returned to the sponsor or its designee for destruction or destroyed at the site, as applicable. The 
investigator will retain the original documentation regarding clinical study material accountability, 
return, and/or destruction, and copies will be sent to the sponsor or designee. 
The investigator will be notified of any expiry date or retest date extension of clinical study material 
during the study conduct. On expiry date notification from the sponsor or designee, the site must 
complete all instructions outlined in the notification, including segregation of expired clinical study 
material for return to the sponsor or its designee for destruction. 
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9.0 
STUDY PLAN 
9.1 
Study Procedures 
The following sections describe the study procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel at each study visit, whenever 
possible. The Schedule of Study Procedures is located in Appendix A. 
9.1.1 Informed Consent Procedure 
The requirements of the ICF are described in Section 14.2. 
A properly signed ICF must be obtained prior to the subject entering into the study, and before any 
protocol-related procedures are performed. 
9.1.1.1 Pharmacogenomic Informed Consent Procedure 
Pharmacogenomics informed consent is a component of the overall study ICF. The requirements are 
described in Section 14.2. 
The pharmacogenomic sample collection is mandatory. 
9.1.2 Demographics, Medical History, and Medication History Procedure 
Demographic information to be obtained will include date of birth, sex, Hispanic ethnicity, race as 
described by the subject, smoking status, and caffeine consumption of the subject at Screening. 
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases that stopped at or prior to signing the ICF. Ongoing conditions are considered 
concurrent medical conditions (see Section 9.1.7). 
Medication history information to be obtained includes any medication relevant to eligibility criteria 
stopped at or within 28 days prior to signing of ICF. 
9.1.3 Physical Examination Procedure 
A physical examination will consist of the following body systems: (1) eyes, including fundoscopy; 
(2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; 
(6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; 
(10) lymph nodes; and (11) other.  
Any abnormal change from the baseline physical examination must be assessed as not clinically 
significant (NCS) or clinically significant (CS) by the investigator and recorded in the source 
document and eCRF. Any CS change or new diagnosis as a result of a CS change, as determined by 
the investigator, will be recorded as an AE in source documentation and on the PTE/AE eCRF 
described in Section 9.6.  
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9.1.4 Weight, Height, and BMI 
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below:  
Height is recorded centimeters without decimal places and for weight it is kilograms (kg) with 1 
decimal place. BMI should be derived as: 
Metric:  
BMI = weight (kg)/[height (m)]2 
Results for BMI will be expressed with 1 decimal place and rounding is not allowed. 
Example: 
Height=176 centimeter (cm) (or 1.76 m), weight=79.2 kg; BMI=79.2/1.762=25.57 kg/m2 captured as 
25.5 kg/m2.  
9.1.5 Vital Sign Procedure 
Vital signs will include oral temperature, respiration, heart rate, and blood pressure and be collected 
at timepoints specified in the Schedule of Study Procedures (Appendix A). Heart rate and blood 
pressure will be measured after at least 5 minutes supine and (when orthostatic vital signs are 
specified) again after 2 minutes standing.  
Vital signs should be measured at the same time of the day across visits if possible. When vital signs 
are scheduled at the same time as blood draws, the blood draw will take priority and vital signs will 
be obtained within approximately 15 minutes before or after the scheduled blood draw. 
9.1.6 Documentation of Concomitant Medications 
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is not 
provided by the sponsor. At each study visit, subjects will be asked whether they have taken any 
medication other than the study medication (used from signing of ICF through the end of the study), 
and all medication including vitamin supplements, over-the-counter medications, and oral herbal 
preparations, must be recorded in the eCRF. Documentation will include generic medication name, 
dose, unit, frequency, route of administration, start and end dates, and reason for use. 
9.1.7 Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at signing of ICF. This includes CS laboratory, ECG, or physical examination abnormalities noted at 
Screening examination. The condition (i.e., diagnosis) should be described. 
9.1.8 Procedures for Clinical Laboratory Samples 
All samples will be collected in accordance with acceptable laboratory procedures on the days/times 
stipulated in the Schedule of Study Procedures (Appendix A). 
Table 4 lists the tests that may be performed for each collected specimen. 
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Table 4 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Urinalysis 
Endocrine 
RBC 
WBC with differential  
(% and absolute) 
Hemoglobin 
Hematocrit 
Platelets 
Prothrombin time/INR 
Activated partial 
thromboplastin time (aPTT) 
ALT 
Albumin 
Alkaline phosphatase 
AST 
Total bilirubin 
Direct bilirubin 
Total protein 
Creatinine 
Blood urea nitrogen 
Creatine kinase 
GGT 
Potassium 
Sodium 
Glucose 
Chloride 
Bicarbonate 
Calcium 
pH 
Specific gravity 
Protein 
Glucose 
Blood  
Nitrite 
Microscopic Analysis 
(only if positive dipstick 
results):  
RBC/high power field 
WBC/high power field 
Epithelial cells, casts etc. 
Prolactin 
TSH 
(and if abnormal) 
reflex FT4 
Diagnostic Screening in Serum 
Diagnostic Screening in Urine/ Blood 
Serum hCG (a) 
FSH (b)  
 
Drug screen including amphetamines, 
barbiturates, benzodiazepines, cannabinoids, 
cocaine, opiates, alcohol, and cotinine (c) 
Urine hCG 
FT4= free T4, FSH= follicle-stimulating hormone, GGT=-glutamyl transferase, hCG= human chorionic gonadotropin, 
RBC=red blood cells, TSH= thyrotropin, WBC=white blood cells. 
(a) Serum hCG pregnancy test will be done at Screening in women subjects.  
(b) FSH level will be obtained for female subjects at Screening if they are postmenopausal (i.e., last regular menstrual 
cycle >2 years) and not surgically sterile. The result must be >40 IU/L for the subject to be enrolled. 
 
