A Phase 3, Randomized Study Investigating the Safety of CVT-301 (Levodopa Inhalation Powder) in Parkinson's Disease (PD) Patients With Motor Response Fluctuations (OFF Phenomena) Compared to an Observational Cohort Control
Phase: PHASE3
Conditions: Idiopathic Parkinson's Disease
Sponsor: Acorda Therapeutics

Civitas Therapeutics, Inc 
 
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1. 
TITLE PAGE 
CLINICAL STUDY PROTOCOL 
 
Protocol Title: 
A Phase 3, Randomized Study Investigating the Safety of  
CVT-301 (Levodopa Inhalation Powder) in Parkinson’s Disease 
Patients With Motor Response Fluctuations (OFF Phenomena) 
Compared to an Observational Cohort Control (SUPPORT-PD™) 
Protocol Number: 
CVT-301-005 
EudraCT Number: 
2014-003799-22 
US IND Number: 
115750 
Development Phase: 
Phase 3 
Study Sponsor: 
Civitas Therapeutics, Inc. 
190 Everett Ave 
Chelsea, MA 02150 
USA 
Protocol Version: 
3.0  
Version Date: 
22-September-2015 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to Civitas Therapeutics.  Any 
unauthorized copying or use of this document is prohibited. 
 

Civitas Therapeutics, Inc 
CVT-301-005 
CIVITAS THERAPEUTICS PROTOCOL APPROVAL PAGE 
Acorda Therapeutics, Inc., a duly authorized 
signatory for Civitas Therapeutics, Inc. 
Version 3.0 
22-Sep-2015 
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INVESTIGATOR PROTOCOL AGREEMENT PAGE 
I agree: 
• To assume responsibility for the proper conduct of the study at this site. 
• To conduct the study in compliance with this protocol, any future amendments, and 
with any other study conduct procedures provided by Civitas Therapeutics. 
• Not to implement any changes to the protocol without written agreement from Civitas 
Therapeutics and prior review and written approval from the Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) except where necessary to 
eliminate an immediate hazard to patients. 
• That I am thoroughly familiar with the appropriate use of the study drug, as described 
in this protocol and any other information provided by Civitas Therapeutics 
including, but not limited to, the current Investigator’s Brochure. 
• That I am aware of, and will comply with, good clinical practice (GCP) and all 
applicable regulatory requirements. 
• To ensure that all persons assisting me with the study are adequately informed about 
the Civitas Therapeutics study drug and have been trained on their study-related 
duties and functions as described in the protocol. 
 
Signature: 
 
 
Date: 
 
 
Name 
(print): 
 
 
 
 
 
Principal Investigator 
 
 
 
 
 

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LIST OF CONTACTS 
Sponsor: 
Civitas Therapeutics, Inc. 
190 Everett Ave 
Chelsea, MA 02150 
USA 
Sponsor’s Responsible Medical Director: 
 
 
 
  
  
 
CRO Global Study Manager: 
  
 
CRO Medical Monitors: 
 
 
 
CRO Safety (Pharmacovigilance) Reporting: 
 
 
 
 
Clinical Laboratory: 
 
 
 
 
 
Spirometry and ECG Central Laboratory 
 
 
DLco-Related Services and Analysis 
 

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USA 
Rater Training, Diary, and Endpoint 
Surveillance 
 
 
 
 

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2. 
SYNOPSIS 
Title of Study: 
A Phase 3, Randomized Study Investigating the Safety of CVT‑301 
(Levodopa Inhalation Powder) in Parkinson’s Disease Patients With 
Motor Response Fluctuations (OFF Phenomena) Compared to an 
Observational Cohort Control 
Protocol Number: 
CVT-301-005 
Investigators/Study Sites: 
This study will be conducted at approximately 100 sites in Europe 
and the United States. 
Phase of Development: 
3 
Objectives: 
Primary Objective 
• 
To characterize the pulmonary safety, as assessed by 
spirometry (forced expiratory volume in 1 second [FEV1], 
forced vital capacity [FVC], and FEV1/ FVC ratio), over a 
12-month period within the CVT-301-treated patients. 
Secondary Objectives 
• 
To characterize the pulmonary safety, as assessed by 
spirometry (FEV1, FVC, and FEV1/FVC ratio), over a 
12-month period in the observational (‘standard of care’) 
cohort. 
• 
To estimate the difference between the CVT-301-treated 
patients and the observational cohort on measures of 
pulmonary safety. 
• 
To characterize the effects of CVT-301 on safety over a 
12-month period:  safety will be assessed by adverse event 
(AE) reports, physical examination, standard and orthostatic 
vital signs (blood pressure [BP], heart rate [HR], and 
respiratory rate [RR]), clinical laboratory tests, 12-lead 
electrocardiograms (ECGs), the Parkinson’s Disease 
Impulsive-Compulsive Disorders Questionnaire (QUIP), the 
Epworth Sleepiness Scale, and the Columbia-Suicide 
Severity Rating Scale (C-SSRS).  
• 
To evaluate the effect of CVT-301 on mean change from 
baseline in the UPDRS Part 4 measures of motor 
fluctuations (dyskinesias [Q32-35] and wearing off 
[Q36-39]) measured pre-dose at 6 and 12 months after the 
initiation of CVT-301 treatment. 
• 
To characterize the occurrence and severity of 
examiner-rated dyskinesia following treatment of patients 
experiencing an OFF episode in the clinic over a 12-month 
period  
• 
To describe the effects of CVT-301 on DLco over a 
12-month period. 
 

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Exploratory Efficacy Objectives 
• 
Change from pre-dose in UPDRS Part 3 motor score at 10, 
20, 30, and 60 minutes following treatment of patients 
experiencing an OFF episode. 
• 
Time curves of the UPDRS response at 10, 20, 30 and 60 
minutes will be evaluated descriptively 
• 
Change from pre-dose in UPDRS Part 3 motor score at 10 to 
60 minutes following treatment of patients experiencing an 
OFF episode. 
• 
Proportion of patients with a ≥ 3, ≥ 6, and ≥ 11-point 
reduction in the UPDRS Part 3 motor score from pre-dose to 
post-dose, at 10 to 60 minutes. 
• 
Proportion of patients achieving resolution of an OFF to an 
ON state within 60 minutes after study drug is administered 
in the clinic, maintaining the ON state at 60 minutes after 
study drug administration (per the examiner’s subjective 
assessment). 
• 
Patient-reported total daily OFF time, total daily ON time 
without dyskinesia, total daily ON time with 
non-troublesome dyskinesia, and total daily ON time with 
troublesome dyskinesia, assessed by the patient and recorded 
in the patient diary. 
• 
Change from baseline visit in the 39-Item Parkinson’s 
Disease Questionnaire (PDQ-39). 
• 
Proportion of patients who improved based on the Patient 
Global Impression of Change (PGI-C) rating scale measured 
pre-dose. 
• 
Change from baseline visit in the Schwab and England 
(S&E) Activities of Daily Living (ADL) score. 
• 
Change from baseline visit UPDRS Part 2 score. 
Study Design: 
This study is a 12-month, open-label, randomized, multicenter study 
which will evaluate the safety and effects of CVT-301 for the 
treatment of up to 5 OFF episodes per day in PD patients 
experiencing motor fluctuations (OFF episodes) and will include a 
concurrent observational cohort of PD patients managed using the 
usual standards of care.  Patients must be CVT-301-naïve, however, 
any patients that were enrolled from the CVT-301-002 and 
CVT-301-003 studies under the previous version of this protocol 
will be allowed to continue in the study. Patients will be randomized 
in a 2:1 ratio to the CVT-301 treatment group (CVT-301 at a target 
nominal respirable dose of 50 mg LD FPD) or the observational 
cohort.  Randomization will be differentiated by the patient’s Hoehn 
and Yahr stage (<2.5 versus ≥2.5) to balance the severity of disease 
across each group and by screening spirometry (FEV1 <60% of 
predicted or FEV1/FVC ratio <70% versus FEV1 ≥60% of predicted 
and FEV1/FVC ratio ≥70%). 
Patients assigned to the CVT-301 treatment group may use the 

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prescribed dose of CVT-301 as needed for the treatment of up to 
5 OFF episodes per day in addition to their standard PD medications 
which may be modified as needed for symptomatic treatment over 
the 12-month study.  Each treated episode will require 2-capsule 
inhalations (i.e., 2 capsules used in the inhaler per treated episode) to 
deliver the dose.  
Patients assigned to the observational cohort will not receive 
CVT-301 but will be permitted to be managed using their standard 
PD medications and other PD treatment modalities, which may be 
modified as needed for symptomatic treatment in accordance with 
usual practice over the 12-month study.   
For both the CVT-301 treatment group and the observational cohort, 
additions to and/or modification of the patient’s usual PD treatment 
regimen may take place.  However, oral “as-needed” (PRN) LD 
formulations are not permitted for CVT-301-treated subjects (refer to 
Section 9.4.2 of the protocol for a list of prohibited treatments and 
prohibited medications).  For CVT-301-treated patients, the total 
daily LD dose of the modified PD treatment regimen (not including 
CVT-301) must not exceed 1600 mg per day.   
The study includes a screening period of up to 35 days (with 
2 screening visits) and a treatment period of approximately 
12 months (52±2 weeks) (with 6 treatment/observational visits) plus 
an additional follow-up at a pulmonary laboratory 4 to 5 weeks after 
the last treatment/observational visit.  A longer screening period may 
be permitted with approval from the Sponsor.  Planned 
treatment/observational visits will occur at 0 (pre-dose, baseline) and 
approximately 1, 3, 6, 9, and 12 months.  For the CVT-301 treatment 
group these visits will be treatment visits, and for the observational 
cohort, these will be observational visits.  All patients, regardless of 
study group, will be required to attend all of the screening visits and 
all of the treatment/observational visits.   
Assessments for DLco will be performed at a pulmonary laboratory 
outside of the clinic prior to the first treatment or observational visit, 
within 2 weeks prior to the 3-, 6-, 9-, and 12-month visits, and 4 to 5 
weeks after Treatment Visit/Observational Visit 6 (TV/OV6).  
If a patient in the CVT-301 treatment group develops significant 
tolerability concerns that in the opinion of the investigator are of a 
severity that should necessitate a reduction in dose, including, but 
not limited to the exacerbation or worsening of troublesome 
dyskinesia, other problematic dopaminergic symptoms, or other 
tolerability concerns, a dose reduction from 2 capsules (50 mg LD 
FPD) to 1 capsule (25 mg LD FPD) per treated episode may be 
permitted.  The medical monitor should be contacted, and the 
investigator should use his/her clinical judgment to determine 
whether an additional visit is required and what assessments should 
be performed (e.g., physical examination, spirometry, etc.).  The 
patient should continue to use 1 capsule (25 mg LD FPD) per treated 
episode for a period of at least 1 week.  If the investigator determines 
that the tolerability issue has adequately resolved and that the patient 

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has tolerated this dose for at least 1 week, the patient may at that 
point either resume taking the original dose (2 capsules [50 mg LD 
FPD] per treated episode) or come into the clinic for an unscheduled 
visit to receive a reduced-dose study drug kit (35 mg LD FPD).  
Clinical staff will call the patient 1 to 2 days after the dose escalation 
to see if the patient has any questions or concerns.  If a patient who 
has escalated back to the full dose (50 mg LD FPD per treated 
episode) has another tolerability concern that in the opinion of the 
investigator is of a severity that should necessitate a second 
reduction in dose, an unscheduled visit will be required and a 
reduced-dose study drug kit (35 mg LD FPD per treated episode) 
will be provided.   He/she will remain on the reduced dose (35 mg 
LD FPD) for the remainder of the study; he/she will not be eligible 
for any additional up-titration in dose. 
Safety data will be reviewed by an independent Data Safety 
Monitoring Board (DSMB) that will include relevant medical 
experts asdefined in the DSMB Charter.  Interim analyses, which 
will not affect study conduct, may be performed to support 
regulatory submissions. These analyses will be described in the SAP. 
Screening Period 
All patients will undergo a screening period of up to 35 days before 
entering the treatment period.  The screening period may be 
extended an additional 7 days if repeat screening assessments are 
required.  The screening period will consist of 2 scheduled clinic 
visits:  Screening Visit 1 (SV1) and Screening Visit 2 (SV2).  
Screening Visit 1 (SV1): Within 35 days prior to Treatment 
Visit/Observational Visit 1 (TV/OV1) 
Patients will be instructed to bring all of their medications with them 
to SV1.  Patients will provide written informed consent before any 
study procedures are performed.  Patients will be assessed for 
eligibility based on the inclusion/exclusion criteria.  The patient’s 
medical history (including smoking history) and PD history will be 
documented.  The PD diagnosis will be confirmed using Steps 1 and 
2 of the United Kingdom (UK) Brain Bank Criteria, and the PD 
severity will be staged using the Hoehn and Yahr disease severity 
criteria.  The number of hours of OFF time will be recorded.  
Eligible patients must have, by self-report, motor fluctuations with 
daily OFF time averaging at least 2 hours per day (not including 
early morning OFF time and which will require confirmation using 
the PD Diary over a period of 3 consecutive days).  Each patient’s 
PD medications, including standard LD-containing regimen (number 
of times per day that LD-containing medications are administered 
and the total daily LD dose will be recorded) and other concomitant 
medications will be recorded and reviewed to ensure that specified 
PD and other medications have been stabilized in accordance with 
protocol-defined criteria.  The following assessments will then be 
performed:  Mini Mental State Examination (MMSE) while patient 
is in an ON state; a full physical examination; review of pulmonary 
function and pulmonary history by completion of the Pulmonary 

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Function Baseline Questionnaire; ECG; standard vital signs (BP, 
HR, and RR) and orthostatic vital signs (BP and HR); and 
spirometry for determination of FEV1, FVC, and the FEV1/FVC 
ratio (while the patient is in an ON state).  Patients will undergo 
UPDRS Part 3 assessments while in an ON state, and training on 
self-recognition of ON and OFF states and rating assessments while 
in an ON state. 
Note:  An “ON state” is defined as the time when medication is 
providing benefit with respect to mobility, slowness, and stiffness, 
and may or may not be providing complete alleviation of all PD 
symptoms.  An “OFF state” is defined as the time when medication 
has worn off and is no longer providing benefit with respect to 
mobility, slowness, and stiffness.  OFF episodes may be heralded by 
non-motor symptoms (e.g., pain, anxiety) prior to the appearance of 
motor symptoms.  
Patients will undergo standard home PD Diary training for 
self-rating of OFF states, ON states, and dyskinesia.  Patients will be 
tested (in both ON and OFF states) for competence at self-rating and 
must be within 75% concordance with the ratings of the examiner (at 
least 3 out of 4 half-hour sessions over the course of 2 hours); if 
concordance is not reached, the observation period may be extended 
for an additional 2 hours to obtain agreement on at least 6 of 
8 half-hour sessions.  If needed, the same training and testing may be 
repeated at an unscheduled visit between SV1 and SV2 or at SV2.  If 
patients return for an unscheduled visit between SV1 and SV2 for 
concordance training and testing, the visit must occur more than 3 
days prior to SV2.  If patients do not achieve 75% concordance by 
the end of SV2, they will be considered screen failures. 
Patients will be trained on the proper technique to prepare and use 
the inhaler system using sham (i.e., empty) capsules per the 
Instructions for Use (IFU) while in an ON state.  Patients will 
undergo clinical laboratory tests (patients do not need to be in a 
fasted state, however, fasted status will be documented [fasting will 
be defined as at least 4 hours following the last meal or snack]) 
including serum pregnancy test for women of child-bearing 
potential.  
Patients will remain in the clinic and further PD medications will be 
withheld until they turn into an OFF state.  The spirometry 
evaluations, UPDRS Part 3 assessments, patient training on 
self-report of ON/OFF states, and inhaler training should be repeated 
when patients are in an OFF state.  Note:  If a patient arrives at the 
clinic in an OFF state, these assessments will be done in an OFF 
state first, then they will be repeated in an ON state after the patient 
has taken his/her standard dose of PD medications and reverts to an 
ON state. 
The PD Diary (which will be used to record time OFF, time ON 
without dyskinesia, time ON with non-troublesome dyskinesia, time 
ON with troublesome dyskinesia, and time asleep) and the Screening 
ON/OFF Episodes Log (which will be used to record the discrete 

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number of OFF episodes during their waking day) will be distributed 
to patients, and the instructions for completion will be reviewed.  If 
needed, caregivers will also be trained on how to prepare inhalers for 
patients and how to complete the PD Diary and Screening ON/OFF 
Episodes Log.  The next visit will be scheduled.  Patients will be 
monitored for AEs throughout the visit. 
During the 3 consecutive days prior to SV2, patients will complete 
the PD Diary and the Screening ON/OFF Episodes Log.  Before 
arrival at the clinic for SV2, the patients will take all of their usual 
prescribed non-PD medications and PD medications, including 
LD-containing PD medications.  
Clinic staff will arrange to speak with patients by telephone 
approximately 4 days prior to SV2 to confirm the next study visit 
and to remind patients of the study procedures required prior to the 
next scheduled study visit (including completion of the PD Diary 
and Screening ON/OFF Episodes Log).   
Screening Visit 2 (SV2): At least 4 days after SV1 
For the 3 consecutive days prior to SV2, patients will complete the 
PD Diary and the Screening ON/OFF Episodes Log.  Before arrival 
at the clinic for SV2, the patient will take all of their usual prescribed 
non-PD medications and PD medications, including LD containing 
PD medications. 
At the clinic, the clinic staff will review the PD Diary and Screening 
ON/OFF Episodes Log to determine that patients are able to perform 
these procedures correctly and to determine eligibility.  The staff 
will record any changes in the usual PD medication dose.  Any 
changes in concomitant medications will be recorded.  Patients will 
be trained again on the proper technique to prepare and use the 
inhaler system (using sham capsules) per the IFU.  If the patient has 
undergone training on the inhaler in both the ON and OFF states at 
SV1, the inhaler training at SV2 may be done in either state.  If not, 
the inhaler training at SV2 should be performed in both the ON and 
OFF states.  Patients will be re-trained on how to self-assess their 
ON and OFF states while in ON and OFF states as needed. 
The clinic staff will distribute the PD Diary and the Screening 
ON/OFF Episodes Log and review the instructions for completion.  
The clinic staff will schedule patients to undergo a baseline DLco 
assessment, which will be completed after SV2 and before the first 
treatment or observational visit.  The DLco assessment should be 
performed while the patient is in an ON state (as reported by the 
patient to the pulmonary technician) at the pulmonary function 
facility.  As part of the procedure, a slow vital capacity maneuver 
will be performed, followed by DLco, and then spirometry. 
If needed, the following screening assessments performed at SV1 
may be completed or repeated, if necessary, to verify or re-check 
results:  MMSE (must be assessed in an ON state), full physical 
examination, ECG, standard vital signs (BP, HR, and RR) and 
orthostatic vital signs (BP and HR), spirometry (assessed in both ON 
and OFF states), UPDRS Part 3 (assessed in both ON and OFF 

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states), ON/OFF concordance testing (assessed in both ON and OFF 
states), and clinical laboratory tests (with documentation of fasting 
status) including serum pregnancy test if applicable.   
Patients will be monitored for AEs throughout the visit.  If a patient 
is unable to complete a screening assessment at SV2, an additional 
visit (repeat SV2) may be scheduled prior to 
randomization/treatment assignment. 
The next visit will be scheduled.   
Clinic staff will arrange to speak with patients by telephone 4 to 
6 days prior to TV/OV1 to confirm the DLco assessment has been 
done/scheduled, to confirm the next study visit, to remind patients of 
the study procedures required prior to the next scheduled study visit 
(including completion of the PD Diary and Screening ON/OFF 
Episodes Log).  In addition, clinic staff will remind the patients 
during the call that they must be symptom-free of any flu-like 
syndrome or other respiratory infection for at least 3 days prior to 
TV/OV1 and that they should contact the site if an intervening 
illness occurs prior to TV/OV1.  If a patient has any of these 
symptoms within this time period, the staff will reschedule this visit 
after these symptoms have been resolved for at least 3 days.  The 
screening period may be extended for up to 2 weeks to accommodate 
this recovery.  
During the 3 consecutive days prior to TV/OV1, patients will 
complete the PD Diary and the Screening ON/OFF Episodes Log.  
Before arrival at the clinic for TV/OV1, patients will take all of their 
usual prescribed non-PD medications and PD medications, including 
LD-containing PD medications.   
Randomization/Treatment Assignment 
Following completion of SV2 and prior to randomization, the 
patients’ eligibility criteria will be reviewed by delegated staff.  
Eligible patients will be randomized in a 2:1 ratio to the CVT-301 
treatment group (CVT-301 50 mg PD FPD) or the observational 
cohort.  Randomization will be differentiated by the patient’s Hoehn 
and Yahr stage (<2.5 versus ≥2.5) to balance the severity of disease 
across each treatment group and by screening spirometry (FEV1 
<60% of predicted or FEV1/FVC ratio <70% versus FEV1 ≥60% of 
predicted and FEV1/FVC ratio ≥70%).  Patients who previously 
completed the CVT-301-002 and CVT-301-003 studies will be 
assigned only to the CVT-301 treatment group. Sites must allow 7 
business days between time of randomization and the first treatment 
visit (TV1) to allow time for drug to be shipped and received.   
Treatment/Observational Period 
Patients in both the CVT-301 treatment group and observational 
cohort are required to attend all of the in-clinic treatment/ 
observational visits.  The assessments and procedures for the in-
clinic treatment/observational visits will differ for patients in the 
CVT-301 treatment group compared to the observational cohort.  All 
patients, regardless of treatment group, should continue with their 
usual prescribed standard PD medication regimen for the duration of 

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the study which may be modified for symptomatic treatment during 
the study in accordance with usual practice.  
Treatment Visit/Observational Visit 1 (TV/OV1): At least 7 days 
after SV2 
Patients will complete the Screening ON/OFF Episodes Log and PD 
Diary for the 3 consecutive days prior to TV/OV1.   
Patients will report to the clinic after having taken their usual PD 
medications prior to the visit.  The timing of arrival for TV/OV1 
should be scheduled to increase the likelihood that patients will be in 
the ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at 
home).  Patients will bring to the clinic all of their usual PD 
medications. 
The clinic staff will collect the Screening ON/OFF Episodes Log and 
PD Diary, review the information, sign and date each, and confirm 
that the DLco assessment was performed prior to the visit (and if 
not, the study visit must be re-scheduled).   
Clinic staff will record the time patients took their usual PD 
medications prior to the visit and record any changes in standard PD 
medication dose/regimen.  The following assessments will be 
performed:  review of concomitant medications; PDQ-39 (in an ON 
state); brief physical examination; UPDRS Part 2 (preferably in the 
ON state); S&E ADL scale (preferably in the ON state); ECG; 
standard and orthostatic BP and HR; RR; spirometry (preferably in 
the ON state); clinical laboratory tests (with documentation of 
fasting status) including serum pregnancy test, if applicable; C-
SSRS; Epworth Sleepiness Scale; and the QUIP.   
In addition for the CVT-301 treated group only: 
Clinic staff will distribute the Inhaled Dosing Log for recording the 
number of times the inhaler was used and the number of capsules 
used for each inhalation (to be completed daily throughout the 
12-month treatment period). 
Clinic staff will distribute the PD Diary which will be used to record 
time OFF, time ON without dyskinesia, time ON with non-
troublesome dyskinesia, time ON with troublesome dyskinesia, and 
time asleep (to be completed for the 3 consecutive days prior to the 
treatment visits). The UPDRS Part 4 (Questions 32-35 and 36-39) 
will be completed. 
The clinic staff will provide study drug kits.   
Patients will be trained again on the proper technique to prepare and 
use the inhaler system (using sham capsules) per the IFU.  
Under clinic staff supervision, preferably between 2 and 5 hours 
after receiving their previous dose of oral PD medications (in the 
OFF state), patients will prepare and self-administer their entire dose 
of inhaled study drug.  The dosing time is defined to be when the 
patient’s OFF state is recognized by both the patient and investigator 
to be at a level similar to the investigator-confirmed severity 
experienced at SV1 and preferably between 2 and 5 hours after their 

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prior oral PD medication.    
Vital signs (standard vital signs [BP and HR] and orthostatic vital 
signs [BP and HR]) will be assessed at 20 and 60 minutes post-dose.  
Respiratory rate will be assessed at 10, 20, 30, and 60 minutes 
post-dose.  Patients will be monitored for AEs throughout the visit. 
Upon completion of the 60-minute observations, the patient’s usual 
schedule of standard PD medications will be resumed for the 
remainder of the day (the patient may use the inhaled study drug up 
to 4 more times at home that day after he/she leaves the clinic, if 
needed for OFF episodes).   
Clinic staff will arrange to speak with patients by telephone 1 to 
3 days after the visit to monitor for AEs and to discuss concerns or 
challenges with the inhaler systems or Inhaled Dosing Log.    
All Patients: 
The next study visit will be scheduled.  
Clinic staff will arrange to speak with patients by telephone 2 weeks 
before TV/OV2 to address any concerns or challenges with the 
inhaler systems, PD Diary, or Inhaled Dosing Log (CVT arm only), 
to monitor for any AEs, to confirm the next study visit, to ask the 
patients how many empty study drug kits will be returned at the next 
visit (CVT arm only), and also to remind patients of the study 
procedures required prior to the next scheduled study visit (including 
completion of the PD Diary and applicable, the Inhaled Dosing Log).  
At-Home Dosing for the CVT-301 Treatment Group 
At TV/OV1, TV/OV2, TV/OV3, TV/OV4, and TV/OV5, patients in 
the CVT-301 treatment group will receive study drug kits and the 
IFU to take home with them.  Patients will be instructed to take their 
standard oral PD medications as prescribed on their usual schedule 
of administration, which may be modified as needed for 
symptomatic treatment during the 12-month study.  Additions to 
and/or modification of the patient’s usual PD treatment regimen may 
take place. Oral PRN LD formulations are not permitted for these 
patients (refer to Section 9.4.2 of the protocol for a list of prohibited 
treatments and prohibited medications).  The total daily LD dose of 
the modified PD treatment regimen (not including CVT-301) must 
not exceed 1600 mg per day.   
Patients will be instructed to administer inhaled study drug up to 
5 times during the waking day as close as possible to the time when 
they begin to experience OFF symptoms.  The PD symptomatology 
defining the onset of an OFF state may vary by patient, but typically 
is indicated by the return of PD motor symptoms such as tremor or 
bradykinesia; for some patients, OFF episodes may be heralded by 
non-motor symptoms (e.g., pain or anxiety) shortly prior to the 
appearance of motor symptoms.   
Study drug may not be used for the treatment of early morning OFF 
periods (i.e., morning akinesia).  Patients may not take their inhaled 
study drug within 45 minutes following their previous dose of 
standard oral PD medication.  These patients may not take oral PRN 

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medications to manage OFF states during the study. 
In the event that an OFF state is not sufficiently resolved within 
45 minutes of completing the last capsule inhalation, patients may 
resume their usual prescribed PD medication, if they have not 
already done so (i.e., according to their standard dose 
schedule/regimen); patients may not re-dose with inhaled study drug 
for that episode.  If patients experience more than 5 OFF episodes 
per day that require treatment, they should adhere to their standard 
oral regimen for management of any additional OFF episodes; they 
may not treat these episodes with additional inhalations of study 
drug.  
Patients will complete the PD Diary for the 3 consecutive days prior 
to TV/OV2, TV/OV3, TV/OV4, TV/OV5, and TV/OV6.  Patients 
will complete the Inhaled Dosing Log every day during the 
12-month treatment period.  As described previously, patients will 
be contacted by the clinic staff 1 to 3 days after TV/OV1 and 
2 weeks (± 3 days) prior to each visit for TV/OV2, TV/OV3, 
TV/OV4, TV/OV5, and TV/OV6. 
They will bring the PD Diary, Inhaled Dosing Log, empty capsules, 
inhalers, and unused supplies to the each clinic visit.  Unused 
supplies can be re-dispensed to the patient at each clinic visit, in 
addition to a sufficient number of new study drug kits to supply the 
patient until his/her next visit. Note: Any open kit (even if partially 
unused) may not be re-dispensed. If the patient begins to run low on 
study supplies in between treatment visits, they should contact the 
site. 
Treatment Visit/Observational Visit 2 (TV/OV2): 1 month (4 
weeks ±5 days) after TV/OV1 
Patients will bring their usual PD medications and report to the clinic 
after having taken their usual PD medications prior to the visit.  The 
timing of administration of the usual morning dose of PD medication 
may be adjusted by the investigator to accommodate the patient’s 
and/or clinic’s schedule.  Following their usual morning PD 
medication, no further non-study PD medications will be used until 
following completion of all assessments.  The timing of arrival 
should be scheduled to increase the likelihood that patients will be in 
an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at 
home).  
Clinic staff will record any changes in standard PD medication 
dose/regimen and record the time that patients took their usual PD 
medications prior to the visit.  The following assessments will be 
performed:  recording of any changes in concomitant medications; 
brief physical examination; spirometry (preferably in the ON state); 
standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP 
and HR). 
In addition for the CVT-301 treated group only: 
Patients will complete the PD Diary for the 3 consecutive days prior 
to TV2 and the Inhaled Dosing Log daily throughout the treatment 

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period.  The clinic staff will review, sign, and date the PD Diary and 
Inhaled Dosing Log and collect all used and unused supplies.  
Unused supplies can be re-dispensed to the patient, in addition to a 
sufficient number of new study drug kits to supply the patient until 
his/her next visit. Note: Any open kit (even if partially unused) may 
not be re-dispensed. The staff will also review inhaler training, 
provide the PD Diary and Inhaled Dosing Log and review 
instructions for completion.  Patients will be instructed to collect 
used empty capsules and return them at the next visit along with the 
PD Diary, Inhaled Dosing Log, and other study supplies.  
The patient will remain in the clinic until he/she goes into the OFF 
state.  In the OFF state, the patients will undergo UPDRS Part 3 
assessments, immediately pre-dose, following which the patient will 
prepare and then self-administer (under staff supervision) the entire 
dose of inhaled study drug. The dosing time is defined to be when 
the patient’s OFF state is recognized by both the patient and 
investigator to be at a level similar to the investigator-confirmed 
severity experienced at SV1 and preferably between 2 and 5 hours 
after their prior oral PD medication.    
Exploratory efficacy responses will be assessed by recording:  (1) 
UPDRS Part 3 evaluations at 10, 20, 30, and 60 minutes post-dose; 
(2) the occurrence and severity of dyskinesia; and (3) whether the 
patient converted to an ON state during the 60-minute post-dose time 
period and if so, whether he/she was still in an ON state at 
60 minutes post-dose.  
Adverse events will be monitored throughout the visit. 
Upon completion of the 60-minute observations, resumption of 
normal medications is permitted for the remainder of the day (the 
patient may use the inhaled study drug 4 more times at home after 
he/she leaves the clinic on that day if needed for OFF episodes). 
All patients:  
The next study visit will be scheduled.  The clinic staff will schedule 
patients to undergo DLco at the pulmonary function lab, to occur 
within 2 weeks prior to the next study visit.  The evaluation should 
be performed while the patient is in an ON state (as reported by the 
patient to the pulmonary technician).  As part of the procedure, a 
slow vital capacity will be performed, followed by DLco, and then 
spirometry. 
Clinic staff will arrange to speak with patients by telephone 2 weeks 
(± 3 days) prior to TV/OV3 to address any potential concerns or 
challenges with the PD Diary, inhaler systems or Inhaled Dosing 
Log (CVT arm only), to monitor for any AEs, to confirm that the 
DLco  assessment has been done/scheduled, to confirm the next 
study visit, to ask the patients how many empty study drug kits will 
be returned at the next visit (CVT arm only), and to remind patients 
of the study procedures required before the next visit (including 
completion of the PD Diary and the Inhaled Dosing Log, as 
applicable).   

