A Phase 3 Open-label, Multicenter Study to Evaluate the Long-term Safety and Tolerability of Inhaled LIQ861(Treprostinil) in Pulmonary Arterial Hypertension (WHO Group 1) Patients
Phase: PHASE3
Conditions: Primary Pulmonary Hypertension
Sponsor: Liquidia Technologies, Inc.

 
 
CLINICAL RESEARCH PROTOCOL 
 
 
 
A Phase 3 Open-label, Multicenter Study to Evaluate the Long-term 
Safety and Tolerability of Inhaled LIQ861(Treprostinil) in Pulmonary 
Arterial Hypertension (WHO Group 1) Patients  
 
INSPIRE:  Investigation of the Safety and Pharmacology of Dry Powder Inhalation of 
Treprostinil 
 
Protocol Number:  
LTI-301 
Investigational Product:  
LIQ861 
Version: 
Amendment 3  
(20 March 2019) 
 
 
CONFIDENTIAL STATEMENT 
The information contained in this document and all information provided to you related to 
LIQ861 (“Study Drug”) are the confidential and proprietary information of Liquidia 
Technologies (Sponsor) and except as may be required by federal, state or local laws or 
regulations, may not be disclosed to others without prior written permission of the Sponsor.  The 
Principal Investigator may, however, disclose such information to supervised individuals 
working on the Study Drug, provided such individuals agree to maintain the confidentiality of 
such information. 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 3 of 67 
INVESTIGATOR PROTOCOL AGREEMENT 
Protocol Title: 
A Phase 3 Open-label, Multicenter Study to Evaluate the Long-term Safety 
and Tolerability of LIQ861 (Treprostinil) in Pulmonary Arterial 
Hypertension (WHO Group 1) Patients  
Protocol Number: 
LTI-301 
Version: Amendment 3 (20 March 2019) 
 
 
By my signature, I  
• 
Confirm that my staff and I have carefully read and understand this protocol and the 
Investigator’s Brochure (IB) and are thoroughly familiar with the appropriate use of the 
investigational drug described herein.   
• 
Agree to comply with the conduct and terms of the study specified herein and with any other 
study procedures provided by the Sponsor, Liquidia Technologies, or designee 
• 
Agree to comply with US Food and Drug Administration (FDA) regulations, the 
International Conference on Harmonization (ICH) GCP guidelines, the Declaration of 
Helsinki, and all applicable rules, regulations, and federal, state, and local laws relating to the 
conduct of clinical studies and the protection of human subjects.  
• 
Agree not to implement changes to the protocol without agreement from the Sponsor and 
prior written approval (where required) from the Institutional Review Board (IRB) or Ethics 
Committee (EC), except when necessary to eliminate an immediate hazard to the subjects.  
• 
Agree to onsite monitoring of the electronic case report forms (eCRFs) and source 
documents by Liquidia Technologies or designee and to audit by Liquidia Technologies or 
designee and appropriate regulatory authorities, including, but not limited to, the FDA and 
IRB/EC inspectors. 
• 
Agree to supervise the conduct of the study and maintain responsibility for training and 
supervising all personnel who have delegated responsibilities under my leadership.  The 
protocol and other important study materials will be available to study staff throughout the 
conduct of the study. 
 
 
 
Investigator's Signature 
 
Date 
 
 
 
Print Name 
 
 
 
 
 
 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 4 of 67 
SUMMARY OF AMENDMENT CHANGES 
Date of Revision 
Version 
Summary of Changes 
March 20, 2019 
Amendment 3 
1. Edited eGFR limit from < 35 to < 30 to reflect 
FDA’s Guidance for definition of severe renal 
impairment. 
2. Edited the exclusion criteria for the PK sub-study to 
< 45 for GFR. 
3. Updated language in Section 3.1 to remove conflict 
with study procedures and time and events tables.   
4. Baseline day is corrected in Section 6.2.1. 
5. Clarified timing of predose PK measurements.  
6. Included adverse event assessment on Day 1 of PK 
sub-study. 
7. Clarification of study assessments that may be 
performed before or after study drug administration 
starting at Week 2 and throughout the study. 
8. Addition of specific Study Termination Visit. 
9. Clarified that Treatment-Emergent Adverse Events 
(TEAEs) and Serious Adverse Events (SAEs) 
should be recorded for administration of both 
LIQ861 and Tyvaso. 
10. Added ADE to the assessment of relatedness. 
11. Updated SAE/SADE reporting requirements and 
contact information. 
12. Clarification on drug reconciliation. 
13. Updated Exclusion Criteria #3 to include 
intravenous (IV) prostacyclin analogues or 
agonists. 
14. Removed examples of serious or life-threatening 
diseases in Exclusion Criteria #9. 
15. Time and events table updated to include Study 
Termination Visit and Assessment of PAH 
Symptoms (PK Sub-study), add Day 2 for 
collection of Inhalation Device Survey, add 
expectation to collect AEs on Day 1 of PK Sub-
study, and update footnotes.  
16. Updated study personnel contact information. 
17. Editorial updates which do not affect the content of 
the protocol. 
January 7, 2019 
Amendment 2 
1. Removed second Liquidia signatory on Protocol 
Approval Page. 
2. Updated study name from INTREPID to INSPIRE. 
3. Removed consent authorized by legal representative 
for ICF. 
4. Described in Section 1.2 that that there is a 
difference in the amount of treprostinil that is 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 5 of 67 
emitted during dosing and the amount of treprostinil 
that is contained within a capsule. 
5. Updated guidance on Initial Dose in Tyvaso 
Transition Patients in Appendix 2 and provided 
rationale for alteration in Section 5.3. 
6. Removed exclusion criteria for maximum Tyvaso 
doses and associated language throughout the 
protocol. 
November 13, 2017 Amendment 1 
1. Addition of Summary of Amendment Changes Log 
2. Addition of Vital Signs assessments to annual 
schedule. 
3. Removed the option of using a 100 µg treprostinil 
capsule in combination with a 25 µg or 50 µg 
capsule when dosing exceeds 100 µg of treprostinil.  
4. Addition of respiratory rate to Vital Signs 
assessments. 
5. Addition of a Brief Physical Examination at Month 
2 (Visit 5). 
6. Clarifications to study procedures, including 
temperature units, PK sample collection volumes, 
timing of procedures with respect to dosing, 
questionnaire administrations, and correction of 
erroneous footnotes in Appendix 1. 
7. Removed language in Appendix 2 which allows the 
investigator to potentially increase the dose of 
LIQ861 to 75 µg within 5 days after initiating 
therapy in Add-on patients. 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 6 of 67 
SYNOPSIS 
PROTOCOL TITLE 
A Phase 3 Open-label, Multicenter Study to Evaluate the Long-term Safety 
and Tolerability of LIQ861 (Treprostinil) in Pulmonary Arterial 
Hypertension WHO Group 1 (PAH) Patients  
PROTOCOL NUMBER 
LTI-301 
INVESTIGATIONAL 
PRODUCT 
LIQ861 at capsule strengths of 25 µg, 50 µg, 75 µg and 100 µg treprostinil.  
LIQ861 will be administered using the RS00 Model 8 dry powder 
inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 
25 µg to 150 µg treprostinil QID in individual patients.  Dosing at levels 
above 150 µg treprostinil QID will require authorization from the Sponsor. 
STUDY OBJECTIVES 
The primary objective of this study is to evaluate the long-term safety and 
tolerability of LIQ861 in patients with PAH. 
The secondary objective of this study is to evaluate the comparative 
bioavailability of treprostinil between two formulations of inhaled therapy. 
STUDY DESIGN & 
DURATION 
Study LTI-301 is a Phase 3 open-label, multicenter study in patients with 
PAH to evaluate the long-term safety and tolerability of LIQ861.  
The study will evaluate the long-term safety and tolerability of LIQ861 in 
PAH patients who have been on stable doses of Tyvaso® for at least 3 
months (“Tyvaso Transition”), or who are taking no more than 2 approved 
non-prostacyclin oral PAH therapies (“LIQ861 Add-on”).   
A subset of patients will be enrolled in a one-directional crossover to 
compare bioavailability and pharmacokinetics of treprostinil as they 
transition from Tyvaso to LIQ861.   
At least 100 PAH patients will be enrolled in the study to evaluate the 
long-term safety and tolerability of LIQ861.     
Dose titration schedules for Tyvaso Transition and LIQ861 Add-on 
patients are described in Appendix 2.   
All patients will be treated on an outpatient basis until regulatory approval 
of LIQ861.   
Scheduled study visits to the clinic will occur at Screening, Baseline (Day 
1), Week 2, Month 1, Month 2, Month 4, and every 4 months thereafter 
(Month 8, Month 12, etc.).  Beginning with Month 6, patients will be called 
to assess safety and LIQ861 tolerance every 4 months (Month 6, Month 10, 
etc.)  During this time, dose titration may be ordered at the Investigator’s 
discretion and in accordance with the guidance provided in Appendix 2.      
Sub-Study - Comparative Bioavailability Assessment 
At least 18 PAH patients on Tyvaso will participate in a comparative 
bioavailability sub-study (“PK sub-study”) comparing treprostinil 
exposure in a one-directional crossover design that utilizes the patient’s 
prescribed Tyvaso dose as the comparator to LIQ861.  A stable dose of 
Tyvaso is defined as remaining on one dose administered QID for at least 
3 months.  