 
The central laboratory will perform all clinical laboratory tests per Appendix A. The results of 
laboratory tests will be returned to the investigator, who is responsible for reviewing and filing these 
results. Additional laboratory or diagnostic testing may be performed by accredited laboratories as 
needed to ensure subject safety, per Investigator discretion. All laboratory safety data will be 
transferred electronically to the sponsor or designee in the format requested by the sponsor. The 
investigator will maintain a copy of the reference ranges for the laboratory used.  
Laboratory reports must be signed and dated by the Investigator or sub-investigator indicating that 
the report has been reviewed and any abnormalities have been assessed for clinical significance. 
All CS laboratory abnormalities must be recorded as a PTE/AE in the subject’s source documents 
and on the appropriate eCRF. A CS laboratory abnormality that has been verified by retesting will be 
followed until the abnormality returns to an acceptable level or a satisfactory explanation has been 
obtained. 
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If subjects experience ALT or AST >3 ×ULN, follow-up laboratory tests (at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR) should be performed within a 
maximum of 7 days and preferably within 48 to 72 h after the abnormality was found. 
(Please refer to Section 7.4 for discontinuation criteria, and Section 9.6.3 for the appropriate 
guidance on Reporting of Abnormal LFT in relation to ALT or AST >3 ×ULN in conjunction with 
total bilirubin >2 ×ULN). 
If the ALT or AST remains elevated >3 ×ULN on these 2 consecutive occasions, the investigator 
must contact the Medical Monitor for consideration of additional testing, close monitoring, possible 
discontinuation of study medication, discussion of the relevant subject details and possible 
alternative etiologies. The abnormality should be recorded as an AE (please refer to Section 9.6.3 
Reporting of Abnormal LFT for reporting requirements). 
9.1.9 Contraception and Pregnancy Avoidance Procedure 
From date of signing of ICF, throughout the duration of the study, and for 30 days after last dose of 
study medication, females of childbearing potential* must use acceptable method(s) of 
contraception; nonsterilized** male subjects who are sexually active with a female partner of 
childbearing potential* must use acceptable method(s) of contraception throughout the duration of 
the study, and for 12 weeks after last dose of study medication. In addition, males must be advised 
not to donate sperm during this period.  
*Females NOT of childbearing potential are defined as those who have been surgically sterilized 
(hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (e.g., defined 
as at least 2 years since last regular menses with an FSH>40 IU/L or at least 5 years since last 
regular menses, confirmed before any study medication is implemented). 
**Sterilized males should be at least 90 days post vasectomy and confirm that they have obtained 
documentation of the absence of sperm in the ejaculate. 
Acceptable methods of contraception in this study include:  
 Abstinence, defined as refraining from heterosexual intercourse during the entire period of 
risk associated with the study treatments. If heterosexual intercourse does occur, an 
acceptable method of birth control is required. 
 Surgical sterilization or postmenopausal 
 Condom, diaphragm, or cervical cap with spermicide  
 Hormonal contraception, including oral, injectable, transdermal, or implantable methods  
 Intrauterine device (IUD) 
Subjects will be provided with information on acceptable methods of contraception as part of the 
subject informed consent process and will be asked to sign an ICF stating that they understand the 
requirements for avoidance of pregnancy, and sperm donation during the course of the study. 
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9.1.10 Pregnancy 
Women who are pregnant or breastfeeding will not be included in this study.  
If any subject is found to be pregnant during the study, she should be withdrawn, and any sponsor-
supplied drug should be immediately discontinued. In addition, any pregnancies in the partner of a 
male subject during the study or for 12 weeks after the last dose, should also be recorded following 
authorization from the subject’s partner.  
If the pregnancy occurs during administration of active study medication, e.g., after Visit 1 or within 
30 days of the last dose of active study medication, the pregnancy should be reported immediately, 
using a pregnancy notification form, to the contact listed in Section 1.0. 
Should the pregnancy occur during or after administration of blinded drug, the investigator must 
inform the subject of their right to receive treatment information. If the subject chooses to receive 
unblinded treatment information, the individual blind should be broken by the investigator. Subjects 
randomized to placebo need not be followed. 
If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time she became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable). 
All reported pregnancies will be followed up to final outcome, using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation after 
the birth of the child will also be conducted. 
9.1.11 ECG Procedure  
Standard 12-lead ECGs will be recorded at timepoints as specified in the Schedule of Study 
Procedures (Appendix A). Triplicate ECGs will be taken at each scheduled time. Additional 
unscheduled ECGs may be recorded where clinically necessary for subject safety. 
When an ECG is scheduled at the same time as blood draws or vital signs then the blood draws and 
vital signs will take priority and the ECG will be obtained before or after the scheduled blood 
draw/vital sign assessment.  
ECG recordings will be obtained in a supine position following an approximate 10-minute period of 
rest. Should technical difficulties occur during recording of the ECG, a reasonable attempt should be 
made to repeat the ECG shortly after the failed attempt.  
ECGs will be interpreted by qualified personnel at the central ECG lab. The investigator or sub-
investigator will categorize the ECG findings using 1 of the following categories: within normal 
limits, abnormal but not CS, or abnormal and CS. All 12-lead ECGs will be stored for manual 
measurement of intervals, if necessary. Twelve-lead ECGs will be recorded using an ECG machine 
that automatically calculates the heart rate and measures PR interval, RR interval, QRS interval, QT 
interval, and QTcF and QTcB (Fridericia’s and Bazett’s correction method) intervals.  
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9.1.12 Pharmacogenomic Sample Collection 
Every subject must sign ICF/be consented for sampling of whole blood for pharmacogenomic 
analysis in order to participate in the study. 
One whole blood sample for DNA isolation and genotyping will be collected at time points specified 
in the Schedule of Study Procedures (Appendix A) and stored under frozen conditions. In addition, 
whole blood samples will be collected at time points specified in the Schedule of Study Procedures 
(Appendix A) for ribonucleic acid (RNA) pharmacogenomic analysis.  
Specific purposes of this pharmacogenomic study include: 
 Identifying genetic reasons why certain people respond differently to CVN424 
 Finding out more information about how CVN424 works 
 Generating information needed for research, development, and regulatory approval of tests to 
predict response to CVN424 
 Identifying variations in genes related to the biological target of CVN424 
This information may be used, for example, to develop a better understanding of the safety and 
efficacy of CVN424 and other study medications, and for improving the efficiency, design and study 
methods of future research studies. 
The samples will be stored for no longer than 15 years after completion of the CVN424 study and/or 
until the drug development of CVN424 is no longer actively pursued by the sponsor or its 
collaborators. No samples will be stored for longer than permitted by the applicable law and samples 
will be destroyed upon notification from the sponsor. “Stored samples” in this context are defined as 
samples that are double coded (the samples are stripped of all personal identifying information but a 
key links the samples to the clinical data collected from the sample donor) and are used in the 
analysis of investigational drug or related drug. 
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; every 
subject must sign the ICF in order to participate in this study. Blood serum/plasma, DNA and/or 
RNA samples can be used to identify markers (e.g., potential metabolites, or drug metabolic enzyme 
and transporter polymorphisms) that may contribute to the variability in CVN424 PK, 
pharmacodynamics, or safety. Also, since pharmacogenomics is an evolving science, many genes 
and their functions are not yet fully understood. Future data may suggest a role of some of these 
genes in drug response, which may lead to additional hypothesis-generating exploratory research and 
diagnostic development on stored samples. 
If necessary and feasible, a second aliquot of blood may be taken if isolation of DNA from the first 
sample was not successful or possible. 
Detailed instructions for the handling and shipping of samples are provided in a separate lab manual. 
Each pharmacogenomic sample for a study subject should be identifiable on the requisition form 
with the subject identification number. 
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9.1.13 PK Sample Collection 
9.1.13.1 Collection of Blood for PK Sampling 
Blood samples (one sample per scheduled time) for analysis of CVN424 plasma concentrations will 
be collected into chilled Vacutainers containing K2EDTA according to the schedules in Table 5 and 
Appendix A. 
Instructions for sample processing and shipment are provided in a separate lab manual. 
Serial blood samples for determination of CVN424 concentrations in plasma will be collected 
according to Table 5. 
Table 5 
Collection of Blood Plasma Samples for PK Analysis  
Study Day 
Time Post-dose (hours). 
1, 8 
Pre-dose and at 3 h post-dose 
15, 27 
Post-dose (time not specified) 
22 
Pre-dose and at 1, 1.5, 2, 4, and 6 h post-dose 
35 
Washout (time not specified) 
The PK samples will be collected at the nominal time point within the allowable windows per Table 
8. The actual time of sample collection will be recorded on the source document and eCRF.  
Placebo samples will not be analyzed by the bioanalytical laboratory except 2 samples per subject 
receiving placebo, 1 following first-dose (i.e., 3 h post-dose) and 1 at the Day 27 visit to ensure from 
a safety perspective that no additional subjects could have been on active treatment.  
9.1.13.2 Bioanalytical Methods 
Plasma concentrations of CVN424 will be measured by high-performance liquid chromatography 
with tandem mass spectrometry or an alternative method of comparable sensitivity and specificity. 
Plasma samples will be archived to support potential post hoc laboratory testing (e.g., biomarkers, 
potential characterization of unknown CVN424 metabolites). 
9.1.14 PK Parameters 
PK parameters of CVN424 will be derived using non-compartmental analysis methods from the 
concentration-time data for all evaluable subjects. Actual sampling times, rather than scheduled 
sampling times, will be used in all computations involving sampling times. The following PK 
parameters (Table 6) will be determined from concentrations of CVN424 in plasma:  
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Table 6 
Pharmacokinetic Parameters 
Symbol/Term 
Definition 
AUC∞  
Area under the plasma concentration-time curve from time 0 to infinity, calculated as 
AUC∞=AUCt+Clast/λz, where Clast is the last quantifiable concentration. 
AUC6 
Area under the plasma concentration-time curve from time 0 to 24 hours, calculated using the 
linear trapezoidal rule. 
Cmax 
Maximum observed concentration. 
CL/F 
Apparent clearance after extravascular administration, calculated as Dose/AUC∞ after a 
single dose. 
λz 
Terminal elimination rate constant, calculated as the negative of the slope of the log-linear 
regression of the natural logarithm concentration-time curve during the terminal phase. 
t1/2z 
Terminal elimination half-life, calculated as ln(2)/λz. 
tmax 
Time to reach Cmax.  
Vz/F 
Apparent volume of distribution during the terminal phase after extravascular administration, 
calculated as (CL/F)/λz. 
 