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Treatment Visit/Observational Visit 3 (TV/OV3): 3 months 
(12±2 weeks) after TV/OV1 
Patients will bring their usual PD medications and report to the clinic 
after having taken their usual PD medications prior to the visit.  The 
timing of administration of the usual morning dose of PD medication 
may be adjusted by the investigator to accommodate the patient’s 
and/or clinic’s schedule.  Following their usual morning PD 
medication, no further non-study PD medications will be used until 
following completion of all assessments.  The timing of arrival 
should be scheduled to increase the likelihood that patients will be in 
an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at 
home). 
Clinic staff will confirm that the DLco assessment has been 
completed within 2 weeks prior to the visit (and if not, re-schedule 
the study visit).  Clinic staff will record any changes in standard PD 
medication dose/regimen and record the time that patients took their 
usual PD medications prior to the visit.  The following assessments 
will be performed:  recording of any changes in concomitant 
medications; C-SSRS; brief physical examination; standard vital 
signs (BP, HR, and RR) and orthostatic vital signs (BP and HR); 
ECG; spirometry (preferably in the ON state); and clinical laboratory 
tests (with documentation of fasting status) including serum 
pregnancy test, if applicable.   
In addition for the CVT-301 treated group only: 
Patients will complete the PD Diary for the 3 consecutive days prior 
to TV3 and the Inhaled Dosing Log daily throughout the treatment 
period.  The clinic staff will review, sign, and date the PD Diary and 
Inhaled Dosing Log and collect all used and unused supplies. 
Unused supplies can be re-dispensed to the patient, in addition to a 
sufficient number of new study drug kits to supply the patient until 
his/her next visit. Note: Any open kit (even if partially unused) may 
not be re-dispensed. The staff will also review inhaler training, 
provide the PD Diary and Inhaled Dosing Log and review 
instructions for completion.  Patients will be instructed to collect 
used empty capsules and return them at the next visit along with the 
PD Diary, Inhaled Dosing Log, and other study supplies. 
The patient will remain in the clinic until he/she goes into the OFF 
state.  In the OFF state, the patient will undergo UPDRS Part 3 
assessments, immediately pre-dose, following which the patient will 
prepare and then self-administer (under staff supervision) the entire 
dose of inhaled study drug. The dosing time is defined to be when 
the patient’s OFF state is recognized by both the patient and 
investigator to be at a level similar to the investigator-confirmed 
severity experienced at SV1 and preferably between 2 and 5 hours 
after their prior oral PD medication.    
Exploratory efficacy responses will be assessed by recording:  (1) 
UPDRS Part 3 evaluations at 10, 20, 30, and 60 minutes post-dose; 

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(2) the occurrence and severity of dyskinesia; and (3) whether the 
patient converted to an ON state during the 60-minute post-dose time 
period and if so, whether he/she was still in an ON state at 
60 minutes post-dose. The PGI-C will be completed, preferably in 
the ON state and must be done before other study evaluations. 
Adverse events will be monitored throughout the visit. 
Upon completion of the 60-minute observations, resumption of 
normal medications is permitted for the remainder of the day (the 
patient may use the inhaled study drug 4 more times at home after 
he/she leaves the clinic on that day if needed for OFF episodes). 
All patients:  
The next study visit will be scheduled.  The clinic staff will schedule 
patients to undergo DLco at the pulmonary function lab, to occur 
within 2 weeks prior to the next study visit.  The evaluation should 
be performed while the patient is in an ON state (as reported by the 
patient to the pulmonary technician).  As part of the procedure, a 
slow vital capacity will be performed, followed by DLco, and then 
spirometry. 
Clinic staff will arrange to speak with patients by telephone 2 weeks 
(± 3 days) prior to TV/OV4 to address any potential concerns or 
challenges with the PD Diary, inhaler systems or Inhaled Dosing 
Log (CVT arm only), to monitor for any AEs, to confirm that the 
DLco assessment has been done/scheduled, to confirm their next 
study visit, to ask the patients how many empty study drug kits will 
be returned at the next visit, and to remind patients of the study 
procedures required before the next visit (including completion of 
the PD Diary and the Inhaled Dosing Log, as applicable).   
Treatment Visit/Observational Visit 4 (TV/OV4): 6 months 
(24±2 weeks) after TV/OV1 
Patients will bring their usual PD medications and report to the clinic 
after having taken their usual PD medications prior to the visit.  The 
timing of administration of the usual morning dose of PD medication 
may be adjusted by the investigator to accommodate the patient’s 
and/or clinic’s schedule.  Following their usual morning PD 
medication, no further non-study PD medications will be used until 
following completion of all assessments.  The timing of arrival 
should be scheduled to increase the likelihood that patients will be in 
an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at 
home).   
They will confirm that the DLco assessment has been completed 
within 2 weeks prior to the visit (and if not, re-schedule the study 
visit).  Clinic staff will record any changes in standard PD 
medication dose/regimen and record the time that patients took their 
usual PD medications prior to the visit.  The following assessments 
will be performed:  recording of any changes in concomitant 
medications; brief physical examination; standard vital signs (BP, 
HR, and RR) and orthostatic vital signs (BP and HR); ECG; 
spirometry (preferably in the ON state); and clinical laboratory tests 

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(with documentation of fasting status) including serum pregnancy 
test, if applicable.   
In addition the following assessments will be recorded: the PDQ-39, 
UPDRS Part 2, and S&E ADL scale (each preferably in the ON 
state); QUIP; Epworth Sleepiness Scale; and C-SSRS. 
In addition for the CVT-301 treated group only: 
Patients will complete the PD Diary for the 3 consecutive days prior 
to TV4 and the Inhaled Dosing Log daily throughout the treatment 
period.  The clinic staff will review, sign, and date the PD Diary and 
Inhaled Dosing Log and collect all used and unused supplies. 
Unused supplies can be re-dispensed to the patient, in addition to a 
sufficient number of new study drug kits to supply the patient until 
his/her next visit. Note: Any open kit (even if partially unused) may 
not be re-dispensed. The staff will also review inhaler training, 
provide the PD Diary and Inhaled Dosing Log and review 
instructions for completion.  Patients will be instructed to collect 
used empty capsules and return them at the next visit along with the 
PD Diary, Inhaled Dosing Log, and other study supplies. The 
UPDRS Part 4 (Questions 32-35 and 36-39) will be completed 
The patient will remain in the clinic until he/she goes into the OFF 
state.  In the OFF state, the patient will undergo UPDRS Part 3 
assessments, immediately pre-dose, following which the patient will 
prepare and then self-administer (under staff supervision) the entire 
dose of inhaled study drug. The dosing time is defined to be when 
the patient’s OFF state is recognized by both the patient and 
investigator to be at a level similar to the investigator-confirmed 
severity experienced at SV1 and preferably between 2 and 5 hours 
after their prior oral PD medication.    
Exploratory efficacy responses will be assessed by recording:  (1) 
UPDRS Part 3 evaluations at 10, 20, 30, and 60 minutes post-dose; 
(2) the occurrence and severity of dyskinesia; and (3) whether the 
patient converted to an ON state during the 60-minute post-dose time 
period and if so, whether he/she was still in an ON state at 
60 minutes post-dose.  The PGI-C will be completed, preferably in 
the ON state and must be done before other study evaluations. 
Adverse events will be monitored throughout the visit. 
Upon completion of the 60-minute observations, resumption of 
normal medications is permitted for the remainder of the day (the 
patient may use the inhaled study drug 4 more times at home after 
he/she leaves the clinic on that day if needed for OFF episodes). 
All patients:  
The next study visit will be scheduled.  The clinic staff will schedule 
patients to undergo DLco at the pulmonary function lab, to occur 
within 2 weeks prior to the next study visit.  The evaluation should 
be performed while the patient is in an ON state (as reported by the 
patient to the pulmonary technician).  As part of the procedure, a 
slow vital capacity will be performed, followed by DLco, and then 
spirometry. 

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Clinic staff will arrange to speak with patients by telephone 2 weeks 
(± 3 days) prior to TV/OV5 to address any potential concerns or 
challenges with the PD Diary, inhaler systems or Inhaled Dosing 
Log (CVT arm only), to monitor for any AEs, to confirm that the 
DLco and spirometry assessments has been done/scheduled, to 
confirm the next study visit, to ask the patients how many empty 
study drug kits will be returned at the next visit, and to remind 
patients of the study procedures required before the next visit 
(including completion of the PD Diary and  the Inhaled Dosing Log, 
as applicable).   
Treatment Visit/Observational Visit 5 (TV/OV5): 9 months 
(36±2 weeks) after TV/OV1  
Patients will bring their usual PD medications and report to the clinic 
after having taken their usual PD medications prior to the visit.  The 
timing of administration of the usual morning dose of PD medication 
may be adjusted by the investigator to accommodate the patient’s 
and/or clinic’s schedule.  Following their usual morning PD 
medication, no further non-study PD medications will be used until 
following completion of all assessments.  The timing of arrival 
should be scheduled to increase the likelihood that patients will be in 
an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at 
home).   
Clinic staff will confirm that the DLco assessment has been 
completed within 2 weeks prior to the visit (and if not, re-schedule 
the study visit).  Clinic staff will record any changes in standard PD 
medication dose/regimen and record the time that patients took their 
usual PD medications prior to the visit.  The following assessments 
will be performed:  recording of any changes in concomitant 
medications; brief physical examination; standard vital signs (BP, 
HR, and RR) and orthostatic vital signs (BP and HR); spirometry 
(preferably in the ON state); clinical laboratory tests (with 
documentation of fasting status) including serum pregnancy test, if 
applicable; and the C-SSRS assessment. 
In addition for the CVT-301 treated group only: 
Patients will complete the PD Diary for the 3 consecutive days prior 
to TV5 and the Inhaled Dosing Log daily throughout the treatment 
period.   
The clinic staff will review, sign, and date the PD Diary and Inhaled 
Dosing Log and will collect all used and unused supplies. Unused 
supplies can be re-dispensed to the patient, in addition to a sufficient 
number of new study drug kits to supply the patient until his/her next 
visit. Note: Any open kit (even if partially unused) may not be re-
dispensed. The staff will also review inhaler training, provide the PD 
Diary and Inhaled Dosing Log and review instructions for 
completion.  Patients will be instructed to collect used empty 
capsules and return them at the next visit along with the PD Diary, 
Inhaled Dosing Log, and other study supplies. 
The patient will remain in the clinic until he/she goes into the OFF 

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state.  In the OFF state, the patient will undergo UPDRS Part 3 
assessments, immediately pre-dose, following which the patient will 
prepare and then self-administer (under staff supervision) the entire 
dose of inhaled study drug. The dosing time is defined to be when 
the patient’s OFF state is recognized by both the patient and 
investigator to be at a level similar to the investigator-confirmed 
severity experienced at SV1 and preferably between 2 and 5 hours 
after their prior oral PD medication.    
The clinic staff will assess: (1) UPDRS Part 3 evaluations at 10, 20, 
30, and 60 minutes post-dose; (2) the occurrence and severity of 
dyskinesia; and (3) whether the patient converted to an ON state 
during the 60-minute post-dose time period and if so, whether he/she 
was still in an ON state at 60 minutes post-dose.  
Adverse events will be monitored throughout the visit. 
Upon completion of the 60-minute observations, resumption of 
normal medications is permitted for the remainder of the day (the 
patient may use the inhaled study drug 4 more times at home after 
he/she leaves the clinic on that day if needed for OFF episodes). 
All patients:  
The next study visit will be scheduled.  The clinic staff will schedule 
patients to undergo DLco at the pulmonary function lab, to occur 
within 2 weeks prior to the next study visit.  The evaluation should 
be performed while the patient is in an ON state (as reported by the 
patient to the pulmonary technician).  As part of the procedure, a 
slow vital capacity will be performed, followed by DLco, and then 
spirometry. 
Clinic staff will arrange to speak with patients by telephone 2 weeks 
(± 3 days) prior to TV/OV6 to address any potential concerns or 
challenges with the PD Diary, inhaler systems or Inhaled Dosing 
Log (CVT arm only), to monitor for any AEs, to confirm that the 
DLco and spirometry assessment has been done/scheduled, to 
confirm their next study visit, to ask the patients how many empty 
study drug kits will be returned at the next visit, and to remind 
patients of the study procedures required before the next visit 
(including completion of the PD Diary and as applicable, the Inhaled 
Dosing Log).   
Treatment Visit/Observational Visit 6 (TV/OV6) / Early 
Withdrawal Visit:12 months (52±2 weeks) after TV/OV1 
Patients will bring their usual PD medications and report to the clinic 
after having taken their usual PD medications prior to the visit.  The 
timing of administration of the usual morning dose of PD medication 
may be adjusted by the investigator to accommodate the patient’s 
and/or clinic’s schedule.  Following their usual morning PD 
medication, no further non-study PD medications will be used until 
following completion of all assessments.  The timing of arrival 
should be scheduled to increase the likelihood that patients will be in 
an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at 
home). 

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Clinic staff will confirm that DLco assessment was performed within 
2 weeks prior to the visit (and if not, re-schedule study visit).  Clinic 
staff will record any changes in standard PD medication 
dose/regimen and record the time that patients took their usual PD 
medications prior to the visit.  The following assessments will be 
performed:  recording of any changes in concomitant medications; 
brief physical examination; standard vital signs (BP, HR, and RR) 
and orthostatic vital signs (BP and HR); ECG; spirometry 
(preferably in the ON state); and clinical laboratory tests (with 
documentation of fasting status) including serum pregnancy test, if 
applicable.   
In addition the following assessments will be recorded: the PDQ-39, 
UPDRS Part 2, and S&E ADL scale (each preferably in the ON 
state); QUIP; Epworth Sleepiness Scale; and C-SSRS. 
In addition for the CVT-301 treated group only:  
Patients will complete the PD Diary for the 3 consecutive days prior 
to TV6 and the Inhaled Dosing Log daily throughout the treatment 
period.  The clinic staff will review, sign, and date the PD Diary and 
Inhaled Dosing Log and collect all used and unused supplies. The 
UPDRS Part 4 (Questions 32-35 and 36-39) will be completed 
The patient will remain in the clinic until he/she goes into the OFF 
state.  Patients will be provided with a new inhaler for dosing at 
TV/OV6 and will use study drug from the supplies brought to the 
visit.  In the OFF state, the patient will undergo UPDRS Part 3 
assessments, immediately pre-dose, following which the patient will 
prepare and then self-administer (under staff supervision) the entire 
dose of inhaled study drug. The dosing time is defined to be when 
the patient’s OFF state is recognized by both the patient and 
investigator to be at a level similar to the investigator-confirmed 
severity experienced at SV1 and preferably between 2 and 5 hours 
after their prior oral PD medication.    
Exploratory efficacy responses will be assessed by recording:  (1) 
UPDRS Part 3 evaluations at 10, 20, 30, and 60 minutes post-dose; 
(2) the occurrence and severity of dyskinesia; and (3) whether the 
patient converted to an ON state during the 60-minute post-dose time 
period and if so, whether he/she was still in an ON state at 
60 minutes post-dose. The PGI-C will be completed, preferably in 
the ON state and must be done before other study evaluations. 
All patients:  
Adverse events will be monitored throughout the visit.  Once all of 
the assessments are complete, patients will be scheduled for a DLco 
assessment 4 to 5 weeks after TV/OV6.  The DLco assessment 
should be performed while the patient is in an ON state (as reported 
by the patient to the pulmonary technician) at the pulmonary 
function facility.  As part of the procedure, a slow vital capacity will 
be performed, followed by DLco, and then spirometry. 
Patients who withdraw prematurely will complete the TV/OV6 
assessments at the time of withdrawal (except the pre-TV/OV6 
DLco assessment) and will be scheduled to undergo a DLco 

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assessment 4 to 5 weeks after TV/OV6. 
Selection of Patients: 
All patients must meet the inclusion criteria and must not meet any 
of the exclusion criteria to be eligible for this study.  Patients 
previously enrolled in the CVT-301-002 and CVT-301-003 studies 
must have completed all of the CVT-301 study visits without any 
safety issues that would preclude participation in this study 
according to the investigator.  Patients who withdrew from either of 
the CVT-301 studies prior to completion, for any reason, will not be 
eligible. 
Inclusion Criteria: 
• 
Has signed and dated an IRB/IEC-approved informed 
consent form before any protocol-specific screening 
procedures are performed. 
• 
Is a male or female aged 30 to 85 years, inclusive.  Women 
of child-bearing potential must use protocol-defined 
contraceptive measures (see Section 11.1.5) and must have a 
negative serum human chorionic gonadotropin (hCG) test at 
screening.  These patients must be willing to remain on their 
current form of contraception for the duration of the study. 
• 
Patients who have idiopathic PD (i.e., not induced by drugs 
or other diseases) as defined by fulfilling Steps 1 and 2 of 
the UK Brain Bank criteria, diagnosed after the age of 30 
years. 
• 
Patients who are classified as Stage 1 to 3 (in the ON state) 
on the modified Hoehn and Yahr scale for staging of PD 
severity. 
• 
Patients who have experienced motor fluctuations for a 
minimum of 2 hours of average daily OFF time per waking 
day (excluding early morning OFF time) by self-report and 
confirmed by the PD Diary (on 3 consecutive days) during 
the screening period. 
• 
Patients who are on a LD-containing therapy, not including 
Rytary (or equivalent), must be stable on oral LD-containing 
therapy for at least 2 weeks prior to SV1 with a 
LD/dopamine decarboxylase inhibitor (DDI)-containing 
regimen.  
• 
Patients who are on a LD containing therapy, when 
including Rytary (or equivalent), should be on a stable dose 
for at least 6 weeks prior to SV1 
• 
The frequency of L-dopa administrations must be at least 3 
times during the waking day and a total daily LD dose of 
≤1600 mg (exclusive of PRN LD-containing medications).   
• 
Patients should be stable on other PD medications for at 
least 4 weeks prior to SV1.   
• 
Patients must have a ≥25% difference between UPDRS Part 
3 scores recorded in their ON and OFF states at screening. 
• 
Patients must have normal cognition as confirmed by a score 

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of ≥25 on the MMSE, performed in the ON state. 
• 
Patients must be able to perform a spirometry maneuver in 
the ON and OFF states, and must have a screening 
FEV1 ≥50% of predicted and an FEV1/FVC ratio >60% in 
the ON state at screening.  (A pulmonologist will review the 
spirometry tracings/morphology of any patient with an 
FEV1 that is ≥50% to <60% of predicted or an FEV1/FVC 
ratio that is >60% to <70% in order to determine potential 
eligibility.  All CVT-301-naïve patients with an FEV1/FVC 
ratio of >60% to <70% will be required to undergo a 
bronchodilator challenge and the results must be reviewed 
prior to entry into the study.  Patients with an FEV1/FVC 
ratio that is >60% to <70% will complete spirometry before 
and after the administration of a bronchodilator in a 
pulmonary function laboratory.  Testing will be performed 
in accordance with the 2005 ATS/European Respiratory 
Society [ERS] criteria prior to randomization.  The results of 
the bronchodilator challenge will be reviewed by a 
pulmonologist prior to potential randomization.)   
Exclusion Criteria: 
• 
Patients who have dyskinesia of a severity that would 
significantly interfere with their ability to participate or 
perform study procedures. 
• 
Pregnant or lactating females or females wishing to become 
pregnant. 
• 
Patients who have any known contraindication to the use of 
LD, including a history of malignant melanoma or a history 
of narrow-angle glaucoma.   
• 
Patients who have had previous surgery for PD (including 
but not limited to deep brain stimulation [DBS] or cell 
transplantation). 
• 
Patients with a history of psychotic symptoms requiring 
treatment, or suicide ideation or attempt within the prior 
12 months (stable regimens [for at least 4 weeks prior to 
SV1] of anti-depressant and certain low-dose atypical 
antipsychotic medications are permitted, in case they are 
indicated to treat symptoms other than psychotic symptoms).   
• 
Patients who have cancer with the exception of the 
following:  basal cell carcinoma or successfully treated 
squamous cell carcinoma of the skin; cervical carcinoma in 
situ; prostatic carcinoma in situ; or other malignancies 
curatively treated and with no evidence of disease recurrence 
for at least 3 years. 
• 
Patients taking certain prohibited medications (see 
Section 9.4.2). 
• 
Patients with a history of drug or alcohol abuse within the 
prior 12 months. 

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• 
Patients with chronic obstructive pulmonary disease 
(COPD), asthma, or other chronic respiratory disease within 
the last 5 years. 
• 
Patients with any contraindication to performing routine 
spirometry or who are unable to perform a spirometry 
maneuver (see Appendix 20 for a list of contraindications).  
• 
Patients with a current history of symptomatic orthostatic 
hypotension despite adequate treatment.   
• 
Patients with any condition that in the investigator’s opinion 
would make patients unsuitable or interfere with their 
participation in the study.  Potential issues of concern should 
be raised to the medical monitor during eligibility review. 
• 
Patients who have any clinically significant abnormality or 
finding from examination, tests, or history that may 
compromise patient safety.  
• 
Patients who have been treated with an investigational drug 
within 4 weeks or 5 half-lives (whichever is longer) prior to 
the beginning of the screening period  (this includes 
investigational formulations of marketed products). 
• 
Prior exposure to CVT-301. 
Planned Sample Size: 
Approximately 250 CVT-301 treatment patients and 115 control 
patients will be enrolled in this study. It is assumed that the drop-out 
rate will be approximately 25%. 
Investigational Therapy (for 
the CVT-301 treatment 
group): 
CVT-301 (levodopa inhalation powder [LIP]) 
Each dose will be administered using 2 sequential inhalations of 
CVT-301-filled capsules.  CVT-301 capsules will be delivered using 
the CVT-301 inhalers.  
 
 
 
 The capsules provided to the 
CVT-301 treatment group (target nominal respirable dose of 
approximately 50 mg LD FPD) will deliver approximately 25 mg 
LD FPD to the lung per capsule inhalation. 
Reference Therapy: 
There will be no reference therapy or placebo.   
Patients in both the CVT-301 treatment group and the observational 
cohort will be managed with their standard PD treatment throughout 
the study; modification of the standard PD treatment is permissible, 
as outlined in this protocol.  
Treatment Duration: 
The planned treatment period will be 52 ±2 weeks.  Each patient in 
the CVT-301 treatment group will self-administer up to 5 doses of 
inhaled study drug per day.  The maximum planned screening period 
is approximately 5 weeks.  A follow-up pulmonary evaluation will 
occur at 4 to 5 weeks after the treatment period ends. 
Criteria for Evaluation: 
Safety 
Pulmonary safety will be evaluated from assessments of lung 

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function, as measured from spirometry (FEV1, FVC, FEV1/FVC 
ratio).  In addition, DLco will be evaluated. 
Safety will also be assessed from physical examinations, AE reports, 
standard and orthostatic vital signs (BP, HR, and RR), clinical 
laboratory values (hematology and biochemistry), ECGs, the QUIP, 
Epworth Sleepiness Scale, the C-SSRS, UPDRS Part 4 (Questions 
32-35 and 36-39), and occurrence and severity of examiner-rated 
dyskinesia after study drug is administered in the clinic.  
Exploratory Efficacy  
• 
UPDRS Part 3 motor score, assessed pre-dose and at 10, 20, 
30, and 60 minutes following treatment in the clinic. 
Occurrence of an ON state during the 60-minute post-dose 
period and if an ON state occurs during the 60-minute 
post-dose, whether or not the patient is still in the ON state 
at 60 minutes post-dose. 
• 
Occurrence of an ON state during the 60-minute post-dose 
period and if an ON state occurs during the 60-minute 
post-dose, whether or not the patient is still in the ON state 
at 60 minutes post-dose  
• 
PD diary information on total daily ON time without 
dyskinesia, total daily ON time with troublesome dyskinesia, 
total daily ON time with non-troublesome dyskinesia, and 
total daily OFF time for the 3 consecutive days prior to each 
treatment visit  
• 
PDQ-39  
• 
PGI-C  
• 
S&E ADL 
• 
UPDRS Part 2 
Statistical Methods and 
Planned Analyses: 
For all statistical analyses of the CVT-301 treatment group, the visit 
at which the CVT-301 treatment was initiated will be used as the 
baseline.  However, for all enrolled patients who were previously 
included in the CVT-301-002 or CVT-301-003 studies, TV/OV1 of 
the CVT-301-005 study will be used as baseline.  For the 
observational cohort, the assessments at TV/OV1 will be used as 
baseline.   
All patients who are enrolled in CVT-301-005 and receive at least 
1 dose of CVT-301 will be included in the safety and exploratory 
endpoint analyses.  Patients in the observational cohort will be 
included in the analyses if they provide any data after TV/OV1. 
Safety Analyses  
The extent of exposure to study treatment will be summarized for the 
patients who received CVT-301 treatment.  The time period between 
TV/OV1 and TV/OV6 (or Early Withdrawal Visit) will be used as 
the measure of extent of exposure for patients randomized to the 
observational cohort.  Adverse events will be tabulated by treatment 
group according to the Medical Dictionary for Regulatory Activities 
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(TEAEs) will be summarized by body system and preferred term.  
For patients in the observational cohort, the AEs collected between 
TV/OV1 and TV/OV6 (or Early Withdrawal Visit) will be 
considered as TEAEs.  Furthermore, the time of onset of the TEAEs 
will be summarized.  For vital signs, ECG parameters, spirometry 
measurements, and DLco, the changes from pre-dose to post-dose 
assessments of the corresponding day will be calculated and 
described using descriptive statistics.  For spirometry, DLco, and 
safety laboratory variables, the differences in pre-dose values 
between the study days will be described.  Furthermore, the changes 
in the spirometry values and difference between the groups will be 
estimated using a Mixed Model for Repeated Measurements 
(MMRM) similar to the one used for the exploratory endpoint 
variables.  The proportion of patients with abnormal spirometry 
values will be tabulated using different criteria for the threshold 
(e.g., at least 10% or 20% change from baseline at any single visit, at 
least 10% or 20% change from baseline on at least 2 consecutive 
visits).  The proportions of patients meeting ATS quality criteria 
(and also for those ‘rejected’) will be summarized.  All spirometry 
analyses will be performed both for all patients regardless of the 
ATS quality criteria and separately excluding the assessments not 
meeting the ATS quality criteria.  Changes from baseline to follow-
up in the rating scales for assessing suicidality, somnolence, and 
impulse control disorders will be summarized descriptively.  
Demographics and baseline characteristics will be summarized 
descriptively. 
Exploratory Endpoint Analyses 
The objectives related to the exploratory endpoints will primarily be 
assessed for the CVT-301-treated patients.  The same objectives will 
be explored for the pool of CVT-301 naïve patients and patients who 
were previously enrolled in the CVT-301-002 or CVT-301-003 
studies, if feasible.   
The changes from baseline in continuous exploratory endpoint 
variables will be estimated using an MMRM.  The model will 
include visit and the stratification variables (Hoehn and Yahr stage 
and screening FEV1 and/or FEV1/FVC) as fixed factors.  The 
baseline value will be used as a covariate..   
The categorical data will be primarily evaluated descriptively.  Each 
visit will be evaluated separately for the categorical endpoints. 
The exploratory endpoint data collected from the patients in the 
observational cohort will be summarized with descriptive statistics. 
 