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 7 of 67 
SYNOPSIS 
The dose titration schedule for Tyvaso Transition patients is described in 
Appendix 2.   
Patients participating in this sub-study will have a trough level PK blood 
sample collected prior to self-administering their Tyvaso dose at the 
Investigational site at Baseline (morning dose Day 1), under the 
supervision of study staff.  Following administration of Tyvaso, blood will 
be collected for PK analysis of treprostinil through 4 hours post-dose and 
the patients will remain in the clinic for safety observations per Investigator 
discretion.  After the 4 hour post-dose blood draw, the patients will be 
transitioned to LIQ861 for subsequent doses of treprostinil in accordance 
with their typical dosing regimen.  If the initial LIQ861 dose (based on the 
instructions in Appendix 2) is tolerated, patients will take two more doses 
of LIQ861, 4 hours apart, during Day 1.   If the initial LIQ861 dose is not 
tolerated, dose adjustments may be made as needed during the next two 
doses taken on Day 1.   
On the morning of Day 2, patients will have a trough level PK blood sample 
collected prior to self-administering their LIQ861 dose at the 
Investigational site, under the supervision of study staff.  This dose should 
be the same as the last tolerated dose taken on Day 1.  Following 
administration of LIQ861, blood will be collected for PK analysis of 
treprostinil through 4 hours post-dose.  After the final PK blood collection 
on Day 2, patients will continue in the study, with QID dosing of LIQ861, 
following the procedures and visit schedule for all other study patients. 
NUMBER OF 
SUBJECTS 
A minimum of 100 patients will be enrolled and observed to support 
evaluation of safety and tolerance for LIQ861 use.  Patients will continue 
to receive LIQ861 and the study will continue until LIQ861 is 
commercially available or the study is terminated by the Sponsor.  Patients 
may withdraw from study participation at any time and the patient’s 
physician may request withdrawal for medical or safety reasons at any 
time. 
The PK sub-study will contain at least 18 patients with full PK profiles for 
each formulation of inhaled treprostinil, all of whom will continue in the 
study upon completion of Day 2 PK collections. 
NUMBER OF SITES 
Up to 50 sites 
PARTICIPATING 
COUNTRIES 
United States (US) 
SUBJECT 
POPULATION  
Patients with WHO Group 1 PAH who are  
• 
Stable (at least 3 months on same dose) on Tyvaso therapy, or; 
• 
on no more than two approved stable background therapies for ≥ 3 
months  
Inclusion Criteria 
A patient will be eligible for inclusion in this study only if all of the 
following criteria are met: 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 8 of 67 
SYNOPSIS 
1. An Institutional Review Board (IRB) approved informed consent is 
signed and dated by the patient prior to any study-related activities. 
2. The patient is 18 years of age or older. 
3. If the patient is a female of childbearing potential, then the patient has 
a negative pregnancy test at the Baseline Visit and agrees to practice 
adequate birth control throughout the duration of the study.  If the 
patient is postmenopausal or has documented surgical sterilization, a 
pregnancy test and birth control is not necessary.  It is the Investigator’s 
responsibility for determining whether the patient has adequate birth 
control for study participation. 
4. The patient has been diagnosed with PAH belonging to the following 
subgroups of the updated Nice Clinical Classification Group 1, which 
include: 
a. Idiopathic PAH (1.1), or  
b. Heritable PAH (1.2), or  
c. Drug and toxin induced PAH (1.3), or 
d. PAH associated with connective tissue disease (1.4.1), HIV 
infection (1.4.2), or congenital heart disease (1.4.4) with simple 
systemic-to-pulmonary shunt at least 1 year after surgical repair 
5.  The patient is NYHA Functional Class II - IV at Screening and: 
a. has documented stable doses of Tyvaso for at least 3 months prior 
to screening and is willing and able to transition from their 
prescribed dose of inhaled therapy to study drug, or 
b. has documented stable doses of no more than two approved oral 
therapies for at least 3 months prior to screening and is willing and 
able to add LIQ861 to their treatment regimen. 
6. The patient can complete a baseline six-minute walk distance (6MWD) 
≥ 150 m. 
7. The patient has had evidence of FEV1 ≥ 60% and FEV1/FVC ratio ≥ 
60% during the 6-month period prior to enrollment. 
Exclusion Criteria 
A Patient is not eligible for inclusion in the study if any of the following 
criteria apply:  
1. The patient's clinical condition is such that, in the opinion of the 
Investigator, they are not expected to remain clinically stable for the 
duration of the study. 
2. Patients with pulmonary hypertension (PH) in the Updated Nice 
Classification Groups 2-5, or PAH Group 1 subgroups not covered by 
the inclusion criteria (e.g., associated with portal hypertension [1.4.3] 
or with schistosomiasis [1.4.5]) 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 9 of 67 
SYNOPSIS 
3. The patient is currently taking oral or IV prostacyclin analogues or 
agonists, including treprostinil and selexipag 
4. The patient has had any PAH medication (except for anticoagulants) 
discontinued within 14 days of Baseline.  
5. The patient has had a new type of chronic therapy (including but not 
limited to oxygen, a different class of vasodilator, diuretic, digoxin, 
and digitalis) for pulmonary hypertension added within 30 days of 
Baseline.   
6. The patient has uncontrolled systemic hypertension as evidenced by 
persistent systolic blood pressure greater than 160 mmHg or diastolic 
blood pressure greater than 100 mmHg. 
7. The patient has a history of hemodynamically significant left-sided 
heart disease including, but not limited to: aortic or mitral valve 
disease, 
pericardial 
constriction, 
restrictive 
or 
congestive 
cardiomyopathy, or coronary artery disease (CAD). 
8. The patient has had an atrial septostomy. 
9. The patient has any serious or life-threatening disease other than 
conditions associated with PAH. 
10. The patient is taking any excluded medications listed in the 
Investigator’s Brochure, namely inhibitors and inducers of CYP2C8 
(See Appendix 3). 
11. The patient has a hypersensitivity or allergy to any of the ingredients 
of LIQ861 or other clinically relevant allergies (clinical relevance per 
Investigator judgment). 
12. The patient has had a pulmonary infarction (defined as infarction in 
more than one lung segment documented by V/Q scan or pulmonary 
angiography) within two weeks of Screening. 
13. The patient has had a stroke or transient ischemic attack (TIA) within 
six months of Screening.  
14. The patient has evidence of an active uncontrolled sepsis or systemic 
infection during Screening. 
15. The patient is pregnant or lactating. 
16. The patient has any musculoskeletal disease or any other disease that 
would limit ambulation. 
17. The patient has participated in an investigational product or device 
study within the 30 days prior to Screening. 
18. The patient has current evidence of drug abuse in the opinion of the 
Investigator. 
19. The patient has severe hepatic impairment as evidenced by any history 
of ascites AND encephalopathy. 
20. The patient has severe renal impairment (eGFR < 30). 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 10 of 67 
SYNOPSIS 
Additional Exclusion Criteria for PK Sub-Study 
1. The patient meets any of Primary Exclusion Criteria #1 – 19. 
2. The patient has moderate or severe renal impairment (eGFR < 45). 
SAFETY ANALYSES 
The primary endpoint will be the incidence of treatment-emergent Adverse 
Events (AEs) and Serious Adverse Events (SAEs) grouped by MedDRA 
System Organ Class, dose level, time on drug, and relationship to dose 
titration. 
Safety endpoints are as follows: 
• 
Incidence of treatment-emergent drug/device-related adverse 
events  
• 
Changes from Baseline to Month 2/Early Termination in clinical 
laboratory, physical exam findings, and vital signs. 
EXPLORATORY 
ANALYSES 
For all patients: 
• 
Change from Baseline to Week 2 and Months 1, 2, 4 and every 4 
months thereafter in 6MWD 
• 
Change from Baseline to Week 2 and Months 1, 2, 4 and every 4 
months thereafter in NYHA Functional Class status 
• 
Change from Baseline to Week 2 and Months 1, 2, 4 and every 4 
months thereafter in NT-proBNP levels 
• 
Change from Baseline to Month 2, Month 4, and every 12 months 
thereafter in the Minnesota Living with Heart Failure Quality of 
Life Questionnaire 
• 
Time to and reason for discontinuation of LIQ861 
For transitioning from Tyvaso only: 
• 
Proportion of patients maintaining a sustained treatment transition 
through the end of Month 2.  Sustained treatment transition is 
defined as meeting all of the following conditions:  1) current 
treatment with LIQ861 through at least 2 months beyond transition 
from Tyvaso, 2) no interruptions to study treatment totaling more 
than 7 days prior to the end of Month 2, and 3) no treatment with 
any prostacyclin or prostacyclin analogs apart from administration 
of LIQ861.  
• 
Comparison of LIQ861 dose achieved at sustained treatment to 
previous Tyvaso dose 
• 
Patient satisfaction with the LIQ861 DPI compared to the 
inhalation device from which they are transitioning using a simple 
questionnaire assessing device preference (Appendix 5). 
PHARMACOKINETIC 
ANALYSES 
For patients in the PK sub-study only: 
• 
Individual pharmacokinetic parameters for treprostinil will be 
summarized 
by 
treatment 
using 
descriptive 
statistics.  
Pharmacokinetic parameters such as the maximum observed 
plasma concentration (Cmax), time to Cmax (Tmax), the area 
under the plasma concentration versus time curve from time 0 
(predose) to time infinity (AUCinf), AUC from time 0 to time of 
last measurable plasma concentration (AUClast), the percentage of 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 11 of 67 
SYNOPSIS 
AUC that is extrapolated beyond the last measurable concentration 
(AUCext), the terminal phase rate constant (λz), the apparent 
systemic clearance (CL/F), the apparent volume of distribution in 
the terminal phase (Vz/F), mean residence time (MRT), and the 
terminal phase half-life (t½) will be calculated using non-
compartmental analyses. 
• 
An assessment of comparative bioavailability of treprostinil will 
also be made between LIQ861 and Tyvaso based on dose-
normalized AUCinf calculations for the two treatments. 
STATISTICAL 
CONSIDERATIONS 
• 
Individual and mean plots of plasma concentrations versus time 
after administration of treprostinil will be constructed and 
displayed for relevant treatment comparisons.  
• 
Plasma concentrations will be summarized by treatment using 
descriptive statistics (sample size, mean, median, coefficient of 
variation [CV%], standard deviation [SD], minimum, and 
maximum).  Corresponding by-patient data listings will be 
tabulated. 
• 
Derived plasma PK parameters will be summarized by treatment 
using descriptive statistics (sample size, arithmetic and geometric 
mean, CV%, SD of the arithmetic mean, median, minimum, and 
maximum).   
• 
The number and percentage of patients who experience at least 1 
AE will be presented by severity, relationship to study drug, 
MedDRA System Organ Class (SOC), preferred term, and dose 
level of one or both drugs administered.  Clinically significant vital 
signs findings and changes from Baseline values will be tabulated 
and summarized.  Clinical laboratory results will be tabulated. 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 12 of 67 
TABLE OF CONTENTS 
PROTOCOL APPROVAL PAGE .........................................................................................2 
INVESTIGATOR PROTOCOL AGREEMENT .................................................................3 
SUMMARY OF AMENDMENT CHANGES .......................................................................4 
SYNOPSIS ................................................................................................................................6 
TABLE OF CONTENTS ......................................................................................................12 
1. 
INTRODUCTION ..........................................................................................................17 
1.1. Background & Rationale for LIQ861 Development ...............................................17 
1.2. Description of LIQ861 ............................................................................................18 
1.3. Development Program ............................................................................................19 
1.4. Rationale for the Current Study ..............................................................................19 
2. 
STUDY OBJECTIVES ..................................................................................................19 
3. 
INVESTIGATIONAL PLAN ........................................................................................19 
3.1. Overall Study Design and Plan ...............................................................................19 
3.2. Endpoints ................................................................................................................21 
3.2.1. Primary Endpoint ........................................................................................21 
3.2.2. Safety Endpoints .........................................................................................21 
3.2.3. Pharmacokinetic Endpoints .........................................................................22 
3.2.4. Exploratory Endpoints ................................................................................22 
4. 
SELECTION OF STUDY POPULATION ..................................................................22 
4.1. Inclusion Criteria .....................................................................................................22 
4.2. Exclusion Criteria....................................................................................................23 
4.3. Removal of Patients from Therapy/Premature Discontinuation .............................24 
5. 
TREATMENTS ..............................................................................................................25 
5.1. Treatments Administered ........................................................................................25 
5.2. Identity of Investigational Product(s)......................................................................25 
5.2.1. LIQ861 ........................................................................................................25 
5.2.2. Labeling.......................................................................................................26 
5.2.3. Storage and Handling ..................................................................................26 
5.3. Selection of Doses in the Study ..............................................................................26 
5.4. Selection and Timing of Dose for Each Patient ......................................................27 
5.5. Prior and Concomitant Therapy ..............................................................................27 
5.6. Prohibited Therapy ..................................................................................................27 
5.7. Dose Modification ...................................................................................................27 
5.8. Treatment Compliance ............................................................................................27 
5.8.1. Study Drug Accountability .........................................................................27 
6. 
STUDY PROCEDURES ................................................................................................28 
6.1. Study Measurements and Assessments ...................................................................28 
6.1.1. Assessment of Safety ..................................................................................28 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 13 of 67 
6.1.2. Exploratory Assessments ............................................................................28 
6.2. Study Phases and Procedures ..................................................................................28 
6.2.1. Screening Phase (Visit 1; Day -28 through Day 0) .....................................28 
6.2.2. Baseline – (Visit 2; Day 1) ..........................................................................29 
6.2.3. Baseline – PK Sub-Study (Visit 2; Day 1 & Day 2) ...................................29 
6.2.4. Visit 3 (Week 2) ..........................................................................................31 
6.2.5. Visits 4 & 5 (Month 1 & Month 2) .............................................................32 
6.2.6. Visits 6+ (Month 4) .....................................................................................33 
6.2.6.1. 
In Clinic at Month 4 and Every 4 Months thereafter until Study 
Termination Visit ............................................................................33 
6.2.6.2. 
Phone Visits (every 4 months starting at Month 6) ........................34 
6.2.6.3. 
Study Termination Visit ..................................................................34 
6.2.7. Follow-up for Withdrawn Patients ..............................................................34 
6.3. Unscheduled Visits .................................................................................................35 
6.4. Pharmacokinetic Assessments ................................................................................35 
6.5. Clinical Laboratory Tests ........................................................................................36 
6.6. Physical Examinations ............................................................................................36 
6.7. Vital Signs ...............................................................................................................36 
6.8. Six-Minute Walk Test (6MWT) .............................................................................37 
6.9. Assessment Windows .............................................................................................37 
6.10. Patient Questionnaires .............................................................................................37 
7. 
ADVERSE EVENTS ......................................................................................................37 
7.1. Definition of a Treatment-Emergent Adverse Event ..............................................37 
7.1.1. Definition of a Suspected Adverse Reaction ..............................................38 
7.1.2. Definition of an Adverse Reaction ..............................................................38 
7.1.3. Definition of Unexpected Adverse Event or Unexpected Suspected 
Adverse Reaction ........................................................................................39 
7.1.4. Definition of a Serious Adverse Event or Serious Suspected Adverse 
Reaction.......................................................................................................39 
7.2. Adverse Device Effect and Serious Adverse Device Effect ...................................40 
7.2.1. Unanticipated Adverse Device Effects .......................................................40 
7.3. Severity of TEAEs/SAEs ........................................................................................41 
7.4. Assessment of Relatedness to Study Drug or Device .............................................41 
7.5. Method, Frequency, and Time Period for Detecting Adverse Events and Serious 
Adverse Events........................................................................................................41 
7.6. Reporting AEs and SAEs ........................................................................................42 
7.6.1. Reporting Adverse Events...........................................................................42 
7.6.2. Timeframes for Reporting SAEs/SADEs ...................................................42 
7.6.3. SAE/SADE Information to Report .............................................................42 
7.6.4. SAE/SADE Reporting Contact Information ...............................................43 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 14 of 67 
7.6.5. Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
TEAEs and SAEs ........................................................................................43 
7.6.6. Documenting SAEs/SADEs ........................................................................43 
7.6.7. Regulatory/Ethics reporting requirement ....................................................43 
7.6.8. Follow-up of TEAEs and SAEs ..................................................................44 
8. 
STATISTICS ...................................................................................................................44 
8.1. Determination of Sample Size ................................................................................44 
8.2. Analysis Populations ...............................................................................................44 
8.3. Baseline Characteristics and Patient Disposition ....................................................44 
8.4. Hypothesis ...............................................................................................................44 
8.5. Exploratory Analyses ..............................................................................................45 
8.6. Noncompartmental Pharmacokinetic Analyses (PK sub-study) .............................45 
8.7. Safety Analyses .......................................................................................................46 
8.7.1. Prior and Concomitant Medications............................................................46 
9. 
RESPONSIBILITIES .....................................................................................................46 
9.1. Investigator Responsibilities ...................................................................................46 
9.1.1. Good Clinical Practice ................................................................................46 
9.1.2. Institutional Review Board (IRB)/Ethics Committee (EC) Approval ........46 
9.1.3. Informed Consent ........................................................................................46 
9.1.4. Conflicts of Interest .....................................................................................47 
9.1.5. Confidentiality ............................................................................................47 
9.1.6. Study Files and Retention of Records .........................................................47 
9.1.7. Case Report Forms ......................................................................................47 
9.1.8. Drug Accountability ....................................................................................48 
9.1.9. Inspections ..................................................................................................48 
9.2. Sponsor Responsibilities .........................................................................................48 
9.2.1. Study Materials and Instructions .................................................................48 
9.2.2. Protocol Modifications ................................................................................48 
9.3. Joint Investigator/Sponsor Responsibilities ............................................................49 
9.3.1. Access to Information for Monitoring ........................................................49 
9.3.2. Study Discontinuation .................................................................................49 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 15 of 67 
10. REFERENCES ...............................................................................................................50 
APPENDIX 1.  TIME AND EVENTS SCHEDULES ........................................................51 
APPENDIX 2.  GUIDANCE FOR LIQ861 DOSE SELECTION AND TITRATION ...55 
APPENDIX 3.  INHIBITORS AND INDUCERS OF CYP2C8 ........................................59 
APPENDIX 4.  PK SAMPLE COLLECTION, PROCESSING, AND SHIPMENT.......60 
APPENDIX 5.  INHALATION DEVICE USER SURVEY ...............................................61 
APPENDIX 6.  ASSESSMENT OF HEPATIC AND RENAL IMPAIRMENT ..............62 
APPENDIX 7.  6MWT INSTRUCTIONS AND WORKSHEET ......................................63 
 