Additional plasma PK parameters may be calculated, including analyses by gender (if possible).  
9.1.15 Documentation of Screen Failure 
Investigators must account for all subjects who sign ICF. If the subject is found to be not eligible at 
this visit, the investigator should complete the eCRF screen failure form. 
The primary reason for screen failure is recorded in the eCRF using the following categories: 
 PTE/AE 
 Did not meet inclusion criteria or did meet exclusion criteria 
 Significant protocol deviation 
 Lost to follow-up 
 Voluntary withdrawal 
 Study termination 
 Other 
Subject numbers assigned to subjects who fail screening should not be reused.  
If a subject fails screening, but is later successfully re-screened, the data for the subject will be 
entered as if these were two separate subjects. Therefore, the data should be entered as follows: 
1. The screen failure data should be entered as a screen failure subject. 
2. Re-screened subjects should be assigned a new subject number and treated as a stand-alone 
subject. 
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9.1.16 Documentation of Randomization 
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible for 
randomization into the treatment phase. 
If the subject is found to be not eligible for randomization, the investigator should record the primary 
reason for failure on the applicable eCRF. 
9.2 
Monitoring Subject Treatment Compliance 
Study medication will first be administered (on Day 1) while subjects are under observation at the 
investigative site. Subsequent doses will be self-administered at home, or at the investigative site on 
selected Study Visit days. The date and time of each observed dose will be recorded in the source 
documents and on the eCRFs.  
At each weekly visit, subjects will return to the site all study medication bottles, whether empty or 
full, for assessment of treatment compliance. 
An inventory of the study medication supplies dispensed will be performed by the site pharmacist or 
authorized study designee and recorded onto the Drug Accountability Log in the subject’s source 
document records or equivalent.  
9.3 
Schedule of Observations and Procedures 
The schedule for all study-related procedures for all evaluations is shown in Appendix A and is not 
comprehensively duplicated in the following sections.  
9.3.1 Observations and Procedures 
9.3.1.1 Screening 
Screening activities must occur within 28 days prior to randomization. Subjects will be screened in 
accordance with predefined inclusion and exclusion criteria as described in Section 7.0. See Section 
9.1.15 for procedures for documenting screening failures. Subjects who are screening failures may 
be screened a second time if their reason for failing screening is thought to be resolved. Re-screened 
subjects will receive a new Screening number. 
Subjects who have passed initial Screening procedures (Appendix A) will receive standardized 
instruction in how to complete the Patient Motor Diary (i.e., Hauser diary). After training, subjects 
and a skilled rater will complete Patient Motor Diary entries for at least 4 consecutive half-hour 
periods during a screening visit. The concordance testing session must include at least one ON and 
one OFF period; the test session will extend for up to 4 additional 30 min. periods until there is at 
least one in each state. Concordance must reach acceptance criterion (75%) for study eligibility.  
Following a successful concordance test and prior to randomization, subjects must complete the 
Patient Motor Diary at home over 2 days and demonstrate (a) acceptable quality of the diary, with no 
more than 4 errors per day); and (b) average daily OFF time of at least 2 h and not one day below 1.0 
h. 
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9.3.1.2 Study Visit, Baseline and Randomization (Day 0) 
All eligible subjects who are being enrolled will present to their local site for a Baseline and 
Randomization visit. Baseline efficacy and safety assessments will be performed, including (but not 
limited to) UPDRS, CGI, PGI, Questionnaire for Impulsive-Compulsive Disorders (QUIP).  
Following baseline assessments, subjects’ treatment assignment will be randomized using the online 
interactive response system.  
Arrangements will be made for the subject to attend their Day 1 visit. 
9.3.1.3 Study Visit, Day 1 
A urine hCG pregnancy test will be performed for female subjects of childbearing potential; 
pregnant women must not receive study drug.  
The first dose of study drug (CVN424 or placebo) will be administered under direction of site 
personnel. Subjects not randomized to placebo will initiate treatment with 50 mg CVN424. Vital 
signs will be assessed hourly through at least 3 h post-dose. Orthostatic vital signs (non-triplicate) 
will be recorded pre-dose and at 3 h post-dose. Triplicate ECG will be obtained prior to dosing and 
approximately 3 h post-dose. Additional monitoring of vital signs and ECGs may continue beyond 3 
h post-dose at the discretion of the Investigator. 
Investigator or their delegate will manage incident AEs according to their medical judgment. The 
first dose of CVN424 may elicit an increase in body temperature and heart rate lasting several hours. 
These signs can be expected to spontaneously resolve within 24 h post-dose, and to lessen with 
repeated dosing. Antipyretic medication (e.g., Acetaminophen Extended Release Caplets, 650 mg) 
can be administered for symptomatic relief of fever.  
A blood sample for PK analysis will be collected pre-dose and at 3 h post-dose, according to Table 
5.  
Subjects will be given a 10 day supply of study drug (as suspension in amber colored bottles) to be 
taken home and stored under refrigeration until use. Study drug will be self-administered each 
morning through Day 27 ±1 day.  
9.3.1.4 Study Visit, Day 8 ±2 days 
All subjects will present to their local site on Day 8 ±2 days, returning to the site all bottles of study 
medication, whether empty or unused.  
Subjects will not take study drug at home on the morning of the Day 8 Study Visit. Administration 
of the daily dose of study drug will be deferred until after collection of a blood sample for 
determination of the study drug “trough” concentration. 
Beginning on Visit Day 8, the high-dose cohort will increase their dosage to 150 mg CVN424 per 
day. This step-wise increase is intended to limit the changes that the first dose of 150 mg CVN424 
may elicit in vital signs (notably, increased temperature and heart rate, which were dose-dependent 
and not clinically significant in a healthy volunteer study). The low-dose arm will continue to 
receive 50 mg per day.  
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Vital signs will be assessed hourly through at least 3 h post-dose. Orthostatic vital signs (non-
triplicate) will be recorded pre-dose and at 3 h post-dose. Triplicate ECG will be obtained prior to 
dosing and approximately 3 h post-dose. Investigator or their delegate will manage incident AEs 
according to their medical judgment. Additional monitoring of vital signs and ECGs may continue 
beyond 3 h post-dose at the discretion of the Investigator. 
A blood sample for PK analysis will be collected pre-dose and at 3 h post-dose, according to Table 
5. During blood sampling, one additional tube of blood plasma will be collected for archiving 
(frozen storage) to support potential post hoc laboratory testing (e.g., biomarkers, potential 
characterization of unknown CVN424 metabolites). 
After safety assessments, subjects will be given a 10 day supply of study drug to be taken home and 
stored under refrigeration until use.  
9.3.1.5 Study Visit, Day 15 ±2 days 
All subjects will present to their local site on Day 15 ±2 days, returning to the site all bottles of study 
medication, whether empty or unused.  
Each subject will have completed a Patient Motor Diary recording their capabilities, limitations and 
motor symptoms over the prior 2 days (e.g., Days 13 and 14). Site will conduct assessments to 
complete the UPDRS, PGI, CGI, Epworth Sleepiness Scale, and Questionnaire for Impulsive-
Compulsive Disorders. An untimed sample will be collected for PK analysis. 
After safety assessments, subjects will be given a 10 day supply of study drug to be taken home and 
stored under refrigeration until use.  
9.3.1.6 Study Visit, Day 22 ±2 days 
All subjects will present to their local site on Day 22 ±2 days, returning to the site all bottles of study 
medication, whether empty or unused (time not specified). 
Subjects will not take study drug at home on the morning of the Day 22 Study Visit. Administration 
of the daily dose of study drug will be deferred until after collection of a blood sample for 
determination of the study drug “trough” concentration. Following observed dosing, serial blood 
plasma samples will be collected for PK analysis according to the schedule in Table 5. 
After safety assessments, subjects will be given a supply of study drug sufficient to last through 
dosing Day 27 ±1 day to be taken home and stored under refrigeration until use.  
9.3.1.7 Study Visit, Day 27 ±1 day 
All subjects will present to their local site on Day 27 ±1 day, returning to the site all bottles of study 
medication, whether empty or unused.  