 

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3. 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
CIVITAS THERAPEUTICS PROTOCOL APPROVAL PAGE ...................................................2 
INVESTIGATOR PROTOCOL AGREEMENT PAGE .................................................................3 
LIST OF CONTACTS .....................................................................................................................4 
2. 
SYNOPSIS ...................................................................................................................6 
3. 
TABLE OF CONTENTS ...........................................................................................28 
4. 
LIST OF ABBREVIATIONS.....................................................................................31 
5. 
INTRODUCTION ......................................................................................................34 
5.1. 
Background and Rationale ..........................................................................................34 
5.2. 
Rationale .....................................................................................................................36 
6. 
STUDY OBJECTIVES ..............................................................................................40 
7. 
INVESTIGATIONAL PLAN .....................................................................................41 
8. 
STUDY POPULATION .............................................................................................43 
8.1. 
Inclusion Criteria ........................................................................................................43 
8.2. 
Exclusion Criteria .......................................................................................................44 
8.3. 
Removal of Patients from Study .................................................................................45 
9. 
TREATMENTS ..........................................................................................................46 
9.1. 
Details of Study Treatment for the CVT-301 Treatment Group ................................46 
9.2. 
Randomization and Administration of Study Treatment ............................................48 
9.3. 
Treatment Accountability and Compliance (for the CVT-301 Treatment 
Group) .........................................................................................................................48 
9.4. 
Prior and Concomitant Illnesses and Medications ......................................................49 
10. 
STUDY PROCEDURES ............................................................................................51 
10.1. 
Screening Period .........................................................................................................51 
10.2. 
Randomization to Study Drug ....................................................................................55 
10.3. 
Treatment/Observational Period .................................................................................55 
11. 
DESCRIPTION OF ASSESSMENTS .......................................................................75 
11.1. 
Safety Assessments .....................................................................................................75 
11.2. 
Exploratory Efficacy Assessments .............................................................................83 
11.3. 
Other Assessments Used for Baseline Disease Characteristics for all Patients ..........85 
11.4. 
Appropriateness of Measurements .............................................................................86 

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12. 
DATA MANAGEMENT AND STATISTICAL ANALYSIS...................................86 
12.1. 
Determination of Sample Size ....................................................................................87 
12.2. 
Study Populations .......................................................................................................87 
12.3. 
Definition of Baseline .................................................................................................87 
12.4. 
Background and Demographic Characteristics ..........................................................87 
12.5. 
Safety Analysis ...........................................................................................................88 
12.6. 
Exploratory Efficacy Analysis ....................................................................................89 
13. 
STUDY MANAGEMENT .........................................................................................90 
13.1. 
Approval and Consent ................................................................................................90 
13.2. 
Financing and Insurance .............................................................................................90 
13.3. 
Discontinuation of the Study by the Sponsor .............................................................90 
13.4. 
Study Documentation .................................................................................................91 
13.5. 
Data Handling .............................................................................................................91 
13.6. 
Study Monitoring and Auditing ..................................................................................91 
13.7. 
Retention of Records ..................................................................................................92 
13.8. 
Use of Study Findings ................................................................................................92 
13.9. 
Publication ..................................................................................................................92 
14. 
REFERENCES ...........................................................................................................94 
15. 
APPENDICES – TABLE OF CONTENTS ...............................................................96 
APPENDIX 1:  OVERALL VISIT SCHEDULE SCHEMATIC ..................................................98 
APPENDIX 2:  TIME AND EVENTS TABLE—SCREENING VISIT 1 (SV1) 
(WITHIN 35 DAYS PRIOR TO TV/OV1) ................................................................99 
APPENDIX 3:  TIME AND EVENTS TABLE—SCREENING VISIT 2 (SV2) (AT 
LEAST 4 DAYS AFTER SV1) ................................................................................100 
APPENDIX 4:  TIME AND EVENTS TABLE—TREATMENT VISIT 1 (TV1) (AT 
LEAST 7 DAYS AFTER SV2) ................................................................................101 
APPENDIX 5:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 1 (OV1) 
(AT LEAST 7 DAYS AFTER SV2) ........................................................................103 
APPENDIX 6:  TIME AND EVENTS TABLE—TREATMENT VISIT 2 (TV2) (1 
MONTH [4 WEEKS ±5 DAYS] AFTER TV1) .......................................................104 
APPENDIX 7:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 2 (OV2) 
(1 MONTH [4 WEEKS ±5 DAYS] AFTER OV1) ..................................................106 
APPENDIX 8:  TIME AND EVENTS TABLE—TREATMENT VISIT 3 (TV/OV3) (3 
MONTHS [12±2 WEEKS] AFTER TV1) ...............................................................107 

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APPENDIX 9:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 3 (OV3) 
(3 MONTHS [12±2 WEEKS] AFTER OV1) ...........................................................109 
APPENDIX 10:  TIME AND EVENTS TABLE—TREATMENT VISIT 4 (TV4) (6 
MONTHS [24±2 WEEKS] AFTER TV1) ...............................................................110 
APPENDIX 11:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 4 (OV4) 
(6 MONTHS [24±2 WEEKS] AFTER OV1) ...........................................................112 
APPENDIX 12:  TIME AND EVENTS TABLE—TREATMENT VISIT 5 (TV5) (9 
MONTHS [36±2 WEEKS] AFTER TV1) ...............................................................113 
APPENDIX 13:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 5 (OV5) 
(9 MONTHS [36±2 WEEKS] AFTER OV1) ...........................................................115 
APPENDIX 15:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 6 (OV6) 
VISIT (12 MONTHS [52±2 WEEKS] AFTER OV1)/EARLY 
WITHDRAWAL VISIT ...........................................................................................118 
APPENDIX 16:  IN-CLINIC ASSESSMENT OF ON/OFF STATES AND 
DYSKINESIA ..........................................................................................................119 
APPENDIX 17:  LABORATORY PARAMETERS ...................................................................120 
APPENDIX 18:  UK PARKINSON’S DISEASE SOCIETY BRAIN BANK  
CLINICAL DIAGNOSTIC CRITERIA* .................................................................121 
APPENDIX 19:  MODIFIED HOEHN AND YAHR PD SEVERITY SCALE 
ASSESSMENT .........................................................................................................123 
APPENDIX 20:  CONTRAINDICATIONS TO PERFORMING ROUTINE 
SPIROMETRY .........................................................................................................124 
APPENDIX 21:  CVT-301 SYSTEM ADDITIONAL INFORMATION ...................................125 
 
LIST OF IN-TEXT TABLES 
Page 
Table 1 
Details of Study Drug .................................................................................................46 
Table 2 
Details of Reduced-Dose Study Drug1 .......................................................................47 
Table 3 
Classification of Adverse Events by Intensity ............................................................79 
Table 4 
Classification of Adverse Events by Relationship to Study Medication ....................80 
 
 

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4. 
LIST OF ABBREVIATIONS 
ADL 
Activities of Daily Living 
AE 
adverse event 
ANCOVA 
analysis of covariance 
ATS 
American Thoracic Society 
AUC 
area under the plasma concentration-time curve 
AUClast 
area under the plasma concentration-time curve from time zero to the time of the 
last quantifiable concentration 
BP 
blood pressure 
CD 
carbidopa 
CD/LD 
carbidopa/levodopa 
CFR 
Code of Federal Regulations 
Cmax 
maximal plasma concentration 
COMT 
catechol-O-methyltransferase 
COPD 
chronic obstructive pulmonary disease 
CRO 
contract research organization 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DDI 
dopamine decarboxylase inhibitor 
DPPC 
dipalmitoyl phosphatidylcholine 
DBP 
diastolic blood pressure 
DBS 
deep brain stimulation 
DLco 
carbon monoxide diffusing capacity 
DSMC 
Data Safety Monitoring Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ERS 
European Respiratory Society 
FEV1 
forced expiratory volume in 1 second 
FPD 
fine particle dose (i.e., pulmonary-delivered dose) 
FDA 
Food and Drug Administration 
FVC 
forced vital capacity 
GCP 
good clinical practice 
GI 
gastrointestinal  
hCG 
human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 

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HPMC 
hydroxypropyl methylcellulose 
HR 
heart rate 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
LD 
levodopa 
LIP 
levodopa inhalation powder (CVT-301) 
MAO-B 
monoamine oxidase-B 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
millimeters mercury 
MMRM 
Mixed Model for Repeated Measurements 
MMSE 
Mini Mental State Examination 
NaCl 
sodium chloride 
NHANES III 
Third National Health and Nutrition Examination Survey 
NOAEL 
no-observed-adverse-effect level 
PD 
Parkinson’s disease 
PDQ-39 
39-Item Parkinson’s Disease Questionnaire 
PGI-C 
Patient Global Impression of Change 
PK 
pharmacokinetic 
PRN 
as needed 
QUIP 
Parkinson’s Disease Impulsive-Compulsive Disorders Questionnaire 
RR 
respiratory rate 
S&E 
Schwab and England 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
SV1 
Screening Visit 1 
SV2 
Screening Visit 2 
T0 
time of completion of inhalation of the last capsule of inhaled study treatment 
administered 
tmax 
time to maximal drug concentration 
TEAE 
treatment-emergent adverse event 

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TV/OV1 
Treatment Visit/Observational Visit 1 
TV/OV2 
Treatment Visit/Observational Visit 2 
TV/OV3 
Treatment Visit/Observational Visit 3 
TV/OV4 
Treatment Visit/Observational Visit 4 
TV/OV5 
Treatment Visit/Observational Visit 5 
TV/OV6 
Treatment Visit/Observational Visit 6 
UK 
United Kingdom 
UPDRS 
Unified Parkinson’s Disease Rating Scale 
USA 
United States of America 
 
 

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5. 
INTRODUCTION 
5.1. 
Background and Rationale 
5.1.1. 
Background on Motor Fluctuations in Parkinson’s Disease Patients 
Levodopa (LD) remains the “standard of care” for the management of motor symptoms for 
Parkinson’s disease (PD) patients.  However, long-term treatment with LD is complicated by the 
development of motor fluctuations, also referred to as hypomobility or OFF episodes.  The 
development of OFF episodes relates to both pharmacokinetic (PK) and pharmacodynamic 
factors.  Over time, patients frequently experience a progressive shortening of the duration of LD 
clinical effect, leaving patients vulnerable to episodic OFF episodes which may be disabling.  It 
is estimated that up to half of LD-treated PD patients develop such motor fluctuations within 5 
years (Parkinson Study Group 1996, LeWitt 2008, Stocchi 2010). 
Following oral ingestion, LD is absorbed through an active transport mechanism that is specific 
for large neutral L-amino acids in the proximal small intestine.  The absorption of LD is subject 
to considerable inter- and intra-patient variability and is affected significantly by alterations in 
gastrointestinal (GI) motility and food intake.  Frequently, poor absorption following 
administration of a standard oral LD dose results in sub-therapeutic levels, leaving patients 
susceptible to the development of OFF episodes (Baruzzi 1987, Pfeiffer 1996, Olanow 2006). 
Treatment options for patients with motor response fluctuations are limited.  Various strategies 
may be employed to enhance the clinical effectiveness of central dopaminergic stimulation to 
reduce the frequency of motor fluctuations, including the use of dopamine agonists, 
catechol-O-methyltransferase (COMT) inhibitors, extended-release oral LD formulations, or 
modified dosage of their standard oral LD preparations (LeWitt 2008, Olanow 2009). 
Management of OFF episodes is done frequently through adjustment of the inter-dose interval of 
standard oral LD preparations or through administration of unscheduled partial or full doses of 
oral LD-containing products.  However, following treatment with oral LD preparations, 
resumption of motor function is unreliable owing to the challenges in GI transit and LD 
absorption (Ondo 2010), and the development of intermittent OFF episodes remains a significant 
issue despite attempts to manage patients using oral LD agents alone. 
 
 CVT-301 (LD 
inhalation powder) is being developed for the treatment of episodic motor fluctuations (OFF 
episodes) in patients with PD, as an adjunct, as needed (PRN) therapy to provide relief from 
intermittent motor fluctuations (OFF episodes) that affect many PD patients. 
5.1.2. 
Background on CVT-301 (Levodopa Inhalation Powder) 
CVT-301 is a dry powder LD formulation (levodopa inhalation powder [LIP]) designed for 
inhaled delivery using a proprietary delivery system.  Using this technology, a variety of 
medications have been administered previously to humans, including proteins (e.g., insulin, 
human growth hormone) and small molecules (e.g., epinephrine, trospium) (Rave 2007, 

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Chipman 2005, Walvoord 2009, Dewey 2001, Dunbar 2004, Oleson 2010).  This delivery system 
is capable of delivering therapeutics with high efficiency over a range of inspiratory flow rates 
using a passive, breath-actuated device (DeLong 2005). 
CVT-301 is being developed as treatment for episodic motor fluctuations (OFF episodes) in 
patients with PD.  CVT-301 will be used as an adjunct to the patient’s existing decarboxylase 
inhibitor (i.e., carbidopa [CD] or benserazide)-inclusive PD medication regimen. 
In nonclinical studies, CVT-301 pulmonary delivery was associated with rapid LD absorption, 
and was associated with a shorter and less variable time to maximal drug concentration (tmax) 
and less variable maximal plasma concentration (Cmax) compared to oral LD administration.  
These PK attributes translated to pharmacodynamic advantages in a nonclinical model of PD 
(Bartus 2004). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

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5.2. 
Rationale 
Attainment of therapeutic plasma concentrations and restoration of motor function following 
administration of oral LD to PD patients is variable, unreliable, and frequently delayed, not 
uncommonly requiring 1 hour or more to attain therapeutic responses.  
 
 
 
 
  
The more rapid LD absorption following inhaled CVT-301 administration is expected to 
translate to rapid alleviation of motor OFF symptoms in patients experiencing OFF episodes.   
This 12-month study will employ a randomized open-label methodology to investigate the safety 
and effects of CVT-301 (50 mg LD FPD) and will include a concurrent observational cohort of 
PD patients who will not receive study medication, but will continue to take their usual PD 
medications.  Patients must be CVT-301-naïve, however, any patients that were enrolled from 
the CVT-301-002 and CVT-301-003 studies under the previous version of this protocol will be 
allowed to continue in the study Patients will be randomized in a 2:1 ratio to the CVT-301 
treatment group (50 mg LD FPD) or the observational cohort.   
During the 12-month treatment period, patients in the CVT-301 treatment group will 
self-administer an inhaled study drug dose as needed when they experience OFF episodes; study 
medication may be used up to 5 times daily.  Every day during the treatment period, the 
CVT-301 patients will record the following information in the Inhaled Dosing Log:  the number 
of times the inhaler was used and the number of capsules used for each inhalation treatment.  
Patients in each group will continue their standard PD medications, which may be modified 
during the study if needed.  Patients in each group will be required to attend the screening visits 
(Screening Visit 1 [SV1] and Screening Visit 2 [SV2]) and the 6 in-clinic 
treatment/observational visits (Treatment Visit/Observational Visit 1 [TV/OV1], Treatment 
Visit/Observational Visit 2 [TV/OV2], Treatment Visit/Observational Visit 3 [TV/OV3], and 
Treatment Visit/Observational Visit 4 [TV/OV4], Treatment Visit/Observational Visit 5 
[TVOV5], and Treatment Visit/Observational Visit 6 [TV/OV6]).  For the patients in the 
CVT-301 treatment group, these visits will be treatment visits and for the observational cohort, 
these visits will be observational visits. 

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CVT-301-treated patients will be followed in the clinic for the following efficacy measures: 
serial assessments of UPDRS Part 3 motor score following treatment in the clinic, the occurrence 
and severity of dyskinesia following treatment in the clinic, the occurrence of ON states during 
the post-treatment period, the 39-Item Parkinson’s Disease Questionnaire (PDQ-39), the Patient 
Global Impression of Change (PGI-C) rating scale, the Schwab and England (S&E) Activities of 
Daily Living (ADL) score; UPDRS Part 2 score, and UPDRS Part 4 (Questions 32-35 and 36-39) 
score.  In addition, the total daily ON time without dyskinesia, total daily ON time with 
troublesome dyskinesia, total daily ON time with non-troublesome dyskinesia, and total daily 
OFF time will be evaluated in the CVT-301-treated patients based on the PD Diary, which will 
be completed for the 3 consecutive days prior to SV2, TV/OV1, TV/OV2, TV/OV3, TV/OV4, 
TV/OV5, and TV/OV6. 
All patients, regardless of treatment assignment, will undergo the safety assessments.  Patient 
safety will be evaluated using adverse event (AE) reports, physical examination, vital signs 
(blood pressure [BP], heart rate [HR], and respiratory rate [RR]), clinical laboratory tests, 
12-lead electrocardiograms (ECGs), spirometry, carbon monoxide diffusing capacity (DLco) 
maneuver, the Parkinson’s Disease Impulsive-Compulsive Disorders Questionnaire (QUIP), the 
Epworth Sleepiness Scale, and the Columbia-Suicide Severity Rating Scale (C-SSRS).   
The use of a randomized observational cohort in this study is to permit long-term 
contemporaneous temporal comparison to CVT-301-treated patients to describe any potential 
effects of CVT-301 with respect to lung function measurements.  These control patients, who are 
eligible to use any approved treatments to manage their PD motor symptoms, represent a 
randomized study population that remains naïve to inhalation treatment (to avoid potential 
confounding interpretation of lung function data) for their PD which is required to ascertain the 
underlying variability in spirometry and DLco endpoints.  Only a limited number of efficacy 
assessments will be evaluated in the patients randomized to the observational cohort.  Selected 
efficacy measures to assess effects of CVT-301 will be evaluated in the open-label 
CVT-301-treated patients who use CVT-301 inhalation as a treatment of OFF symptoms.   
 
 
 
 
5.2.1. 
Rationale for Selection of Dose 
Because CVT-301 contains LD only (i.e., with no DDI), study drug will be administered only to 
patients taking a DDI-containing LD formulation (e.g., CD or benserazide).  The study is 
designed to evaluate the safety and effect of adjunctive therapy (CVT-301 plus usual prescribed 
standard PD medication regimen).  All patients, regardless of treatment assignment, will 
continue with their usual prescribed standard PD medication regimen for the study duration.   

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The dose level being studied has been observed to be clinically effective, safe, and tolerated in 
healthy adult volunteers as well as in PD patients in 2 completed CVT-301 clinical studies.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The PK data from the selected CVT-301 dose level (50 mg LD FPD) has been well-characterized 
from healthy adult volunteers in 
   
CVT-301 (Levodopa Inhalation Powder) 
 
 
 
 
 
   
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 

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  The dose level of 50 mg LD FPD was selected for further evaluation in this study. 
6. 
STUDY OBJECTIVES 
Primary Objective 
• To characterize the pulmonary safety, as assessed by spirometry (forced expiratory 
volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/ FVC ratio), over 
a 12-month period within the CVT-301-treated patients. 
Secondary Objectives 
• To characterize the pulmonary safety, as assessed by spirometry (FEV1, FVC, and 
FEV1/FVC ratio), over a 12-month period in the observational (‘standard of care’) 
cohort. 
• To estimate the difference between the CVT-301-patients and the observational 
cohort on measures of pulmonary safety. 
• To characterize the effects of CVT-301 on safety over a 12-month period:  safety will 
be assessed by AE reports, physical examination, standard and orthostatic vital signs 
(BP, HR, and RR), clinical laboratory tests, 12-lead ECGs, QUIP, the Epworth 
Sleepiness Scale, and the C-SSRS.  
• To evaluate the effect of CVT-301 on mean change from baseline in the UPDRS 
Part 4 measures of motor fluctuations (dyskinesias [Q32-35] and wearing off 
[Q36-39]) measured pre-dose at 6 and 12 months after the initiation of CVT-301 
treatment. 
• To characterize the occurrence and severity of examiner-rated dyskinesia following 
treatment of patients experiencing an OFF episode in the clinic over a 12-month 
period.  
• To describe the effects of CVT-301 on DLco over a 12-month period. 
Exploratory Efficacy Objectives 
• Change from pre-dose in UPDRS Part 3 motor score at 10, 20, 30, and 60 minutes 
following treatment of patients experiencing an OFF episode. 
• Time curves of the UPDRS response at 10, 20, 30 and 60 minutes will be evaluated 
descriptively 

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• Change from pre-dose in UPDRS Part 3 motor score at 10 to 60 minutes following 
treatment of patients experiencing an OFF episode. 
• Proportion of patients with a ≥ 3, ≥ 6, and ≥ 11-point reduction in the UPDRS Part 3 
motor score from pre-dose to post-dose, at 10 to 60 minutes. 
• Proportion of patients achieving resolution of an OFF to an ON state within 60 
minutes after study drug is administered in the clinic, maintaining the ON state at 60 
minutes after study drug administration (per the examiner’s subjective assessment). 
• Patient-reported total daily OFF time, total daily ON time without dyskinesia, total 
daily ON time with non-troublesome dyskinesia, and total daily ON time with 
troublesome dyskinesia, assessed by the patient and recorded in the patient diary. 
• Change from baseline visit in the 39-Item Parkinson’s Disease Questionnaire (PDQ-
39). 
• Proportion of patients who improved based on the Patient Global Impression of 
Change (PGI-C) rating scale measured pre-dose. 
• Change from baseline visit in the Schwab and England (S&E) Activities of Daily 
Living (ADL) score. 
• Change from baseline visit in the UPDRS Part 2 score. 
7. 
INVESTIGATIONAL PLAN 
This study is a 12-month, open-label, randomized, multicenter study which will evaluate the 
safety and effects of CVT-301 for the treatment of up to 5 OFF episodes per day in PD patients 
experiencing motor fluctuations (OFF episodes) and will include a concurrent observational 
cohort of PD patients managed using the usual standards of care.  Patients must be 
CVT-301-naïve, however, any patients that were enrolled from the CVT-301-002 and 
CVT-301-003 studies under the previous version of this protocol will be allowed to continue in 
the study.  Patients will be randomized in a 2:1 ratio to the CVT-301 treatment group (CVT-301 
at a target nominal respirable dose of 50 mg LD FPD) or the observational cohort.  
Randomization will be differentiated by the patient’s Hoehn and Yahr stage (<2.5 versus ≥2.5) to 
balance the severity of disease across each group and by screening spirometry (FEV1 <60% of 
predicted or FEV1/FVC ratio <70% versus FEV1 ≥60% of predicted and FEV1/FVC ratio 
≥70%). 
Patients assigned to the CVT-301 treatment group may use the prescribed dose of CVT-301 as 
needed for the treatment of up to 5 OFF episodes per day in addition to their standard PD 
medications which may be modified as needed for symptomatic treatment over the 12-month 
study.  Each treated episode will require 2-capsule inhalations (i.e., 2 capsules used in the inhaler 
per treated episode) to deliver the dose.  
Patients assigned to the observational cohort will not receive CVT-301 but will be permitted to 
be managed using their standard PD medications and other PD treatment modalities, which may 
be modified as needed for symptomatic treatment in accordance with usual practice over the 
12-month study.   

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For both the CVT-301 treatment group and the observational cohort, additions to and/or 
modification of the patient’s usual PD treatment regimen may include any PD treatments that are 
currently approved in the patient’s region.  However, oral PRN LD formulations are not 
permitted for CVT-301-treated subjects (refer to Section 9.4.2 for a list of prohibited treatments 
and prohibited medications).  For CVT-301-treated patients, the total daily LD dose of the 
modified PD treatment regimen (not including CVT-301) must not exceed 1600 mg per day. 
The study includes a screening period of up to 35 days (with 2 screening visits) and a treatment 
period of approximately 12 months (52±2 weeks) (with 6 treatment/observational visits) plus an 
additional follow-up at a pulmonary laboratory 4 to 5 weeks after the last treatment/observational 
visit.  A longer screening period may be permitted with approval from the Sponsor.  Planned 
treatment/observational visits will occur at 0 (pre-dose, baseline) and approximately 1, 3, 6, 9, 
and 12 months.  For the CVT-301 treatment group, these visits will be treatment visits and for 
the observational cohort, these will be observational visits.  All patients, regardless of treatment 
group, will be required to attend all of the screening visits and all of the treatment/observational 
visits.  Assessments for DLco will be performed at a pulmonary laboratory outside of the clinic 
prior to the TV/OV1, within 2 weeks prior to the 3-, 6-, 9-, and 12-month visits, and 4 to 5 weeks 
after TV/OV6.  
If a patient in the CVT-301 treatment group develops significant tolerability concerns that in the 
opinion of the investigator are of a severity that should necessitate a reduction in dose, including, 
but not limited to the exacerbation or worsening of troublesome dyskinesia, other problematic 
dopaminergic symptoms, or other tolerability concerns, a dose reduction from 2 capsules (50 mg 
LD FPD) to 1 capsule (25 mg LD FPD) per treated episode may be permitted.  The medical 
monitor should be contacted, and the investigator should use his/her clinical judgment to 
determine whether an additional visit is required and what assessments should be performed 
(e.g., physical examination, spirometry, etc.).  The patient should continue to use 1 capsule (25 
mg LD FPD) per treated episode for a period of at least 1 week.  If the investigator determines 
that the tolerability issue has adequately resolved and that the patient has tolerated this dose for 
at least 1 week, the patient may at that point either resume taking the original dose (2 capsules 
[50 mg LD FPD] per treated episode) or come into the clinic for an unscheduled visit to receive a 
reduced-dose study drug kit (35 mg LD FPD).  Clinical staff will call the patient 1 to 2 days after 
the dose escalation to see if the patient has any questions or concerns.  If a patient who has 
escalated back to the full dose (50 mg LD FPD per treated episode) has another tolerability 
concern that in the opinion of the investigator is of a severity that should necessitate a second 
reduction in dose, an unscheduled visit will be required and a reduced-dose study drug kit (35 
mg LD FPD per treated episode) will be provided.   He/she will remain on the reduced dose (35 
mg LD FPD) for the remainder of the study; he/she will not be eligible for any additional 
up-titration in dose. 
Safety data will be reviewed by an independent Data Safety Monitoring Board (DSMB) that will 
include relevant medical experts (including a neurologist and pulmonologist), an independent 
statistician, and additional representatives (as will be defined in the DSMB Charter).  Safety 
data, including but not limited to AEs, spirometry, vital signs, and ECG data will be reviewed.  
The safety review will be documented in a DSMB Charter prior to the start of the study.  In the 
event that potential safety issues are identified, the committee may recommend modification of 
the study design or study termination, which will be communicated promptly with investigators, 

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Institutional Review Boards (IRBs), Independent Ethics Committees (IECs), and regulatory 
agencies, in accordance with legal and regulatory requirements.   
An overview of the study visit schedule is presented in Appendix 1.  Details on the assessments 
and procedures performed at each visit are presented in Appendix 2 through Appendix 15 and in 
Section 10. 
8. 
STUDY POPULATION 
All patients must meet the inclusion criteria and must not meet any of the exclusion criteria to be 
eligible for this study.  Patients previously enrolled in the CVT-301-002 and CVT-301-003 
studies must have completed all of the CVT-301 study visits without any safety issues that would 
preclude participation in this study according to the investigator.  Patients who withdrew from 
either of the CVT-301 studies prior to completion, for any reason, will not be eligible. 
8.1. 
Inclusion Criteria 
In order to be eligible to enter the study, patients must meet all of the following criteria: 
1. Has signed and dated an IRB/IEC-approved informed consent form before any 
protocol-specific screening procedures are performed. 
2. Is a male or female aged 30 to 85 years, inclusive.  Women of child-bearing potential 
must use protocol-defined contraceptive measures (see Section 11.1.5) and must have a 
negative serum human chorionic gonadotropin (hCG) test at screening.  These patients 
must be willing to remain on their current form of contraception for the duration of the 
study. 
3. Patients who have idiopathic PD (i.e., not induced by drugs or other diseases) as defined 
by fulfilling Steps 1 and 2 of the United Kingdom (UK) Brain Bank criteria, diagnosed 
after the age of 30 years. 
4. Patients who are classified as Stage 1 to 3 (in the ON state) on the modified Hoehn and 
Yahr scale for staging of PD severity. 
5. Patients who have experienced motor fluctuations for a minimum of 2 hours of average 
daily OFF time per waking day (excluding early morning OFF time) by self-report and 
confirmed by the PD Diary (on 3 consecutive days) during the screening period. 
6a. Patients who are on a LD-containing therapy, not including Rytary (or equivalent), must 
be stable on oral LD-containing therapy for at least 2 weeks prior to SV1 with a 
LD/DDI-containing regimen 
6b. Patients who are on a LD-containing therapy, when including Rytary (or equivalent), 
should be on a stable dose for at least 6 weeks prior to SV1. 
6c. The frequency of L-dopa administrations must be at least 3 times during the waking day 
and a total daily LD dose of ≤ 1600 mg.   
7. Patients should be stable on other PD medications for at least 4 weeks prior to SV1.   

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8. Patients must have a ≥25% difference between UPDRS Part 3 scores recorded in their 
ON and OFF states at screening. 
9. Patients must have normal cognition as confirmed by a score of ≥25 on the Mini Mental 
State Examination (MMSE), performed in the ON state. 
10. 10. Patients must be able to perform a spirometry maneuver in the ON and OFF states, 
and must have a screening FEV1 ≥50% of predicted and an FEV1/FVC ratio >60% in the 
ON state at screening.  (A pulmonologist will review the spirometry tracings/morphology 
of any patient with an FEV1 that is ≥50% to <60% of predicted or an FEV1/FVC ratio 
that is >60% to <70% in order to determine potential eligibility.  All CVT-301-naïve 
patients with an FEV1/FVC ratio that is >60% to <70% will be required to undergo a 
bronchodilator challenge and the results must be reviewed prior to entry into the study.  
Patients with an FEV1/FVC ratio that is >60% to <70% will complete spirometry before 
and after the administration of a bronchodilator in a pulmonary function 
laboratory.  Testing will be performed in accordance with the 2005 ATS/European 
Respiratory Society [ERS] criteria prior to randomization.  The results of the 
bronchodilator challenge will be reviewed by a pulmonologist prior to potential 
randomization.)   
8.2. 
Exclusion Criteria 
Patients meeting any of the following exclusion criteria at screening will not be enrolled in the 
study: 
1. Patients who have dyskinesia of a severity that would significantly interfere with their 
ability to participate or perform study procedures. 
2. Pregnant or lactating females or females wishing to become pregnant. 
3. Patients who have any known contraindication to the use of LD, including a history of 
malignant melanoma or a history of narrow-angle glaucoma.   
4. Patients who have had previous surgery for PD (including but not limited to deep brain 
stimulation [DBS] or cell transplantation). 
5. Patients with a history of psychotic symptoms requiring treatment, or suicide ideation or 
attempt within the prior 12 months (stable regimens [for at least 4 weeks prior to SV1] of 
anti-depressant and certain low-dose atypical antipsychotic medications are permitted in 
case they are indicated to treat symptoms other than psychotic symptoms).  
6. Patients who have cancer with the exception of the following:  basal cell carcinoma or 
successfully treated squamous cell carcinoma of the skin; cervical carcinoma in situ; 
prostatic carcinoma in situ; or other malignancies curatively treated and with no evidence 
of disease recurrence for at least 3 years. 
7. Patients taking certain prohibited medications (see Section 9.4.2). 
8. Patients with a history of drug or alcohol abuse within the prior 12 months. 
9. Patients with chronic obstructive pulmonary disease (COPD), asthma, or other chronic 
respiratory disease within the last 5 years. 