 
LIST OF FIGURES 
Figure 1.  
RS00 Model 8 Dry Powder Inhalation Device ................................................18 
Figure 2.  
Schematic of LTI-301 Study Design ...............................................................20 
  
LIST OF TABLES 
Table 1.  
Pharmacokinetic Parameters ............................................................................45 
Table 2.  
Starting LIQ861 dose based upon Tyvaso Dose ..............................................56 
Table 3.  
Tyvaso and LIQ861 Dosing for Patients in the PK Sub-Study .......................57 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 16 of 67 
ABBREVIATIONS 
6MWD 
Six-minute walk distance 
6MWT 
Six-minute walk test 
βhCG 
beta-human chorionic gonadotropin 
λz 
terminal phase rate constant (first-order) 
ADE 
Adverse Device Event 
AE 
adverse event 
AUC 
Area under the curve 
BLQ 
Below the Limit of Quantification 
CFR 
Code of Federal Regulations 
CL/F 
apparent clearance 
Cmax 
peak plasma concentration, observed 
CV 
Coefficient of Variation 
DPI 
Dry Powder Inhalation 
EC 
Ethics committee 
eCRF 
Electronic case report form 
eGFR 
Estimated Glomerular Filtration Rate 
FDA 
Food and Drug Administration  
FEV1 
Forced Expiratory Volume in 1 Second 
Frel 
Relative Bioavailability 
FVC 
Forced Vital Capacity 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
ICF 
Informed Consent Form 
IND 
Investigational New Drug 
IRB/EC 
Institutional Review Board/Independent Ethics Committee 
MedDRA 
Medical Dictionary for Regulatory Activities 
MLWHF 
Minnesota Living with Heart Failure 
mmHg 
millimeters of mercury 
MRT 
mean residence time 
NYHA 
New York Heart Association 
PAH 
Pulmonary arterial hypertension 
PH 
Pulmonary Hypertension 
PK 
pharmacokinetic  
PRINT 
Particle Replication in Nonwetting Templates 
QID 
Four times a day 
QOL 
Quality of life 
SADE 
Serious Adverse Device Effect 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
t½ 
elimination half-life 
TAD 
Tyvaso Approximate Dose 
TEAE 
Treatment-Emergent Adverse Event 
Tmax 
time to peak plasma concentration, observed 
Vz/F 
volume of distribution 
WHO 
World Health Organization 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 17 of 67 
1. 
INTRODUCTION 
1.1. 
Background & Rationale for LIQ861 Development 
Pulmonary arterial hypertension (PAH) is a complex, multifactorial, progressive, and life-
threatening disease characterized by proliferative and obstructive changes in the pulmonary 
vasculature and involving numerous biochemical pathways and cell types.  The disease is 
characterized by elevated pulmonary arterial pressure and right ventricular failure that carries a 
poor prognosis associated with significant morbidity and mortality, having a historical survival 
rate of less than five years.  Endothelial dysfunction is thought to occur early on, leading to cell 
proliferation and structural changes in the pulmonary vasculature that lead to increased pulmonary 
arterial pressure (PAP) and resultant right ventricular enlargement and dysfunction.  In addition, 
endothelial dysfunction results in chronically impaired production of vasoactive mediators, such 
as nitric oxide (NO) and prostacyclin, along with prolonged overexpression of vasoconstrictors, 
such as endothelin-1 (Channick, Voswinckel et al. 2012). 
PAH is part of a larger classification for pulmonary hypertension, which is divided into five groups  
based on World Health Organization (WHO) criteria (designated as WHO Groups 1 through 5), 
as defined at the 5th World Symposium on Pulmonary Hypertension in Nice, France (Simonneau, 
Gatzoulis et al. 2013).  PAH is used to describe exclusively WHO Group 1.  Pulmonary 
hypertension (PH) is used to describe the remaining four groups (WHO Groups 2-5) and also when 
referring to all 5 groups collectively.   
• 
WHO Group 1 - PAH: Pulmonary arterial hypertension.   
• 
WHO Group 2 - PH: Pulmonary hypertension secondary to left heart disease. 
• 
WHO Group 3 - PH: Pulmonary hypertension secondary to lung diseases or hypoxemia. 
• 
WHO Group 4 - PH: Chronic thromboembolic pulmonary hypertension.   
• 
WHO Group 5 - PH: Pulmonary hypertension with unknown mechanisms. 
PAH initially presents as exertional dyspnea, lethargy, and fatigue and is often confused for other 
disease states.  As PAH progresses and right ventricular failure develops, exertional chest pain 
(i.e., angina), exertional syncope, and peripheral edema may develop.  Following confirmation of 
diagnosis based on hemodynamic parameters, treatment is recommended to lower pulmonary 
pressures and treat the symptoms of PAH.  Although no cure exists for PAH, treatment of PAH is 
directed at improving hemodynamic measures (Badesch, Abman et al. 2007), New York Heart 
Association (NYHA) functional class (Miller-Davis, Marden et al. 2006), the six-minute walk 
distance (6MWD) (Babu, Padmakumar et al. 2016), quality of life (QOL) (Babu, Padmakumar et 
al. 2016), and, in some studies, survival.  
The severity of PAH may be classified according to the NYHA heart failure guidelines as follows: 
• 
NYHA Class I:  Patients with cardiac disease having no limitation of activities; ordinary 
physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. 
• 
NYHA Class II:  Patients with cardiac disease resulting in slight limitation of physical activity; 
they are comfortable at rest, however ordinary physical activity results in fatigue, palpitation, 
dyspnea, or anginal pain. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 18 of 67 
• 
NYHA Class III:  Patients with cardiac disease resulting in marked limitation of activity; they 
are comfortable at rest, however less than ordinary physical activity results in fatigue, 
palpitation, dyspnea, or anginal pain. 
• 
NYHA Class IV:  Patients with cardiac disease resulting in inability to carry on any physical 
activity without discomfort.  Symptoms of heart failure or the anginal syndrome may be present 
even at rest with discomfort increasing if any physical activity is undertaken. 
Treprostinil is a chemically stable tricyclic benzidine prostanoid with vasodilator properties that is 
capable of reducing pulmonary vasoconstriction with minimal effects on systemic blood pressure 
(Channick, Voswinckel et al. 2012).  Treprostinil has been approved for the treatment of PAH and 
is marketed by the United Therapeutics Corporation under the trade names Orenitram® (extended 
release oral tablets), Remodulin® (subcutaneous or IV infusion) and Tyvaso (inhaled via 
ultrasonic, pulsed delivery device).  Tyvaso was shown to be effective in the treatment of PAH, 
with an advantage of the inhaled route of administration being that it brings the drug very near the 
desired site of action (pulmonary arteries in the lungs) (McLaughlin, Benza et al. 2010). 
One of the greatest impediments to patient treatment satisfaction with Tyvaso is inconvenience.  
Currently, patients on Tyvaso may require more than 36 breaths per day with the use of a bulky 
nebulizer.  The use of a discrete, hand-held dry powder inhaler to deliver treprostinil to the lungs 
would represent a major improvement in convenience and patient satisfaction, thereby improving 
the quality of life for PAH patients.  Thus, Liquidia is pursuing approval of LIQ861, an inhalation 
dry powder formulation of treprostinil that is produced using Liquidia’s PRINT® Technology 
(Particle Replication in Nonwetting Templates), as an alternative to Tyvaso for the treatment of 
patients with PAH (WHO Group 1).  
1.2. 
Description of LIQ861 
LIQ861 is a capsule containing a dry powder mixture of treprostinil and excipients (bulk powder) 
designed for inhalation using a dry powder inhalation device.  The bulk powder is generated from 
a treprostinil/excipient matrix from which particles of precise size (1 µm) and shape (“pollen-
shaped”) are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3).  
LIQ861 capsules are provided in capsule strengths of 25 µg, 50 µg, 75 µg and 100 µg treprostinil.   
The LIQ861 capsule is intended for use with a handheld monodose dry powder inhalation device.  
The device chosen for clinical trials is the RS00 Model 8 manufactured by Plastiape.  The overall 
design of the RS00 Model 8 device is shown in Figure 1. 
Figure 1.  
RS00 Model 8 Dry Powder Inhalation Device 
 