An untimed blood sample for PK analysis will be collected.  
All subjects will have completed a Patient Motor Diary recording their capabilities, limitations and 
motor symptoms over the prior 2 days (e.g., Days 25 and 26). Site will conduct assessments to 
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complete the UPDRS. PGI, CGI, Epworth Sleepiness Scale, and Questionnaire for Impulsive-
Compulsive Disorders.  
9.3.1.8 Final Study Visit, Day 35 ±2 days 
All subjects will present to their local site on Day 35 ±2 days. Site will conduct assessments to 
complete the UPDRS, PGI, CGI, and Epworth Sleepiness Scale, as well as safety assessments. An 
untimed sample will be collected for PK analysis. The investigator must complete the End of Study 
eCRF page. 
Subjects who have abnormal, clinically significant (CS) findings at the Final Study Visit may be 
asked, per investigator’s discretion, to return to the clinic subsequently to ensure appropriate safety 
follow-up. 
9.3.2 Early Termination 
Subjects who discontinue dosing or decide to check out of the study clinic early will be advised to 
allow the Investigator (or authorized designees) to complete early termination assessments for safety 
purposes prior to discharge. The reason for discontinuation must be documented in the source 
document and eCRF.  
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 
9.4 
Biological Sample Retention and Destruction  
In this study, specimens for genome/gene analysis will be collected as described in Section 9.1.12, 
Pharmacogenomic Sample Collection. After extraction and purification, the genetic material will be 
preserved and retained at a biorepository selected by the sponsor for up to but not longer than 15 
years or as required by applicable law. The sponsor has put into place a system to protect the 
subjects’ personal information to ensure optimal confidentiality and defined standard processes for 
sample and data collection, storage, analysis, and destruction. 
The sample will be labeled with a unique sample identifier similar to labeling in the main study but 
using a code that is different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 
code numbers; the samples are stripped of all personal identifying information but a key linking the 
samples to clinical analysis data exists. This link means that the subject may be identified but only 
indirectly. The code numbers will be kept secure by or on behalf of the Sponsor. 
Subjects who consented and provided a pharmacogenomic sample for DNA and RNA analysis can 
withdraw their consent and request disposal of a stored sample at any time prior to analysis. The 
Investigator will notify the sponsor of any subject who has withdrawn consent for the DNA and 
RNA analysis. 
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9.5 
Definitions 
9.5.1 PTE 
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed the ICF to participate in a study but prior to administration of any study medication; it does 
not necessarily have to have a causal relationship with study participation. 
9.5.2 AE 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (e.g., a CS abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a drug whether or not it is 
considered related to the drug. 
9.5.3 Additional Points to Consider for PTEs and AEs 
An untoward finding generally may: 
 Indicate a new diagnosis or unexpected worsening of a pre-existing condition. (Intermittent 
events for pre-existing conditions underlying disease should not be considered PTEs or AEs) 
 Necessitate therapeutic intervention 
 Require an invasive diagnostic procedure 
 Require discontinuation or a change in dose of study medication or a concomitant medication 
 Be considered unfavorable by the investigator for any reason 
 PTEs/AEs caused by a study procedure (e.g., a bruise after blood draw) should be recorded as a 
PTE/AE 
Diagnoses vs signs and symptoms: 
 Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as a PTE(s) or as an AE(s) 
Laboratory values and ECG findings: 
 Changes in laboratory values or ECG parameters are only considered to be PTEs or AEs if they 
are judged to be CS (i.e., if some action or intervention is required). A laboratory re-test and/or 
continued monitoring of an abnormal value are not considered an intervention. In addition, 
repeated or additional noninvasive testing for verification, evaluation or monitoring of an 
abnormality is not considered an intervention 
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 If abnormal laboratory values or ECG findings are the result of pathology for which there is an 
overall diagnosis (e.g., increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as a PTE or as an AE 
Pre-existing conditions: 
 Pre-existing conditions (present at the time of signing of the ICF) are considered concurrent 
medical conditions and should NOT be recorded as PTEs or AEs. Baseline evaluations (e.g., 
laboratory tests, ECG, X-rays etc.) should NOT be recorded as PTEs unless related to study 
procedures. However, if the subject experiences a worsening or complication of such a 
concurrent condition, the worsening or complication should be recorded appropriately as a PTE 
(worsening or complication occurs before start of study medication) or an AE (worsening or 
complication occurs after start of study medication). Investigators should ensure that the event 
term recorded captures the change in the condition (e.g., “worsening of…”) 
 If a subject has a pre-existing episodic condition (e.g., asthma, epilepsy) any occurrence of an 
episode should only be captured as a PTE/AE if the episodes become more frequent, serious or 
severe in nature, that is, investigators should ensure that the AE term recorded captures the 
change in the condition from Baseline (e.g., “worsening of…”) 
 If a subject has a degenerative concurrent condition (e.g., cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater extent 
to that which would be expected. Again, investigators should ensure that the AE term recorded 
captures the change in the condition (e.g., “worsening of…”) 
Worsening of PTEs or AEs: 
 If the subject experiences a worsening or complication of a PTE after starting administration of 
the study medication, the worsening or complication should be recorded appropriately as an AE. 
Investigators should ensure that the AE term recorded captures the change in the condition (e.g., 
“worsening of…”) 
 If the subject experiences a worsening or complication of an AE after any change in study 
medication, the worsening or complication should be recorded as a new AE. Investigators should 
ensure that the AE term recorded captures the change in the condition (e.g., “worsening of…”) 
Changes in severity of AEs /Serious PTEs: 
 If the subject experiences changes in severity of an AE/serious PTE, the event should be 
captured once with the maximum severity recorded 
Preplanned surgeries or procedures: 
 Preplanned procedures (surgeries or therapies) that were scheduled prior to signing of informed 
consent are not considered PTEs or AEs. However, if a preplanned procedure is performed early 
(e.g., as an emergency) due to a worsening of the pre-existing condition, the worsening of the 
condition should be captured appropriately as a PTE or an AE. Complications resulting from any 
planned surgery should be reported as AEs 
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Elective surgeries or procedures: 
 Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as PTEs or AEs,but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs 
Overdose: 
 Cases of overdose with any medication without manifested side effects are NOT considered 
PTEs or AEs, but instead will be documented on an Overdose page of the eCRF. Any manifested 
side effects will be considered PTEs or AEs and will be recorded on the AE page of the eCRF 
9.5.4 SAEs 
An SAE is defined as any untoward medical occurrence that at any dose: 
1. Results in DEATH. 
2. Is LIFE THREATENING. 
 The term “life threatening” refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event that hypothetically might have caused death if 
it were more severe 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization. 
4. Results in persistent or significant DISABILITY/INCAPACITY. 
5. Leads to a CONGENITAL ANOMALY/BIRTH DEFECT. 
6. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following: 
 May require intervention to prevent items 1 through 5 above 
 May expose the subject to danger, even though the event is not immediately life threatening 
or fatal or does not result in hospitalization 
 Includes any event or synonym described in the Medically Significant AE List (Table 7) 
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Table 7 
Medically Significant AE List  
Term 
Acute respiratory failure/acute respiratory distress 
syndrome 
Hepatic necrosis 
Torsade de pointes / ventricular fibrillation / ventricular 
tachycardia 
Acute liver failure 
Anaphylactic shock 
Malignant hypertension 
Acute renal failure 
Convulsive seizure 
Pulmonary hypertension 
Agranulocytosis 
Pulmonary fibrosis 
Aplastic anemia 
Confirmed or suspected endotoxin shock 
Toxic epidermal necrolysis/Stevens-Johnson syndrome 
Confirmed or suspected transmission of infectious agent by 
a medicinal product 
 