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10. Patients with any contraindication to performing routine spirometry or who are unable to 
perform a spirometry maneuver (see Appendix 20 for a list of contraindications).  
11. Patients with a current history of symptomatic orthostatic hypotension despite adequate 
treatment.   
12. Patients with any condition that in the investigator’s opinion would make patients 
unsuitable or interfere with their participation in the study.  Potential issues of concern 
should be raised to the medical monitor during eligibility review. 
13. Patients who have any clinically significant abnormality or finding from examination, 
tests, or history that may compromise patient safety.  
14. Patients who have been treated with an investigational drug within 4 weeks or 5 half-lives 
(whichever is longer) prior to the beginning of the screening period  (this includes 
investigational formulations of marketed products). 
15. Prior exposure to CVT-301. 
Note:  An active or recent (within 3 days) respiratory infection will not disqualify a patient from 
enrolling in the study.  However, all symptoms should be resolved for at least 3 days prior to the 
baseline visit (TV/OV1) (the screening period may be extended for up to 2 weeks to 
accommodate this recovery). 
8.3. 
Removal of Patients from Study 
A patient may withdraw from the study at any time at his/her own request, or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, or administrative reasons.  
If a patient is discontinued prematurely at any time after entering the study, the investigator will 
make every effort to see the patient and complete the TV/OV6 assessments as shown 
(for patients in the CVT-301 treatment group) or Appendix 15 (for patients in the 
observational cohort).  If a patient is withdrawn due to an AE, the event must be followed, when 
possible, until resolution. 
An end-of-study page in the electronic case report form (eCRF) should be completed for every 
patient who receives study drug (if in the CVT-301 treatment group) or enters the TV/OV1 visit 
(if in the observational cohort), whether or not the patient completes the study.  The reason for 
any early discontinuation should be indicated on this form.  The primary reason for a patient 
withdrawing prematurely should be selected from the following standard categories of early 
termination: 
• Adverse Event:  Clinical or laboratory events occurred that in the medical judgment of 
the investigator for the best interest of the patient are grounds for discontinuation.  
This includes serious and non-serious AEs regardless of relation to study medication. 
• Death:  The patient died. 
• Withdrawal of Consent:  The patient desired to withdraw from further participation in 
the study in the absence of an investigator-determined medical need to withdraw.  If 
the patient gave a reason for withdrawing, it should be recorded in the eCRF. 
14 
Appendix 

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• Protocol Violation:  Significant findings indicating that the study investigator or 
patient failed to adhere to the protocol requirements (e.g., drug noncompliance, 
failure to return for defined number of visits).  The violation necessitated premature 
termination of the patient from the study. 
• Lost to Follow-Up:  The patient stopped coming for visits, and study personnel were 
unable to contact the patient. 
• Other:  The patient was terminated for a reason other than those listed above (to be 
specified on the eCRF). 
9. 
TREATMENTS 
9.1. 
Details of Study Treatment for the CVT-301 Treatment Group 
Basic information about the study drug for the CVT-301 treatment group is provided in Table 1 
and details regarding the reduced-dose study drug for patients with tolerability issues are 
provided in 
 
Table 1 
Details of Study Drug 
 
CVT-301 (Test Product) 
Table 2.
Name 
CVT-301 (levodopa inhalation powder) 
Manufacturer 
Civitas Therapeutics, Inc. 
Doses 
2 CVT-301 capsules delivering a target nominal respirable dose of 
approximately 50 mg LD FPD 
Route 
Inhaled via the CVT-301 inhaler 
Formulation 
Capsules of levodopa inhalation powder 
Capsule Strength 
Capsule fill weight of LD:  42 mg 
Respirable LD dose/FPD per capsule: 25.0 mg  
(Emitted LD per capsule:  35 mg) 
Abbreviations:  FPD=fine particle dose; LD=levodopa. 
 
 

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Table 2 
Details of Reduced-Dose Study Drug1 
 
CVT-301 (Test Product) 
Name 
CVT-301 (levodopa inhalation powder) 
Manufacturer 
Civitas Therapeutics, Inc. 
Doses 
2 CVT-301 capsules delivering a target nominal respirable dose of 
approximately 35 mg LD FPD 
Route 
Inhaled via the CVT-301 inhaler 
Formulation 
Capsules of levodopa inhalation powder 
Capsule Strength 
Capsule fill weight of LD:  30 mg 
Respirable LD dose/FPD per capsule: 17.5 mg  
(Emitted LD per capsule:  25 mg) 
Abbreviations:  FPD=fine particle dose; LD=levodopa. 
1 Reduced-dose study drug kits will be permitted for patients with tolerability issues.  Refer to Section 10.3 
for details on when this dose may be utilized. 
9.1.1. 
CVT-301 Capsule for Inhalation (Test Product) 
 
 
 
 
 
CVT-301 capsules are packaged into blister strips composed of foil-foil blister strips.  
9.1.2. 
Sham Capsule for Inhalation 
Sham inhalation capsules are empty size 00 HPMC capsules that will be used with the inhaler to 
train both staff and patients on the use of the CVT-301 inhaler.  Sham capsules are packaged into 
foil-foil blister strips.  A training inhaler and sham capsules will be provided to patients for the 
inhaler training sessions. 
9.1.3. 
Civitas CVT-301 Inhaler 
CVT-301 capsules will be delivered using the CVT-301 inhaler, which is a 5-inch-long, 
single-capsule-based, breath-actuated inhaler.   
9.1.4. 
Packaging of Inhaled Study Treatment 
Study drug supplies will be packaged into study drug kits.  Each study drug kit will contain 
20 blister strips of CVT-301 capsules (an 8-day supply), an inhaler, and the IFU.  At TV1, TV2, 
TV3, TV4, and TV5, each patient in the CVT-301 treatment group will be issued a sufficient 
supply of study drug kits to accommodate the visit windows.  Kits will be stored at room 
temperature environment (25°C [77°F]) at the clinical sites and may not be stored in excessive 

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heat (i.e., above 40˚C [104˚F]) or excessive cold (i.e., below 2˚C [36˚F]).  Patients will be told to 
store the kits containing the inhalers and study drug at room temperature and will be required to 
return unused study drug, used capsules, and the inhaler from each kit at their subsequent clinic 
visit. 
Reduced-dose study drug kits (at a target nominal dose of 35 mg LD FPD) will be packaged, 
stored, and accounted for in a similar manner.  These kits are to be utilized for patients unable to 
tolerate CVT-301 at a target nominal dose of 50 mg LD FPD, as described in Section 10.3. 
All Investigational Product Complaints must immediately be reported to the sponsor.  
Site study personnel should immediately notify the Site Monitor and provide a description of the 
complaint. Sponsor representatives from IP Supply or Quality Assurance Departments will work 
with the Site Monitor or site study personnel to gather further information needed. Note that this 
is for IP quality complaint notification, not for AE reporting. 
9.2. 
Randomization and Administration of Study Treatment  
9.2.1. 
Randomization and Assignment of Study Treatment  
Following completion of SV2 and prior to randomization, the patients’ eligibility criteria will be 
reviewed by delegated staff.  Upon confirmation of eligibility, the site will randomize an eligible 
patient using the Interactive Web Response System (IWRS).  Sites must allow 7 business days 
between time of randomization and the first treatment visit (TV1) to allow time for drug to be 
shipped and received. 
Eligible patients will be randomized in a 2:1 ratio to CVT-301 treatment (CVT-301 50 mg PD 
FPD) or the observational cohort.  Randomization will be differentiated by the patient’s Hoehn 
and Yahr stage (<2.5 versus ≥2.5) to balance the severity of disease across each treatment group 
and by screening spirometry (FEV1 <60% of predicted or FEV1/FVC ratio <70% versus FEV1 
≥60% of predicted and FEV1/FVC ratio ≥70%).  Patients who previously completed the 
CVT-301-002 and CVT-301-003 studies will be assigned only to the CVT-301 treatment group.  
The study is an open-label study, so patients and clinical staff will not be blinded to study group 
assignment. 
9.2.2. 
Defining “Time 0” (T0) (for the CVT-301 Treatment Group) 
During inhaler training, patients will be instructed to hold their breath following each inhalation 
for approximately 5 seconds after administration of each capsule, in accordance with the IFU.  
For the purposes of timing study assessments, “Time 0” (T0) is defined as the time of completion 
of inhalation of the last capsule of inhaled study treatment administered (i.e., beginning of the 
final breath hold).  In the event that a capsule needs to be re-inhaled, T0 is at the end of the re-
inhalation administration. 
9.3. 
Treatment Accountability and Compliance (for the CVT-301 
Treatment Group) 
The pharmacist or study coordinator will maintain records of study kits delivered to the study 
site, the inventory at the site, the distribution to and use by each patient, and the return of 
materials to the Sponsor for storage or disposal.  These records should include dates, quantities, 

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batch/serial numbers, expiration dates, in-clinic temperature log, and unique code numbers 
assigned to the product and trial patients.  Investigators will maintain records that document 
adequately that the patients were provided with the correct study treatment kits and will reconcile 
the products received from the drug dispensing center.  Investigational product will not be 
returned until accountability has been fully monitored. 
In-clinic administration of study drug will be supervised by study personnel, and at-home PD 
Diary data will be reviewed to ensure patient compliance. 
9.4. 
Prior and Concomitant Illnesses and Medications 
9.4.1. 
Prior and Concomitant Illnesses 
Investigators should document all prior significant illnesses that the patient has experienced 
within 5 years prior to screening.  New illnesses present at the time when informed consent is 
given and for the duration of the study are to be documented as AEs on the eCRF. 
Clinic staff will contact patients 4 to 6 days prior to TV/OV1 to remind them that they must be 
symptom-free of any flu-like syndrome or other respiratory infection for at least 3 days prior to 
the visit and that they should contact the site if an intervening illness occurs prior to TV/OV1.  If 
the patient has any of these symptoms within this time period, this visit will be rescheduled once 
these symptoms have been resolved for at least 3 days.  The screening period may be extended 
for up to 2 weeks to accommodate this recovery. 
9.4.2. 
Prior and Concomitant Medications  
Any medication or therapy that is taken by or administered to the patient during the course of the 
study must be recorded in the eCRF.  The entry must include the dose, regimen, route, 
indication, and dates of use.  In addition, medications taken by or administered to the patient for 
3 months prior to SV1 will be recorded in the eCRF.   
Patients must be stable on oral LD-containing therapy for at least 2 weeks prior to SV1 with an 
LD/DDI-containing regimen, when not including Rytary, and stable for at least 6 weeks prior to 
SV1 when including Rytary. The oral LD regimen must include doses at least 3 times during the 
waking day and a total daily LD dose of ≤1600 mg (exclusive of PRN LD-containing 
medications).  During the study, all patients’ standard PD medication regimen may be altered as 
needed to manage PD symptoms.  Additions to and/or modification of the patient’s usual PD 
treatment regimen may include any PD treatments that are currently approved in the patient’s 
region.  Oral PRN LD formulations are not permitted for CVT-301-treated subjects from 
TV/OV1 to TV/OV6.  For CVT-301-treated patients, the total daily LD dose of the modified PD 
treatment regimen (not including CVT-301) must not exceed 1600 mg per day.  In the event that 
the dose or schedule of the patient’s oral LD-containing medication does change during the 
treatment period, record all changes in medication, including the total LD dose, in the eCRF.   
If the patient is treated with dopamine agonists, COMT inhibitors, monoamine oxidase-B 
(MAO-B) inhibitors, he/she must be on a stable dose for at least 4 weeks prior to SV1 and must 
remain stable throughout the study.  If the patient is on anti-depressant medication or other non-
LD-containing PD medications, the dose must be stable for at least 4 weeks prior to SV1. 

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In countries and/or municipalities where the use of marijuana-based products is legal for medical 
purposes, patients who may be using medical marijuana as a treatment for their PD may be 
enrolled into the study as long as they meet the following parameters: 
1. Medical marijuana has been prescribed to the patient prior to the date of informed 
consent.  Patients who have not already been prescribed medical marijuana prior to 
beginning study participation may not begin medical marijuana use during their 
participation in the study. 
2. Medical marijuana is not being used to treat any contraindicated condition as defined in 
the protocol (i.e., glaucoma, cancer, etc.). 
3. Patients meet all other eligibility criteria (including spirometry). 
4. Patients must agree not to use medical marijuana (smoking, ingestion or any other 
potential route of administration) on clinic days, before coming to the clinic or while in 
the clinic, until all procedures have been completed and they are discharged. 
All patients in this study will take their usual prescribed PD medications during the study 
including on the morning of each in-clinic treatment/observational visit.  The timing of the 
administration of the usual morning dose of PD medications may be adjusted by the investigator 
to accommodate the patient’s and/or clinic’s schedule.  On designated in-clinic dosing days for 
CVT-301-treated patients, if the patient converts to an ON state after the study drug has been 
administered, and all post-treatment study procedures have been performed, the patients will 
resume their standard schedule of PD medications. 
In addition, for CVT-301-treated patients, the inhaled study drug will be used for the treatment 
of OFF episodes in accordance with this protocol.  Patients should not take inhaled study drug 
within 45 minutes following their prior dose of standard oral PD medication.  Also, patients 
should not use inhaled study drug for the treatment of early morning OFF.  Otherwise, study 
drug may be used during the waking day for the treatment of OFF episodes that occur in between 
doses of the patients’ standard oral PD medications.  Patients in the CVT-301 treatment group 
should not take oral PRN PD medications to manage their OFF states throughout the treatment 
period. 
During in-clinic evaluation days, if inhaled study drug does not provide sufficient relief of the 
OFF state to enable the patient to return to an ON state by 60 minutes post-dose, patients will 
receive their usual oral dose of PD medication(s) and may be discharged home when all study 
assessments are completed.  At home, in the event that an OFF state is not sufficiently resolved 
within 45 minutes of completing the last inhalation of CVT-301, patients will be permitted to 
take their next scheduled dose of their usual prescribed PD medication; patients may not re-dose 
with inhaled study drug for that OFF episode.  Patients may use inhaled study drug to manage 
only up to 5 OFF episodes per day.  If patients experience more than 5 OFF episodes per day, 
they should adhere to their usual standard oral regimen to manage these additional episodes. 
Prohibited Therapies 
Medication to treat study-emergent and treatment-emergent illness(es) is generally permitted; 
however, the following therapies/products are expressly prohibited throughout the study: 

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• Apomorphine.  Use of apomorphine is restricted to a frequency of once per day. 
Concomitant use of study medication (CVT-301) with apomorphine, i.e. use within 
the same OFF episode, is excluded. 
• Reserpine.  Patients must not have used reserpine for at least 3 months prior to SV1 
and must not use it for the duration of the study. 
• Antipsychotic medications.  Patients must not have used antipsychotic medications 
for at least 12 months prior to SV1 and must not use them for the duration of the 
study.  Exceptions:  certain low-dose atypical antipsychotic agents are allowed if the 
dose has been stable for at least 4 weeks prior to screening (for example, quetiapine 
≤50 mg/day, risperidone ≤1 mg/day, and olanzapine ≤2.5 mg/day) if used for non-
psychosis-related conditions. 
• Other non-neuroleptic dopamine antagonists or non-specific monoamine oxidase 
inhibitors (MAOIs).  Patients must not have used any of these agents for at least 3 
months prior to SV1 and must not use them for the duration of the study.  Exception:  
In regions where it is approved, domperidone is permitted during the study if the 
maximum daily dose does not exceed 60 mg and if the dose has been stable for at 
least 4 weeks prior to screening. 
• Investigational drugs.  Patients must not have taken any investigational drugs 
(including investigational formulations of marketed products) for at least 4 weeks or 5 
half-lives (whichever is longer) prior to SV1 and must not use them for the duration 
of the study. 
• Smoking.  Current smokers are permitted to participate in the study provided that they 
meet other eligibility requirements (spirometry and concomitant respiratory illness). 
They must agree to and are able to abstain from smoking on the day of each in-clinic 
visit while in-clinic through completion of all assessments for that visit day (including 
screening visits and in-clinic treatment/observational visits). 
• Oral PRN PD medications for CVT-301-treated patients during the treatment period.  
All patients are permitted to take oral PRN PD medications during the screening 
period.  However, oral PRN PD medications are not permitted during the treatment 
period for CVT-301-treated patients. 
10. 
STUDY PROCEDURES 
The overall schedule of assessments is provided in Appendix 1, and specific time and events 
schedules for the screening visits and in-clinic treatment/observational visits are provided in 
Appendix 2 through Appendix 15.  Unless otherwise specified, all assessments will be performed 
by the investigator or other assigned personnel.  
10.1. 
Screening Period 
Patients will undergo a screening period of up to 35 days before entering the treatment period.  
The screening period will consist of 2 scheduled clinic visits: SV1 and SV2.  The screening 
period may be extended an additional 7 days if repeat screening assessments are required.  At 

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SV1, after patients have provided informed consent, they will be assessed for study eligibility in 
ON and OFF states.  At SV2, any screening assessment performed at SV1 will be repeated if 
needed to verify or re-check results, and inhaler training will be performed. 
Patients who do not develop an adequate OFF or ON period at SV1 will be invited to re-attend 
on a subsequent day, but will be withdrawn if further observation shows they are unable to turn 
OFF during a regularly scheduled study visit in accordance with the procedures.  In addition, if a 
patient is unable to complete all assessments or training at the scheduled SV1, he/she may be 
rescheduled to repeat the visit, and/or to return to the clinic for additional training. 
10.1.1. 
Screening Visit 1 (within 35 days prior to TV/OV1) 
Patients should be instructed to bring all of their medications with them to SV1.  The following 
list is a suggested schedule for this visit, with assessments outlined in Appendix 2.  (Note:  If a 
patient arrives at the clinic in an OFF state, assessments will be done in an OFF state first, then 
they will be repeated in an ON state after the patient has taken his/her standard dose of 
LD-containing medications and converted to an ON state.) 
1. Give the patient an explanation of the purpose and nature of the study, and receive his/her 
voluntary written informed consent before any study procedures are performed. 
2. Determine eligibility according to inclusion/exclusion criteria. 
3. Record medical history (including smoking history), concurrent medical conditions, and 
PD history. 
4. Confirm diagnosis of PD using Steps 1 and 2 of the UK Brain Bank criteria in the ON 
state.  (Refer to Section 11.3.1 and Appendix 18.) 
5. Use the modified Hoehn and Yahr scale to assess PD severity (in an ON state).  (Refer to 
Appendix 19.) 
6. Record the estimated average number of hours of OFF time during the waking day (not 
including early morning OFF time) as reported by the patient.  Eligible patients must 
have, by self-report, motor fluctuations with daily OFF time averaging at least 2 hours 
per day (not including early morning OFF time and which will require confirmation using 
the PD Diary over a period of 3 consecutive days).   
7. Check and record all PD medications (including the number of times per day that 
LD-containing medications are administered and total daily LD dose) and other 
concomitant medications.  Confirm that the patient is on stable dosages of PD 
medications (at least 2 weeks for the LD-containing medication, and 4 weeks for the 
other PD medications).  Ensure that specified concomitant medications have been 
stabilized in accordance with protocol-defined criteria. 
8. Perform the MMSE (in an ON state). 
9. Perform a full physical examination. 
10. Complete the Pulmonary Function Baseline Questionnaire. 
11. Record a 12-lead ECG (after patient has been in a supine position for at least 5 minutes, 
as per Section 11.1.3). 

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12. Measure standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and HR).  
Standard vital signs should be taken after the patient has rested in a supine or semi-supine 
position for at least 5 minutes, and orthostatic vital signs should be taken after the patient 
has been standing for 2 minutes (see Section 11.1.2 for suggested detailed procedures). 
13. Perform spirometry to measure FEV1, FVC, and FEV1/FVC ratio to assess lung function 
(this must be performed with the patient in the ON state). 
14. Perform UPDRS Part 3 in an ON state. 
15. Train patients on how to assess their ON and OFF states and how to record their waking 
ON/OFF status in a screening PD Diary (time OFF, time ON without dyskinesia, time 
ON with non-troublesome dyskinesia, time ON with troublesome dyskinesia, and time 
asleep). 
16. Perform concordance testing with the patients (while in the ON and OFF states) for 
recognizing different ON/OFF states and recording them appropriately in the PD Diary.  
Patients will be tested for competence at self-rating and must be within 75% concordance 
with the ratings of the examiner (at least 3 out of 4 half-hour sessions over the course of 2 
hours); if concordance is not reached, the observation period may be extended for an 
additional 2 hours to obtain agreement on at least 6 of 8 half-hour sessions.  The same 
training and testing may be repeated at an unscheduled visit between SV1 and SV2 or at 
SV2.  If patients return for an unscheduled visit between SV1 and SV2 for concordance 
training and testing, the visit must occur more than 3 days prior to SV2.  If patients do not 
achieve 75% concordance by the end of SV2, they will be considered screen failures. 
17. Introduce the inhaler and perform inhaler training using sham capsules with the CVT-301 
inhaler while in the ON state. 
18. Take samples for clinical laboratory tests, including a serum pregnancy test for females 
of childbearing potential (see Appendix 17 for a list of laboratory parameters assessed).  
Patients do not need to be in a fasted state at the time of the laboratory sample; however, 
fasted status will be documented (with fasting defined as at least 4 hours following the 
last meal or snack). 
19. Patients will remain in the clinic and further PD medications will be withheld until they 
turn into an OFF state. 
20. Perform the assessments in the following suggested order while the patient is in an OFF 
state:  spirometry, UPDRS Part 3, patient training on self-report of ON/OFF states, and 
inhaler training using sham capsules with the CVT-301 inhaler. 
21. Distribute the PD Diary; train patients to record time OFF, time ON without dyskinesia, 
time ON with non-troublesome dyskinesia, time ON with troublesome dyskinesia, and 
time asleep for the 3 consecutive days prior to SV2. 
22. Distribute the Screening ON/OFF Episodes Log; train patients to record the number of 
OFF episodes experienced by the patients during their waking day for the 3 consecutive 
days prior to SV2.  

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23. If needed, train caregivers on how to prepare inhalers for patients and how to complete 
the PD Diary and Screening ON/OFF Episodes Log (diaries will be completed based on 
the patient report). 
24. Monitor for AEs throughout the visit. 
25. Review with patients (and their caregivers) the planned schedule of events for the 
remaining study visits, and the responsibilities of self-administration of study drug and of 
recording information in the at-home diaries.  Schedule the next visit. 
26. Ask patients to bring the PD Diary, the Screening ON/OFF Episodes Log, and all of their 
PD medications with them at SV2, to take their usual morning medications prior to the 
visit, and to note the time when they took them. 
The next visit will be scheduled.  The site will call the patient approximately 4 days before SV2 
to confirm the next study visit and to remind patients of the study procedures and the 
requirements noted in 
 in the above list. 
10.1.2. 
Screening Visit 2 (at least 4 days after SV1) 
The purpose of this visit is as follows:  (a) to repeat any screening assessment performed at SV1 
if needed to verify or re-check results for eligibility and safety, (b) to review the PD Diary and 
Screening ON/OFF Episodes Log to confirm eligibility (if these were not done correctly, the site 
may have to reschedule this visit) (c) to perform spirometry and vital signs, if needed to verify or 
re-check results, and (d) to re-train the patient on proper inhalation technique with the inhaler 
and on recording PD Diary and Screening ON/OFF Episodes Log information.  For the 3 
consecutive days prior to SV2, patients will complete the PD Diary and the Screening ON/OFF 
Episodes Log.  Before arrival at the clinic for SV2, the patient will take all of their usual 
prescribed non-PD medications and PD medications, including LD-containing PD medications. 
The following list is a suggested schedule for this visit: 
1. Upon the patient’s arrival to the clinic, reconfirm eligibility from SV1, including review 
of the PD Diary and the Screening ON/OFF Episodes Log.  In the PD Diary, if <80% of 
the awake time is filled in for the 3-day period, the diary training and concordance testing 
must be repeated.  The training and concordance testing will also be repeated if the 
patient has not reached 75% or greater concordance with the examiner at SV1 or at an 
unscheduled visit between SV1 and SV2. 
2. Record any changes in the usual PD medication dose and regimen. 
3. Review concomitant medications. 
4. Perform inhaler re-training using sham capsules with the CVT-301 inhaler and IFU.  If 
the patient has undergone inhaler training in both the ON and OFF states at SV1, it may 
be done in either state at this visit. 
5. Patient training on assessment of the ON/OFF state will be repeated while the patient is 
in the ON and OFF states as needed. 
6. Distribute a new PD Diary and Screening ON/OFF Episodes Log, and instruct the 
patients to complete both of them for the 3 consecutive days prior to TV/OV1. 
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7. Schedule a DLco assessment to be performed at an outside pulmonary laboratory after 
SV2 and prior to treatment assignment/randomization.  The assessment should be 
performed while the patient is in an ON state (as reported by the patient to the pulmonary 
technician) at the pulmonary function facility.  As part of the procedure, a slow vital 
capacity maneuver will be performed, followed by DLco, and then spirometry. 
8. If needed, the following assessments from SV1 may be completed or repeated:  MMSE 
(in ON state); full physical examination; 12-lead ECG; standard vital signs (BP, HR, and 
RR) and orthostatic vital signs (BP and HR); spirometry (in ON and OFF states); UPDRS 
Part 3 (in ON and OFF states); ON/OFF concordance testing (in ON and OFF states); and 
clinical laboratory test, including serum pregnancy test, if applicable (with documentation 
of fasting status).  
9. Monitor for AEs throughout the visit. 
If a patient is unable to complete a screening assessment at SV2, an additional visit (repeat SV2) 
may be scheduled prior to eligibility determination and randomization.  Any repeat assessments 
should be performed in the respective motor state as described for SV1.  The site will contact 
patients by telephone 4 to 6 days prior to TV/OV1 to confirm the DLco assessment has been 
done, to confirm the next study visit, and to remind patients of the study procedures required 
prior to the next scheduled study visit (including completion of the PD Diary and Screening 
ON/OFF Episodes Log).  In addition, the site should remind the patients during the call that they 
must be symptom-free of any flu-like syndrome or other respiratory infection for at least 3 days 
prior to prior to TV/OV1 and that they should contact the site if an intervening illness occurs 
prior to TV/OV1.  If the patient has any of these symptoms within this time period, this visit will 
be rescheduled once these symptoms have been resolved for at least 3 days.  The screening 
period may be extended for up to 2 weeks to accommodate this recovery. 
10.2. 
Randomization to Study Drug 
Following completion of SV2 and prior to randomization, the patients’ eligibility criteria will be 
reviewed by delegated staff.  Eligible patients will be randomized in a 2:1 ratio to CVT-301 
treatment group (CVT-301 50 mg PD FPD) or the observational cohort.  Randomization will be 
differentiated by the patient’s Hoehn and Yahr stage (<2.5 versus ≥2.5) to balance the severity of 
disease across each treatment group and by screening spirometry (FEV1 <60% of predicted or 
FEV1/FVC ratio <70% versus FEV1 ≥60% of predicted and FEV1/FVC ratio ≥70%).  Sites 
must allow 7 business days between time of randomization and the first treatment visit (TV1) to 
allow time for drug to be shipped and received. 
10.3. 
Treatment/Observational Period 
Patients in both the CVT-301 treatment group and observational cohort are required to attend all 
of the in-clinic treatment/observational visits.  For the CVT-301 treatment group, these visits will 
be treatment visits and for the observational cohort, these will be observational visits.  The 
assessments and procedures for the in-clinic treatment/observational visits will differ for patients 
in the CVT-301 treatment group compared to the observational cohort.   