The mouthpiece contains a mesh that aids in particle size reduction and prevents capsule ingestion 
during inhalation.  The inhaler body component contains 2 side buttons, each housing 4 pins for 
piercing a capsule.  A capsule piercing area is located internally, adjacent to the pins.  When a 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 19 of 67 
capsule is inserted in this area, depressing the buttons causes the button pins to pierce the capsule 
ends, thereby preparing the capsule for emptying.  Above the capsule piercing area, there are 2 
tangential air inlets and a circular chamber.  These allow the capsule to spin when the patient 
inhales through the device.  Capsule spinning creates a centrifugal effect on the powder that 
promotes efficient emptying.  Emitted doses from each capsule are less than the labeled capsule 
strengths of treprostinil, which correspond to the amount of powder with which each capsule is 
filled.   
1.3. 
Development Program 
A first-in-human study was performed at the PPD Phase 1 Clinic in Austin, TX under a US 
Investigational New Drug (IND).  Study LTI-101 was a Phase 1, single-center, placebo-controlled, 
double-blinded, randomized study to evaluate the safety and tolerability of the LIQ861 formulation 
and to characterize the pharmacokinetics (PK) of treprostinil as an inhaled dry powder.  Cohorts 
of 8 healthy volunteers were randomly assigned in a 3:1 ratio to receive a single dose of either 
LIQ861 (n = 6) or placebo (n = 2) at dose levels of 25, 50, 75, 100, 125, and 150 µg treprostinil.  
Blood for measurement of treprostinil concentrations was collected through 8 hours post-dose for 
determination of treprostinil noncompartmental PK parameters.   
The median treprostinil Tmax was between 10 and 20 minutes post-dose administration.  Dose 
proportionality was assessed based on Cmax and AUCinf and concluded to be proportional over 
the entire tested dose range of 25 to 150 µg treprostinil.  The LIQ861 formulation was found to be 
well-tolerated after single-dose administration with no serious or unexpected adverse events.  The 
most commonly reported related adverse events (AEs) were cough, throat irritation, inspiratory 
tightness, lightheadedness, and headache; all were described as mild in severity.  There were no 
serious AEs. 
Additional information on the development of the LIQ861 product may be found in the most 
current version of the Investigator’s Brochure. 
1.4. 
Rationale for the Current Study 
Study LTI-301 is a Phase 3 open-label, multicenter study in patients with PAH to evaluate the 
long-term safety and tolerability of LIQ861 and the comparative bioavailability in patients 
transitioning from Tyvaso to LIQ861.  
2. 
STUDY OBJECTIVES 
The primary objective of this study is to evaluate the long-term safety and tolerability of LIQ861 
in patients with PAH. 
The secondary objective of this study is to evaluate the comparative bioavailability of treprostinil 
between two formulations of inhaled therapy 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
Study LTI-301 is a Phase 3 open-label, multicenter study in patients with PAH to evaluate the 
long-term safety and tolerability of LIQ861.  

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 20 of 67 
The study will evaluate the long-term safety and tolerability of LIQ861 in PAH patients who have 
been on stable doses of Tyvaso (treprostinil) inhalation solution for at least 3 months (“Tyvaso 
Transition”), or who are taking no more than 2 approved non-prostacyclin oral PAH therapies 
(“LIQ861 Add-on”).   
A subset of patients will be enrolled in a one-directional crossover to compare the bioavailability 
and pharmacokinetics of treprostinil as they transition from Tyvaso to LIQ861.   
Figure 2.  
Schematic of LTI-301 Study Design 
 