Neuroleptic malignant syndrome / malignant hyperthermia 
 
Spontaneous abortion / stillbirth and fetal death 
 
PTEs that fulfill 1 or more of the serious criteria above are also to be considered SAEs and should be 
reported and followed up in the same manner (see Sections 9.6.2 and 9.7). 
9.5.5 Severity of PTEs and AEs 
The different categories of intensity (severity) are characterized as follows: 
Mild: 
The event is transient and easily tolerated by the subject. 
Moderate: 
The event causes the subject discomfort and interrupts the subject’s usual activities. 
Severe: 
The event causes considerable interference with the subject’s usual activities. 
9.5.6 Causality of AEs 
The relationship of each AE to study medication(s) will be assessed using the following categories: 
Related: 
An AE that follows a reasonable temporal sequence from administration of a drug (including the 
course after withdrawal of the drug), or for which possible involvement of the drug can be 
argued, although factors other than the drug, such as underlying diseases, complications, 
concomitant drugs and concurrent treatments, may also be responsible. 
Not Related: 
An AE that does not follow a reasonable temporal sequence from administration of a drug 
and/or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs and concurrent treatments. 
9.5.7 Relationship to Study Procedures 
Relationship (causality) to study procedures should be determined for all PTEs and AEs. 
The relationship should be assessed as Related if the investigator considers that there is reasonable 
possibility that an event is due to a study procedure. Otherwise, the relationship should be assessed 
as Not Related. 
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9.5.8 Start Date  
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician. 
9.5.9 Stop Date  
The stop date of the AE/serious PTE is the date at which the subject recovered, the event resolved 
but with sequelae or the subject died. 
9.5.10 
Frequency  
Episodic AEs/serious PTE (e.g., vomiting) or those which occur repeatedly over a period of 
consecutive days are intermittent. All other events are continuous. 
9.5.11 
Action Concerning Study Medication  
 Drug withdrawn – a study medication is stopped due to the particular AE 
 Dose not changed – the particular AE did not require stopping a study medication 
 Unknown – only to be used if it has not been possible to determine what action has been taken 
 Not Applicable – a study medication was stopped for a reason other than the particular AE 
e.g., the study has been terminated, the subject died, dosing with study medication was already 
stopped before the onset of the AE 
9.5.12 
Outcome 
 Recovered/Resolved – Subject returned to first assessment status with respect to the AE/serious 
PTE 
 Recovering/Resolving – the intensity is lowered by one or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved, but has not 
returned to the normal range or to baseline; the subject died from a cause other than the 
particular AE/serious PTE with the condition remaining “recovering/resolving” 
 Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the 
intensity of the diagnosis, signs/ symptoms or laboratory value on the last day of the observed 
study period has got worse than when it started; is an irreversible congenital anomaly; the subject 
died from another cause with the particular AE/serious PTE state remaining “Not recovered/not 
resolved” 
 Resolved with sequelae – the subject recovered from an acute AE/serious PTE but was left with 
permanent/significant impairment (e.g., recovered from a cardiovascular accident but with some 
persisting paresis 
 Fatal – the AEs/PTEs which are considered as the cause of death 
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 Unknown – the course of the AE/serious PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study 
9.6 
Procedures 
9.6.1 Collection and Reporting of AEs 
9.6.1.1 PTE and AE Collection Period 
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication Day 1 or 
until screen failure. For subjects who discontinue prior to study medication administration, PTEs are 
collected until the subject discontinues study participation. 
Collection of AEs will commence from the time that the subject is first administered study 
medication Day 1. Collection of AEs will continue until 14 days following last dose. Ascertainment 
of AEs with onset or worsening after the Final Study Visit on Day 35 and within 14 days of last dose 
will rely on spontaneous reporting by the subject or caregiver.  
9.6.1.2 PTE and AE Reporting 
At each study visit, the investigator or designee will assess whether any subjective AEs have 
occurred. A neutral question, such as “How have you been feeling since your last visit?” may be 
asked. Subjects may report AEs occurring at any other time during the study. Subjects experiencing 
a serious PTE must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or there is a satisfactory explanation for the change. Non-
serious PTEs, related or unrelated to the study procedure, need not to be followed-up for the 
purposes of the protocol. 
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or until there is a satisfactory explanation for the changes 
observed. All PTEs and AEs will be documented in the PTE/AE page of the eCRF, whether or not 
the investigator concludes that the event is related to the drug treatment. The following information 
will be documented for each event: 
1. Event term. 
2. Start and stop date and time. 
3. Frequency. 
4. Severity. 
5. Investigator’s opinion of the causal relationship between the event and administration of 
study medication(s) (related or not related) (not completed for PTEs). 
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details 
of the suspected procedure. 
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7. Action concerning study medication (not applicable for PTEs). 
8. Outcome of event. 
9. Seriousness. 
9.6.2 Collection and Reporting of SAEs 
When an SAE occurs through the AE collection period it should be reported according to the 
following procedure: 
An SAE form must be completed, in English, and signed by the investigator immediately or within 
24 h of first onset or notification of the event. The information should be completed as fully as 
possible but contain, at a minimum: 
 A short description of the event and the reason why the event is categorized as serious 
 Subject identification number 
 Investigator’s name 
 Name of the study medication(s) 
 Causality assessment 
The SAE form should be transmitted within 24 h to the attention of the contact listed in Section 1.0.  
Any SAE spontaneously reported to the investigator following the AE collection period should be 
reported to the sponsor if considered related to study participation. 
Reporting of Serious PTEs will follow the procedure described for SAEs. 
9.6.3 Reporting of Abnormal LFT 
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. 
If a subject is noted to have ALT or AST >3 ×ULN and total bilirubin >2 ×ULN for which an 
alternative etiology has not been identified, the event should be recorded as an SAE and reported as 
per Section 9.6.2. The investigator must contact the Medical Monitor for discussion of the relevant 
subject details and possible alternative etiologies, such as acute viral hepatitis A or B or other acute 
liver disease or medical history/concurrent medical conditions. Follow-up laboratory tests as 
described in Section 9.1.8 must also be performed.  
9.7 
Follow-up of SAEs 
If information is not available at the time of the first report becomes available at a later date, the 
investigator should complete a follow-up SAE form or provide other written documentation and fax 
it immediately within 24 h of receipt. Copies of any relevant data from the hospital notes (e.g., 
ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the addressee, if 
requested. 
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All SAEs should be followed up until resuspension or permanent outcome of the event. The 
timelines and procedure for follow-up reports are the same as those for the initial report. 
9.7.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities  
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities, including the European 
Medicines Agency (EMA), investigators and IRBs or IECs, as applicable, in accordance with 
national regulations in the countries where the study is conducted. Relative to the first awareness of 
the event by/or further provision to the sponsor or sponsor’s designee, SUSARs will be submitted to 
the regulatory authorities as expedited report within 7 days for fatal and life-threatening events and 
15 days for other serious events, unless otherwise required by national regulations. The sponsor will 
also prepare an expedited report for other safety issues where these might materially alter the current 
benefit-risk assessment of an investigational medicinal product or that would be sufficient to 
consider changes in the investigational medicinal products administration or in the overall conduct 
of the trial. The investigational site also will forward a copy of all expedited reports to his or her IRB 
or IEC in accordance with national regulations. 
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10.0 
STUDY-SPECIFIC COMMITTEES 
None. 
(Review of incident and cumulative safety data and findings during study is the responsibility of the 
Medical Monitor and sponsor’s Responsible Medical Officer.) 
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11.0 
DATA HANDLING AND RECORDKEEPING 
AEs, PTEs, medical history, and concurrent conditions will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization 
Drug Dictionary. All terms will be coded using the dictionary version available at the start of the 
study. 
11.1 
CRFs (Electronic) 
Completed eCRFs are required for each subject who signs an informed consent. 
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRF. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. Data are transcribed directly onto eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by sponsor 
personnel (or designees) and will be answered by the site.  
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for change. Reasons for significant corrections should additionally be included.  
The Investigator must review the eCRFs for completeness and accuracy and must sign and date the 
appropriate eCRFs as indicated. Furthermore, the investigator must retain full responsibility for the 
accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits by 
study monitors. The sponsor or its designee will be permitted to review the subject’s medical and 
hospital records pertinent to the study to ensure accuracy of the eCRFs. The completed eCRFs are 
the sole property of the sponsor and should not be made available in any form to third parties, except 
for authorized representatives of appropriate governmental health or regulatory authorities, without 
written permission of the sponsor. 
11.2 
Record Retention 
The investigator agrees to keep the records stipulated in Section 12.1 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated ICFs, subject authorization forms regarding the use of 
personal health information (if separate from the ICFs), copy of eCRFs, including the audit trail, and 
detailed records of drug disposition to enable evaluations or audits from regulatory authorities, the 
sponsor or its designees. Any source documentation printed on degradable thermal sensitive paper 
should be photocopied by the site and filed with the original in the subject’s chart to ensure long-
term legibility. Furthermore, ICH E6 Section 4.9.5 requires the investigator to retain essential 
documents specified in ICH E6 (Section 8) until at least 2 years after the last approval of a marketing 
application for a specified drug indication being investigated or, if an application is not approved, 
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until at least 2 years after the investigation is discontinued and regulatory authorities are notified. In 
addition, ICH E6 Section 4.9.5 states that the study records should be retained until an amount of 
time specified by applicable regulatory requirements or for a time specified in the Clinical Study Site 
Agreement between the investigator and sponsor. 
Refer to the Phase 1 Site Specifications document for the sponsor’s requirements on record 
retention. The investigator should contact and receive written approval from the sponsor before 
disposing of any such documents. 
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12.0 
STATISTICAL METHODS 
12.1 
Statistical and Analytical Plans 
A statistical analysis plan (SAP) will be prepared and finalized prior to unblinding of subjects’ 
treatment assignment. This document will provide further details regarding the definition of analysis 
sets, analysis variables and analysis methodology to address all study objectives. 
A targeted data review will be conducted prior to unblinding of subjects’ treatment assignment. This 
review will assess the accuracy and completeness of the study database, subject evaluability, and 
appropriateness of the planned statistical methods. 
12.1.1 Analysis Sets 
Safety Set 
The Safety Analysis Set will consist of all subjects who enrolled and received at least 1 dose of study 
drug, classified according to the treatment they actually received. Subjects in this analysis set will be 
used for demographic, baseline characteristics and safety summaries. 
Efficacy Set 
The primary Efficacy Analysis set will consist of all subjects who were eligible, randomized, and 
received at least one dose of study drug, classified according to the treatment actually received. 
Secondary tests of efficacy will assess subjects who were eligible, randomized, and judged 
compliant with treatment and follow-up as classified prior to breaking the blind. The former is less 
stringent than a formal intent-to-treatment sample but estimates the efficacy one might expect among 
subjects who start using CVN424 at a specified dose, acknowledging that some will be intolerant or 
non-compliant. The latter estimates the maximal efficacy, the efficacy one might expect among 
subjects who are tolerant of and compliant with treatment. Subjects in this analysis set will be used 
for efficacy analyses. 
PK Set 
The PK set will consist of all subjects who received at least 1 dose of study drug and have at least 1 
measurable plasma concentration. Subjects in this analysis set will be used for analysis of 
pharmacodynamics. 
If any subjects are found to be noncompliant in dosing schedule or with incomplete data, a decision 
will be made on a case-by-case basis as to their inclusion in the analysis prior to breaking the blind, 
but they will be presented in the subject listings. 
12.1.2 Analysis of Demographics and Other Baseline Characteristics 
Descriptive statistics (N, mean, SD [standard deviation], median, minimum, and maximum) will be 
generated for continuous demographic variables and baseline characteristics variables (age, height, 
weight, and BMI) for placebo, each CVN424 dose level, CVN424 overall, and overall. The number 
and percentage of subjects in each class of the categorical demographic variables and baseline 
characteristics variables (gender, ethnicity, and race) will be tabulated for placebo, each CVN424 
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dose level, CVN424 overall, and overall. Individual subject demographic and baseline characteristics 
data will be listed. 
Demographic variables of screen failure subjects and reasons for screen failures will be summarized 
overall for subjects who are screened, but not enrolled in the study. Individual demographic 
characteristics, date of informed consent, and reason for screen failure will be listed. 
12.1.3 PK Analysis 
The concentration of CVN424 in plasma will be summarized by dose over each scheduled sampling 
time using descriptive statistics. Individual plasma concentration data versus time will be presented 
in a data listing. 
PK parameters of CVN424 will be derived using non-compartmental analysis methods from the 
concentration-time data for all subjects in the PK set. Actual sampling times, rather than scheduled 
sampling times, will be used in all computations involving sampling times. The following PK 
parameters will be determined from concentrations of CVN424 in plasma:  
Symbol/Term 
Definition 
AUC∞  
Area under the plasma concentration-time curve from time 0 to infinity, calculated as 
AUC∞=AUCt+Clast/λz, where Clast is the last quantifiable concentration. 
AUC6 
Area under the plasma concentration-time curve from time 0 to 6 hours, calculated using the 
linear trapezoidal rule. 
Cmax 
Maximum observed concentration. 
CL/F 
Apparent clearance after extravascular administration, calculated as Dose/AUC∞ after a 
single dose. 
λz 
Terminal elimination rate constant, calculated as the negative of the slope of the log-linear 
regression of the natural logarithm concentration-time curve during the terminal phase. 
t1/2z 
Terminal elimination half-life, calculated as ln(2)/λz. 
tmax 
Time to reach Cmax.  
Vz/F 
Apparent volume of distribution during the terminal phase after extravascular administration, 
calculated as (CL/F)/λz. 
 