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All patients, regardless of treatment assignment, should continue with their usual prescribed 
standard PD medication regimen for the duration of the study which may be modified for 
symptomatic treatment during the study in accordance with usual practice.  
Patients assigned to the CVT-301 treatment group may use the prescribed dose of CVT-301 as 
needed for the treatment of up to 5 OFF episodes per day in addition to their standard PD 
medications which may be modified as needed for symptomatic treatment over the 12-month 
study.  Each treated episode will require 2-capsule inhalations (i.e., 2 capsules used in the inhaler 
per treated episode) to deliver the dose.  
Patients assigned to the observational cohort will not receive CVT-301 but will be managed with 
their prescribed PD medications, which may be modified as needed for symptomatic treatment 
over the 12-month study.   
For both the CVT-301 treatment group and the observational cohort, additions to and/or 
modification of the patient’s usual PD treatment regimen may include any PD treatments that are 
currently approved in the patient’s region.  However, oral PRN LD formulations are not 
permitted for CVT-301-treated subjects (refer to Section 9.4.2 for a list of prohibited treatments 
and prohibited medications).  For CVT-301-treated patients, the total daily LD dose of the 
modified PD treatment regimen (not including CVT-301) must not exceed 1600 mg per day.  
Changes in the medications, doses, or frequency of medication administration will be 
documented in the eCRF.   
During this period, CVT-301 patients will self-administer inhaled study treatment (CVT-301 50 
mg LD FPD) up to 5 times daily to treat OFF episodes during their waking day.  The first dose of 
open-label study drug will be given in the clinic at TV1; patients will be given study drug kits at 
TV1, TV2, TV3, TV4, and TV5. 
The treatment/observational period includes 6 separate in-clinic treatment/observational visits 
over approximately 1 year.  The sequence of timing the patient’s morning dose of PD 
medications and clinic arrival should be discussed with the patient to increase the likelihood that 
the patient will reliably be in an ON state upon arrival and turn OFF during the office visit.  
Patients will take their morning dose of PD medications and should eat their standard breakfast 
prior to arrival at the clinic. 
If a patient in the CVT-301 treatment group develops significant tolerability concerns that in the 
opinion of the investigator are of a severity that should necessitate a reduction in dose, including, 
but not limited to the exacerbation or worsening of troublesome dyskinesia, other problematic 
dopaminergic symptoms, or other tolerability concerns, a dose reduction from 2 capsules (50 mg 
LD FPD) to 1 capsule (25 mg LD FPD) per treated episode may be permitted.  The medical 
monitor should be contacted, and the investigator should use his/her clinical judgment to 
determine whether an additional visit is required and what assessments should be performed 
(e.g., physical examination, spirometry, etc.).  The patient should continue to use 1 capsule (25 
mg LD FPD) per treated episode for a period of at least 1 week.  If the investigator determines 
that the tolerability issue has adequately resolved and that the patient has tolerated this dose for 
at least 1 week, the patient may at that point either resume taking the original dose (2 capsules 
[50 mg LD FPD] per treated episode) or come into the clinic for an unscheduled visit to receive a 
reduced-dose study drug kit (35 mg LD FPD).  Clinical staff will call the patient 1 to 2 days after 
the dose escalation to see if the patient has any questions or concerns.  If a patient who has 

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escalated back to the full dose (50 mg LD FPD per treated episode) has another tolerability 
concern that in the opinion of the investigator is of a severity that should necessitate a second 
reduction in dose, an unscheduled visit will be required and a reduced-dose study drug kit (35 
mg LD FPD per treated episode) will be provided.   He/she will remain on the reduced dose (35 
mg LD FPD) for the remainder of the study; he/she will not be eligible for any additional 
up-titration in dose. 
Refer to Appendix 2 through Appendix 15 for tables of study assessments at each visit during the 
treatment period. 
10.3.1. 
Telephone Calls Before Treatment/Observational Visits 
• Telephone calls should be made to patients 4 to 6 days before TV/OV1 for the 
following reasons:  to confirm the DLco assessment has been done (must be 
completed prior to TV/OV1); to confirm the next study visit; to remind patients to 
complete the PD Diary and the Screening ON/OFF Episodes Log for the 
3 consecutive days prior to the visit; to remind them to bring the PD Diary, Screening 
ON/OFF Episodes Log, and all of their PD medications with them to the visit; to 
remind them to take their usual morning medications and eat their standard breakfast 
prior to the visit; and to remind them to note the time when they take these morning 
medications.  In addition, the site should remind patients that they must be 
symptom-free of any flu-like syndrome or other respiratory infection for at least 
3 days prior to the visit and that they should contact the site if an intervening illness 
occurs prior to TV/OV1.  If a patient has any of these symptoms within this time 
period, reschedule this visit after these symptoms have been resolved for at least 3 
days.  The screening period may be extended for up to 2 weeks to accommodate this 
recovery. 
• Telephone calls should be made to patients in the CVT-301 treatment arm 1 to 3 days 
after TV1 to address any potential concerns or challenges with the inhaler systems or 
Inhaled Dosing Log.    
• Telephone calls should be made to patients in the CVT-301 treatment group 2 weeks 
(± 3 days) before TV2, TV3, TV4, and TV5, and TV6 for the following reasons:  to 
address any concerns or challenges with the inhaler systems, PD Diary, or Inhaled 
Dosing Log; to monitor for any AEs; to confirm the DLco assessment has been 
done/scheduled (prior to TV3, TV4, TV5, and TV6); to confirm the next study visit; 
to remind patients to complete the PD Diaries for the 3 consecutive days prior to 
TV2, TV3, TV4, TV5, and TV6; to remind patients to complete the Inhaled Dosing 
Log every day during the treatment period; to remind them to bring their PD Diaries, 
Inhaled Dosing Logs, study drug kits, and all of their PD medications with them to 
the visits; to remind them to take their usual morning medications and eat their 
standard breakfast prior to the visits; to ask how many empty study drug kits will be 
returned at the next visit; and to remind them to note the time when they take their 
usual morning medications. 
• Telephone calls should be made to the patients in the observational cohort 2 weeks (± 
3 days) prior to OV2 to monitor for AEs and to confirm the next study visit, and prior 

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to OV3, OV4, OV5, and OV6 to monitor for AEs, to confirm that the DLco 
assessment has been done/scheduled, and to confirm the next study visit. 
10.3.2. 
Treatment Visit/Observational Visit 1 (at least 7 days after SV2) 
10.3.2.1. Treatment Visit 1 for the CVT-301 Treatment Group 
Patients will complete the Screening ON/OFF Episodes Log and PD Diary for the 3 consecutive 
days prior to TV1.   
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of arrival for TV1 should be scheduled to increase the likelihood that patients will be 
in the ON state upon arrival (i.e., they should arrive to the clinic as shortly as feasible after 
taking their standard oral PD medications at home).  Patients will bring to the clinic all of their 
usual prescribed PD medications. 
On Arrival to the Clinic  
The following list is a suggested schedule for this visit: 
• Collect, review, sign, and date the PD Diary and Screening ON/OFF Episodes Log 
and document whether these were completed correctly. 
• Confirm that the DLco assessment has been performed.  If the DLco assessment has 
not been completed prior to the visit, the study visit must be re-scheduled. 
• Record the time that patients took their usual PD medications prior to the visit. 
• Record any changes in the usual PD medication dose/regimen. 
• Record all concomitant medications. 
• Perform the PDQ-39 in an ON state. 
• Perform a brief physical examination. 
• Patients will complete the UPDRS Part 2 and S&E ADL scales (preferably in the ON 
state). 
• Patients will complete the UPDRS Part 4 (Questions 32-35 and 36-39). 
• Perform a 12-lead ECG. 
• Record standard and orthostatic BP and HR.  Record RR. 
• Perform spirometry (preferably performed in the ON state; record the patient’s motor 
state on the spirometry source record). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Perform the baseline assessments using the C-SSRS, Epworth Sleepiness Scale, and 
the QUIP. 
• Distribute the PD Diary and review instructions for completion for recording time 
asleep, time OFF, time ON without dyskinesia, time ON with non-troublesome 

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dyskinesia, and time ON with troublesome dyskinesia (to be completed for the 
3 consecutive days prior to TV2, TV3, TV4, TV5, and TV/6). 
• Distribute the Inhaled Dosing Log and review instructions for completion for 
recording the number of times the inhaler was used and the number of capsules used 
for each inhalation treatment (to be completed daily throughout the 12-month 
treatment period). 
• Distribute study drug kits to patients.  Instruct patients to collect used empty capsules 
and return them at the next visit along with the PD Diary, Inhaled Dosing Log, and 
other study supplies. 
• Re-train patients on the proper use of the inhaler with sham capsules, including a 
review of the IFU. 
Study Drug Dosing 
Immediately pre-dose, perform a spirometry assessment (record the patient’s ON/OFF state on 
the spirometry source record).  Under clinic staff supervision, preferably between 2 and 5 hours 
after receiving their standard dose of PD medication (in the OFF state), patients will prepare and 
self-administer their first dose of study drug from the study drug kits provided (i.e., 2 capsule 
inhalations of CVT-301).  Patients will be permitted sips of water between capsule inhalations as 
needed. The dosing time is defined to be when the patient’s OFF state is recognized by both the 
patient and investigator to be at a level similar to the investigator-confirmed severity experienced 
at SV1 and preferably between 2 and 5 hours after their prior oral PD medication.   
Note: Instructions for how to properly use the CVT-301 system are outlined in the Instructions 
for Use document that is included with every CVT-301 study kit.  Refer to 
 for 
additional system information. 
Post-dose (10 – 60 minutes) 
The following post-dose safety evaluations will be performed: 
• Record vital signs (standard and orthostatic BP and HR) at 20 and 60 minutes. 
post-dose.   
• Record RR at 10, 20, 30, and 60 minutes post-dose. 
• Monitor for AEs throughout the visit. 
Upon completion of the 60-minute observations, resumption of normal medications is permitted 
for the remainder of the day (the patient may use the inhaled study drug 4 more times at home 
after he/she leaves the clinic on that day if needed for OFF episodes).  The next visit will be 
scheduled.  Clinic staff will arrange to speak with patients by telephone 1 to 3 days after 
TV/OV1 to monitor for AEs and to address any potential concerns or challenges with the inhaler 
systems or Inhaled Dosing Log.  Additionally, clinic staff will arrange to speak with patients by 
telephone 2 weeks (± 3 days) before each visit for TV2, TV3, TV4, TV5, and TV6 to address 
any concerns or challenges with the inhaler systems, PD Diary, or Inhaled Dosing Log, to 
monitor for any AEs, to confirm the DLco assessment has been done/scheduled (prior to TV3, 
TV4, TV5, and TV6), to confirm the next study visit, to ask the patients how many empty study 
drug kits will be returned at the next visit, and also to remind patients of the study procedures 
Appendix 21

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required prior to the next scheduled study visit (including completion of the PD Diary and 
Inhaled Dosing Log). 
10.3.2.2. Observational Visit 1 for the Observational Cohort  
Patients will complete the Screening ON/OFF Episodes Log and PD Diary for the 3 consecutive 
days prior to OV1.   
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of arrival for OV1 should be scheduled to increase the likelihood that patients will be 
in the ON state upon arrival (i.e., they should arrive to the clinic as shortly as feasible after 
taking their standard oral PD medications at home).  Patients will bring to the clinic all of their 
usual PD medications. 
On Arrival to the Clinic  
The following list is a suggested schedule for this visit: 
• Collect, review, sign, and date the PD Diary and Screening ON/OFF Episodes Log 
and document whether these were completed correctly. 
• Confirm that the DLco assessment has been performed.  If the DLco assessment has 
not been completed prior to the visit, the study visit must be re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record all concomitant medications. 
• Perform the PDQ-39 in an ON state 
• Perform a brief physical examination. 
• Patients will complete the UPDRS Part 2 and S&E ADL scales (preferably in the ON 
state). 
• Record standard and orthostatic BP and HR.  Record RR. 
• Perform a 12-lead ECG. 
• Perform spirometry (preferably performed in the ON state; record the patient’s motor 
state on the spirometry source record). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Perform the baseline assessments using the C-SSRS, Epworth Sleepiness Scale, and 
the QUIP. 
• Monitor for AEs. 
The next visit will be scheduled and the patient will be discharged from the visit. 
10.3.3. 
At-Home Dosing for the CVT-301 Treatment Group 
At TV1, TV2, TV3, TV4, and TV5, patients in the CVT-301 treatment group will receive study 
drug kits and the IFU to take home with them.  Patients will be instructed to take their standard 

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oral PD medications as prescribed on their usual schedule of administration, which may be 
modified as needed for symptomatic treatment during the 12-month study.  Additions to and/or 
modification of the patient’s usual PD treatment regimen may include any PD treatments that are 
currently approved in the patient’s region.  Oral PRN LD formulations are not permitted for 
these patients (refer to Section 9.4.2 for a list of prohibited treatments and prohibited 
medications).  The total daily LD dose of the modified PD treatment regimen (not including 
CVT-301) must not exceed 1600 mg per day.   
Patients will be instructed to administer inhaled study drug up to 5 times during the waking day 
as close as possible to the time when they begin to experience OFF symptoms.  The PD 
symptomatology defining the onset of an OFF state may vary by patient, but typically is 
indicated by the return of PD motor symptoms such as tremor or bradykinesia; for some patients, 
OFF episodes may be heralded by non-motor symptoms (e.g., pain or anxiety) shortly prior to 
the appearance of motor symptoms.   
Study drug may not be used for the treatment of early morning OFF periods (i.e., morning 
akinesia).  Patients may not take their inhaled study drug within 45 minutes following their 
previous dose of standard oral PD medication.  These patients may not take oral PRN 
medications to manage OFF states during the study. 
In the event that an OFF state is not sufficiently resolved within 45 minutes of completing the 
last capsule inhalation, patients may resume their usual prescribed PD medication, if they have 
not already done so (i.e., according to their standard dose schedule/regimen); patients may not 
re-dose with inhaled study drug for that episode.  If patients experience more than 5 OFF 
episodes per day that require treatment, they should adhere to their standard oral regimen for 
management of any additional OFF episodes; they may not treat these episodes with additional 
inhalations of study drug.  
Patients will complete the PD Diary for the 3 consecutive days prior to TV2, TV3, TV4, TV5, 
and TV6.  Patients will complete the Inhaled Dosing Log every day during the 12-month 
treatment period.  As described previously, patients will be contacted by the clinic staff 1 to 
3 days after TV1 and 2 weeks (± 3 days) prior to each visit for TV2, TV3, TV4, TV5, and TV6. 
They will bring the PD Diary, Inhaled Dosing Log, empty capsules, inhalers, and unused 
supplies to the each clinic visit.  If the patient begins to run low on study supplies in between 
treatment visits, they should contact the site.  Unused supplies can be re-dispensed to the patient 
at each clinic visit, in addition to a sufficient number of new study drug kits to supply the patient 
until his/her next visit. Note: Any open kit (even if partially unused) may not be re-dispensed. 
10.3.4. 
Treatment Visit/Observational Visit 2 (1 month [4 weeks ±5 days] after 
TV/OV1) 
10.3.4.1. Treatment Visit 2 for the CVT-301 Treatment Group 
Patients will complete the PD Diary for the 3 consecutive days prior to TV2 and the Inhaled 
Dosing Log daily throughout the treatment period.  Patients will bring their usual PD 
medications, the PD Diary, Inhaled Dosing Log, used supplies, including empty capsules and 
inhalers, as well as any unused supplies to the clinic visit.   

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Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further non-study PD medications will be used until following 
completion of all assessments.  The timing of arrival should be scheduled to increase the 
likelihood that patients will be in an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at home).  
The following procedures will be done: 
• Collect, review, sign, and date the PD Diary and Inhaled Dosing Log.   
• Collect used empty capsules and inhalers and unused supplies. 
• Record any changes in the usual PD medication dose/regimen. 
• Record the time that patients took their usual PD medications prior to the visit. 
• Record any changes in concomitant medications. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Perform the C-SSRS. 
• Distribute new study drug kits.  
• Review inhaler training with the patient. 
• Distribute the PD Diary and Inhaled Dosing Log and review instructions for 
completion. 
• Instruct patients to collect used empty capsules, the PD Diary, Inhaled Dosing Log, 
and other study supplies and to bring these items to the next visit. 
• The patient will remain in the clinic until they go into the OFF state.  After 
confirmation of an OFF state (between 2 and 5 hours after the patient has taken 
his/her oral PD medication), record the time of the OFF state and then perform a pre-
dose UPDRS Part 3 assessment. Under clinic staff supervision, patients will prepare 
and self-administer their entire dose of inhaled CVT-301. The dosing time is defined 
to be when the patient’s OFF state is recognized by both the patient and investigator 
to be at a level similar to the investigator-confirmed severity experienced at SV1 and 
preferably between 2 and 5 hours after their prior oral PD medication.    
• Perform serial UPDRS Part 3 assessments at 10, 20, 30, and 60 minutes post-dose. 
• Observe the patient for the appearance of dyskinesia and note in the eCRF if the 
patient experiences dyskinesia at any time within the 60-minute post-dose period.  

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Also, if applicable, record the maximum severity of dyskinesia during the 60-minute 
post-dose period.  
• Observe the patient for the occurrence of an ON state during the 60-minute post-dose 
period and note whether this occurs.  If the patient converts to the ON state, note 
whether or not the patient is still in the ON state at 60 minutes post-dose. 
• Monitor patients for AEs throughout the visit. 
Upon completion of the 60-minute observations, resumption of normal medications is permitted 
for the remainder of the day (the patient may use the inhaled study drug 4 more times at home 
after he/she leaves the clinic on that day if needed for OFF episodes). 
The next visit will be scheduled.  Clinic staff will arrange to speak with patients by telephone 
2 weeks (± 3 days) before TV3 to address any concerns or challenges with the inhaler systems, 
PD Diary, or Inhaled Dosing Log, to monitor for any AEs, to confirm the DLco assessment has 
been done/scheduled, to confirm the next study visit, to ask the patients how many empty study 
drug kits will be returned at the next visit, and to remind patients of the study procedures 
required before the next visit (including completion of the PD Diary and Inhaled Dosing Log).  
Clinic staff will also schedule a DLco assessment within 2 weeks prior to TV3.  The DLco 
assessment should be performed in an ON state (as reported by the patient to the pulmonary 
technician) in the pulmonary function facility.  As part of the procedure, a slow vital capacity 
maneuver will be first, followed by DLco, and then spirometry. 
10.3.4.2. Observational Visit 2 for the Observational Cohort 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further PD medications will be used until following completion of 
all assessments.  The timing of arrival should be scheduled to increase the likelihood that patients 
will be in an ON state upon arrival (i.e., they should arrive to the clinic as shortly as feasible after 
taking their standard oral PD medications at home).  Patients will bring to the clinic all usual PD 
medications. 
The following procedures will be done: 
• Record any changes in the usual PD medication dose/regimen. 
• Record any changes in concomitant medications. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Perform the C-SSRS. 
• Monitor patients for AEs. 

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The next study visit will be scheduled.  Clinic staff will arrange to speak with patients by 
telephone 2 weeks (± 3 days) prior to OV3 to monitor for AEs, to confirm that the DLco 
assessment has been done/scheduled, and to confirm the next study visit.  The DLco assessment 
will be scheduled to occur within 2 weeks prior to the next visit and should be performed while 
the patient is in an ON state (as reported by the patient to the pulmonary technician) at the 
pulmonary function facility.  As part of the procedure, a slow vital capacity will be performed, 
followed by DLco, and then spirometry. 
10.3.5. 
Treatment Visit/Observational Visit 3 (3 months [12±2 weeks] after TV/OV1) 
10.3.5.1. Treatment Visit 3 for the CVT-301 Treatment Group 
Patients will complete the PD Diary for the 3 consecutive days prior to TV3 and the Inhaled 
Dosing Log daily throughout the treatment period.  Patients will bring their usual PD 
medications, the PD Diary, Inhaled Dosing Log, used supplies, including empty capsules and 
inhalers, as well as any unused supplies to the clinic visit. 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further non-study PD medications will be used until following 
completion of all assessments.  The timing of arrival should be scheduled to increase the 
likelihood that patients will be in an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at home).  Patients will bring 
to the clinic all usual PD medications. 
The following procedures will be done: 
• Collect, review, sign, and date the PD Diary and Inhaled Dosing Log.   
• Collect used empty capsules and inhalers and unused supplies. 
• Confirm that the DLco assessment was performed within 2 weeks prior to TV3.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record the time that patients took their usual PD medications prior to the visit. 
• Record any changes in concomitant medications. 
• Patients should complete the PGI-C preferably in the ON state, and this must be done 
prior to other study assessments. 
• The C-SSRS should be completed. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform a 12-lead ECG. 

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• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Distribute new study drug kits. 
• Review inhaler training with the patient. 
• Distribute the PD Diary and Inhaled Dosing Log and review instructions for 
completion. 
• Instruct patients to collect used empty capsules, the PD Diary, Inhaled Dosing Log, 
and other study supplies and to bring these items to the next visit. 
• The patient will remain in the clinic until they go into the OFF state.  After 
confirmation of an OFF state (between 2 and 5 hours after the patient has taken 
his/her oral PD medication), record the time of the OFF state and then perform a pre-
dose UPDRS Part 3 assessment.Under clinic staff supervision, patients will prepare 
and self-administer their entire dose of inhaled CVT-301. The dosing time is defined 
to be when the patient’s OFF state is recognized by both the patient and investigator 
to be at a level similar to the investigator-confirmed severity experienced at SV1 and 
preferably between 2 and 5 hours after their prior oral PD medication.    
• Perform serial UPDRS Part 3 assessments at 10, 20, 30, and 60 minutes post-dose. 
• Observe the patient for the appearance of dyskinesia and note in the eCRF if the 
patient experiences dyskinesia at any time within the 60-minute post-dose period.  
Also, if applicable, record the maximum severity of dyskinesia during the 60-minute 
post-dose period. 
• Observe the patient for the occurrence of an ON state during the 60-minute post-dose 
period and note whether this occurs.  If the patient converts to the ON state, note 
whether or not the patient is still in the ON state at 60 minutes post-dose. 
• Monitor patients for AEs throughout the visit. 
Upon completion of the 60-minute observations, resumption of normal medications is permitted 
for the remainder of the day (the patient may use the inhaled study drug 4 more times at home 
after he/she leaves the clinic on that day if needed for OFF episodes). 
The next visit will be scheduled.  Clinic staff will arrange to speak with patients by telephone 
2 weeks (± 3 days) before TV4 to address any concerns or challenges with the inhaler systems, 
PD Diary, or Inhaled Dosing Log, to monitor for any AEs, to confirm the DLco assessment has 
been done/scheduled, to confirm the next study visit, to ask the patients how many empty study 
drug kits will be returned at the next visit, and to remind patients of the study procedures 
required before the next visit (including completion of the PD Diary and Inhaled Dosing Log).  
Clinic staff will also schedule a DLco assessment within 2 weeks prior to TV4.  The DLco 
assessment should be performed in an ON state (as reported by the patient to the pulmonary 

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technician) in the pulmonary function facility.  As part of the procedure, a slow vital capacity 
maneuver will be first, followed by DLco, and then spirometry. 
10.3.5.2. Observational Visit 3 for the Observational Cohort 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further PD medications will be used until following completion of 
all assessments.  The timing of arrival should be scheduled to increase the likelihood that patients 
will be in an ON state upon arrival (i.e., they should arrive to the clinic as shortly as feasible after 
taking their standard oral PD medications at home).  Patients will bring to the clinic all usual PD 
medications. 
The following procedures will be done: 
• Confirm that the DLco assessment was performed within 2 weeks prior to OV3.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record any changes in concomitant medications. 
• Perform the C-SSRS. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform a 12-lead ECG. 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Monitor patients for AEs. 
The next visit will be scheduled, and clinic staff will arrange to speak with patients by telephone 
2 weeks (± 3 days) prior to OV4 to monitor for AEs, to confirm the DLco assessment has been 
done/scheduled, and to confirm the next study visit.  The DLco assessment will be scheduled to 
occur within 2 weeks prior to the next visit and should be performed while the patient is in an 
ON state (as reported by the patient to the pulmonary technician) at the pulmonary function 
facility.  As part of the procedure, a slow vital capacity will be performed, followed by DLco, 
and then spirometry. 

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10.3.6. 
Treatment Visit/Observational Visit 4 (6 months [24±2 weeks] after TV/OV1) 
10.3.6.1. Treatment Visit 4 for the CVT-301 Treatment Group 
Patients will complete the PD Diary for the 3 consecutive days prior to TV4 and the Inhaled 
Dosing Log daily throughout the treatment period.  Patients will bring their usual PD 
medications, the PD Diary, Inhaled Dosing Log, used supplies, including empty capsules and 
inhalers, as well as any unused supplies to the clinic visit. 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further non-study PD medications will be used until following 
completion of all assessments.  The timing of arrival should be scheduled to increase the 
likelihood that patients will be in an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at home). 
The following procedures will be done: 
• Collect, review, sign, and date the PD Diary and Inhaled Dosing Log.   
• Collect used empty capsules and inhalers and unused supplies. 
• Confirm that the DLco assessment was performed within 2 weeks prior to TV4.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record the time that patients took their usual PD medications prior to the visit. 
• Record any changes in concomitant medications. 
• PDQ-39, PGI-C, UPDRS Part 2, and S&E ADL should be completed, preferably in 
an ON state, and must be done prior to other study evaluations. 
• Patients will complete the UPDRS Part 4 (Questions 32-35 and 36-39). 
• The C-SSRS, Epworth Sleepiness Scale, and QUIP should be completed. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform a 12-lead ECG. 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Distribute new study drug kits.  

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• Review inhaler training with the patient. 
• Distribute the PD Diary and Inhaled Dosing Log and review instructions for 
completion. 
• Instruct patients to collect used empty capsules, the PD Diary, Inhaled Dosing Log, 
and other study supplies and to bring these items to the next visit. 
• The patient will remain in the clinic until they go into the OFF state.  After 
confirmation of an OFF state (between 2 and 5 hours after the patient has taken 
his/her oral PD medication), record the time of the OFF state and then perform a pre-
dose UPDRS Part 3 assessment. Under clinic staff supervision, patients will prepare 
and self-administer their entire dose of inhaled CVT-301. The dosing time is defined 
to be when the patient’s OFF state is recognized by both the patient and investigator 
to be at a level similar to the investigator-confirmed severity experienced at SV1 and 
preferably between 2 and 5 hours after their prior oral PD medication.    
• Perform serial UPDRS Part 3 assessments at 10, 20, 30, and 60 minutes post-dose. 
• Observe the patient for the appearance of dyskinesia and note in the eCRF if the 
patient experiences dyskinesia at any time within the 60-minute post-dose period.  
Also, if applicable, record the maximum severity of dyskinesia during the 60-minute 
post-dose period. 
• Observe the patient for the occurrence of an ON state during the 60-minute post-dose 
period and note whether this occurs.  If the patient converts to the ON state, note 
whether or not the patient is still in the ON state at 60 minutes post-dose. 
• Monitor patients for AEs throughout the visit. 
Upon completion of the 60-minute observations, resumption of normal medications is permitted 
for the remainder of the day (the patient may use the inhaled study drug 4 more times at home 
after he/she leaves the clinic on that day if needed for OFF episodes). 
The next visit will be scheduled.  Clinic staff will arrange to speak with patients by telephone 
2 weeks (± 3 days) before TV5 to address any concerns or challenges with the inhaler systems, 
PD Diary, or Inhaled Dosing Log, to monitor for any AEs, to confirm the DLco assessment has 
been done/scheduled, to confirm the next study visit, to ask the patients how many empty study 
drug kits will be returned at the next visit, and to remind patients of the study procedures 
required before the next visit (including completion of the PD Diary and Inhaled Dosing Log).  
Clinic staff will also schedule a DLco assessment within 2 weeks prior to TV5.  The DLco 
assessment should be performed in an ON state (as reported by the patient to the pulmonary 
technician) at the pulmonary function facility.  As part of the procedure, a slow vital capacity 
maneuver will be performed, followed by DLco, and then spirometry.   
10.3.6.2. Observational Visit 4 for the Observational Cohort 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further PD medications will be used until following completion of 

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all assessments.  The timing of arrival should be scheduled to increase the likelihood that patients 
will be in an ON state upon arrival (i.e., they should arrive to the clinic as shortly as feasible after 
taking their standard oral PD medications at home).  Patients will bring to the clinic all usual PD 
medications. 
The following procedures will be done: 
• Confirm that the DLco assessment was performed within 2 weeks prior to OV4.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record any changes in concomitant medications. 
• Perform the PDQ-39, UPDRS Part 2, and S&E ADL (each preferably in the ON state 
and must be done prior to other study evaluations). 
• Perform the C-SSRS, Epworth Sleepiness Scale, and the QUIP. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform a 12-lead ECG. 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Monitor patients for AEs. 
The next visit will be scheduled and the clinic staff will arrange to call the patient 2 weeks prior 
to OV5 to monitor for AEs, to confirm the DLco assessment has been done/scheduled, and to 
confirm the next study visit.  The DLco assessment will be scheduled to occur within 2 weeks 
prior to the next visit and should be performed while the patient is in an ON state (as reported by 
the patient to the pulmonary technician) at the pulmonary function facility.  As part of the 
procedure, a slow vital capacity will be performed, followed by DLco, and then spirometry. 
10.3.7. 
Treatment Visit/Observational Visit 5 (9 months [36±2 weeks] after TV/OV1) 
10.3.7.1. Treatment Visit 5 for the CVT-301 Treatment Group 
Patients will complete the PD Diary for the 3 consecutive days prior to TV5 and the Inhaled 
Dosing Log daily throughout the treatment period.  Patients will bring their usual PD 
medications, the PD Diary, Inhaled Dosing Log, used supplies, including empty capsules and 
inhalers, as well as any unused supplies to the clinic visit. 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 

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investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further non-study PD medications will be used until following 
completion of all assessments.  The timing of arrival should be scheduled to increase the 
likelihood that patients will be in an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at home).   
The following procedures will be done: 
• Collect, review, sign, and date the PD Diary and Inhaled Dosing Log.   
• Collect used empty capsules and inhalers and unused supplies. 
• Confirm that the DLco assessment was performed within 2 weeks prior to TV5.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record the time that patients took their usual PD medications prior to the visit. 
• Record any changes in concomitant medications. 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Perform the C-SSRS. 
• Distribute new study drug kits. 
• Review inhaler training with the patient. 
• Distribute the PD Diary and Inhaled Dosing Log and review instructions for 
completion. 
• Instruct patients to collect used empty capsules, the PD Diary, Inhaled Dosing Log, 
and other study supplies and to bring these items to the next visit. 
• The patient will remain in the clinic until they go into the OFF state.  After 
confirmation of an OFF state (between 2 and 5 hours after the patient has taken 
his/her oral PD medication), record the time of the OFF state and then perform a pre-
dose UPDRS Part 3 assessment. Under clinic staff supervision, patients will prepare 
and self-administer their entire dose of inhaled CVT-301. The dosing time is defined 
to be when the patient’s OFF state is recognized by both the patient and investigator 
to be at a level similar to the investigator-confirmed severity experienced at SV1 and 
preferably between 2 and 5 hours after their prior oral PD medication.    

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• Perform serial UPDRS Part 3 assessments at 10, 20, 30, and 60 minutes post-dose. 
• Observe the patient for the appearance of dyskinesia and note in the eCRF if the 
patient experiences dyskinesia at any time within the 60-minute post-dose period.  
Also, if applicable, record the maximum severity of dyskinesia during the 60-minute 
post-dose period. 
• Observe the patient for the occurrence of an ON state during the 60-minute post-dose 
period and note whether this occurs.  If the patient converts to the ON state, note 
whether or not the patient is still in the ON state at 60 minutes post-dose. 
• Monitor patients for AEs throughout the visit. 
Upon completion of the 60-minute observations, resumption of normal medications is permitted 
for the remainder of the day (the patient may use the inhaled study drug 4 more times at home 
after he/she leaves the clinic on that day if needed for OFF episodes). 
The next visit will be scheduled.  Clinic staff will arrange to speak with patients by telephone 
2 weeks (± 3 days) before TV6 to address any concerns or challenges with the inhaler systems, 
PD Diary, or Inhaled Dosing Log, to monitor for any AEs, to confirm the DLco assessment has 
been done/scheduled to confirm the next study visit, to ask the patients how many empty study 
drug kits will be returned at the next visit, and to remind patients of the study procedures 
required before the next visit (including completion of the PD Diary and Inhaled Dosing Log).  
Clinic staff will also schedule a DLco assessment within 2 weeks prior to TV6.  The DLco 
assessment should be performed in an ON state (as reported by the patient to the pulmonary 
technician) in the pulmonary function facility.  As part of the procedure, a slow vital capacity 
maneuver will be first, followed by DLco, and then spirometry. 
10.3.7.2. Observational Visit 5 for the Observational Cohort 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further non-study PD medications will be used until following 
completion of all assessments.  The timing of arrival should be scheduled to increase the 
likelihood that patients will be in an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at home).  Patients will bring 
to the clinic all usual PD medications. 
The following procedures will be done: 
• Confirm that the DLco assessment was performed within 2 weeks prior to OV5.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record any changes in concomitant medications. 
• Perform a brief physical examination. 

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• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Perform the C-SSRS. 
• Monitor patients for AEs. 
The next visit will be scheduled and the clinic staff will arrange to call the patient 2 weeks prior 
to OV6 to monitor for AEs, to confirm that the DLco assessment has been done/scheduled, and 
to confirm the next study visit.  The DLco assessment will be scheduled to occur within 2 weeks 
prior to the next visit and should be performed while the patient is in an ON state (as reported by 
the patient to the pulmonary technician) at the pulmonary function facility.  As part of the 
procedure, a slow vital capacity will be performed, followed by DLco, and then spirometry. 
10.3.8. 
Treatment Visit/Observational Visit 6 / Early Withdrawal Visit (12 months 
[52±2 weeks] after TV/OV1) 
10.3.8.1. Treatment Visit 6 / Early Withdrawal Visit for the CVT-301 Treatment Group 
Patients will complete the PD Diary for the 3 consecutive days prior to TV6 and the Inhaled 
Dosing Log daily up until TV6.  Patients will bring their usual PD medications, the PD Diary, 
Inhaled Dosing Log, used supplies including empty capsules and inhalers, as well as any unused 
supplies to the clinic visit. 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further non-study PD medications will be used until following 
completion of all assessments.  The timing of arrival should be scheduled to increase the 
likelihood that patients will be in an ON state upon arrival (i.e., they should arrive to the clinic as 
shortly as feasible after taking their standard oral PD medications at home).  Patients will bring 
to the clinic all usual PD medications. 
The following procedures will be done: 
• Collect, review, sign, and date the PD Diary and Inhaled Dosing Log.   
• Collect used empty capsules and inhalers and unused supplies. 
• Confirm that the DLco assessment was performed within 2 weeks prior to TV6.  If 
the DLco has not been completed prior to the visit, the visit must be rescheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record the time that patients took their usual PD medications prior to the visit. 
• Record any changes in concomitant medications. 