At least 100 PAH patients will be enrolled in the study to evaluate the long-term safety and 
tolerability of LIQ861.  All patients will be treated on an outpatient basis until regulatory approval 
of LIQ861.   
Tyvaso Transition patients will receive training on the use of the dry powder inhalation (DPI) 
device and then administer their first dose of LIQ861 at the Investigational site at the Baseline 
Visit (Day 1) under the supervision of study staff and will remain in the clinic for safety per 
Investigator discretion.  The initial LIQ861 treprostinil dose will be matched to the comparable 
prescribed Tyvaso dose at transition (Appendix 2); subsequently, LIQ861 will be maintained on a 
QID dosing schedule for the duration of the study.  During this time, dose titration may be ordered 
at the Investigator’s discretion and in accordance with the Guidance for LIQ861 Dose Selection 
and Titration (Appendix 2). 
Add-on patients will receive training on the use of the DPI and then administer their first dose of 
LIQ861 at the Investigational site at Baseline (Day 1) under the supervision of study staff.  Study 
drug will be administered for LIQ861 Add-on patients initially at 25μg treprostinil in LIQ861 QID 
with timing of dose titrations chosen at the Investigator’s discretion while maintaining a QID 
dosing schedule (Appendix 2).  Alterations to the dosing interval (e.g., 3 times a day or 5 times a 
day) must be approved by the Sponsor. 
Scheduled study visits to the clinic will occur at Screening, Baseline (Day 1), Week 2, Month 1, 
Month 2, Month 4, and every 4 months thereafter (e.g., Month 8, Month 12, etc.) until study 
termination or regulatory approval.  During this time, dose titration may be ordered at the 
Investigator’s discretion and in accordance with the Guidance for LIQ861 Dose Selection and 
Titration (Appendix 2). 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 21 of 67 
Telephone contact to assess adverse events (AEs), concomitant medications, and PAH symptoms 
will be made every 4 months beginning at Month 6 (e.g., Month 6, Month 10, etc.) until the Study 
Termination Visit.  Telephone contact is not necessary during months in which a study visit is 
scheduled.  The Study Termination Visit will occur after regulatory approval of LIQ861 or after 
the Sponsor decides to terminate the development program.   
Patients that clinically worsen on open-label LIQ861, as determined by Investigator’s discretion 
may be withdrawn from the study and rescue therapy initiated per standard of care.   
Sub-Study - Comparative Bioavailability Assessment 
At least 18 PAH patients on Tyvaso (stable doses QID for at least 3 months) will be included in a 
comparative bioavailability sub-study (“PK sub-study”) comparing treprostinil exposure in a one-
directional crossover design that utilizes the patient’s prescribed Tyvaso dose as the comparator to 
LIQ861.   
The dose titration schedule for these patients is described in Appendix 2.   
Patients participating in this sub-study will have a trough level PK blood sample collected prior to 
self-administering their Tyvaso dose at the Investigational site at Baseline (morning dose Day 1), 
under the supervision of study staff.  Following administration of Tyvaso, blood will be collected 
for PK analysis of treprostinil through 4 hours post-dose and the patients will remain in the clinic 
for safety observations per Investigator discretion.  After the 4 hour post-dose blood draw, the 
patients will be transitioned to LIQ861 for subsequent doses of treprostinil in accordance with their 
typical dosing regimen.  If the initial LIQ861 dose (based on the instructions in Appendix 2) is 
tolerated, patients will take two more doses of LIQ861, 4 hours apart, during Day 1.  If the initial 
LIQ861 dose is not tolerated, dose adjustments may be made as needed during the next two doses 
taken on Day 1. 
On the morning of Day 2, patients will have a trough level PK blood sample collected prior to self-
administering their LIQ861 dose at the Investigational site, under the supervision of study staff.  
This dose should be the same as the last tolerated dose taken on Day 1.  Following administration 
of LIQ861, blood will be collected for PK analysis of treprostinil through 4 hours post-dose.  After 
the final PK blood collection on Day 2, patients will continue in the study, with QID dosing of 
LIQ861, following the procedures and visit schedule for all other study patients. 
3.2. 
Endpoints 
3.2.1. 
Primary Endpoint 
The primary endpoint will be the incidence of Treatment-Emergent Adverse Events (TEAEs) and 
Serious Adverse Events (SAEs) grouped by MedDRA System Organ Class, dose level, time on 
drug, and relationship to dose titration. 
3.2.2. 
Safety Endpoints 
Safety endpoints are as follows: 
• Incidence of treatment-emergent drug/device-related adverse events  
• Changes from Baseline to Month 2/Early Termination in clinical laboratory, physical exam 
findings, and vital signs 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 22 of 67 
3.2.3. 
Pharmacokinetic Endpoints 
For patients in the PK sub-study only: 
• Individual pharmacokinetic parameters for treprostinil will be summarized by treatment 
using descriptive statistics.  Pharmacokinetic parameters such as the maximum observed 
plasma concentration (Cmax), time to Cmax (Tmax), the area under the plasma 
concentration versus time curve from time 0 (predose) to time infinity (AUCinf), AUC 
from time 0 to time of last measurable plasma concentration (AUClast), the percentage of 
AUC that is extrapolated beyond the last measurable concentration (AUCext), the terminal 
phase rate constant (λz), the apparent systemic clearance (CL/F), the apparent volume of 
distribution in the terminal phase (Vz/F), mean residence time (MRT), and the terminal 
phase half-life (t½) will be calculated using non-compartmental analyses. 
• An assessment of comparative bioavailability of treprostinil will also be made between 
LIQ861 and Tyvaso based on dose-normalized AUCinf calculations for the two treatments. 
3.2.4. 
Exploratory Endpoints 
For all patients: 
• Change from Baseline to Week 2 and Months 1, 2, 4 and every 4 months thereafter in 
6MWD 
• Change from Baseline to Week 2 and Months 1, 2, 4 and every 4 months thereafter in 
NYHA Functional Class status 
• Change from Baseline to Week 2 and Months 1, 2, 4 and every 4 months thereafter in NT-
proBNP levels 
• Change from Baseline to Month 2, Month 4, and every 12 months thereafter in the 
Minnesota Living with Heart Failure (MLWHF) Quality of Life Questionnaire 
• Time to and reason for discontinuation of LIQ861 
For transitioning from Tyvaso only: 
• Proportion of patients maintaining a sustained treatment transition through the end of 
Month 2.  Sustained treatment transition is defined as meeting the following conditions: 1) 
current treatment with LIQ861 through at least 2 months beyond transition from Tyvaso, 
2) no interruptions to study treatment totaling more than 7 days prior to the end of Month 
2, and 3) no treatment with any prostacyclin or prostacyclin analogs apart from 
administration of LIQ861.  
• Comparison of LIQ861 dose achieved at sustained treatment to previous Tyvaso dose 
• Patient satisfaction with the LIQ861 DPI compared to the inhalation device from which 
they are transitioning from using a simple questionnaire to assess device preference 
(Appendix 5). 
4. 
SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
A patient will be eligible for inclusion in this study only if the following criteria are met: 
1. An Institutional Review Board (IRB) approved informed consent is signed and dated by the 
patient prior to any study-related activities. 
2. The patient is 18 years of age or older. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 23 of 67 
3. If the patient is a female of childbearing potential, then the patient has a negative pregnancy 
test at the Baseline Visit and agrees to practice adequate birth control throughout the duration 
of the study.  If the patient is postmenopausal or has documented surgical sterilization, a 
pregnancy test and birth control is not necessary.  It is the Investigator’s responsibility for 
determining whether the patient has adequate birth control for study participation. 
4. The patient has been diagnosed with PAH belonging to the following subgroups of the updated 
Nice Clinical Classification Group 1 (Simonneau, Gatzoulis et al. 2013), which include: 
a. Idiopathic PAH (1.1), or  
b. Heritable PAH (1.2), or  
c. Drug and toxin induced PAH (1.3), or 
d. PAH associated with connective tissue disease (1.4.1), HIV infection (1.4.2), or congenital 
heart disease (1.4.4) with simple systemic-to-pulmonary shunt at least 1 year after surgical 
repair 
5. The patient has been diagnosed with PAH and is NYHA Functional Class II - IV at Screening.  
a. has documented stable doses of approved inhaled therapy for at least 3 months prior to 
screening and is willing and able to transition from their prescribed dose of inhaled therapy 
to study drug, or 
b. has documented stable doses of no more than two approved oral therapies for at least 3 
months prior to screening and is willing and able to add LIQ861 to their treatment regimen. 
6. The patient can complete a baseline six-minute walk distance (6MWD) ≥ 150 m. 
7. The patient has had evidence of FEV1 ≥ 60% and FEV1/FVC ratio ≥ 60% during the 6-month 
period prior to enrollment. 
4.2. 
Exclusion Criteria 
A Patient is not eligible for inclusion in the study if any of the following criteria apply:  
1. The patient's clinical condition is such that, in the opinion of the Investigator, they are not 
expected to remain clinically stable for the duration of the study. 
2. Patients with PH in the Updated Nice Classification Groups 2-5, or PAH Group 1 subgroups 
not covered by the inclusion criteria (e.g., associated with portal hypertension [1.4.3] or with 
schistosomiasis [1.4.5]). 
3. The patient is currently taking oral or intravenous (IV) prostacyclin analogues or agonists, 
including treprostinil and selexipag. 
4. The patient has had any PAH medication (except for anticoagulants) discontinued within 14 
days of Baseline.  
5. The patient has had a new type of chronic therapy (including but not limited to oxygen, a 
different class of vasodilator, diuretic, digoxin, and digitalis) for pulmonary hypertension 
added within 30 days of Baseline.  
6. The patient has uncontrolled systemic hypertension as evidenced by persistent systolic blood 
pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 24 of 67 
7. The patient has a history of hemodynamically significant left-sided heart disease including, 
but not limited to: aortic or mitral valve disease, pericardial constriction, restrictive or 
congestive cardiomyopathy, or coronary artery disease (CAD). 
8. The patient has had an atrial septostomy. 
9. The patient has any serious or life-threatening disease other than conditions associated with 
PAH. 
10. The patient is taking any excluded medications listed in the Investigator’s Brochure, namely 
inhibitors and inducers of CYP2C8 (See Appendix 3). 
11. The patient has a hypersensitivity or allergy to any of the ingredients of LIQ861 or other 
clinically relevant allergies (clinical relevance per Investigator judgment). 
12. The patient has had a pulmonary infarction (defined as infarction in more than one lung 
segment documented by V/Q scan or pulmonary angiography) within two weeks of 
Screening. 
13. The patient has had a stroke or transient ischemic attack (TIA) within six months of 
Screening.  
14. The patient has evidence of an active uncontrolled sepsis or systemic infection during 
Screening. 
15. The patient is pregnant or lactating. 
16. The patient has any musculoskeletal disease or any other disease that would limit ambulation.  
17. The patient has participated in an investigational product or device study within the 30 days 
prior to Screening. 
18. The patient has current evidence of drug abuse in the opinion of the Investigator. 
19. The patient has severe hepatic impairment as evidenced by any history of ascites AND 
encephalopathy. 
20. The patient has severe renal impairment (eGFR < 30). 
Additional Exclusion Criteria for PK Sub-Study 
1. The patient meets any of Primary Exclusion Criteria #1 – 19. 
2. The patient has moderate or severe renal impairment (eGFR < 45). 
4.3. 
Removal of Patients from Therapy/Premature Discontinuation 
Patients will be encouraged to complete the study and all assessments.  A patient will be 
discontinued from the study for the following medical or administrative reasons: 
• Occurrence of a TEAE that represents an unacceptable risk to the patient and when 
continued participation in the investigational study is not warranted, in judgment of the 
Investigator.  The Investigator must follow the patient until the AE resolves or 
satisfactorily stabilizes 
• Patient request  
• Pregnancy  