Additional plasma PK parameters may be calculated, including analyses by gender (if possible). 
Descriptive statistics (arithmetic mean, SD, median, minimum and maximum) will be used to 
summarize most plasma (PK) parameters for CVN424. Geometric mean and coefficient of variation 
will be computed for right-skewed measures, e.g., Cmax and AUCs. Plots of Cmax and AUCs versus 
doses will be generated. 
Pharmacodynamic analyses will investigate the possible relationship between CVN424 PK 
parameters and efficacy and safety outcomes. Population analysis of results may be considered. 
Details of planned PK analyses will be presented in the SAP. 
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12.1.4 Safety Analysis 
12.1.4.1 AEs 
All AEs will be coded by System Organ Class and Preferred Term using MedDRA. Treatment-
emergent AEs with onset occurring within 30 days (onset date – last date of dose +1 ≤30) after study 
drug administration will be listed and included in the summary tables. Treatment-emergent AEs will 
be summarized by placebo, each CVN424 dose level and CVN424 overall by System Organ Class 
and Preferred Term. The following summary tables will be included in the report: summary of 
TEAEs and drug-related AEs, relationship of AEs to study drug (related vs not-related), severity of 
AEs and related AEs. AEs leading to study drug discontinuation and SAEs will be listed. Subgroup 
analyses will examine AEs among subjects categorized by selected demographic and disease 
characteristics. Data listings will be provided for all AEs including PTE, TEAEs, AEs leading to 
study drug discontinuation, and SAEs. All AEs will be listed. 
12.1.4.2 Clinical Laboratory Evaluation 
Individual results of laboratory tests from hematology, chemistry, urinalysis, and endocrine panels 
that are abnormal and CS will be summarized and listed. Observed values and change from baseline 
to post-dose laboratory data will be summarized for placebo, each CVN424 dose level and CVN424 
overall. All clinical laboratory data will be listed. 
12.1.4.3 Vital Signs 
Individual results of vital signs that are abnormal and CS will be summarized and listed. Observed 
values and changes from Baseline in vital sign measurements will be summarized by placebo, each 
CVN424 dose level and CVN424 overall. All vital sign data will be provided in the data listings. 
12.1.4.4 ECGs 
Individual results of quantitative ECG parameters from the 12-lead safety ECGs that are abnormal 
and CS will be summarized and listed. Observed values and changes from baseline in quantitative 
ECG parameters will be summarized by placebo, each CVN424 dose level and CVN424 overall. 
Shift tables may be generated for the investigator’s ECG interpretations that changed from baseline 
to the post-dose collections by above groups. All ECG data will be provided in the data listings. 
12.1.4.5 Other Variables 
Physical exam findings and suicidal assessments will be presented in data listings. 
12.1.5 Efficacy Analysis 
Serial assessments of average daily hours of OFF time as recorded in the Patient Motor Diary over 
the two days prior to each visit will be analyzed using mixed model for repeated measures 
(MMRM). The model will include fixed terms for treatment, visit, treatment x visit interaction and 
baseline measurement with subject-level unstructured covariance among repeated measurements. 
Other covariance structures may be used in case the model does not converge using unstructured 
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covariance structure. Additional covariates may be included based on review prior to breaking the 
blind. Two co-primary estimands of efficacy will estimate treatment-dependent difference in change 
from baseline to Day 27, one for each active dose vs. placebo, and will be tested using linear 
contrasts of least-square means. Each co-primary comparison will test for significance at one-tailed p 
< 0.1 to control the overall type 1 error rate at 20% based on Dunnett's method for comparing two 
treatments to the same control. Additional contrasts will be used to test for a dose-dependent effect 
of treatment and to estimate dosage-dependent differences in change from baseline at all other visits. 
Additional and exploratory efficacy endpoints will be analyzed in the same model and using the 
same estimands. 
Responder analysis will ascertain the incidence of clinically significant improvement.  
Subgroup analyses will ascertain the potential impact on efficacy of subgroup variables reflecting 
various demographic and disease-related characteristics. 
12.2 
Interim Analysis and Criteria for Early Termination 
A futility analysis may be conducted once at least 50 patients have completed their Day 27 
assessments. The focus of this unblinded analysis will be to assess the change from baseline in 2-day 
average OFF time at Day 27 as recorded in the Patient Motor Diary. Analysis of safety events and 
additional endpoints may be included. The analysis will be conducted by a biostatistician of the CRO 
who is not otherwise involved with the conduct of the study. Investigators, their study staff, patients, 
CRO team members, and the Sponsor will remain blinded. The outcomes of this analysis will 
include a recommendation to the Sponsor to: 
1. Continue the study as planned; or 
2. Discontinue randomization into one active treatment arm because of futility; or  
3. Discontinue the study because of futility on both active treatment arms 
The futility analysis will be described in the SAP. 
12.3 
Determination of Sample Size 
The safety and tolerability of single- and repeated (7 daily) administration of CVN424, including 
doses higher than in the present study, were previously demonstrated in a study with 64 healthy 
volunteers. The target sample size of 45 subjects per treatment arm (total N=135) is considered to be 
sufficient for the preliminary evaluation of CVN424 safety, tolerability, and efficacy in a PD 
population. The study will have 90% power to detect at least one instance of any TEAE with an 
expected incidence of 0.10 per participant exposed at a given dosage of CVN424.  
When the true effect of both dosages is zero, the study will have an 80% probability of declaring 
neither dosage of CVN424 significantly better than placebo at reducing OFF time based on the one-
tailed p < 0.1 criterion, allowing 20% non-evaluable (e.g., loss to follow-up, incomplete data) and 
assuming a SD of 3 h for the change in OFF time from baseline to 27 days. When the true effect of a 
dosage is a reduction in average OFF time of at least 1.5 h, the study will have an 80% probability of 
declaring that dosage of CVN424 significant based on the one-tailed p < 0.1 criterion. By this 
construction, the study has 80% power to detect whether CVN424 does not reduce OFF time and 
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80% power to detect whether CVN424 at one or both of the two dosages tested reduces OFF time by 
at least 1.5 h. 
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13.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Study-Site Monitoring Visits 
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. The 
investigator and institution guarantee access to source documents by the sponsor or its designee 
(contract research organization) and by the IRB or IEC. 
All aspects of the study and its documentation will be subject to review by the sponsor or designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, study 
medication, subject medical records, informed consent documentation, documentation of subject 
authorization to use personal health information (if separate from the ICFs), and review of eCRFs 
and associated source documents. It is important that the investigator and other study personnel are 
available during the monitoring visits and that sufficient time is devoted to the process. 
13.2 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
designee (and IRB or IEC, as required) to determine the appropriate course of action. There will be 
no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria. 
The site should document all protocol deviations in the subject’s source documents. In the event of a 
significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as required). 
Significant deviations include, but are not limited to, those that involve fraud or misconduct, 
increase the health risk to the subject, or confound interpretation of primary study assessment. A 
Protocol Deviation Form should be completed by the site and signed by the sponsor or designee for 
any significant deviation from the protocol. 
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. Table 8 
defines the windows allowed for sample collections.  
Protocol Deviation Forms are to be completed for PK samples collected outside of the following 
intervals: 
Table 8 
Windows for PK Blood Sample Collection 
Minutes 
Nominal Sampling Time 
Pre-dose 
Pre-dose (0 h) 
±5 
immediately post-dose to ≤6 h 
±15 
>6 h to 12 h post-dose 
±60 
>12 h post-dose 
 