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• Perform the PDQ-39, PGI-C, UPDRS Part 2, and S&E ADL (each preferably in the 
ON state and must be done before other assessments). 
• Patients will complete the UPDRS Part 4 (Questions 32-35 and 36-39). 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform a 12-lead ECG. 
• The C-SSRS, Epworth Sleepiness Scale, and QUIP should be completed. 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• The patient will remain in the clinic until they go into the OFF state.  After 
confirmation of an OFF state (between 2 and 5 hours after the patient has taken 
his/her oral PD medication), record the time of the OFF state and then perform a pre-
dose UPDRS Part 3 assessment. Under clinic staff supervision, patients will prepare 
and self-administer their entire dose of inhaled CVT-301.  The dosing time is defined 
to be when the patient’s OFF state is recognized by both the patient and investigator 
to be at a level similar to the investigator-confirmed severity experienced at SV1 and 
preferably between 2 and 5 hours after their prior oral PD medication.   A new inhaler 
will be provided for this dose, and patients will use study drug from the supplies 
brought to the visit. 
• Perform serial UPDRS Part 3 assessments at 10, 20, 30, and 60 minutes post-dose. 
• Observe the patient for the appearance of dyskinesia and note in the eCRF if the 
patient experiences dyskinesia at any time within the 60-minute post-dose period.  
Also, if applicable, record the maximum severity of dyskinesia during the 60-minute 
post-dose period. 
• Observe the patient for the occurrence of an ON state during the 60-minute post-dose 
period and note whether this occurs.  If the patient converts to the ON state, note 
whether or not the patient is still in the ON state at 60 minutes post-dose. 
• Monitor patients for AEs throughout the visit. 
Once all of the assessments are complete, schedule the patient to undergo a DLco assessment 
4 to 5 weeks after completion of TV6.  The DLco assessment should be performed in an ON 
state (as reported by the patient to the pulmonary technician) in the pulmonary function facility.  
As part of the procedure, a slow vital capacity maneuver will be first, followed by DLco, and 
then spirometry. 

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10.3.8.2. Observational Visit 6 / Early Withdrawal Visit for the Observational Cohort 
Patients will report to the clinic after having taken their usual PD medications prior to the visit.  
The timing of administration of the usual morning dose of PD medication may be adjusted by the 
investigator to accommodate the patient’s and/or clinic’s schedule.  Following their usual 
morning PD medication, no further PD medications will be used until following completion of 
all assessments.  The timing of arrival should be scheduled to increase the likelihood that patients 
will be in an ON state upon arrival (i.e., they should arrive to the clinic as shortly as feasible after 
taking their standard oral PD medications at home).  Patients will bring to the clinic all usual PD 
medications. 
The following procedures will be done: 
• Confirm that the DLco assessment was performed within 2 weeks prior to OV6.  If 
the DLco assessment has not been completed prior to the visit, the study visit must be 
re-scheduled. 
• Record any changes in the usual PD medication dose/regimen. 
• Record any changes in concomitant medications. 
• Perform the PDQ-39, UPDRS Part 2, and S&E ADL (each preferably in the ON state 
and must be before other study evaluations). 
• Perform a brief physical examination. 
• Record standard vital signs (BP, HR, and RR) and orthostatic vital signs (BP and 
HR). 
• Perform 12-lead ECG. 
• Perform spirometry assessment (preferably in the ON state; however, if the patient is 
not in an ON state, perform the evaluation and record the motor state with each 
assessment). 
• The C-SSRS, Epworth Sleepiness Scale, and QUIP should be completed. 
• Collect blood for clinical laboratory tests including serum pregnancy test, if 
applicable.  Document fasting status. 
• Monitor patients for AEs. 
Once all of the assessments are complete, schedule the patient for a DLco assessment 4 to 
5 weeks after OV6.  The DLco assessment should be performed while the patient is in an ON 
state (as reported by the patient to the pulmonary technician) at the pulmonary function facility.  
As part of the procedure, a slow vital capacity will be performed, followed by DLco, and then 
spirometry. 
10.3.9. 
Early Withdrawal Visit 
Patients in the CVT-301 treatment group who withdraw prematurely will complete the TV6 
assessments for the CVT-301 patients (see Section 10.3.8.1), except for the pre-TV6 DLco 
assessment, at the time of withdrawal.  Patients in the observational cohort who withdraw 

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prematurely will complete the OV6 assessments for the observational cohort (see 
Section 10.3.8.2), except for the pre- OV6 DLco assessment, at the time of withdrawal.   
All patients who withdraw early, regardless of treatment group, will be scheduled to undergo a 
DLco assessment 4 to 5 weeks after completion of the Early Withdrawal Visit.  The DLco 
assessment should be performed in an ON state (as reported by the patient to the pulmonary 
technician) in the pulmonary function facility.  As part of the procedure, a slow vital capacity 
maneuver will be first, followed by DLco, and then spirometry. 
10.3.10. 
Unscheduled Visits 
An unscheduled visit may occur when indicated at the discretion of the Investigator.  The 
following are potential circumstances for unplanned visits: 
• If concordance is not reached during SV1, the same training and testing may be 
repeated at an unscheduled visit between SV1 and SV2 or at SV2.  If patients return 
for an unscheduled visit between SV1 and SV2 for concordance training and testing, 
the visit must occur more than 3 days prior to SV2.   
• If a patient is unable to complete a screening assessment at SV2 (repeat SV2), an 
additional visit may be scheduled prior to eligibility determination and 
randomization.  Any repeat assessments should be performed in the respective motor 
state as described for SV1.   
• If a patient develops significant tolerability concerns that in the opinion of the 
investigator are of a severity that should necessitate a reduction in dose, including, 
but not limited to, exacerbation or worsening of troublesome dyskinesia, other 
problematic dopaminergic symptoms, or other tolerability concerns, a dose reduction 
(from 2- to 1-capsule inhalation per dose) will be permitted.  The medical monitor 
should be contacted, and the investigator should use his/her clinical judgment to 
determine if an additional unscheduled visit is required and what assessments should 
be performed (e.g., physical examination, spirometry, etc.).   
11. 
DESCRIPTION OF ASSESSMENTS 
11.1. 
Safety Assessments 
Safety will be assessed from physical examination, AE reporting, standard and orthostatic vital 
signs (BP, RR, and HR), clinical laboratory values (hematology and biochemistry), ECGs, and 
spirometry and DLco for evaluation of pulmonary function.  In addition, UPDRS Part 4, and 
evaluations for assessing suicidality, somnolence, and impulse control disorders will be done. 
11.1.1. 
Physical Examination 
A complete physical examination (head, eyes, ears, nose, and throat [HEENT], heart, lungs, 
abdomen, skin, cervical and axillary lymph nodes, neurological, and musculoskeletal systems) 
will be performed at the visits specified in Appendix 2 through Appendix 15.  Genital, rectal, and 
breast examination may be excluded if not clinically indicated.  Height (cm) and weight (kg) will 
be assessed at screening by qualified personnel.  Physical examinations will be performed by a 

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physician.  In addition, medical history will be recorded at screening, including smoking history, 
if applicable. 
A brief physical exam to verify continued patient eligibility and to follow up any change in 
medical history will be performed at visits specified in Appendix 2 through Appendix 15.  
Symptom-driven brief physical examinations will be performed as clinically indicated at any 
study visit.  All changes identified as clinically noteworthy must be recorded as AEs. 
11.1.2. 
Vital Signs 
Standard Vital Signs 
Vital sign measurements will include RR, BP (systolic [SBP] and diastolic [DBP]), and HR after 
the patient has rested in a supine or semi-supine position for at least 5 minutes. 
Blood pressure must be assessed using an appropriate device, and the arm position must be 
standardized for each patient using a cuff size that is appropriate for the patient.  These 
measurements are to be taken in the same arm for the duration of the study.  The position of the 
cuff on the arm should be in line with the heart with the arm lying next to the patient when semi-
supine and should be in line with the heart at approximately a 45-degree angle from horizontal 
for the standing measurements.  “Standard” BP and HR measurements should be taken after 
resting in a supine or semi-supine position for at least 5 minutes. 
Respiratory rate should be recorded for 30 seconds, and the value multiplied by 2 for the rate per 
minute. 
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur.  If out-of-range BP, RR, or HR results are observed, the assessments may be repeated at 
the investigator’s discretion.  Any confirmed, clinically significant vital sign measurements must 
be recorded as AEs. 
Orthostatic Vital Signs 
At screening (SV1 or SV2) and at each subsequent study visit and in the event of a clinically 
significant finding that could be suggestive of symptomatic orthostatic hypotension (e.g., 
dizziness, lightheadedness, or other AE), orthostatic vital signs will be performed.  During the 
orthostatic vital signs assessment, at least one other staff member familiar with the study (not 
measuring vital signs) must be present should symptoms or an AE occur.   
In order to obtain orthostatic vital signs, patients should undergo the following procedures in 
sequential order: 
1. After the supine/semi-supine BP and HR measurements have been done, the patient will 
be asked to sit on the edge of the bed/table with feet on the floor (or with feet dangling 
from the bed/tableside depending on the height of the bed/table) for approximately 30 
seconds. 
2. The person performing the assessment will then ask the question, “Are you ready to 
stand?” 
• If the patient responds in the affirmative, the patient will proceed to stand and then be 
asked to remain standing for 2 minutes.  After standing for 2 minutes, BP and HR will 
be recorded. 

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• If the patient states that he or she is not ready to stand, the patient will be allowed to 
sit as positioned for 1 additional minute and will be asked again if they are ready to 
stand.  The patient will proceed to stand.  After standing for 2 minutes, one 
measurement will be taken for BP and HR. 
• If the individual is still unable to stand, vital signs will be measured while the patient 
is in an upright seated position. 
Orthostatic hypotension will be defined as a reduction in SBP of 20 mmHg or more, and/or a 
reduction in DBP of 10 mmHg or more, for the standing measurement compared to the 
semi-supine measurement.  If orthostatic hypotension is suspected, the measurement process 
may be repeated at the investigator’s discretion.  Any changes of potential clinical concern will 
be recorded as AEs. 
11.1.3. 
Electrocardiogram 
Standard 12-lead ECGs will be obtained after the patient has rested in a supine position for at 
least 5 minutes.  Electrocardiograms will be measured using an ECG machine that automatically 
calculates the HR and measures PR, QRS, QT, QT interval corrected using Bazett’s formula 
(QTcB) and QT interval corrected using Fridericia’s formula (QTcF).   
Please refer to Appendix 2 through Appendix 15 regarding specific times of ECG assessments at 
individual study visits.  
Electrocardiogram equipment will be provided to each study site to perform all assessments. 
Electrocardiograms will be repeated if clinically significant abnormalities are observed or 
artifacts are present.  Electrocardiograms will be reviewed by qualified staff and over-read by the 
Central ECG Laboratory. 
11.1.4. 
Laboratory Parameters 
Hematology, clinical chemistry, and additional laboratory parameters to be tested are listed in 
Appendix 17.  Patients do not need to be in a fasted state at the time of any laboratory sample; 
however, fasted status will be documented (with fasting defined as at least 4 hours following the 
last meal or snack). 
Laboratory samples will be analyzed by a central laboratory (ACM Global Central Laboratory) to 
ensure consistent interpretation of results.  In the event of an unexplained clinically significant 
abnormal laboratory test value, the test should be repeated immediately and followed up until it 
has returned to the normal range and/or an adequate explanation of the abnormality is found. 
11.1.5. 
Pregnancy Status 
Women of child-bearing potential must have a negative pregnancy test (serum hCG test) at 
screening.  A serum hCG test will be performed at screening (SV1 or SV2) and at TV/OV1, 
TV/OV3, TV/OV4, TV/OV5, and TV/OV6, if applicable. 
If sexually active and the female is of child-bearing potential, the patient (and his/her partner) 
should use adequate contraceptive measures for the duration of the study.  Adequate measures 
should consist of 2 forms of contraception (except in cases of surgical sterilization), at least 1 of 
which must be a barrier method (e.g., male partner uses condoms, plus female partner uses 

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diaphragm and spermicidal gel, or cervical cap and spermicidal gel, or intrauterine device, or 
oral contraceptive pill). 
Female patients found to be pregnant will be withdrawn from further treatment, but will be 
followed for the duration of their pregnancy. 
11.1.6. 
Spirometry 
The following is a description of the pulmonary function testing at clinical sites: 
Pulmonary function will be measured by spirometry using the guideline specified by the Third 
National Health and Nutrition Examination Survey (NHANES III) (Hankinson 1999).  
Spirometry (with the exception of spirometry being performed in conjunction with DLco) will be 
performed by trained and qualified staff at each study site.  Spirometry data will be reviewed by 
a central spirometry laboratory (Biomedical Systems, Inc.) which will provide a quality 
over-read of all evaluations based on acceptability and repeatability metrics in accordance with 
ATS criteria (Miller  et al., 2005).  FEV1, FVC and FEV1/FVC ratio will be recorded from the 
single “best test” (based on effort with highest summed FEV1 and FVC).  Variables and 
comparisons will include the actual and expected forced FEV1, FVC, and FEV1/FVC ratio.  
Patients with FEV1 <50% of predicted for race, age, sex, and height, or FEV1/FVC ratio ≤60% 
in the ON state at screening will be excluded from the study.  A pulmonologist will review the 
spirometry tracings/morphology of any patient with an FEV1 that is ≥50% to <60% of predicted 
or an FEV1/FVC ratio that is >60% to <70% at screening in order to determine eligibility.  All 
patients with an FEV1/FVC ratio that is >60% to <70% at screening will complete spirometry 
before and after the administration of a bronchodilator in a pulmonary function 
laboratory.  Testing will be performed in accordance with the 2005 ATS/ERS criteria.  The 
results of the bronchodilator challenge will be reviewed by a pulmonologist. Any subject 
requiring pulmonary adjudication at screening will not be randomized until after full 
pulmonologist review and approval. 
Spirometry assessments will be done at the time points indicated in Appendix 2 through 
Appendix 15.  The patient’s motor state at the time of each spirometry assessment will be 
recorded.  At SV1, spirometry assessments should be done while the patient is in both the ON 
and OFF states.  At SV2, spirometry assessments will be done only if a repeat measurement is 
needed for assessing eligibility. 
Spirometry equipment will be provided to each study site to perform all spirometry assessments. 
11.1.7. 
Carbon Monoxide Diffusing Capacity  
Patients will undergo diffusing capacity of the lungs for carbon monoxide (DLco) assessments, 
which will be performed in accordance with ATS criteria (Miller  et al., 2005), at a dedicated 
pulmonary function facility after SV2 (and prior to TV/OV1), within 2 weeks prior to TV/OV3, 
TV/OV4, TV/OV5, and TV/OV6, and at 4 to 5 weeks after TV/OV6, as described in the 
Appendix 2 through Appendix 15.  These assessments should be performed while the patient is 
in the ON state (as reported by the patient to the pulmonary technician).  Trained and qualified 
pulmonary function facility technicians will perform a slow vital capacity maneuver, followed by 
DLco, and then spirometry. 

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DLco and slow vital capacity maneuvers will be assessed and processed in accordance with 
ATS/ERS standards.  Spirometry procedures will be conducted at the same visits in the same 
manner as those conducted at clinical sites in accordance with ATS criteria (see Section 11.1.6). 
All DLco data collected at pulmonary function labs will be sent to and reviewed by a central 
Pulmonary Function Testing reviewer (TechEd Consultants).   
11.1.8. 
Adverse Events 
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
or, if present at the start of the study, worsens during the study, regardless of the suspected cause 
of the event.  Changes in conditions present at screening and new symptoms, physical signs, 
syndromes, or diseases should be noted on the AE page of the eCRF during the study.  Any AEs 
reported prior to the first study treatment (or TV/OV1) will be considered baseline AEs, and AEs 
reported from first treatment (or TV/OV1) will be considered treatment-emergent adverse events 
(TEAEs).  
AEs may be volunteered spontaneously by the patient, discovered as a result of general 
questioning by the study staff, or determined by physical examination.  At each visit, the patient 
will be asked, “Have you experienced any problems since your last visit?”  All AEs will be 
recorded on the eCRF.  For all AEs, the investigator must pursue and obtain information 
adequate both to determine the outcome of the AE and to assess whether it meets the criteria for 
classification as a serious AE requiring immediate notification.  Follow-up of the AE, even after 
the date of therapy discontinuation, is required if the AE persists until the event resolves or 
stabilizes at a level acceptable to the investigator. 
In order to avoid vague, ambiguous, or colloquial expressions, all AEs should be recorded in 
standard medical terminology rather than the patient’s own words.  Each AE will also be 
described in terms of duration, frequency, intensity, association with the study medication, 
assessment of possible causes, actions taken, and outcome, using choices given on the eCRF.  
Specific guidelines for classifying AEs by intensity and relationship to study medication are 
given in Table 3 and 
 respectively. 
Table 3 
Classification of Adverse Events by Intensity 
MILD:  An event that is easily tolerated by the patient, causing minimal discomfort and not 
interfering with everyday activities. 
Table 4,
MODERATE:  An event that is sufficiently discomforting to interfere with normal everyday 
activities. 
SEVERE:  An event that prevents normal everyday activities. 
 
 

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Table 4 
Classification of Adverse Events by Relationship to Study Medication 
Definitely not related:  The AE is definitely not related to the drug.  This designation should be 
reserved for those events which occur prior to study treatment or for those events which cannot be 
even remotely related to study participation (e.g., injuries sustained in an automobile accident as a 
passenger). 
Unlikely related:  There is no reasonable association between the study treatment and the suspected 
event and the event could have been produced by the patient's clinical state or other modes of therapy 
administered to the patient. 
Possibly related:  The suspected adverse event may or may not follow a reasonable temporal 
sequence from study treatment administration but seems to be the type of reaction that cannot be 
dismissed as unlikely.  The event could have been produced or mimicked by the patient's clinical state 
or by other modes of therapy concomitantly administered to the patient. 
Probably related:  The suspected adverse event follows a reasonable temporal sequence from study 
treatment administration, abates upon discontinuation of the treatment, and cannot be reasonably 
explained by the known characteristics of the patient's clinical state. 
Definitely related:  This designation should be reserved for those events which have no uncertainty 
in their relationship to treatment administration. 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the experience should be noted.  If the intensity category changes over a number of 
days, then those changes should be recorded separately (with distinct onset dates). 
11.1.9. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any AE that meets 1 or more of the following 
criteria: 
• The event results in death. 
• The event is life-threatening. 
• The event is permanently disabling (incapacitating or interfering with the ability to 
resume usual life patterns). 
• The event results in unplanned inpatient hospitalization or prolongation of existing 
hospitalization. 
• The event is a congenital anomaly. 
• The event requires medical intervention of any kind in order to prevent any of the 
aforementioned outcomes. 
A serious AE is not necessarily severe; for example, an overnight hospitalization for a diagnostic 
procedure must be reported as a serious AE even though the occurrence is not medically serious.  
By the same token, a severe AE is not necessarily serious:  for example, nausea of several hours’ 
duration may be rated as severe but may not be considered serious. 
An SAE occurring during the study or within 4 weeks of stopping the treatment must be reported 
to the 
 and will be communicated to the Sponsor.  Any such SAE 
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24 hours of occurrence or when the investigator becomes aware of the event.  Notification 
can be made using the following fax or email address for the 
: 
  
 
The event must also be recorded on the standard AE eCRF.  Preliminary reports of SAEs must be 
followed by detailed descriptions later on, including clear and anonymized photocopies of 
hospital case reports, consultant reports, autopsy reports, and other documents when requested 
and applicable.  SAE reports must be made whether or not the investigator considers the event to 
be related to the investigational drug. 
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded.  Clinical, laboratory, and diagnostic measures should be employed as needed in order 
to determine the etiology of the problem.  The investigator must report all additional follow-up 
evaluations to the 
 within 10 calendar days.  All SAEs will be 
followed until the investigator and Sponsor agree the event is satisfactorily resolved. 
11.1.10. 
Suspected Unexpected Serious Adverse Reactions 
Adverse events which meet all of the following criteria will be classified as suspected 
unexpected serious adverse reactions (SUSARs) and will be reported to the appropriate 
regulatory authorities in accordance with applicable regulatory requirements for expedited 
reporting: 
• Serious 
• Unexpected (i.e., is not consistent with the applicable product information such as the 
Investigator's Brochure for an unapproved investigational product or summary of 
product characteristics or product insert for an authorized product) 
• There is at least a reasonable possibility that there is a causal relationship between the 
event and the medicinal product.  
It is the Sponsor’s responsibility to report SUSARs to the IRBs, IECs, and regulatory agencies in 
each country, although this responsibility may be delegated to the contract research organization 
(CRO).  The procedures for notifying the health authorities and the IRBs/IECs of all 
SAEs/SUSARs (as appropriate) will be documented in the CRO study-specific and Sponsor 
standard operating procedure (SOP).  SUSARs will be reported to the appropriate health 
authorities within 7 or 15 days (as appropriate). 
11.1.11. 
Other Significant Adverse Events 
To ensure patient safety, the investigator should also notify the medical monitor should any AE 
occur that is considered significant but does not meet criteria for an SAE, or that is considered 
unexpected.  An unexpected AE is an AE that is not identified in nature, intensity, or frequency 
in the investigational drug brochure.  The medical monitor and/or Sponsor may then choose to 
discontinue the patient from the study.  In addition, any field monitor who notes a significant AE 

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or medical condition while reviewing the eCRFs or source documents at the site must 
immediately convey this information to the medical monitor. 
11.1.12. 
Other Safety Assessments 
11.1.12.1. UPDRS Part 4 (CVT-301 Treatment Group) and Examiner-Rated Dyskinesia 
The UPDRS Part 4 is an assessment of potential complications of PD therapies.  Questions 32-35 
(related to dyskinesias) and 36-39 (related to clinical fluctuations) only will be completed for the 
CVT-301 patients as indicated in the time and events tables in Appendix 2 through Appendix 15.   
Additionally, during the post-dosing follow-up period at TV/OV2, TV/OV3, TV/OV4, TV/OV5, 
and TV/OV6, observe the patient for the appearance of dyskinesia, and note in the eCRF if the 
patient experiences dyskinesia within the 60-minute post-dose period.  If applicable, record the 
maximum severity of any dyskinesia during the 60-minute post-dose period.  The examiner will 
also note if the patient converts to the ON state during the 60-minute post-dose period and if so, 
whether the patient is still in the ON state at 60 minutes post-dose. 
11.1.12.2. Columbia-Suicidality Severity Rating Scale 
The C-SSRS is a measure of suicidal ideation and behavior.  The rating scale has 4 general 
categories:  suicidal ideation, intensity of ideation, suicidal behavior, and actual attempts.  An 
initial baseline version will be given at TV/OV1, and a “since last visit” version will be given at 
all treatment visits to detect any emergence of suicidal ideation or behavior.  The clinic staff 
should address any emerging neuropsychiatric needs in the event that the C-SSRS indicates 
active suicidal ideation. 
11.1.12.3. Epworth Sleepiness Scale 
The Epworth Sleepiness Scale is used to determine the level of daytime sleepiness.  There are 
8 situations listed (e.g., sitting and reading, watching television) for which patients rate their 
likelihood of dozing or sleeping (0=would never doze or sleep, 1=slight chance of dozing or 
sleeping, 2=moderate chance of dozing or sleeping, and 3=high chance of dozing or sleeping).  A 
score of 10 or more is considered sleepy, and a score of 18 or more is very sleepy.  The baseline 
assessment will be completed at TV/OV1 of this study.  As described in the time and events 
tables in Appendix 2 through Appendix 15, additional assessments will be completed at TV/OV4 
and TV/OV6. 
11.1.12.4. Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease 
The QUIP is an instrument used to measure the extent of impulsive and compulsive behaviors in 
PD patients.  The QUIP has 3 sections:  Section 1 assesses gambling, sexual, buying, and eating 
disorders; Section 2 assesses other compulsive behaviors (punding, hobbyism, and walkabout); 
and Section 3 assesses compulsive medication use.  The baseline assessment will be completed 
at TV/OV1 of this study.  As described in the time and events tables in Appendix 2 through 
Appendix 15, additional assessments will be completed at TV/OV4 and TV/OV6. 

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11.2. 
Exploratory Efficacy Assessments  
Exploratory efficacy will be evaluated primarily for the CVT-301-treated patients.  Exploratory 
fficacy will be evaluated from both in-clinic, at-home assessments, and patient-reported 
assessments as outlined by the criteria below.  A limited number of patient-reported assessments 
identified in the subsections below (i.e., the PDQ-39, UPDRS Part 2, and S&E ADL) will also be 
performed in the observational cohort. 
In-Clinic Criteria: 
• UPDRS Part 3 motor score 
• Occurrence of an ON state during the 60-minute post-dose period and if an ON state 
occurs during the 60-minute post-dose, whether or not the patient is still in the ON 
state at 60 minutes post-dose 
At-Home Criteria and/or Patient-Reported Assessments: 
• Total daily OFF time at home, total daily ON time without dyskinesia, total daily ON 
time with non-troublesome dyskinesia, and total daily ON time with troublesome 
dyskinesia, based on the PD Diary.  
• PDQ-39 
• PGI-C 
• S&E ADL 
• UPDRS Part 2 
11.2.1. 
Assessment of ON and OFF States and Dyskinesia (CVT-301 Treatment Group) 
An “OFF state” is defined as the time when medication is not providing benefit with respect to 
mobility, slowness, and stiffness.  OFF episodes may be heralded by non-motor symptoms (e.g., 
pain, anxiety) prior to the appearance of motor symptoms.   
An “ON state” is defined as the time when medication is providing benefit with respect to 
mobility, slowness, and stiffness, and may or may not be providing complete alleviation of all 
PD symptoms. 
For recording motor state in the PD Diary, when patients are in an ON state, the presence and 
extent of dyskinesia (involuntary twisting, turning movements that are an effect of medication) 
will also be noted: 
• ON with no dyskinesia 
• ON with non-troublesome dyskinesia (ON with dyskinesia that does not interfere 
with function or cause meaningful discomfort) 
• ON with troublesome dyskinesia (ON with dyskinesia that interferes with function or 
causes meaningful discomfort) 
These ON and OFF definitions are to be used in training the patients to recognize and record 
their ON and OFF states.  Patients will record their ON and OFF states in their diaries at home.   

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11.2.1.1. In-Clinic Assessments (CVT-301 Treatment Group) 
See Section 11.1.12.1. 
11.2.1.2. At-Home Assessments 
11.2.1.2.1. PD Diary 
During the 3 consecutive days prior to SV2 and TV/OV1, TV/OV2, TV/OV3, TV/OV4, 
TV/OV5, and TV/OV6, patients in the CVT-301 treatment group will record their waking 
ON/OFF status (time OFF, time ON without dyskinesia, time ON with non-troublesome 
dyskinesia, time ON with troublesome dyskinesia) and time asleep in the PD Diary (also referred 
to as the PD Home Diary or “Hauser diary”) (Hauser 2000).   
Patients in the observational cohort will complete the PD Diary for 3 consecutive days prior to 
SV2 and TV/OV1, but will not be required to complete the PD Diary for the remainder of the 
study.  
New diaries will be distributed to appropriate patients at each study visit, except for TV/OV6, 
and patients will bring the completed diaries to the following clinic visit.  Information in the 
diaries will be reviewed, signed, and dated by clinic staff. 
11.2.1.2.2. Screening ON/OFF Episodes Log (for the Screening Period) 
All patients will record the discrete number of OFF episodes experienced by the patient during 
their waking day in the Screening ON/OFF Episodes Log for the 3 consecutive days prior to SV2 
and TV/OV1.  These logs will be distributed at SV1 and SV2, and patients will bring the 
completed logs to the clinic at SV2 and TV/OV1.  Information in the logs will be reviewed, 
signed, and dated by clinic staff. 
11.2.1.2.3. Inhaled Dosing Log (for the Treatment Period) for CVT-301 Treatment Group 
Every day during the treatment period, patients in the CVT-301 treatment group will record the 
number of times the inhaler was used and the number of capsules used for each inhalation 
treatment.  New logs will be distributed at TV/OV1, TV/OV2, TV/OV3, TV/OV4, and TV/OV5, 
and patients will bring the completed logs to the clinic at TV/OV2, TV/OV3, TV/OV4, TV/OV5, 
and TV/OV6.  Information in the logs will be reviewed and recorded by clinic staff. 
11.2.2. 
UPDRS Part 3 (CVT-301 Treatment Group) 
The UPDRS Part 3 is the motor section of the UPDRS examination, given by interview with 
actions by the patient.  Some questions require multiple ratings to be assigned to each extremity.  
The areas addressed by this exam include speech, facial expression, tremor at rest, postural 
tremor, rigidity, finger taps, hand movements, rapid alternating movement (hands), leg agility, 
arising from a chair, posture, gait, postural stability, and body bradykinesia/ hypokinesia. 
The UPDRS Part 3 will be assessed at screening in both ON and OFF states to familiarize the 
patient with the study evaluations as well as to document each patient’s response to his/her own 
PD medications; to enter the study, the difference between UPDRS Part 3 scores in the ON and 
OFF states must be ≥25%.  

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The percent difference is calculated as follows: 
([UPDRS III value in OFF state] – [UPDRS III value in ON state])/ UPDRS III value in OFF state 
The UPDRS Part 3 assessments will be done for the CVT-301 patients at TV/OV2, TV/OV3, 
TV/OV4, TV/OV5 and TV/OV6, immediately before and at various time points after study 
medication dosing, as indicated in the time and events tables in Appendix 2 through Appendix 
15. 
11.2.3. 
PDQ-39 
The PDQ-39 is a self-report questionnaire that covers 8 aspects of quality of life:  mobility, 
activities of daily living, emotions, stigma, social support, cognitions, communication, and 
bodily discomfort.  Scores are reported for each of the 8 quality of life scales and for the total of 
all 39 items. 
The PDQ-39 will be completed upon arrival for patients assigned to the CVT-301 treatment 
group and the observational cohort as indicated in the time and events tables in Appendix 2 
through Appendix 15. 
11.2.4. 
PGI-C (CVT-301 Treatment Group) 
For this study, the PGI-C is a 7-point scale that requires the patient to rate their overall condition 
with regard to PD by answering the following question:  How has the addition of study drug 
changed your Parkinson’s disease?  This change is rated as 1 = much improved; 2 = improved; 
3 = a little improved; 4 = no change; 5 = a little worse; 6 = worse; or 7 = much worse.  If the 
assessment is not done, then the score is marked as 0; any values of zero are not included in any 
analyses and thus are treated as missing. 
The PGI-C scale will be completed by the patients in the CVT-301 treatment group as indicated 
in the time and events tables in Appendix 2 through Appendix 15. 
11.2.5. 
Schwab & England Activities of Daily Living 
The S&E ADL scale will be completed by a qualified rater upon arrival for patients assigned to 
the CVT-301 treatment group and the observational cohort as indicated in the time and events 
tables in Appendix 2 through Appendix 15, preferably while the patient is in the ON state. 
11.2.6. 
UPDRS Part 2 
The UPDRS Part 2 is an evaluation of the ADL; this will be completed by a qualified rater upon 
arrival for patients assigned to the CVT-301 treatment group and the observational cohort as 
indicated in the time and events tables in Appendix 2 through Appendix 15, preferably while the 
patient is in the ON state.   
11.3. 
Other Assessments Used for Baseline Disease Characteristics for all 
Patients 
Patients’ PD diagnosis will be documented by the UK Brain Bank criteria, and PD severity will 
be staged using the modified Hoehn and Yahr disease severity scale.  The MMSE is used to 
assess the patient’s cognitive state. 