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 25 of 67 
• Significant non-compliance with study procedures or dosing regimen 
The Investigator may discontinue individual patients from the study at any time.  Patients may 
voluntarily withdraw at any time.   
All patients withdrawn from the study because of a TEAE will continue to be followed for at least 
4 months after removal from LIQ861 treatment or until the adverse event(s) resolves or stabilizes 
(Section 6.2.7). 
The Investigator will be responsible for obtaining final clinical assessments on patients that early 
terminate from the study.  If a patient is discontinued or withdraws from the study after receiving 
at least one dose of LIQ861 and withdraws/terminates prior to completion of the final assessments, 
then the site will make every effort to conduct a Study Termination Visit.  
Unscheduled visits may be conducted at the Investigator’s discretion for patient safety monitoring, 
following up on TEAEs/SAEs, or other reasons that will be documented.  Assessments at 
unscheduled visits will be symptom driven and conducted at the Investigator’s discretion.    
5. 
TREATMENTS 
5.1. 
Treatments Administered  
LIQ861 will be self-administered by the patients in the study after receiving adequate training by 
qualified study staff.  LIQ861 administration must occur only in accordance with the procedures 
described in this protocol and detailed instructions that are supplied for distribution to the study 
patients. 
5.2. 
Identity of Investigational Product(s) 
LIQ861 is a capsule containing a pre-loaded amount of a white to off-white dry powder containing 
treprostinil and excipients (bulk powder), which is intended to be inhaled with the use of the RS00 
Model 8 DPI (Figure 1).  The bulk powder, which is manufactured by Liquidia Technologies, 
consists of particles of precise size (1 µm) and shape (“pollen-shaped”) that are created from a 
treprostinil/excipient matrix using Liquidia’s PRINT Technology.   
5.2.1. 
LIQ861 
The LIQ861 formulation is comprised of treprostinil sodium (drug substance salt) and five 
excipients: trehalose dihydrate, Polysorbate 80, leucine, sodium citrate, and sodium chloride.  The 
mass proportion of the excipients in the pollen-shaped particles greatly exceeds the strength of 
treprostinil in the mixture (See Investigator’s Brochure).  As such, the fill weights of bulk powder 
are much greater than the dosage strength of active drug substance.  Four capsule strengths of 
LIQ861 have been manufactured for this study: 
• The 25 μg treprostinil capsule strength is a capsule that is filled with 5 mg LIQ861 bulk 
powder. 
• The 50 μg treprostinil capsule strength is a capsule that is filled with 10 mg LIQ861 
bulk powder. 
• The 75 μg treprostinil capsule strength is a capsule that is filled with 15 mg LIQ861 
bulk powder. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 26 of 67 
• The 100 μg treprostinil capsule strength is a capsule that is filled with 20 mg LIQ861 
bulk powder. 
For dose levels in excess of 100 μg treprostinil, multiple capsules of lower capsule strength may 
be used in immediate succession to achieve the desired dose of treprostinil.  A dose level of 125 µg 
should be delivered with a combination of a 75 µg and a 50 µg capsule, and a dose level of 150 µg 
should be delivered with a combination of two 75 µg capsules. 
5.2.2. 
Labeling 
Study drug will bear a label that meets applicable laws for an investigational drug, which may 
include, but is not limited to, the following information: 
• Federal law statement 
• Lot number 
• Box number  
• Storage information 
• Capsule Strength 
• Expiration date 
• Name of Sponsor 
5.2.3. 
Storage and Handling 
All study drug will be kept in a locked area with limited access and stored at 15°-30°C (59°-86°F).  
When in the possession of patients, all study drug should be stored in a cool, dry area.  Study drug 
is packaged, per strength, as four capsules per bottle, with eight bottles and two DPIs per box.  
5.3. 
Selection of Doses in the Study 
The results of study LTI-101 showed that the observed exposures of treprostinil after inhalation of 
LIQ861 are proportional to administered dose levels consistent with the capsule strengths selected 
for this study.  Mean Cmax and AUCinf values from the LTI-101 study were compared with mean 
exposure levels reported in published literature and in the Drug Approval Reviews from the FDA.  
Commonalities between the exposures observed in the LTI-101 study and those reported for 
Tyvaso were used to project a Tyvaso Approximate Dose (TAD) for LIQ861.  This assessment 
was the basis of the original dose selection guidance (LTI-301 Protocol Amendment 1, 13-Nov-
2017).   
Review of interim PK data from crossover patients in LTI-301 has shown that the initial TAD for 
LIQ861 may be providing lower plasma exposure than originally projected. The estimated 
treprostinil doses delivered from Tyvaso appear to result in plasma exposures that are more 
consistent with the estimated emitted doses from LIQ861.  The trend of observed plasma exposures 
from within-patient PK comparisons in interim LTI-301 data review, combined with estimates of 
expected emitted doses from LIQ861 administration, are the basis of revised initial transition dose 
selection guidance provided in Table 2 and the directed dose administrations for future PK patients 
provided in Table 3 (see Appendix 2).    
If the patient is not already on Tyvaso, the starting dose will be LIQ861 QID at the 25 µg 
treprostinil capsule strength.  For patients transitioning from Tyvaso, patients should start at doses 
recommended in the Guidance for LIQ861 Dose Selection and Titration, Appendix 2.  For all 
patients, dosing may be titrated per instructions provided in Appendix 2. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 27 of 67 
5.4. 
Selection and Timing of Dose for Each Patient 
Patients will receive QID administration of study drug on an outpatient basis until regulatory 
approval of LIQ861 for the treatment of PAH or until the sponsor decides to amend or terminate 
the study. 
5.5. 
Prior and Concomitant Therapy  
Medications taken within 3 months of screening will be documented in the patient’s notes and 
electronic case report form (eCRF).  
Any new or changed concomitant medication (prescriptions and non-prescriptions), including PGI 
use, will be recorded in the source documents and eCRF throughout the study, including any 
medication taken between the Screening Visit and initiation of treatment with LIQ861.  
5.6. 
Prohibited Therapy  
Patients may not be treated with LIQ861 if concurrently receiving any of the following 
medications: 
• CYP2C8 inhibitors and inducers, listed in Appendix 3 
• Oral administered prostacyclin analogues and agonists, such as treprostinil and selexipag 
5.7. 
Dose Modification 
When dosing is to exceed 100 μg treprostinil, administration of LIQ861 capsules should be 
administered as follows to achieve the target dose: 
To achieve a target dose of 125 µg treprostinil, the subject should administer one 50 μg treprostinil 
capsule followed by one 75 μg treprostinil capsule. 
To achieve a target dose of 150 µg treprostinil, the subject should administer one 75 μg treprostinil 
capsule followed by another 75 μg treprostinil capsule. 
Based on data from the LTI-101 study, dose levels of up to 150 μg treprostinil in LIQ861 are well-
tolerated.  Authorization from the Sponsor is required prior to dosing at levels above 150 μg 
treprostinil. 
5.8. 
Treatment Compliance 
Patients will self-administer the study drug at home.  At each visit, the patient will receive a 
sufficient and documented quantity of capsules intended to last through the next visit.  Patients 
should be instructed to return unused study medication at each study visit for product 
accountability.  Sealed investigational product may be re-dispensed to the same patient.  Any other 
returned study medication should be retained for product accountability.   
5.8.1. Study Drug Accountability 
All study drug will be administered in accordance with the conditions of this protocol.  Only 
authorized site personnel may supply or dispense study drug.  In rare instances, a courier may be 
used to retrieve drug from a study site and deliver it to a patient.  Study drug orders, records of 
study drug receipt, dispensing, and running inventory will be examined and reconciled throughout 
the study.  Only patients enrolled in the study may receive study drug, in accordance with all 
applicable regulatory requirements.  Upon the completion of the study, study drug will be 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 28 of 67 
subjected to final reconciliation.  At that time, all unused, partially used, and fully used study drug 
along with a packing slip must be returned to a designated facility.   
6. 
STUDY PROCEDURES 
6.1. 
Study Measurements and Assessments 
6.1.1. 
Assessment of Safety 
Safety assessments will include the following: 
• AEs and SAEs, both reported and observed 
• Adverse device events (ADE) 
• Physical examination 
• Vital sign measurements 
• Venous blood for clinical laboratory tests will include hematology, coagulation, and blood 
chemistry.  
6.1.2. 
Exploratory Assessments 
While this study is not designed to make conclusions on efficacy, exploratory assessments of 
efficacy endpoints will be made as previously described.  
6.2. 
Study Phases and Procedures 
A Time and Events Schedule is provided in Appendix 1.   
6.2.1. Screening Phase (Visit 1; Day -28 through Day 1)  
The initial Screening Visit may be conducted up to 28 days prior to Baseline on Day 1.  The 
following procedures/assessments will be performed at Screening:   
• Informed consent (must be done prior to any of the following procedures, including 
asking patients to discontinue prohibited medications) 
• Record medical history and patient demographics 
• Documentation of prohibited, prior, and current medications with duration of treatment 
• Height, weight, and age 
• Vital Signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 
• Serum pregnancy test (for all females of child bearing potential) 
• Venous blood for clinical laboratory tests  
• Venous blood for infectious disease screen (HIV, hepatitis B, and hepatitis C analysis)  
• Six-minute walk test (6MWT)  
• Pulmonary function testing (FEV1 and FEV1/FVC ratio), with or without 
bronchodilator 
• NYHA Functional Class Assessment 
• Assessment of hepatic and renal impairment (See Appendix 6) 
• Full physical examination   
• Confirm patient meets all eligibility criteria 
• Schedule next study visit (Baseline) 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 29 of 67 
The results of all laboratory assessments must be returned and reviewed prior to enrolling the 
patient for Day 1 procedures. 
6.2.2. Baseline – (Visit 2; Day 1) 
The description of assessments in this section is intended for patients that are NOT enrolled in the 
PK Sub-Study.  Patients who are enrolled in the PK Sub-Study should follow the assessments 
described in Section 6.2.3.   
The following assessments are to be completed at Baseline and prior to dose administration: 
• Eligibility re-assessment 
• Brief physical examination 
• Vital signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 
• Weight 
• Venous blood for clinical laboratory tests, including NT-proBNP  
• Urine pregnancy test (for all females of child bearing potential, Day 1 only)  
• 6MWT  
• NYHA Functional Class Assessment 
• MLWHF questionnaire 
• Assessment of PAH Symptoms 
• Device training   
• Prior medications 
• Record time of last dose of inhaled treprostinil  
• Administer first dose of LIQ861 (after all other predose assessments) 
o Note that for Tyvaso transition patients, the time of LIQ861 administration 
should be at least 4 hours after the last dose of Tyvaso 
The following assessments are to be completed after dose administration: 
• Inhalation Device User Survey 
o The Inhalation Device User Survey should only be administered to Tyvaso 
Transition patients. 
• Concomitant medications 
• Treatment-Emergent Adverse Events 
• Study Drug Dispensation 
• Schedule Next Visit 
6.2.3. 
Baseline – PK Sub-Study (Visit 2; Day 1 & Day 2) 
The description of assessments in this section is intended ONLY for patients that are enrolled in 
the PK Sub-Study.  Patients that are NOT enrolled in the PK Sub-Study should follow the 
assessments described in Section 6.2.2.   
Day 1 
The following assessments are to be completed at Baseline and prior to Tyvaso administration on 
Day 1: 
• Eligibility re-assessment 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 30 of 67 
• Brief physical examination 
• Vital signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 
• Weight 
• Venous blood for clinical laboratory tests, including NT-proBNP 
• Urine pregnancy test (for all females of child bearing potential, Day 1 only)  
• 6MWT  
• NYHA Functional Class Assessment  
• Assessment of PAH Symptoms 
• Prior medications 
• Record time of last dose of inhaled treprostinil  
• Plasma for baseline PK measurement (must be taken before Tyvaso administration, 
within 30 minutes of dose administration) 
• Final dose of Tyvaso (after all other predose assessments) 
o Note that this must be the first dose of the day.  If the subject has taken Tyvaso 
prior to arrival at the clinic, the PK sub-study should not be conducted or the 
visit should be rescheduled. 
The following assessments are to be completed after Tyvaso administration on Day 1, but before 
the first dose of LIQ861 is administered: 
• Plasma for PK measurements at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, and 180 minutes 
and 4 hours after Tyvaso administration.  Actual times of blood collection for each 
timepoint must be recorded.  
• Adverse Events 
• Concomitant medications 
• Venous blood for clinical laboratory tests at 4 hours after Tyvaso administration  
• MLWHF questionnaire 
• DPI Training 
The second treprostinil dose of the day should be the first administration of LIQ861.  The following 
assessments are to be completed after the first dose of LIQ861 is administered: 
• Treatment-Emergent Adverse Events  
• Concomitant medications 
• Inhalation Device User Survey 
• Study Drug Dispensation 
• Schedule Next Visit 
Day 2 
The following assessments are to be completed at Baseline and prior to study drug administration 
on Day 2: 
• Treatment-Emergent Adverse Events 
• Eligibility re-assessment 
• Brief physical examination 
• Vital signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 31 of 67 
• Weight 
• Venous blood for clinical laboratory tests, including NT-proBNP  
• DPI re-training  
• Concomitant medications 
• Record time of last dose of inhaled treprostinil  
• Plasma for baseline PK measurement (must be taken before LIQ861 administration, 
within 30 minutes of dose administration) 
• Administer dose of LIQ861 (after all other predose assessments)  
o Note that this should be the first dose of the day.  If the subject has taken LIQ861 
prior to arrival at the clinic, then Day 2 of the PK sub-study should be 
rescheduled. 
The following assessments are to be completed after the first study drug administration on Day 2: 
• Plasma for PK measurements at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, and 180 minutes 
and at 4 hours after study drug administration.  Actual times of blood collection for 
each timepoint must be recorded.   
• Concomitant medications 
• Venous blood for clinical laboratory tests at 4 hours after study drug administration  
• Study Drug Dispensation 
• Schedule next visit 
• Treatment-Emergent Adverse Events 
• Inhalation Device User Survey  
6.2.4. 
Visit 3 (Week 2) 
Visit 3 should be scheduled approximately 2 weeks ± 2 days from the first administration of 
LIQ861.   
The following assessments may be conducted before or after study drug administration at Visit 3: 
• NYHA Functional Class Assessment  
• Collect unused study drug 
• Study drug accountability 
• Study drug dispensation 
• Schedule next visit  
• Assess PAH Symptoms 
• Consider dosing adjustments and record any prescribed changes 
The following assessments will be conducted prior to study drug administration at Visit 3: 
• Vital signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 
• Venous blood for clinical laboratory tests, including NT-proBNP  
• DPI re-training 
• Concomitant medications 
• Treatment-Emergent Adverse Events 
• Record time of last dose of inhaled treprostinil  
• Administration of study drug 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 32 of 67 
o Note that the time of LIQ861 administration should be at least 4 hours after the 
last dose of LIQ861. 
The following assessments will be conducted after study drug administration at Visit 3: 
• 6MWT (within 15 to 60 minutes after administration of LIQ861) 
• Concomitant medications 
• Treatment-Emergent Adverse Events 
• Inhalation Device User Survey  
o The Inhalation Device User Survey should only be administered to Tyvaso 
Transition patients.  
6.2.5. 
Visits 4 & 5 (Month 1 & Month 2) 
Visits 4 and 5 should be scheduled approximately 1 and 2 months ± 3 days from the first 
administration of LIQ861, respectively.   
The following assessments may be done before or after study drug administration at Visits 4 & 5: 
• Brief Physical Examination (Visit 5 only) 
• NYHA Functional Class Assessment   
• Collect unused study drug 
• Study drug accountability 
• Study drug dispensation 
• Schedule next visit  
• Assess PAH Symptoms 
• Consider dosing adjustments and record any prescribed changes 
The following assessments will be conducted prior to study drug administration at Visits 4 & 5: 
• Vital signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 
• Venous blood for clinical laboratory tests, including NT-proBNP 
• DPI re-training 
• Concomitant medications 
• Treatment-Emergent Adverse Events 
• Record time of last dose of inhaled treprostinil  
• Administration of study drug  
o Note that the time of LIQ861 administration should be at least 4 hours after the 
last dose of LIQ861 
The following assessments will be conducted after study drug administration at Visits 4 & 5: 
• 6MWT (within 15 to 60 minutes after administration of LIQ861) 
• MLWHF questionnaire (Visit 5 only) 
• Concomitant medications 
• Treatment-Emergent Adverse Events 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 33 of 67 
6.2.6. 
Visits 6+ (Month 4) 
6.2.6.1. 
In Clinic at Month 4 and Every 4 Months thereafter until Study Termination 
Visit 
Visit 6 should be scheduled approximately 4 months ± 7 days from the first administration of 
LIQ861 and in-clinic follow-up visits should be scheduled every 4 months ± 7 days thereafter.   
The following assessments may be done before or after study drug administration at Visit 6 and 
all subsequent in clinic follow-up visits: 
• Full Physical Examination (at Visit 6 and every 12 months thereafter) 
• NYHA Functional Class Assessment   
• Collect unused study drug 
• Study drug accountability  
• Assess PAH Symptoms 
• Consider dosing adjustments and record any prescribed changes 
• Study drug dispensation 
• Schedule next visit  
• Schedule telephone follow-up visit for 8 weeks from the current visit to assess AEs, 
concomitant medications, PAH symptoms, and dose adjustment.  
The following assessments will be conducted prior to study drug administration at Visit 6 and all 
subsequent in clinic follow-up visits: 
• Vital signs (temperature, blood pressure, respiratory rate, and heart rate) collected 
after the patient has been upright and rested for at least 5 minutes (at Visit 6 and 
every 12 months thereafter) 
• Weight (at Visit 6 and every 12 months thereafter) 
• Venous blood for clinical laboratory tests  
o NT-proBNP collected at every 4 month visit 
o Hematology and Blood Chemistry collected at Visit 6 and every 12 months 
thereafter 
• DPI re-training 
• Concomitant medications 
• Treatment-Emergent Adverse Events 
• Record time of last dose of inhaled treprostinil  
• Administration of study drug  
o Note that the time of LIQ861 administration should be at least 4 hours after 
the last dose of LIQ861 
The following assessments will be conducted after study drug administration at Visit 6 and all 
subsequent in clinic follow-up visits: 
• 6MWT (within 15 to 60 minutes after administration of LIQ861) 
• Inhalation Device User Survey (at Visit 6 and every 12 months thereafter) 
o The Inhalation Device User Survey should only be administered to Tyvaso 
Transition patients. 
• MLWHF questionnaire (at Visit 6 and every 12 months thereafter) 
• Concomitant medications 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 34 of 67 
• Treatment-Emergent Adverse Events 
6.2.6.2. 
Phone Visits (every 4 months starting at Month 6)  
Phone visits (conducted by telephone call) should be scheduled approximately every 4 months ± 3 
days starting at Month 6. 
The following assessments should be conducted during the Phone Visit: 
• Concomitant medications. 
• Treatment-Emergent Adverse Events.  
• Assess PAH Symptoms. 
• Consider dosing adjustments and record any prescribed changes. 
• Confirm date of next in clinic follow-up visit. 
6.2.6.3. 
Study Termination Visit 
Study termination visits will occur when a patient is discontinued from the study or once the 
Sponsor has decided to terminate the study.  
The following assessments should be conducted during the Study Termination Visit: 
• Full Physical Examination 
• Weight and height 
• Vital Signs (temperature, blood pressure, respiratory rate, and heart rate) collected after 
the patient has been upright and rested for at least 5 minutes 
• Venous blood for clinical laboratory tests, including NT-proBNP  
• 6MWT 
• NYHA Functional Class Assessment 
• Assess PAH Symptoms 
• Inhalation Device User Survey 
o The Inhalation Device User Survey should only be administered to Tyvaso 
Transition patients. 
• MLWHF questionnaire 
• Record time of last dose of LIQ861 
• Treatment-Emergent Adverse Events 
• Concomitant medications 
• Collect unused study drug 
• Study drug accountability 
At the Study Termination Visit, Study Drug Dispensation will not be performed and future visits 
should only be scheduled for follow-up visits in the event of an Early Termination.  All remaining 
supply of Study Drug should be collected and reconciled. 
 