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13.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing 
visit. The auditor may ask to visit the facilities where laboratory samples are collected, where the 
medication is stored and prepared, and any other facility used during the study. In addition, there is 
the possibility that this study may be inspected by regulatory agencies, including those of foreign 
governments (e.g., the FDA, the United Kingdom Medicines and Healthcare products Regulatory 
Agency, the Pharmaceuticals and Medical Devices Agency of Japan). If the study site is contacted 
for an inspection by a regulatory body, the sponsor should be notified immediately. The investigator 
and institution guarantee access for quality assurance auditors to all study documents as described in 
Section 13.1. 
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14.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual participants (i.e., subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, 
and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct the study 
according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the “Responsibilities of the Investigator” that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities. 
14.1 
IRB and/or IEC Approval 
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC has 
direct participation in this study, written notification regarding his or her abstinence from voting 
must also be obtained. Those Americas sites unwilling to provide names and titles of all members 
due to privacy and conflict of interest concerns should instead provide a Federal Wide Assurance 
Number or comparable number assigned by the Department of Health and Human Services. 
The sponsor or designee will supply relevant documents for submission to the respective IRB or IEC 
for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of the 
ICFs, and, if applicable, subject recruitment materials and/or advertisements and other documents 
required by all applicable laws and regulations, must be submitted to a central or local IRB or IEC 
for approval. The IRB’s or IEC’s written approval of the protocol and subject informed consent must 
be obtained and submitted to the sponsor or designee before commencement of the study (i.e., before 
shipment of the sponsor-supplied drug or study specific screening activity). The IRB or IEC 
approval must refer to the study by exact protocol title, number, and version date; identify versions 
of other documents (e.g., ICF) reviewed; and state the approval date. The sponsor will ship 
drug/notify site once the sponsor has confirmed the adequacy of site regulatory documentation and, 
when applicable, the sponsor has received permission from competent authority to begin the trial. 
Until the site receives drug/notification no protocol activities, including screening may occur. 
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by subjects, local safety reporting requirements, reports and updates 
regarding the ongoing review of the study at intervals specified by the respective IRB or IEC, and 
submission of the investigator’s final status report to IRB or IEC. All IRB and IEC approvals and 
relevant documentation for these items must be provided to the sponsor or its designee. 
Subject incentives should not exert undue influence for participation. Payments to subjects must be 
approved by the IRB or IEC and sponsor. 
14.2 
Subject Information, Informed Consent, and Subject Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
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applicable laws and regulations. The ICF, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and disclosures 
of the subject’s personal and personal health information for purposes of conducting the study. The 
ICF and the subject information sheet (if applicable) further explain the nature of the study, its 
objectives, and potential risks and benefits, as well as the date informed consent is given. The ICF 
will detail the requirements of the participant and the fact that he or she is free to withdraw at any 
time without giving a reason and without prejudice to his or her further medical care. 
The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF and 
if applicable, the subject authorization form. The ICF, subject authorization form (if applicable), and 
subject information sheet (if applicable) must be approved by both the IRB or IEC and the sponsor 
prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject. It is the responsibility 
of the investigator to explain the detailed elements of the ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) to the subject. Information should be given 
in both oral and written form whenever possible and in the manner deemed appropriate by the IRB 
or IEC. In the event the subject is not capable of rendering adequate written informed consent, then 
the subject’s legally acceptable representative may provide such consent for the subject in 
accordance with applicable laws and regulations. 
The subject, or the subject’s legally acceptable representative, must be given ample opportunity to: 
(1) inquire about details of the study and (2) decide whether or not to participate in the study. If the 
subject, or the subject’s legally acceptable representative, determines he or she will participate in the 
study, then the ICF and subject authorization form (if applicable) must be signed and dated by the 
subject, or the subject’s legally acceptable representative, at the time of consent and prior to the 
subject entering into the study. The subject or the subject’s legally acceptable representative should 
be instructed to sign using their legal names, not nicknames, using blue or black ballpoint ink. The 
investigator must also sign and date the ICF and subject authorization (if applicable) at the time of 
consent and prior to subject entering into the study; however, the sponsor may allow a designee of 
the investigator to sign to the extent permitted by applicable law. 
Once signed, the original ICF, subject authorization form (if applicable), and subject information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document the 
date the subject signs the informed consent in the subject’s medical record. Copies of the signed ICF, 
the signed subject authorization form (if applicable), and subject information sheet (if applicable) 
shall be given to the subject. 
All revised ICFs must be reviewed and signed by relevant subjects or the relevant subject’s legally 
acceptable representative in the same manner as the original informed consent. The date the revised 
consent was obtained should be recorded in the subject’s medical record, and the subject should 
receive a copy of the revised ICF. 
Subjects who consented and provided a pharmacogenomic sample for DNA analysis can withdraw 
their consent and request disposal of a stored sample at any time prior to analysis. Notify sponsor of 
consent withdrawal. 
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14.3 
Subject Confidentiality 
The sponsor and designees affirm and uphold the principle of the subject’s right to protection against 
invasion of privacy. Throughout this study, a subject’s source data will only be linked to the 
sponsor’s clinical study database or documentation via a unique identification number. As permitted 
by all applicable laws and regulations, limited subject attributes, such as sex, age, or date of birth, 
and subject initials may be used to verify the subject and accuracy of the subject’s unique 
identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (e.g., FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission and 
discharge summaries for hospital admissions occurring during a subject’s study participation, and 
autopsy reports. Access to a subject’s original medical records requires the specific authorization of 
the subject as part of the informed consent process (see Section 14.2). 
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (i.e., subject name, address, and other identifier fields 
not collected on the subject’s eCRF). 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy 
14.4.1 Publication and Disclosure 
The investigator is obliged to provide the sponsor with complete test results and all data derived by 
the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the Clinical Study Site Agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other than 
study recruitment materials and/or advertisements, is the sole responsibility of the sponsor. 
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. Manuscript authorship for any 
peer-reviewed publication will appropriately reflect contributions to the production and review of the 
document. All publications and presentations must be prepared in accordance with this section and 
the Clinical Study Site Agreement. In the event of any discrepancy between the protocol and the 
Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail. 
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. 
14.4.2 Clinical Trial Registration  
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations, and guidance, the sponsor will register this clinical trial on 
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ClinicalTrials.gov (and possibly on other publicly accessible websites) within 21 days after the first 
participant is consented.  
Sponsor contact information, along with investigator’s city, state (for North American investigators), 
country, and recruiting status will be registered and available for public viewing. For some registries, 
sponsor will assist callers in locating trial sites closest to their homes by providing the investigator 
name, address, and phone number to callers requesting trial information. Once subjects receive 
investigator contact information, they may call the site and request enrollment into the trial. The 
investigative sites are encouraged to handle such trial inquiries according to their established subject 
screening process. If the caller asks additional questions beyond the topic of trial enrollment, they 
should be referred to the sponsor. Any investigator who objects to sponsor providing their contact 
information to callers must provide sponsor with a written notice requesting that their information 
not be listed on the registry site. 
14.4.3 Clinical Trial Results Disclosure  
At the conclusion of the study, the sponsor will post the results on ClinicalTrials.gov or other 
publicly accessible websites, as required by applicable national and local laws and/or regulations. 
14.5 
Insurance and Compensation for Injury 
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject compensation 
and treatment for injury. If the investigator has questions regarding this policy, he or she should 
contact the sponsor or sponsor’s designee. 
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15.0 
REFERENCES 
 
1. https://www.apdaparkinson.org/what-is-parkinsons/, accessed on 26 Jan 2018. 
2. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, et al. Genome-wide atlas 
of gene expression in the adult mouse brain. Nature 2007;445(7124):168-76. 
3. Wichmann T, DeLong MR, Guridi J, Obeso JA. Milestones in research on the 
pathophysiology of Parkinson's disease. Mov Disord. 2011 May;26(6):1032-41. 
doi:  10.1002/mds.23695. 
 