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11.3.1. 
UK Brain Bank Criteria 
Steps 1 and 2 of the UK Brain Bank criteria will be used to confirm the patient’s PD diagnosis.  
Step 1 requires that the patient have certain signs and symptoms of Parkinsonian syndrome, and 
Step 2 lists exclusion criteria that the patient must not have to be diagnosed with PD.  The UK 
Brain Bank criteria are presented in Appendix 18 and discussed in Hughes (1992). 
11.3.2. 
Modified Hoehn and Yahr PD Severity Scale Assessment 
PD severity will be staged using the modified Hoehn and Yahr disease severity scale (refer to 
Appendix 19). 
11.3.3. 
MMSE 
The MMSE is a brief, 30-point test used to screen for cognitive impairment.  The categories 
tested include orientation to time, orientation to place, registration, attention and calculation, 
recall, language, repetition, and complex commands.  Any score ≥25 points is considered 
normal.  Scores below 25 can indicate mild (21-24 points), moderate (10-20), or severe (0-9) 
cognitive impairment. 
11.3.4. 
Pulmonary Function Baseline Questionnaire 
The patient’s pulmonary history will be recorded by completing the Pulmonary Function 
Baseline Questionnaire at screening.  Site staff will administer the Pulmonary Function Baseline 
Questionnaire to all patients.  The questionnaire includes sections for recording asthma, COPD, 
and other lung or airway disease symptom history.  There is also a section for recording patient-
reported instances of current pulmonary symptomology. 
11.4. 
Appropriateness of Measurements 
All safety assessments to be used in this study are commonly used, standard measurements 
frequently seen in PD studies and/or pulmonary studies.  The modified Hoehn and Yahr disease 
severity scale is a validated method of assessing the severity of PD, and the UPDRS Part 3 is a 
validated tool measuring the motor aspects of a PD patient.  The UPDRS Part 2, UPDRS Part 4, 
and S&E ADL rating scales are also standard tools for the assessment of PD patients.  Rater 
training in UPDRS Part 2, UPDRS Part 3, UPDRS Part 4, S&E ADL and C-SSRS scales will be 
given to clinic staff members who plan to administer the tests.  The PDQ-39 is a validated 
quality of life measure for PD patients.  The PGI-C scale is a tool for assessing patient-perceived 
changes in their overall disease condition.  The PD Diary to be used in this study (also referred to 
as the Hauser diary) has been validated for use in PD patients as a tool to assess patient-defined 
clinical status at home over a period of time (recording daily OFF time, ON time, and time with 
non-troublesome and troublesome dyskinesia). 
12. 
DATA MANAGEMENT AND STATISTICAL ANALYSIS 
Completed eCRFs for this study will be entered by electronic data capture (EDC) into the study 
database.  The statistical analysis of these data will be performed by the Sponsor or its 
representative.  The statistical evaluation will be performed using the Statistical Analysis 
Software (SAS®) Version 9.3 or higher (SAS Institute, Cary, NC).  All data will be listed, and 

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summary tables will be provided.  Summary statistics will be presented by treatment group 
(when applicable). 
This section describes the statistical analysis as it is foreseen at the time of planning the study.  
Any major deviations from this plan, the reasons for such deviations, and all alternative or 
additional statistical analyses that may be performed will be described in the statistical analysis 
plan (SAP), which will give a detailed technical description of all statistical analyses.   The SAP 
will serve as a compliment to the protocol and supersedes it in case of differences. 
12.1. 
Determination of Sample Size 
Approximately 250 CVT-301 treatment patients and 115 control patients will be enrolled in this 
study. It is assumed that the drop-out rate will be approximately 25%. 
Assuming that there is no difference in the changes from baseline between the CVT-301-treated 
patients and the observational cohort in regards to FEV1, the study has the following power for 
the comparison between the 2 groups.  The upper limit of the 95% confidence interval for the 
difference between the 2 groups in change from baseline in FEV1 will be less than 0.121 L with 
90% power, assuming 188 and 86 patients completing the study in the CVT-301 treatment group 
and observational cohort, respectively.   
12.2. 
Study Populations 
All patients who are enrolled in CVT-301-005 and receive at least 1 dose of CVT-301 will be 
included in the safety population.  The patients in the observational cohort will be included in the 
analyses if they provide any data after TV/OV1. 
12.3. 
Definition of Baseline 
In all statistical analyses of the CVT-301 treatment group, the visit at which the CVT-301 
treatment was initiated will be used as the baseline.  However, for all patients who were included 
in the CVT-301-002 or CVT-301-003 studies, TV/OV1 of the CVT-301-005 study will be used 
as baseline.  For the observational cohort, the assessments at TV/OV1 will be used as baseline.   
12.4. 
Background and Demographic Characteristics 
Demographics and baseline characteristics will be summarized descriptively for patients treated 
with CVT-301 and for the patients in the observational cohort.  In addition to the total CVT-301 
group, the data from the CVT-301 naïve patients who are enrolled in this study and from the 
patients who were previously enrolled in the CVT-301-002 or CVT-301-003 studies will be 
summarized separately.  At least the following variables will be summarized: 
• Demographics (age, gender, race, height, weight) 
• Smoking history (current, former, never: pack-years for current and former smoker) 
• History of PD (UK Brain Bank criteria, time since diagnosis of PD, duration of LD 
treatment) 

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• LD treatment at baseline (total daily dose, dosing frequency, decarboxylase inhibitor 
[CD or benserazide], use of standard/quick/controlled release LD, use of COMT 
inhibitor) 
• Other antiparkinsonian treatment at baseline (use of dopamine agonists, MAO-B 
inhibitors, anticholinergics, amantadine, or other treatment) 
• Disease severity (modified Hoehn and Yahr stage [in the ON state], UPDRS Part 3 at 
screening) 
• Cognitive status (MMSE) 
• Average daily number of OFF episodes experienced (determined from Screening 
ON/OFF Episodes and Treatment Log. 
12.5. 
Safety Analysis 
The disposition of the patients will be summarized by tabulating the number of screened, 
randomized, completed, and discontinued patients.  The reasons for premature discontinuations 
will be tabulated. 
The extent of exposure to study treatment will be summarized for the patients who received 
CVT-301 treatment.  The time period between TV/OV1 and TV/OV6 (or Early Withdrawal 
Visit) will be used as the measure of extent of exposure for the patients randomized to the 
observational cohort.  Adverse events will be tabulated by treatment group according to the 
Medical Dictionary for Regulatory Activities (MedDRA).  Study-emergent and 
treatment-emergent adverse events (TEAEs) will be summarized by body system and preferred 
term.  For patients in the observational cohort, the AEs collected between TV/OV1 and TV/OV6 
(or Early Withdrawal Visit) will be considered as TEAEs.   Furthermore, the time of onset of the 
TEAEs will be summarized.  
For vital signs, ECG parameters, spirometry measurements, and DLco, the changes from 
pre-dose to post-dose assessments of the corresponding day will be calculated and described 
using descriptive statistics.  For spirometry, DLco, and safety laboratory variables, the 
differences in pre-dose values between the study days will be described.  Furthermore, the 
changes in the spirometry values and difference between the groups will be estimated using a 
Mixed Model for Repeated Measurements (MMRM) similar to the one used for the efficacy 
variables.  The proportion of patients with abnormal spirometry values will be tabulated using 
different criteria for the threshold (e.g., at least 10% or 20% change from baseline at any single 
visit, at least 10% or 20% change from baseline on at least 2 consecutive visits).  The proportions 
of patients meeting ATS quality criteria (and also for those ‘rejected’) will be summarized.  All 
spirometry analyses will be performed both for all patients regardless of the ATS quality criteria 
and separately excluding the assessments not meeting the ATS quality criteria.   
At least the following variables will be analyzed: 
• Vital signs:  standard and orthostatic systolic and diastolic BP and HR. 
• ECG:  HR, PR, QRS, QT and RR intervals, QTcB (Bazett's correction formula 
calculated as QT/RR1/2) and QTcF (Fridericia's correction formula calculated as 

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QT/RR1/3).  ECG parameter values or parameter changes of potential clinical concern 
will be tabulated.  
• Spirometry: FEV1, FVC, and the FEV1/FVC ratio during specified treatment visits 
and over the course of the study will be evaluated.  The number and proportion of 
patients with pre-specified changes in spirometry parameters will be tabulated. 
Changes from baseline to follow-up in the rating scales for assessing suicidality, somnolence, 
and impulse control disorders will be summarized descriptively.   
12.5.1. 
Interim Safety Data Review 
Safety data will be reviewed by a DSMC that will include relevant medical experts (including a 
neurologist and pulmonologist), an independent statistician, and additional representatives (as 
will be defined in the DSMC Charter).  Safety data, including but not limited to AEs, spirometry, 
vital signs, and ECG data will be reviewed.  The safety review will be documented in a DSMC 
Charter prior to the start of the study.  In the event that potential safety issues are identified, the 
committee may recommend modification of the study design or study termination, which will be 
communicated promptly with investigators, IRBs, IECs, and regulatory agencies, in accordance 
with legal and regulatory requirements.  Interim analyses, which will not affect study conduct, 
may be performed to support regulatory submissions. These analyses will be described in the 
SAP. 
12.6. 
Exploratory Efficacy Analysis 
The derivation of the exploratory efficacy variables will be defined in detail in the SAP. 
The changes from baseline in continuous exploratory efficacy variables will be estimated using 
an MMRM.  The model will include visit and the stratification variables (Hoehn and Yahr stage 
and screening FEV1 and/or FEV1/FVC) as fixed factors.  The baseline value will be used as a 
covariate.  For variables which do not have a pre-treatment baseline assessment, OFF-state 
baseline UPDRS Part 3 score will be used as the baseline covariate.  An unstructured covariance 
structure will be applied for the MMRM.  In case the model will not converge with the 
unstructured covariance structure, compound symmetry will be used instead.  
The sensitivity analyses will be specified in the SAP.  Sensitivity analysis will be performed at 
least for the method to handle missing data (e.g., last observation carried forward, pattern 
mixture model using multiple imputation instead of MMRM), definition of analysis population 
(e.g., patients completing the study instead of observed cases), and statistical method (e.g., 
analysis of covariance [ANCOVA] models separately for each visit instead of MMRM). 
The categorical data will be primarily evaluated descriptively.  Each visit will be evaluated 
separately for the categorical endpoints. 
The exploratory efficacy data collected from the patients in the observational cohort will be 
summarized with descriptive statistics. 

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13. 
STUDY MANAGEMENT 
13.1. 
Approval and Consent 
13.1.1. 
Regulatory Guidelines 
The study will be performed under good clinical practice (GCP) in accordance with the 
guidelines of the International Conference on Harmonisation (ICH), in accordance with United 
States of America (USA) Investigational New Drug (IND) regulations (21 Code of Federal 
Regulations [CFR] 312), and the local national laws (as applicable). 
13.1.2. 
Institutional Review Board/Independent Ethic Committees 
Conduct of the study must be approved by an appropriately constituted IRB or IEC.  Approval is 
required for the study protocol, investigational drug brochure, protocol amendments, informed 
consent forms, patient information sheets, and advertising materials.  No drug will be shipped to 
a site until written IRB or IEC authorization has been received by the Sponsor or its 
representative. 
13.1.3. 
Informed Consent 
For each study patient, written informed consent will be obtained prior to any protocol-related 
activities.  As part of this procedure, the principal investigator or one of his/her associates must 
explain orally and in writing the nature, duration, and purpose of the study, and the action of the 
drug in such a manner that the patient is aware of the potential risks, inconveniences, or adverse 
effects that may occur.  The patient should be informed that he/she may withdraw from the study 
at any time, and the patient will receive all information that is required by local regulations and 
ICH guidelines.  The principal investigator will provide the Sponsor or its representative with a 
copy of the IRB/IEC-approved informed consent form prior to the start of the study. 
13.2. 
Financing and Insurance 
Prior to the trial commencing, the Sponsor (or its designee) and the investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study.  This agreement 
will be documented in a financial agreement that will be signed by the investigator (or the 
institution signatory) and the Sponsor (or its designee). 
The Sponsor has insurance coverage for trial-related, medicine-induced injury, and other 
liabilities incurred during clinical trials which will provide compensation for any study-related 
injury according to the guidelines set out by the Association of the British Pharmaceutical 
Industry, namely “Clinical Trials Compensation for Medicine Induced Injury.”  The Sponsor will 
provide local country-specific insurance, as required. 
13.3. 
Discontinuation of the Study by the Sponsor 
The Sponsor reserves the right to discontinue the study at this site or at multiple sites for safety 
or administrative reasons at any time.  In particular, a site that does not recruit at a reasonable 
rate may be discontinued.  Should the study be terminated and/or the site closed for whatever 
reason, all documentation, clinical supplies, and study medication pertaining to the study must be 
returned to the Sponsor or its representative. 

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13.4. 
Study Documentation 
By signing a copy of country-specific regulatory forms, the principal investigator acknowledges 
that he/she has received a copy of the investigational drug brochure on CVT-301 and assures the 
Sponsor that he/she will comply with the protocol and the provisions stated in the country-
specific forms.  No changes in this protocol can be made without the Sponsor’s written approval. 
The investigator (CRO, if applicable) will supply the Sponsor with the following documents: 
• Original, signed Food and Drug Administration (FDA) Form 1572 and other 
country-specific forms 
• Original signed FDA financial disclosure forms 
• Curricula vitae for all investigators listed on country-specific forms 
• Copy of principal investigator’s medical licensure/medical registration number 
• Signed protocol signature page 
• List of IRB/IEC members and their occupations/affiliations or multiple assurance 
number 
• Letter indicating IRB/IEC approval to conduct the protocol 
• Copy of IRB/IEC-approved informed consent form 
• The Sponsor will supply the investigator with the following documents: 
• Clinical study protocol 
• Investigational drug brochure 
• Sample informed consent form 
• Case report forms/ instruction manual 
• Insurance letter 
13.5. 
Data Handling 
Any data to be recorded directly in the eCRF (to be considered as source data) will be identified 
at the start of the trial. 
Accurate and reliable data collection will be assured by 100% verification and cross-check of the 
eCRFs against the investigator’s records by the study monitor.  A comprehensive validation 
check program will verify the data, and queries will be generated for resolution by the 
investigator.  During monitoring visits, the monitor will also generate data queries via the eCRF 
system for resolution by the investigator. 
13.6. 
Study Monitoring and Auditing 
This study will be monitored at all stages of its development by the clinical research personnel 
employed by the Sponsor or its representative.  Monitoring will include personal visits and 
telephone communication to assure that the investigation is conducted according to protocol and 
in order to comply with guidelines of GCP.  On-site review of eCRFs will include a review for 

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completeness and clarity, and consistency with source documents available for each patient.  
Note that a variety of original documents, data, and records may be considered as source 
documents in this trial. 
Medical advisors and clinical research associates or assistants may request to witness patient 
evaluations occurring as part of this protocol.  The investigator and appropriate personnel will be 
periodically requested to attend meetings/workshops organized by the Sponsor to assure 
acceptable protocol execution.  The study may be subject to audit by the Sponsor, by the CRO, 
or by regulatory authorities.  If such an audit occurs, the investigator must agree to allow access 
to required patient records.  By signing this protocol, the investigator grants permission to 
personnel from the Sponsor, its representatives, and appropriate regulatory authorities for on-site 
monitoring of all appropriate study documentation, as well as on-site review of the procedures 
employed in eCRF generation, where clinically appropriate. 
13.7. 
Retention of Records 
The investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of patient health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability and Accountability Act of 1996 [HIPAA] Privacy Regulation) or 
equivalent. The investigator shall ensure that study patients authorize the use and disclosure of 
protected health information in accordance with HIPAA Privacy Regulation and in a form 
satisfactory to the Sponsor. 
The investigator must arrange for retention of study records at the site.  The nature of the records 
and the duration of the retention period must meet the requirements of the relevant regulatory 
authority.  In addition, because this is an international study, the retention period must meet the 
requirements of the most stringent authority.  The investigator should take measures to prevent 
accidental or premature destruction of these documents. 
13.8. 
Use of Study Findings 
By signing the study protocol, the investigator agrees to the use of results of the study for the 
purposes of national and international registration.  If necessary, the authorities will be notified 
of the investigator’s name, address, qualifications, and extent of involvement.  Reports covering 
clinical and biometric aspects of the study will be prepared by the Sponsor or its representative. 
13.9. 
Publication 
As a multicenter trial, the Sponsor intends to publish clinical data from all centers participating 
in the investigation.  A publication committee selected by the Sponsor will submit draft 
manuscripts to an assigned authorship committee for their comments.  In conformity with the 
uniform requirements for manuscripts submitted to biomedical journals published by the 
International Committee of Medical Journal Editors, investigators whose contribution consists 
solely in the collection of data will not be named individually as authors (Kassirer 1991).  
Rather, those investigators will receive a collective authorship as the “CVT-301 Study Group” 
and will be identified in a note. 

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Individual investigators and/or their associates subsequently may publish additional findings of 
this study in scientific journals or present them at scientific meetings, provided that the Sponsor 
is given ample opportunity to review any proposed abstract, manuscript, or slide presentation 
prior to its submission.  This review is required to ensure that the Sponsor is aware of all written 
and oral presentations of the data and does not imply any editorial review or restriction of the 
contents of the presentation or use. 
 

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14. 
REFERENCES 
Bartus RT, Emerich D, Snodgrass-Belt P, Fu K, Salzberg-Brenhouse H, Lafreniere D, Novak L, 
Lo E-S, Cooper T, Basile AS. A pulmonary formulation of L-dopa enhances its 
effectiveness in a rat model of Parkinson’s disease. JPET 2004; 310 (2):828-835. 
 
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of PD – 2009. 
Neurology 2009; 72(Suppl 4):S1-136. 
Olanow CW, Obeso JA, Stocchi F. Continuous dopamine receptor treatment of Parkinson’s 
disease: scientific rationale and clinical implications. Lancet Neurology 2006; 5:677-687. 
Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 2005; 
26:319-338. 
LeWitt PA. Levodopa for the Treatment of Parkinson’s Disease. N Engl J Med 2008; 359:2468-
2476. 
Kassirer JP, Angell M. On authorship and acknowledgments. N Engl J Med 1991; 325(21): 
1510-1512. 
Hauser RA, Friedlander J, Zesiewicz TA, Adler CH, Seeberger LC, O’Brien CF, Molho ES, 
Factor SA. A home diary to assess functional status in patients with Parkinson’s disease 
with motor fluctuations and dyskinesia. Clin Neuropharmacol 2000; 23(2):75-81. 
Hankinson JL, Odencrantz JR, Fedan, KB. Spirometric reference values from a sample of the 
general US population. Am J Respir Crit Care Med 1999; 159:179-187. 
Dunbar J, Illeperuma A, Milovanovic J, Loewy J, Osborn C, Ahluwalia P, Richards J, Ehrich 
EW. A placebo- and active-comparator-controlled dose escalation study of the 
pharmacokinetics, pharmacodynamics, and safety of inhaled large porous particle (AIR®) 
epinephrine in normal volunteers. J Allergy Clin Immunol 2004; Abstract 937: S260. 
Dewey RB, Hutton JT, LeWitt PA, Factor SA. A randomized, double-blind, placebo-controlled 
trial of subcutaneously injected apomorphine for Parkinsonian off-state events. Arch 
Neurol 2001; 58:1385-1392. 
DeLong M, Wright J, Dawson M, Meyer T, Sommerer K, Dunbar C. Dose delivery 
characteristics of the AIR® pulmonary delivery system over a range of inspiratory flow 
rates. J Aerosol Med 2005; 18 (4):452-459. 
Chipman J, Lucas R, Jackson B, Blizzard C, Mant T, Cleverly A, Spaldin V, Johnston L, Cutler 
G. Pharmacokinetic and safety results of a human single-dose comparison of somatropin
inhalation powder (SIP) vs. subcutaneous (SC) injection of somatropin. Program of the 
87th Annual Meeting of the Endocrine Society, San Diego, CA, 2005. 
Baruzzi A, Contin M, Riva R, et al. Influence of meal ingestion time on pharmacokinetics of 
orally administered levodopa in Parkinsonian patients. Clin Neuropharmacol 1987; 10 
(6):527-37. 
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic 
Parkinson’s disease: a clinico-pathological study of 100 cases. JNNP 1992; 55:181-184. 

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Walvoord EC, de la Pena A, Park S, Silverman B, Cuttler L, Rose SR, Cutler G, Drop S, 
Chipman JJ. Inhaled growth hormone (GH) compared with subcutaneous GH in children 
with GH deficiency: pharmacokinetics, pharmacodynamics, and safety. J Clin Endocrinol 
Metab 2009; 94:2052–2059.
Stocchi F, Rascol O, Kieburtz K, Poewe W, Jankovic J, Tolosa E, Barone P, Lang AE, Olanow 
CW. Initiating levodopa/carbidopa therapy with and without entacapone in early 
Parkinson’s disease: the STRIDE-PD study. Ann Neurol 2010; 68:18-27. 
Rave K, de la Pena A, Tibaldi FS, Zhang L, Silverman B, Hausmann M, Heinemann L, 
Muchmore DB. AIR inhaled insulin in subjects with chronic obstructive pulmonary 
disease: pharmacokinetics, glucodynamics, safety, and tolerability. Diabetes Care 2007; 
30 (7):1777-1782. 
Pfeiffer RF. Antiparkinsonian agents: drug interactions of clinical significance. Drug Safety 
1996; 14 (5):343-354. 
Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in 
DATATOP subjects requiring carbidopa/levodopa. Ann Neurol 1996; 39:37–45. 
Ondo WG, Shinawi L, Moore S. Comparison of orally dissolving carbidopa/levodopa (Parcopa) 
to conventional oral carbidopa/levodopa: a single-dose, double-blind, double-dummy, 
placebo-controlled, crossover trial. Movement Disorders 2010; 25(16):2724-2727. 
Oleson L, Turncliff RZ, Silberman B, Fogarty C, Ehrich E. ALKS 27 (Trospium Inhalation 
Powder) improves lung function following single administration in subjects with COPD. 
Am J Respir Crit Care Med 2010; 181:A4457. 

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15. 
APPENDICES – TABLE OF CONTENTS 
Appendix 1 
Overall Visit Schedule Schematic 
Appendix 2 
Time and Events Table—Screening Visit 1 (SV1) (within 35 days 
prior to TV/OV1) 
Appendix 3 
Time and Events Table—Screening Visit 2 (SV2) (at least 4 days 
after SV1) 
Appendix 4 
Time and Events Table—Treatment Visit 1 (TV1) (at least 7 days 
after SV2)  
Appendix 5 
Time and Events Table—Observational Visit 1 (OV1) (at least 7 
days after SV2)  
Appendix 6 
Time and Events Table—Treatment Visit 2 (TV2) (1 Month 
[4 Weeks ±5 days] after TV1) 
Appendix 7 
Time and Events Table—Observational Visit 2 (OV2) (1 Month 
[4 Weeks ±5 days] after OV1) 
Appendix 8 
Time and Events Table—Treatment Visit 3 (TV3) (3 Months 
[12±2 Weeks] after TV1) 
Appendix 9 
Time and Events Table—Observational Visit 3 (OV3) (3 Months 
[12±2 Weeks] after OV1) 
Appendix 10 
Time and Events Table—Treatment Visit 4 (TV4) (6 Months 
[24±2 Weeks] after TV1)  
Appendix 11 
Time and Events Table—Observational Visit 4 (OV4) (6 Months 
[24±2 Weeks] after OV1)  
Appendix 12 
Time and Events Table—Treatment Visit 5 (TV5) (9 Months 
[36±2 Weeks] after TV1) 
Appendix 13 
Time and Events Table—Observational Visit 5 (OV5) (9 Months 
[36±2 Weeks] after OV1) 
Appendix 14 
Time and Events Table—Treatment Visit 6 (TV6) (12 Months 
[52±2 Weeks] after TV1)/ Early Withdrawal Visit 
Appendix 15 
Time and Events Table—Observational Visit 6 (OV6) (12 Months 
[52±2 Weeks] after OV1)/ Early Withdrawal Visit 

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Appendix 16 
In-Clinic Assessment of ON/OFF States and Dyskinesia 
Appendix 17 
Laboratory Parameters 
Appendix 18 
UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic 
Criteria 
Appendix 19 
Modified Hoehn and Yahr PD Severity Scale Assessment 
Appendix 20 
Contraindications to Performing Routine Spirometry 
 

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APPENDIX 1:  OVERALL VISIT SCHEDULE SCHEMATIC 
Abbreviations:  DLco = carbon monoxide diffusing capacity; M = month; SV = screening visit; TV/OV = Treatment Visit/Observational Visit; W = weeks. 

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APPENDIX 2:  TIME AND EVENTS TABLE—SCREENING VISIT 1 (SV1) (WITHIN 35 DAYS PRIOR 
TO TV/OV1) 
Procedures1 
At arrival 
(assess in ON or 
OFF state) 
Assess in  
ON state2 
 
Assess in 
OFF state 
End of SV1 
Post-SV1 
Telephone 
Contact 
Consent 
X 
 
 
 
 
Eligibility according to inclusion/exclusion criteria 
X 
 
 
 
 
Medical history including PD history and smoking history 
X 
 
 
 
 
Confirm PD diagnosis and severity (UK Brain Bank/Modified Hoehn 
and Yahr scale) 
 
X 
 
 
 
Record average number of OFF hours during waking 
X 
 
 
 
 
PD medications (confirm as stable) 
X 
 
 
 
 
Concomitant medications 
X 
 
 
 
 
MMSE 
 
X 
 
 
 
Physical examination (full) 
X 
 
 
 
 
Pulmonary Function Baseline Questionnaire 
X 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR)  
X 
 
 
 
 
Spirometry 
 
X 
X 
 
 
UPDRS Part 3 
 
X 
X 
 
 
Patient training on self-report of ON/OFF states  
 
X 
X 
 
 
ON/OFF concordance testing 
 
X 
X 
 
 
Inhaler training using sham capsules 
 
X 
X 
 
 
Clinical laboratory tests (including serum pregnancy test, if applicable) 
X3 
 
 
 
 
Distribute PD Diary and Screening ON/OFF Episodes Log and review 
instructions for completion4 
 
 
 
X 
 
Monitor for AEs 
X 
 
Schedule next visit 
 
 
 
X 
 
Post-SV1 telephone contact: call patient ~4 days prior to SV2 
 
 
 
 
X 
1Procedures appear in the table in the suggested order of completion. 
2If patient arrives in OFF state, perform OFF assessments first, then have patient take next regularly scheduled dose of PD meds and complete ON assessments. 
3Document whether patient is fasting (≥4 hours after last snack or meal). 
4The PD Diary and Screening ON/OFF Episodes Log are to be completed for the 3 consecutive days prior to SV2. 

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APPENDIX 3:  TIME AND EVENTS TABLE—SCREENING VISIT 2 (SV2) (AT LEAST 4 DAYS AFTER 
SV1) 
Procedures1 
At arrival 
(assess in ON or 
OFF state) 
Assess in  
ON state 
Assess in 
OFF state 
End of 
SV2 
Post-SV2 
Telephone 
Contact 
Confirm eligibility through review of complete PD Diary and Screening 
ON/OFF Episodes Log2 
X 
 
 
 
 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
Record any changes in concomitant medications 
X 
 
 
 
 
Inhaler training using sham capsules and IFU3 
 
X 
X 
 
 
Patient training on assessment of ON/OFF state 
 
X 
X 
 
 
Distribute PD Diary and Screening ON/OFF Episodes Log and review 
instructions for completion4 
 
 
 
X 
 
Monitor for AEs 
X 
 
Schedule DLco assessment (to be completed prior to TV/OV1) and next visit 
 
 
 
X 
 
Post-SV2 telephone contact: call patient 4 to 6 days prior to TV/OV1 
 
 
 
 
X 
Screening procedures from SV1 that can be completed/repeated at SV2, 
if necessary: 
At arrival 
(assess in ON or 
OFF state) 
Assess in  
ON state 
Assess in 
OFF state 
 
 
MMSE 
 
X 
 
 
 
Physical examination (full) 
X 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X 
 
 
 
 
Spirometry 
 
X 
X 
 
 
UPDRS Part 3 
 
X 
X 
 
 
ON/OFF concordance testing 
 
X 
X 
 
 
Clinical laboratory tests (including serum pregnancy test, if applicable) 
X5 
 
 
 
 
1Procedures appear in the table in the preferred order of completion. 
2Refer to Section 10.1.2 of protocol for management of incorrect or incomplete patient diaries. 
3If the patient has undergone inhaler training in both the ON and OFF states at SV1, it may be done in either state at this visit. 
4The PD Diary and Screening ON/OFF Episodes Log are to be completed for the 3 consecutive days prior to TV/OV1. 
5Document whether patient is fasting (≥4 hours after last snack or meal). 