6.2.7. 
Follow-up for Withdrawn Patients  
Follow-up should occur for all patients that are removed from the study (Early Termination) for at 
least 4 months after receiving the last dose of LIQ861 or until all TEAEs are resolved or stabilized.  
If the patient was withdrawn from treatment with the study drug for clinical worsening, follow-up 
visits should be scheduled at the discretion of the investigator for the longer of the following 
periods: 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 35 of 67 
• at least 4 months from receiving the last dose of LIQ861, 
• until, in the opinion of the investigator, the patient is no longer clinically worsened from 
his or her baseline state, or  
• until, in the opinion of the investigator, clinical worsening from baseline state is no longer 
attributed to treatment with LIQ861.   
Follow-up visits may be conducted as telephone calls or in person visits at the Investigational site.  
At a minimum, follow-up visits should occur at approximately 2 weeks ± 2 days, and at 2 months 
and 4 months after receiving the last dose of LIQ861 and include the following assessments: 
• Treatment-Emergent Adverse Events 
• Concomitant medications 
If the patient was withdrawn from treatment with the study drug for clinical worsening, additional 
assessments for the signs and symptoms that lead to judgement of clinical worsening should be 
made at all follow-up visits within 4 months of Early Termination or until the signs and symptoms 
that lead to judgement of clinical worsening are resolved. 
6.3. 
Unscheduled Visits 
Unscheduled visits, including telephone calls, may be conducted as needed based on the 
Investigator’s medical judgment.  At a minimum, the following safety assessments should be 
recorded at any unscheduled visits:   
• Treatment-Emergent Adverse Events. 
• Concomitant medications. 
• Dose adjustments. 
The following safety assessments may also be recorded at unscheduled visits: 
• Physical examination findings. 
• Clinical laboratory tests as indicated per Investigator judgment. 
• PAH symptoms. 
6.4. 
Pharmacokinetic Assessments 
Blood samples for noncompartmental pharmacokinetic analysis will be collected during the PK 
Sub-Study only as outlined in the Time and Events Schedule in Appendix 1.  Approximately 3 mL 
of whole blood will be collected from an indwelling catheter for each blood draw to yield 
approximately 1.5 mL of plasma collected for bioanalytical analysis.    
Blood samples will be collected in lavender-top tubes with potassium (K2) EDTA at the following 
nominal time points defined in the time and events schedule (actual blood sampling times must be 
recorded in the source and eCRF): predose (within 30 minutes of dose administration) and at 5, 
10, 15, 20, 25, 30, 45, 60, 90, 120, and 180 minutes and 4 hours after the start of Tyvaso or LIQ861 
inhalation.  
Collecting, Processing, and Shipping Pharmacokinetic Samples 
Blood samples will be drawn and processed for plasma as described in Appendix 4.  The yield of 
plasma will be subdivided into 2 samples (~0.75 mL each) and frozen at -20°C within 60 minutes 
of sample collection.  One set of these samples will be shipped to the bioanalytical lab for analysis, 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 36 of 67 
as described in Appendix 4, and the other set will be stored at -20°C at the site until disposition 
instructions are communicated by Liquidia or designee.  
6.5. 
Clinical Laboratory Tests  
All routine samples will be analyzed by a licensed clinical laboratory.  The clinical laboratory tests 
are as follows: 
• Hematology/Coagulation: hemoglobin, hematocrit, white blood cell count with differential, 
and red blood cell count 
• Blood Chemistry:  Alanine aminotransferase (ALT; SGPT) and Aspartate aminotransferase 
(AST; SGOT), blood urea nitrogen (BUN), creatinine, alkaline phosphatase, sodium, 
potassium, magnesium, calcium, chloride, and uric acid.  
• Biomarkers:  NT-proBNP 
• Serum pregnancy test:  βhCG test for females of childbearing potential 
• Urine pregnancy test:  hCG test for females of childbearing potential (Baseline Visit only) 
Blood for clinical labs should be collected at predose and at 4 hours post-dose on Day 1 and on 
Day 2 for patients in the PK sub-study.  For all other visits, blood should be collected only at 
predose. 
The Investigator is responsible for determining if out of range laboratory values are clinically 
significant or not.  All clinically significant values will be recorded as AEs in the eCRF and 
followed until stabilization, resolution, or loss to follow up.  Once resolved, the appropriate 
AE/SAE eCRF page(s) will be updated. 
Details on sample collection and processing procedures will be provided in a separate laboratory 
manual. 
6.6. 
Physical Examinations 
A full physical exam (PE) will consist of assessments of the following: skin, ears, nose, throat, 
head, eyes, lungs/chest, heart, abdomen, musculoskeletal, extremities, neurologic, and lymphatic.      
A brief physical exam includes all the body systems of the full PE, except for eyes, 
musculoskeletal, and neurologic. 
All physical exam findings must be assessed as not clinically significant or clinically significant 
by the Investigator and recorded in the source document and eCRF.  Clinically significant changes 
noted in PE findings should be recorded as an AE. 
6.7. 
Vital Signs 
Vital signs will be obtained per site standard of care to include oral temperature (°F or °C, with 
units indicated), blood pressure (mmHg), respiratory rate (breaths per minute), and heart rate (beats 
per minute [bpm]).  Blood pressure, respiratory rate, and heart rate will be obtained after the patient 
has been upright and rested for at least 5 minutes.     