 
 
 
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Appendix A: Schedule of Study Procedures 
Visit Number 
SCREENING 
1 
2 
3 
4 
5 
6 
7 
 
Early  
Term-
ination  
Study Day:  
Days 
-28 to -1  
 
Days  
-2 & -1 
Day 0 
 
Day 1 
Day 8  
±2 days 
Day 15  
±2 days 
Day 22 
±2 days 
Day 27 
±1 day 
 
Day 35 
±2 days 
Informed consent 
X (a) 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics  
X (a) 
 
 
 
 
 
 
 
 
 
Medical history 
X(a) 
 
 
 
 
 
 
 
 
 
Concurrent medical 
conditions 
X (a) 
 
 
 
 
 
 
 
 
 
Medication history 
X (a) 
 
 
 
 
 
 
 
 
 
Vital signs and weight 
(b) 
X (a) 
 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination  
X (a) 
 
X 
 
X 
 
 
X 
X 
X 
Height and BMI 
X (a) 
 
 
 
 
 
 
X 
X 
X 
Clinical laboratory tests 
(c) 
X (a) 
 
X 
X 
X 
 
 
X 
X 
X 
Screening laboratory 
tests (d) 
X (a) 
 
 
 
 
 
 
 
 
 
Patient Motor Diary 
(Hauser diary) (e) 
X 
X 
 
 
 
X 
 
X 
 
 
Concomitant 
medications 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
ECG (f) 
X (a) 
 
 
X 
X 
 
 
X 
X 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
 
Study drug dosing (g) 
 
 
 
< - 
- 
- 
- 
- > 
 
 
DNA sample collection 
(h) 
 
 
X 
 
 
 
 
 
 
 
RNA collection (i) 
 
 
 
X 
 
 
 
 
 
 
PK blood collection (j) 
 
 
 
X 
X (k) 
X 
X 
X 
X 
X 
PTE assessment (l) 
X 
 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug 
accountability 
 
 
 
 
X 
X 
X 
X 
X 
X 
Unified Parkinson’s 
Disease Rating Scale 
(UPDRS) 
 
 
X 
 
 
X 
 
X 
X 
X 
CGI 
 
 
X 
 
 
X 
 
X 
X 
X 
PGI 
 
 
X 
 
 
X 
 
X 
X 
X 
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Visit Number 
SCREENING 
1 
2 
3 
4 
5 
6 
7 
 
Early  
Term-
ination  
Study Day:  
Days 
-28 to -1  
 
Days  
-2 & -1 
Day 0 
 
Day 1 
Day 8  
±2 days 
Day 15  
±2 days 
Day 22 
±2 days 
Day 27 
±1 day 
 
Day 35 
±2 days 
Epworth Sleepiness 
Scale 
 
 
X 
 
 
X 
 
X 
X 
X 
Questionnaire for 
Impulsive-Compulsive 
Disorders (QUIP) 
 
 
X 
 
 
X 
 
X 
 
X 
Beck Depression 
Inventory  
 
 
X 
 
 
 
 
X 
 
X 
(a) Initial Screening items, to be completed prior to other Screening assessments. Screening activities must occur within 
28 days of randomization,but may be completed in fewer than 28 days. Screening days are nominally called Day -28 
to Day -1,but will not necessarily correspond numerically to the calendar days prior to the Baseline Visit. By the 
same convention, the Patient Motor Diary will be recorded at home over 2 consecutive days during screening, but 
not necessarily on the 2 days immediately prior to the Baseline visit (Day 0). 
(b) Vital signs (oral temperature, respiration, heart rate, and blood pressure) and weight will be recorded at Screening, 
Baseline, Day 1, and at subsequent Study Visits. On Day 1 and Day 8, the assessments will be conducted pre-dose 
[within 90 minutes prior to dosing], and at least hourly through 3 h post-dose. Triplicate orthostatic vital signs 
(blood pressure and heart rate) will be recorded 15 minutes apart at baseline. Orthostatic vital signs (non-triplicate) 
will be recorded pre-dose and at 3 h post-dose on Days 1 and 8. Orthostatic vital signs will be measured after at least 
5 minutes supine and again at 2 minutes after standing at each scheduled orthostatic timepoint. 
(c) Clinical laboratory tests (hematology, serum chemistry, urinalysis, and endocrine) will be collected at Screening, 
Baseline, Day 8, Day 27, Day 35, and Early Termination (if applicable) visits. Urine hCG pregnancy test will be 
performed on female subjects of childbearing potential on Day 1 prior to dosing. 
(d) Screening laboratory testing will include all items included under ‘Clinical Laboratory Tests” plus urine drug & 
cotinine screen, and for female subjects a serum pregnancy test (hCG). An FSH level will be obtained on post-
menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). One additional 
tube for plasma and one for serum will be collected for archiving (frozen storage) to support potential post hoc 
laboratory testing.  
(e) Subjects will receive standardized instruction in how to complete the Patient Motor Diary (Hauser diary). After 
training, subjects who have passed initial Screening procedures will complete Patient Motor Diary entries for 4 
consecutive 30-minute periods during a screening visit while observed and scored by a skilled rater. The 
concordance testing session must include at least one ON and one OFF period; the test session will extend for up to 
4 additional 30 min. periods until there is at least one in each state. Concordance must be within 75% for subject 
eligibility.  
Following a successful concordance test and prior to randomization, subjects must complete the Patient Motor Diary 
at home over 48 h and demonstrate both an acceptable quality of the diary, with no more than 4 errors per day, and 
average daily OFF time of at least 2 h and not one day below 1.0 h. 
In advance of Study Visits on Day 15 and 27, subjects will complete Diary entries recording their capabilities, 
limitations and motor symptoms over the prior 2 days (e.g., Days 13 and 14, or Days 25 and 26). 
(f) Triplicate standard 12-lead ECG will be recorded at Screening and on Days 1 and 8 pre-dose [within 1 h prior to 
dosing] and 3 h (+/- 15 minutes) post-dose. Triplicate standard 12-lead ECG will also be recorded at screening and 
on Day 27, Day 35 and Early Termination (if applicable). 
(g) Upon randomization, the first dose of study drug will be administered under direction of site personnel. Near the 
conclusion of the Day 1 visit and subsequent weekly visits, subjects will be given a supply of study drug (as 
suspension in amber colored bottles) to be taken home and stored under refrigeration until use. Study drug will be 
self-administered each morning on days 2-28. However, for scheduled Study Visits on or around day 22, dosing 
must be deferred until after collection of a blood sample for determination of the study drug “trough” concentration. 
(h) One blood sample will be collected for pharmacogenomic analysis at baseline; this will only be collected once per 
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subject. 
(i) A whole blood sample will be collected pre-dose and 3 h post-dose on Day 1 for RNA pharmacogenomic analysis.  
(j) Blood samples for PK analyses will be collected at timepoints indicated in Table 5. 
(k) At Day 8 visit, one additional tube of blood plasma will be collected for archiving (frozen storage) to support 
potential post hoc laboratory testing (e.g., biomarkers, potential characterization of unknown CVN424 metabolites). 
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
   
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Appendix B: Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. The responsibilities imposed on Investigators by the FDA are 
summarized in the “Statement of Investigator” (Form 1572) which must be completed and 
signed before the Investigator may participate in this study.  
The Investigator agrees to assume the following responsibilities by signing a Form 1572. 
1. Conduct the study in accordance with the protocol. 
2. Personally conduct or supervise the staff who will assist in the protocol. 
3. Ensure that study related procedures, including study specific (non routine/nonstandard 
panel) screening assessments are NOT performed on potential subjects, prior to the 
receipt of written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the study are 
informed of these obligations. 
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that 
conform to 21 CFR Part 56 ICH, and local regulatory requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity 
and all anticipated risks to subjects. Make at least yearly reports on the progress of the 
study to the IRB/IEC and issue a final report within 3 months of study completion. 
7. Ensure that requirements for informed consent, as outlined in 21 CFR Part 50 ICH and 
local regulations, are met. 
8. Obtain valid ICF from each subject who participates in the study and document the date 
of consent in the subject’s medical chart. Valid informed consent is the most current 
version approved by the IRB/IEC.  
9. Prepare and maintain adequate case histories of all persons entered into the study, 
including eCRFs, hospital records, laboratory results, etc., and maintain these data for a 
minimum of 2 years following notification by the sponsor that all investigations have 
been discontinued or that the regulatory authority has approved the marketing 
application. The Investigator should contact and receive written approval from the 
sponsor before disposing of any such documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified 
essential documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-
supplied drugs, and return to sponsor or destroy all unused sponsor-supplied drugs per 
sponsor instructions.  
12. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the 
sponsor within 24 h. 
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Appendix C: Investigator Consent to Use of Personal Information  
Cerevance will collect and retain personal information of Investigator, including his or her name, 
address, and other personally identifiable information. In addition, Investigator’s personal 
information may be transferred to other parties located in countries throughout the world (e.g., 
the United Kingdom, United States, and Japan), including the following: 
 Cerevance, its affiliates, and licensing partners 
 Business partners assisting Cerevance, its affiliates, and licensing partners 
 Regulatory agencies and other health authorities 
 IRBs and IECs 
 Investigator’s personal information may be retained, processed, and transferred by Cerevance 
and these other parties for research purposes including the following: 
 Assessment of the suitability of Investigator for the study and/or other clinical studies 
 Management, monitoring, inspection, and audit of the study 
 Analysis, review, and verification of the study results 
 Safety reporting and pharmacovigilance relating to the study 
 Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study 
 Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may 
contain the same chemical compound present in the study medication 
 Inspections and investigations by regulatory authorities relating to the study 
 Self-inspection and internal audit within Cerevance, its affiliates, and licensing partners 
 Archiving and audit of study records 
 Posting Investigator site contact information, study details and results on publicly accessible 
clinical trial registries, databases, and websites 
 Investigator’s personal information may be transferred to other countries that do not have 
data protection laws that offer the same level of protection as data protection laws in 
Investigator’s own country. 
 Investigator acknowledges and consents to the use of his or her personal information by 
Cerevance and other parties for the purposes described above. 
 
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