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APPENDIX 4:  TIME AND EVENTS TABLE—TREATMENT VISIT 1 (TV1) (AT LEAST 7 DAYS 
AFTER SV2) 
Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 
min 
Post-
dose 
15 
min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV1 
Post-TV1 
Telephone 
Contacts 
Collect, review, sign, and date Screening ON/OFF 
Episodes Log and PD Diary 
X 
 
 
 
 
 
 
 
 
 
Confirm DLco assessment2 has been completed prior to 
visit; if DLco not done, the study visit must be 
re-scheduled 
X 
 
 
 
 
 
 
 
 
X 
Record time of patient’s prior usual PD medication dose 
X 
 
 
 
 
 
 
 
 
 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
 
 
 
 
 
 
 
 
 
PDQ-39 (in ON state) 
X 
 
 
 
 
 
 
 
 
 
Physical examination (brief) 
X 
 
 
 
 
 
 
 
 
 
UPDRS Part 2 (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
 
S&E ADL (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
 
UPDRS Part 4 (Questions 32-35 and 36-39)  
X 
 
 
 
 
 
 
 
 
 
Electrocardiogram 
X3 
 
 
 
 
 
 
 
 
Standard and orthostatic BP and HR 
X3 
 
 
 
X 
 
X 
 
 
Respiratory rate 
X3 
 
X 
 
X 
X 
X 
 
 
Spirometry 
X4 
X 
 
 
 
 
 
 
 
 
Clinical laboratory tests (including serum pregnancy test, 
if applicable) 
X3,5 
 
 
 
 
 
 
 
 
C-SSRS  
X3 
 
 
 
 
 
 
 
 
Epworth sleepiness scale  
X3 
 
 
 
 
 
 
 
 
QUIP  
X3 
 
 
 
 
 
 
 
 
Distribute PD Diary and Inhaled Dosing Log and review 
instructions for completion 
X6 
 
 
 
 
 
 
 
 
 
Distribute study drug kits  
X 
 
 
 
 
 
 
 
 
 
Review inhaler training 
X 
 
 
 
 
 
 
 
 
 
Self-administration of study drug 
 
 
X1 
 
 
 
 
 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
 
 
 
 
 
 
 
X 
 
Post-TV1 telephone contact:  call patient 1-3 days after 
TV1 
 
 
 
 
 
 
 
 
 
X 

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Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 
min 
Post-
dose 
15 
min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV1 
Post-TV1 
Telephone 
Contacts 
Post-TV1 telephone contact:  call patient 2 weeks (± 3 
days)  before TV2 
 
 
 
 
 
 
 
 
 
X 
1First dose of study medication occurs preferably between 2 and 5 hours after patient has taken normal morning dose of PD medication and after all pre-dose 
assessments are complete.  
2 DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
3Procedures can be done at any point after arrival but must be completed before dosing. 
4Preferably in the ON state. 
5Document whether patient is fasting (≥4 hours after last snack or meal). 
6The PD Diary is to be completed for the 3 consecutive days prior to TV2; the Inhaled Dosing Log is to be completed daily through TV6. 
 

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APPENDIX 5:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 1 (OV1) (AT LEAST 7 DAYS 
AFTER SV2) 
Procedures 
Assess in Either ON or OFF 
State Unless Otherwise 
Noted 
End of OV1 
Post- OV1 
Telephone 
Contact 
Collect, review, sign, and date Screening ON/OFF Episodes Log and PD Diary 
X 
 
 
Confirm DLco assessment1 has been performed prior to visit; and if not complete, 
re-schedule study visit 
X 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
Concomitant medications 
X 
 
 
PDQ-39 (in ON state) 
X (ON) 
 
 
UPDRS Part 2 (preferably in ON state) 
X (ON) 
 
 
S&E ADL (preferably in ON state) 
X (ON) 
 
 
Physical examination (brief) 
X 
 
 
Standard and orthostatic BP and HR 
X 
 
 
Respiratory rate 
X 
 
 
Electrocardiogram 
X 
 
 
Spirometry (preferably in ON state) 
X (ON) 
 
 
Clinical laboratory tests (including serum pregnancy test, if applicable) 
X2 
 
 
C-SSRS  
X 
 
 
Epworth sleepiness scale  
X 
 
 
QUIP  
X 
 
 
Monitor for AEs 
X 
 
Schedule next visit 
 
X 
 
Post-OV1 telephone contact:  call patient 2 weeks (± 3 days)  before OV2 
 
 
X 
1DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
2Document whether patient is fasting (≥4 hours after last snack or meal). 
 
 

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APPENDIX 6:  TIME AND EVENTS TABLE—TREATMENT VISIT 2 (TV2) (1 MONTH [4 WEEKS ±5 
DAYS] AFTER TV1) 
Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV2 
Post-TV2 
Telephone 
Contact 
Collect, review, sign, and date PD Diary and Inhaled Dosing Log 
X 
 
 
 
 
 
 
 
 
Collect empty capsules, inhalers, and unused supplies 
X 
 
 
 
 
 
 
 
 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
 
 
 
 
Record time of patient’s prior usual PD medication dose 
X 
 
 
 
 
 
 
 
 
Record any changes in concomitant medications 
X 
 
 
 
 
 
 
 
 
Physical examination (brief) 
X 
 
 
 
 
 
 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and 
HR) 
X3 
 
 
 
 
 
 
 
Spirometry (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
C-SSRS  
X 
 
 
 
 
 
 
 
 
Distribute study drug kits  
X 
 
 
 
 
 
 
 
 
Review inhaler training 
X 
 
 
 
 
 
 
 
 
Distribute PD Diary and Inhaled Dosing Log and review 
instructions for completion 
X4 
 
 
 
 
 
 
 
 
UPDRS Part 3 
 
X5 
 
X 
X 
X 
X 
 
 
Self-administration of study drug (in OFF state) 
 
 
X1 
 
 
 
 
 
 
Monitor for dyskinesia and ON/OFF states 
 
 
 
X 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
 
 
 
 
 
 
X 
 
Schedule DLco visit at pulmonary site (14±3 days before next 
visit)2  
 
 
 
 
 
 
 
X 
 
Post-TV2 telephone contact: call patient 2 weeks (± 3 days)  
before TV3 
 
 
 
 
 
 
 
 
X 
1Dosing of study medication occurs preferably between 2 and 5 hours after patient has taken normal morning dose of PD medication and after all pre-dose 
assessments are complete. 
2DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
3Assessment can be done at any point after arrival but must be completed before dosing. 

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4The PD Diary is to be completed for the 3 consecutive days prior to TV3; the Inhaled Dosing Log is to be completed daily through TV6. 
5Confirm patient is in the OFF state prior to pre-dose UPDRS Part 3 assessment. 

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APPENDIX 7:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 2 (OV2) (1 MONTH [4 
WEEKS ±5 DAYS] AFTER OV1) 
Procedures 
Assess in Either ON or 
OFF State Unless 
Otherwise Noted 
End of OV2 
Post- OV2 
Telephone 
Contact 
Record any changes in usual PD medication dose/regimen 
X 
 
 
Record any changes in concomitant medications 
X 
 
 
Physical examination (brief) 
X 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X 
 
 
Spirometry (preferably in ON state) 
X (ON) 
 
 
C-SSRS  
X 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
X 
 
Schedule DLco visit at pulmonary site (14±3 days before next visit)1  
 
X 
 
Post- OV2 telephone contact:  call patient 2 weeks (± 3 days)  before OV3 
 
 
X 
1 DLco to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
 

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APPENDIX 8:  TIME AND EVENTS TABLE—TREATMENT VISIT 3 (TV/OV3) (3 MONTHS [12±2 
WEEKS] AFTER TV1) 
Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV3 
Post-TV3 
Telephone 
Contact  
Collect, review, sign, and date PD Diary and Inhaled Dosing Log 
X 
 
 
 
 
 
 
 
 
Collect empty capsules, inhalers, and unused supplies 
X 
 
 
 
 
 
 
 
 
Confirm DLco assessment2 has been completed prior to visit; if 
not done, the study visit must be re-scheduled 
X 
 
 
 
 
 
 
 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
 
 
 
 
Record time of patient’s prior usual PD medication dose 
X 
 
 
 
 
 
 
 
 
Record any changes in concomitant medications 
X 
 
 
 
 
 
 
 
 
PGI-C (preferably in an ON state) 
X3 
 
 
 
 
 
 
 
 
C-SSRS 
X 
 
 
 
 
 
 
 
 
Physical examination (brief) 
X 
 
 
 
 
 
 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X3 
 
 
 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
 
 
 
 
Spirometry (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
Clinical laboratory tests (including serum pregnancy test, if 
applicable) 
X4 
 
 
 
 
 
 
 
 
Distribute study drug kits  
X 
 
 
 
 
 
 
 
 
Review inhaler training 
X 
 
 
 
 
 
 
 
 
Distribute PD Diary and Inhaled Dosing Log and review 
instructions for completion 
X5 
 
 
 
 
 
 
 
 
UPDRS Part 3 
 
X6 
 
X 
X 
X 
X 
 
 
Self-administration of study drug (in OFF state) 
 
 
X1 
 
 
 
 
 
 
Monitor for dyskinesia and ON/OFF states 
 
 
 
X 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
 
 
 
 
 
 
X 
 
Schedule DLco visit at pulmonary site (14±3 days before next 
visit)  
 
 
 
 
 
 
 
X 
 

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Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV3 
Post-TV3 
Telephone 
Contact  
Post-TV3 telephone contact:  call patient 2 weeks (± 3 days)  
before TV4 
 
 
 
 
 
 
 
 
X 
1Dosing of study medication occurs at least 1 hour after patient has taken normal morning dose of PD medication and after all pre-dose assessments are complete. 
2DLco to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
3Assessment can be done at any point after arrival but must be completed before dosing. 
4Document whether patient is fasting (≥4 hours after last snack or meal). 
5The PD Diary is to be completed for the 3 consecutive days prior to TV4; the Inhaled Dosing Log is to be completed daily through TV6. 
6Confirm patient is in the OFF state prior to pre-dose UPDRS Part 3 assessment. 
 
 

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APPENDIX 9:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 3 (OV3) (3 MONTHS [12±2 
WEEKS] AFTER OV1) 
Procedures 
Assess in Either ON or 
OFF State Unless 
Otherwise Noted 
End of OV3 
Post- OV3 
Telephone 
Contact 
Confirm DLco assessment1 has been performed prior to visit; and if not complete, 
re-schedule study visit 
X 
 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
Record any changes in concomitant medications 
X 
 
 
C-SSRS  
X 
 
 
Physical examination (brief) 
X 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X 
 
 
Electrocardiogram 
X 
 
 
Spirometry (preferably in ON state) 
X (ON) 
 
 
Clinical laboratory tests (including serum pregnancy test, if applicable) 
X2 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
X 
 
 Schedule DLco visit at pulmonary site (14±3 days before next visit)  
 
X 
 
Post- OV3 telephone contact: call patient 2 weeks (± 3 days)  before OV4 
 
 
X 
1DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
2Document whether patient is fasting (≥4 hours after last snack or meal).  
 

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APPENDIX 10:  TIME AND EVENTS TABLE—TREATMENT VISIT 4 (TV4) (6 MONTHS [24±2 
WEEKS] AFTER TV1) 
Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV4 
Post-TV4 
Telephone 
Contact 
Collect, review, sign, and date PD Diary and Inhaled Dosing Log 
X 
 
 
 
 
 
 
 
 
Collect empty capsules, inhalers, and unused supplies 
X 
 
 
 
 
 
 
 
 
Confirm DLco assessment2 has been completed prior to visit; if 
not done, the study visit must be re-scheduled 
X 
 
 
 
 
 
 
 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
 
 
 
 
Record time of patient’s prior usual PD medication dose 
X 
 
 
 
 
 
 
 
 
Record any changes in concomitant medications 
X 
 
 
 
 
 
 
 
 
PDQ-39 (preferably in ON state) 
X3 
 
 
 
 
 
 
 
 
PGI-C (preferably in ON state) 
X3 
 
 
 
 
 
 
 
 
UPDRS Part 2 (preferably in ON state) 
X3 
 
 
 
 
 
 
 
 
S&E ADL (preferably in ON state) 
X3 
 
 
 
 
 
 
 
 
UPDRS Part 4 (Questions 32-35 and 36-39) 
X 
 
 
 
 
 
 
 
 
C-SSRS  
X 
 
 
 
 
 
 
 
 
Epworth Sleepiness Scale  
X 
 
 
 
 
 
 
 
 
QUIP  
X 
 
 
 
 
 
 
 
 
Physical examination (brief) 
X 
 
 
 
 
 
 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and 
HR) 
X4 
 
 
 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
 
 
 
 
Spirometry (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
Clinical laboratory tests (including serum pregnancy test, if 
applicable) 
X5 
 
 
 
 
 
 
 
 
Distribute study drug kits  
X 
 
 
 
 
 
 
 
 
Review inhaler training 
X 
 
 
 
 
 
 
 
 
Distribute PD Diary and Inhaled Dosing Log and review 
instructions for completion 
X6 
 
 
 
 
 
 
 
 

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Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV4 
Post-TV4 
Telephone 
Contact 
UPDRS Part 3 
 
X7 
 
X 
X 
X 
X 
 
 
Self-administration of study drug (in OFF state) 
 
 
X1 
 
 
 
 
 
 
Monitor for dyskinesia and ON/OFF states 
 
 
 
X 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
 
 
 
 
 
 
X 
 
Schedule DLco visit at pulmonary site (14±3 days before next 
visit) 
 
 
 
 
 
 
 
X 
 
Post-TV4 telephone contact: call patient 2 weeks (± 3 days)  
before TV5 
 
 
 
 
 
 
 
 
X 
1Dosing of study medication occurs at least 1 hour after patient has taken normal morning dose of PD medication and after all pre-dose assessments are complete. 
2DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
3Preferably in the ON state; but these must be performed before any other study evaluation. 
4Assessment can be done at any point after arrival but must be completed before dosing. 
5Document whether patient is fasting (≥4 hours after last snack or meal). 
6The PD Diary is to be completed for the 3 consecutive days prior to TV/OV5; the Inhaled Dosing Log is to be completed daily through TV/OV6. 
7Confirm patient is in the OFF state prior to pre-dose UPDRS Part 3 assessment. 
 
 

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APPENDIX 11:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 4 (OV4) (6 MONTHS [24±2 
WEEKS] AFTER OV1) 
Procedures 
Assess in Either ON or 
OFF State Unless 
Otherwise Noted 
End of OV4 
Post- OV4 
Telephone 
Contact 
Confirm DLco assessment1 has been performed prior to visit; and if not complete, 
re-schedule study visit 
X 
 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
Record any changes in concomitant medications 
X 
 
 
PDQ-39 (preferably in ON state) 
X (ON)2 
 
 
UPDRS Part 2 (preferably in ON state) 
X (ON)2 
 
 
S&E ADL (preferably in ON state) 
X (ON)2 
 
 
C-SSRS  
X 
 
 
Epworth Sleepiness Scale  
X 
 
 
QUIP  
X 
 
 
Physical examination (brief) 
X 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X 
 
 
Electrocardiogram 
X 
 
 
Spirometry (preferably in ON state) 
X (ON) 
 
 
Clinical laboratory tests (including serum pregnancy test, if applicable) 
X3 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
X 
 
 Schedule DLco visit at pulmonary site (14±3 days before next visit)  
 
X 
 
Post- OV4 telephone contact:  call patient 2 weeks (± 3 days)  before OV5 
 
 
X 
1 DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
2Preferably in the ON state; but these must be performed before any other study evaluation. 
3Document whether patient is fasting (≥4 hours after last snack or meal).  
 

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APPENDIX 12:  TIME AND EVENTS TABLE—TREATMENT VISIT 5 (TV5) (9 MONTHS [36±2 
WEEKS] AFTER TV1) 
Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV5 
Post-TV5 
Telephone 
Contact 
Collect, review, sign, and date PD Diary and Inhaled Dosing 
Log 
X 
 
 
 
 
 
 
 
 
Collect empty capsules, inhalers, and unused supplies 
X 
 
 
 
 
 
 
 
 
Confirm DLco assessment2 has been completed prior to visit; if 
not done, the study visit must be re-scheduled 
X 
 
 
 
 
 
 
 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
 
 
 
 
Record time of patient’s prior usual PD medication dose 
X 
 
 
 
 
 
 
 
 
Record any changes in concomitant medications 
X 
 
 
 
 
 
 
 
 
Physical examination (brief) 
X 
 
 
 
 
 
 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and 
HR) 
X3 
 
 
 
 
 
 
 
Spirometry (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
Clinical laboratory tests (serum pregnancy test, if applicable) 
X4 
 
 
 
 
 
 
 
 
C-SSRS  
X 
 
 
 
 
 
 
 
 
Distribute study drug kits  
X 
 
 
 
 
 
 
 
 
Review inhaler training 
X 
 
 
 
 
 
 
 
 
Distribute PD Diary and Inhaled Dosing Log and review 
instructions for completion 
X5 
 
 
 
 
 
 
 
 
UPDRS Part 3 
 
X6 
 
X 
X 
X 
X 
 
 
Self-administration of study drug (in OFF state) 
 
 
X1 
 
 
 
 
 
 
Monitor for dyskinesia and ON/OFF states 
 
 
 
X 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
 
 
 
 
 
 
X 
 
Schedule DLco visit at pulmonary site (14±3 days before next 
visit)  
 
 
 
 
 
 
 
X 
 
Post-TV5 telephone contact:  call patient 2 weeks (± 3 days)  
before TV6 
 
 
 
 
 
 
 
 
X 

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1Dosing of study medication occurs at least 1 hour after patient has taken normal morning dose of PD medication and after all pre-dose assessments are complete. 
2DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
3Assessment can be done at any point after arrival, but must be completed before dosing. 
4Document whether patient is fasting (≥4 hours after last snack or meal). 
5The PD Diary is to be completed for the 3 consecutive days prior to TV6; the Inhaled Dosing Log is to be completed daily through TV6. 
6Confirm patient is in the OFF state prior to pre-dose UPDRS Part 3 assessment. 
 
 

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APPENDIX 13:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 5 (OV5) (9 MONTHS [36±2 
WEEKS] AFTER OV1) 
Procedures 
Assess in Either ON or 
OFF State Unless 
Otherwise Noted 
End of OV5 
Post- OV5 
Telephone 
Contact 
Confirm DLco assessment1 has been performed prior to visit; and if not complete, 
re-schedule study visit 
X 
 
 
X 
Record any changes in usual PD medication dose/regimen 
X 
 
 
Record any changes in concomitant medications 
X 
 
 
Physical examination (brief) 
X 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X 
 
 
Spirometry (preferably in ON state) 
X (ON) 
 
 
Clinical laboratory tests (serum pregnancy test, if applicable) 
X2 
 
 
C-SSRS  
X 
 
 
Monitor for AEs 
X 
Schedule next visit 
 
X 
 
Schedule DLco visit at pulmonary site (14±3 days before next visit) 
 
X 
 
Post- OV5 telephone contact:  call patient 2 weeks (± 3 days)  before OV6 
 
 
X 
1DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
2Document whether patient is fasting (≥4 hours after last snack or meal). 
 
 

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APPENDIX 14:  TIME AND EVENTS TABLE—TREATMENT VISIT 6 (TV6) (12 MONTHS [52±2 
WEEKS] AFTER TV1)/EARLY WITHDRAWAL VISIT 
Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV6 
Post-TV6 
Assessment
s 
Collect, review, sign, and date PD Diary and Inhaled Dosing 
Log 
X 
 
 
 
 
 
 
 
 
Collect empty capsules, inhalers, and unused supplies 
X 
 
 
 
 
 
 
 
 
Confirm DLco assessment2 has been completed prior to visit; if 
not done, the study visit must be re-scheduled3 
X 
 
 
 
 
 
 
 
 
Record any changes in usual PD medication dose/regimen 
X 
 
 
 
 
 
 
 
 
Record time of patient’s prior usual PD medication dose 
X 
 
 
 
 
 
 
 
 
Record any changes in concomitant medications 
X 
 
 
 
 
 
 
 
 
PDQ-39 (preferably in ON state) 
X4 
 
 
 
 
 
 
 
 
PGI-C (preferably in ON state) 
X4 
 
 
 
 
 
 
 
 
UPDRS Part 2 (preferably in ON state) 
X4 
 
 
 
 
 
 
 
 
S&E ADL (preferably in ON state) 
X4 
 
 
 
 
 
 
 
 
UPDRS Part 4 (Questions 32-35 and 36-39) 
X 
 
 
 
 
 
 
 
 
Physical examination (brief) 
X 
 
 
 
 
 
 
 
 
Vital signs (standard BP, HR and RR and orthostatic BP and 
HR) 
X5 
 
 
 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
 
 
 
 
C-SSRS  
X 
 
 
 
 
 
 
 
 
Epworth Sleepiness Scale  
X 
 
 
 
 
 
 
 
 
QUIP  
X 
 
 
 
 
 
 
 
 
Spirometry (preferably in ON state) 
X 
 
 
 
 
 
 
 
 
Clinical laboratory tests (including serum pregnancy test, if 
applicable) 
X6 
 
 
 
 
 
 
 
 
Provide new inhaler for treatment 
 
X 
 
 
 
 
 
 
 
UPDRS Part 3 
 
X7 
 
X 
X 
X 
X 
 
 
Self-administration of study drug (in OFF state) 
 
 
X1 
 
 
 

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Procedures 
Arrival 
Pre-
dose 
Time 0 
(Dosing)1 
10 min 
Post-
dose 
20 min 
Post-
dose 
30 min 
Post-
dose 
60 min 
Post-
dose 
End of 
TV6 
Post-TV6 
Assessment
s 
Monitor for dyskinesia and ON/OFF states 
 
 
 
X 
 
 
Monitor for AEs 
X 
 
 
Schedule DLco visit2 to occur at pulmonary site in 4-5 weeks 
 
 
 
 
 
 
 
X 
 
Post-TV6 DLco assessment2 at 4-5 weeks after TV6 or Early 
Withdrawal Visit3 
 
 
 
 
 
 
 
 
X 
1Dosing of study medication occurs at least 1 hour after patient has taken normal morning dose of PD medication and after all pre-dose assessments are complete. 
2DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
3Patients who withdraw early will undergo all of the TV6 assessments except the pre-TV6 DLco assessment.  Patients will be scheduled to undergo the post-TV6 DLco assessment 
4-5 weeks after completion of the Early Withdrawal Visit. 
4Preferably in the ON state, but these must be performed before any other study evaluation. 
5Assessment can be done at any point after arrival but must be completed before dosing. 
6Document whether patient is fasting (≥4 hours after last snack or meal). 
7Confirm patient is in the OFF state prior to pre-dose UPDRS Part 3 assessment. 
 
 

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APPENDIX 15:  TIME AND EVENTS TABLE—OBSERVATIONAL VISIT 6 (OV6) VISIT (12 MONTHS 
[52±2 WEEKS] AFTER OV1)/EARLY WITHDRAWAL VISIT 
Procedures 
Assess in Either ON or 
OFF State Unless 
Otherwise Noted 
End of OV6 
Post- OV6 
Assessments 
Confirm DLco assessment1  has been performed prior to visit; and if not complete, 
re-schedule study visit2 
X 
 
 
Record any changes in usual PD medication dose/regimen 
X 
 
 
Record any changes in concomitant medications 
X 
 
 
PDQ-39 (preferably in ON state) 
X (ON)3 
 
 
UPDRS Part 2 (preferably in ON state) 
X (ON)3 
 
 
S&E ADL (preferably in ON state) 
X (ON)3 
 
 
Physical examination (brief) 
X 
 
 
Vital signs (standard BP, HR, and RR and orthostatic BP and HR) 
X 
 
 
Electrocardiogram 
X 
 
 
Spirometry (preferably in ON state) 
X (ON) 
 
 
C-SSRS  
X 
 
 
Epworth Sleepiness Scale  
X 
 
 
QUIP  
X 
 
 
Clinical laboratory tests (including serum pregnancy test, if applicable) 
X3 
 
 
Monitor for AEs 
X 
 
 
Schedule DLco visit1 to occur at pulmonary site in 4-5 weeks 
 
X 
 
Post- OV6 DLco assessment1 at 4-5 weeks after OV6 or Early Withdrawal Visit2 
 
 
X 
 
1DLco is to be performed in a dedicated pulmonary facility and includes slow vital capacity maneuver, DLco, and spirometry. Preferably in the ON state. 
2 Patients who withdraw early will undergo all of the OV6 assessments except the pre- OV6 DLco assessment.  Patients will be scheduled to undergo the post- OV6 DLco assessment 4-5 
weeks after completion of the Early Withdrawal Visit. 
3Preferably in the ON state, but these must be performed before any other study evaluation. 
4Document whether patient is fasting (≥4 hours after last snack or meal). 
 
 

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APPENDIX 16:  IN-CLINIC ASSESSMENT OF ON/OFF STATES AND 
DYSKINESIA 
An “OFF state” is defined as the time when medication has worn off and is no longer providing 
benefit with respect to mobility, slowness, and stiffness.  OFF episodes may be heralded by non-
motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms.   
An “ON state” is defined as the time when medication is providing benefit with respect to 
mobility, slowness, and stiffness, and may or may not be providing complete alleviation of all 
PD symptoms. 
For recording motor state in the PD Diary, when patients are in an ON state, the presence and 
extent of dyskinesia (involuntary twisting, turning movements that are an effect of medication) 
will also be noted: 
• ON with no dyskinesia 
• ON with non-troublesome dyskinesia (ON with dyskinesia that does not interfere 
with function or cause meaningful discomfort) 
• ON with troublesome dyskinesia (ON with dyskinesia that interferes with function or 
causes meaningful discomfort) 
These ON and OFF definitions are to be used in training the patients to recognize and record 
their ON and OFF states.  Patients will record their ON and OFF states in their diaries at home.   
In the clinic, the examiner will note the occurrence of dyskinesia during the 60-minute post-dose 
period and the maximum severity (mild, moderate, or severe) of any dyskinesia during the 
60-minute post-dose period.  The examiner will also note if the patient converts to the ON state 
during the 60-minute post-dose period and if so, whether the patient is still in the ON state at 
60 minutes post-dose. 
 

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APPENDIX 17:  LABORATORY PARAMETERS 
Hematology 
Platelet Count  
RBC Indices: 
Automated WBC Differential: 
RBC Count 
MCV 
Neutrophils 
WBC Count (absolute)  
MCH 
Lymphocytes 
Reticulocyte Count 
MCHC 
Monocytes 
Hemoglobin 
 
Eosinophils 
Hematocrit 
 
Basophils 
 
Clinical Chemistry 
Urea 
Potassium 
AST (SGOT) 
Total and direct bilirubin 
Creatinine 
Chloride 
ALT (SGPT) 
Uric Acid 
Glucose 
Total CO2 
GGT 
Albumin 
Sodium 
Calcium 
Alkaline phosphatase 
Total Protein 
 
Other screening tests 
Pregnancy test (serum) at screening (SV1 or SV2) and at TV/OV1, TV/OV3, TV/OV4, TV/OV5, and 
TV/OV6, if applicable; magnesium; C-Reactive Protein 
 
 

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APPENDIX 18:  UK PARKINSON’S DISEASE SOCIETY BRAIN BANK  
CLINICAL DIAGNOSTIC CRITERIA* 
Step 1. Diagnosis of Parkinsonian syndrome 
• Bradykinesia 
• At least one of the following 
o Muscular rigidity 
o 4-6 Hz rest tremor 
o Postural instability not caused by primary visual, vestibular, cerebellar, or 
proprioceptive dysfunction 
Step 2. Exclusion criteria for Parkinson’s disease 
• History of repeated strokes with stepwise progression of parkinsonian features 
• History of repeated head injury 
• History of definite encephalitis 
• Oculogyric crises 
• Neuroleptic treatment at onset of symptoms 
• More than one affected relative 
• Sustained remission 
• Strictly unilateral features after 3 years 
• Supranuclear gaze palsy 
• Cerebellar signs 
• Early severe autonomic involvement 
• Early severe dementia with disturbances of memory, language, and praxis 
• Babinski sign 
• Presence of cerebral tumor or communication hydrocephalus on imaging study 
• Negative response to large doses of levodopa in absence of malabsorption 
• MPTP exposure 
Step 3. Supportive prospective positive criteria for Parkinson’s disease 
Three or more required for diagnosis of definite Parkinson’s disease in combination with 
: 
• Unilateral onset 
• Rest tremor present 
• Progressive disorder 
Step 1

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• Persistent asymmetry affecting side of onset most 
• Excellent response (70-100%) to levodopa 
• Severe levodopa-induced chorea 
• Levodopa response for 5 years or more 
• Clinical course of ten years or more 
*From: Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease. 
A clinico-pathological study of 100 cases. JNNP 1992;55:181-184. 
 
 

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APPENDIX 19:  MODIFIED HOEHN AND YAHR PD SEVERITY SCALE 
ASSESSMENT 
The modified Hoehn and Yahr PD severity assessment uses the following scale: 
• Stage 0 = No signs of disease. 
• Stage 1 = Unilateral disease. 
• Stage 1.5 = Unilateral plus axial involvement. 
• Stage 2 = Bilateral disease, without impairment of balance. 
• Stage 2.5 = Mild bilateral disease, with recovery on pull test. 
• Stage 3 = Mild to moderate bilateral disease; some postural instability; physically 
independent. 
• Stage 4 = Severe disability; still able to walk or stand unassisted. 
• Stage 5 = Wheelchair-bound or bedridden unless aided. 
 
 

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APPENDIX 20:  CONTRAINDICATIONS TO PERFORMING ROUTINE 
SPIROMETRY 
• Recent myocardial infarction or unstable angina within 1 month 
• Hemoptysis 
• Pneumothorax, current or within prior 3 months 
• Pulmonary embolus within prior 3 months 
• Thoracic, abdominal, or cerebral aneurysms 
• Recent eye surgery within prior 3 months 
• Presence of an acute disease process that might interfere with test performance 
• Recent surgery of thorax or abdomen 
• Any history of syncope associated with forced exhalation 
 
 

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APPENDIX 21:  CVT-301 SYSTEM ADDITIONAL INFORMATION 
All instructions for how to properly use the CVT-301 system are outlined in the Instructions for 
Use document that is included with every CVT-301 study kit.  The following additional 
observations by patients when using the system have been noted by some investigational sites: 
• Patients may experience black sputum. No clinical correlate to this finding occurred 
(small number of patients) 
• Patients may see powder emitted from the inhaler while completing an inhalation. 
• Patients may see powder emitted from their mouths when exhaling after use of the 
system. 
• Patients may note some built-up powder falling off of the inhaler following multiple 
uses. Although cleaning is not necessary, system cleaning instructions are noted 
under the “More Information” section of the Instructions for Use. 
• Patients may attempt to push the capsule through the foil instead of peeling the blister 
open which can damage the capsule and impair drug delivery.  Make sure patients are 
informed not to push the capsule through the foil. 
• Patients may not hear the “whirl” of the capsule upon inhalation.   As noted in the 
Instructions for Use, if this occurs patients should repeat the inhalation steps to ensure 
that the drug is delivered.  If whirling sound is still not heard, patients should: 
o Check that a capsule is inserted 
o Make sure mouthpiece is firmly attached 
o Inhale deeper or longer