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 37 of 67 
6.8. 
Six-Minute Walk Test (6MWT) 
The 6MWT should be performed as described by the guidelines from the American Thoracic 
Society (ATS 2002).  Required equipment, detailed instructions, and a worksheet for data 
collection is provided in Appendix 7. 
6.9. 
Assessment Windows 
The actual time of the assessments must be recorded.  At the Baseline visit, 6MWT should be 
performed prior to administration of inhaled treprostinil (Tyvaso or LIQ861), and the actual start 
and end time should be recorded.  At all subsequent visits, 6MWT should be performed between 
15 and 60 minutes after administration of LIQ861, and the actual start and end time should be 
recorded. 
Collection of PK samples should occur as close to the nominal timepoint as possible.  The 
actual time of PK sample collection will be recorded.  All other assessments should be scheduled 
around the collection of PK samples at their nominal timepoints.   
6.10. 
Patient Questionnaires 
For all patients, the MLWHF questionnaire (Rector and Cohn 1992)will be administered at 
Baseline (Day 1), Visit 5 (Month 2), Visit 6 (Month 4), and every 12 months thereafter. 
For all Tyvaso Transition patients, responses to the Inhalation Device User Survey (Appendix 5) 
will be collected at Baseline (Day 1), Visit 3 (Week 2), Visit 6 (Month 4), and every 12 months 
thereafter.   
7. 
ADVERSE EVENTS 
The Investigator is responsible for the detection and documentation of events meeting the 
definition of an AE or SAE as provided in this protocol.  Only Treatment-Emergent AEs (TEAEs) 
and SAEs (occurring after the first inhalation of LIQ861, or Tyvaso in the PK sub-study, through 
the appropriate follow-up period) will be recorded in this study.    
Definitions and terminology relevant to IND Safety Reports, as referenced in the U.S. Code of 
Federal Regulations, are addressed below. 
7.1. 
Definition of a Treatment-Emergent Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related.  All AEs that occur after the time of treatment with the 
investigational product will be considered a Treatment Emergent AE (TEAE). 
A TEAE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a drug, without any judgment about 
causality.  
A TEAE does include any: 
• Exacerbation of a pre-existing illness. 
• Increase in frequency or intensity of a pre-existing episodic event or condition. 
• Condition detected or diagnosed after study drug administration even though it may have been 
present prior to the start of the study. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 38 of 67 
• Continuous persistent disease or symptoms present at baseline that worsen following the start 
of the study. 
• Events considered by the investigator to be related to study-mandated procedures. 
• Abnormal assessments (e.g., change in physical examination), if they represent a clinically 
relevant finding, that were not present at Baseline or worsened during the course of the study. 
• Laboratory test abnormalities, if they represent a clinically relevant finding, symptomatic or 
not, which were not present at Baseline or worsened during the course of the study. 
A TEAE does not include a/an: 
• Medical or surgical procedure (e.g., surgery, endoscopy, tooth extraction, transfusion); the 
condition that leads to the procedure is an AE. 
• Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
cosmetic elective surgery, social and/or convenience admissions). 
• Overdose of either study drug or concurrent medication without any signs or symptoms. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen during the 
study is not considered an AE. 
7.1.1. 
Definition of a Suspected Adverse Reaction 
Suspected adverse reaction means any TEAE for which there is a reasonable possibility that the 
drug caused the TEAE.  For the purposes of IND safety reporting, ‘reasonable possibility’ means 
there is evidence to suggest a causal relationship between the drug and the TEAE.  A suspected 
adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which 
means any adverse event caused by a drug.   
The following examples are the types of evidence that would suggest a causal relationship between 
the drug and the TEAE and would justify the consideration of an event as a suspected adverse 
reaction:   
• A single occurrence of an event that is uncommon and known to be strongly associated 
with drug exposure (e.g., angioedema, throat irritation).  
• One or more occurrences of an event that is not commonly associated with drug exposure, 
but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture).  
Suspected adverse reactions are the subset of all adverse events for which there is a reasonable 
possibility that the drug caused the event.  Inherent in this definition, and in the requirement to 
report them, is the need to evaluate the available evidence and render judgment about the likelihood 
that the drug actually caused the adverse event.  FDA considers the definition of suspected adverse 
reaction and the application of the reasonable possibility of causality standard to be consistent with 
the concepts and discussion about causality in the International Conference on Harmonization 
(ICH) E2A guidance. 
7.1.2. 
Definition of an Adverse Reaction 
An adverse reaction means any adverse event caused by a drug.  Adverse reactions are a subset of 
all suspected adverse reactions for which there is reason to conclude that the drug caused the event. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 39 of 67 
7.1.3. 
Definition of Unexpected Adverse Event or Unexpected Suspected Adverse 
Reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigator’s Brochure or is not listed at the specificity or severity that has been observed.  For 
example, under this definition, hepatic necrosis would be unexpected (by virtue of greater severity) 
if the Investigator’s Brochure referred only to elevated hepatic enzymes or hepatitis.  
"Unexpected," as used in this definition, also refers to TEAEs or suspected adverse reactions that 
are mentioned in the Investigator’s Brochure as occurring with a class of drugs, or as anticipated 
from the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation.  For example, although angioedema is anticipated to 
occur in some patients exposed to drugs in the Angiotensin-Converting Enzyme (ACE) inhibitor 
class and angioedema would be described in the Investigator’s Brochure as a class, the first case 
of angioedema observed with the drug under investigation should be considered unexpected for 
reporting purposes. 
This definition relies entirely on a listing of the adverse events or suspected adverse reactions in 
the Investigator’s Brochure as the basis for determining if newly acquired information generated 
from clinical trials or reported from other sources is unexpected.  The suspected adverse reactions 
listed in the Investigator’s Brochure (i.e., “expected”) are those observed with the investigational 
drug and for which a causal relationship between the event and the drug is suspected or confirmed.   
7.1.4. 
Definition of a Serious Adverse Event or Serious Suspected Adverse Reaction 
A TEAE or suspected adverse reaction is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes:   
a. Death. 
b. A life-threatening TEAE. 
• A TEAE or suspected adverse reaction is considered “life-threatening” if, in the 
view of either the investigator or sponsor, its occurrence places the patient at 
immediate risk of death.  It does not include a TEAE or suspected adverse reaction 
that, had it occurred in a more severe form, might have caused death.   
c. Inpatient hospitalization or prolongation of existing hospitalization. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen during the study is not considered a TEAE. 
• Complications that occur during hospitalization are TEAEs.  If a complication 
prolongs hospitalization, the event is an SAE. 
• “Inpatient” hospitalization means the patient has been formally admitted to a 
hospital for medical reasons.  This may or may not be overnight.  It does not include 
presentation at a casualty or emergency room. 
d. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
• This is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, accidental 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 40 of 67 
trauma (i.e., sprained ankle) that may interfere or prevent everyday life functions 
but do not constitute a substantial disruption. 
e. A congenital anomaly in the offspring of a patient who received drug. 
f. Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition.  Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in patient hospitalization, or the 
development of drug dependency or drug abuse. 
• Medical and scientific judgment should be used in deciding whether prompt 
reporting is appropriate in this situation. 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.  An SAE 
is not necessarily severe (e.g., an overnight hospitalization for a diagnostic procedure must be 
reported as an SAE even though the occurrence is not medically serious).  Similarly, a severe AE 
is not necessarily serious (e.g., nausea lasting for several hours may be rated as severe but may not 
be considered serious). 
7.2. 
Adverse Device Effect and Serious Adverse Device Effect 
An Adverse Device Event (ADE) is defined as any untoward and unintended response to a medical 
device.  In this case, an ADE would refer to any untoward and unintended response to the RS00 
Model 8 DPI. 
A Serious Adverse Device Effect (SADE) is an adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made or if 
circumstances had been less opportune. 
A device event may also be a SAE if the product involved a participant in the clinical trial.  A test 
article (device) that malfunctioned prior to use in a clinical research participant would not be a 
SAE for the participant.  However, if the device malfunctioned or broke once use was attempted 
by the participant; it would be reportable as an AE, or as a SAE if serious criteria were met. 
7.2.1. 
Unanticipated Adverse Device Effects 
Unanticipated adverse device effect is any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the investigational 
plan or application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of participants. 
All unanticipated adverse device effects must be reported by the Investigator to the Sponsor 
within 3 days from identification or awareness of the event.  Investigators are responsible for 
preparing and submitting complete, accurate, and timely reports to the reviewing IRB of any 
unanticipated adverse device effect occurring during an investigation as soon as possible, but in 
no event, later than 10 working days after they first learn of the effect.  

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 41 of 67 
Any device that is associated with an unanticipated adverse device effect should be collected 
from the patient in accordance with the same procedures as any other used device (i.e., device 
accountability and marked for destruction). 
If the Sponsor determines that an unanticipated adverse device effect, as reported by an 
Investigator, presents an unreasonable risk to the subject, the Sponsor shall terminate all 
investigations or parts of investigations presenting that risk as soon as possible. 
7.3. 
Severity of TEAEs/SAEs 
The severity (mild, moderate, or severe) of each TEAE/SAE must be assessed by the Investigator, 
or designee.  The following criteria should be considered when assessing severity:  
• Mild 
The symptom is barely noticeable to the patient and does not 
influence performance or functioning.   
• Moderate 
The symptom is of sufficient severity to make the patient 
uncomfortable, and performance of daily activities is 
influenced.  Treatment for the symptom may be needed. 
• Severe 
The symptom causes severe discomfort.  Treatment for the 
symptom may be necessary. 
7.4. 
Assessment of Relatedness to Study Drug or Device 
The Investigator will assess each TEAE and ADE for causality based on their medical judgment 
and the observed symptoms associated with the event.  Each TEAE and ADE will be assessed as 
related or unrelated to study drug based on the following criteria: 
• Unrelated 
This category applies to those TEAEs and ADEs that the 
Investigator determines are most likely due to extraneous causes 
(disease, environment, etc.) and does not follow a reasonable 
temporal relationship.   
• Related 
This category applies to those TEAEs and ADEs that the 
Investigator determines are most likely due to test drug or 
device. 
7.5. 
Method, Frequency, and Time Period for Detecting Adverse Events and 
Serious Adverse Events 
At appropriate intervals (e.g., at every study visit and telephone contact), patients should be 
assessed for TEAEs and SAEs.  After the patient has had an opportunity to spontaneously mention 
any problems, the Investigator should inquire about TEAEs by asking a non-leading question such 
as the following: 
1. “How are you feeling?” 
2. “Have you had any medical problems since your last assessment/visit?” 
3. “Have you taken any new medicines since your last assessment/visit?” 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 42 of 67 
7.6. 
Reporting AEs and SAEs  
7.6.1. 
Reporting Adverse Events 
AEs occurring from when the patient signs the Informed Consent Form (ICF) until the last study 
event will be recorded.  All AEs and SAEs occurring prior to the first inhalation of LIQ861 will 
be recorded in the medical history.  Also, any sign, symptom, or disease present before the first 
inhalation of LIQ861 are considered AEs only if they have worsened after the first inhalation of 
LIQ861. 
If the investigator detects an AE in a study patient after the last scheduled follow-up visit and 
considers the event related to treatment with LIQ861, the investigator should report it to the 
Sponsor’s Medical Monitor. 
The investigator should report all AEs on the AE page(s) of the eCRF and source documents, 
regardless of seriousness, severity, and causality.  Whenever possible, an AE will be reported using 
a diagnostic term (e.g., “common cold” or “upper respiratory infection” rather than “runny nose, 
cough, mild fever”) and should be described with the attributes described in terms of severity 
(Section 7.3) and relatedness (Section 7.4). 
7.6.2. 
Timeframes for Reporting SAEs/SADEs 
Prompt notification of the Sponsor regarding SAEs/SADEs is essential so that ethical and 
regulatory responsibilities and legal obligations can be satisfied.  The Investigator must report 
SAEs/SADEs according to the following time frames:      
• Death or Life-Threatening Event: 
o Initial notification must be provided to the Sponsor’s Medical Monitor, or designee, 
within 24 hours of the Investigational site learning of the death or life-threatening 
event (regardless of causality).   
o Complete SAE/SADE information (i.e., all SAE/SADE pages) must be sent to the 
Sponsor’s Medical Monitor or designee and the Sponsor’s clinical operations lead, 
or designee, within 24 hours of receipt of the information by the Investigational 
site.  
o Follow-up information must be sent to the Sponsor’s Medical Monitor, or designee, 
within 24 hours of receipt of the information by the Investigational site.  
• All other SAEs 
 
o Complete SAE information (i.e., all SAE pages) must be sent to the Sponsor’s 
Medical Monitor, or designee, within 24 hours of receipt of the information by the 
Investigational site. 
o Follow-up information must be sent to the Sponsor’s Medical Monitor, or designee, 
and the Sponsor’s clinical operations lead, or designee, within 24 hours of receipt 
of the information by the Investigational site.  
7.6.3. 
SAE/SADE Information to Report 
At a minimum, initial SAE/SADE reports must contain the site name and number, patient ID, 
patient demographic information, details of study drug administration, the serious adverse event 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 43 of 67 
term, onset date, severity, relationship to study drug, and a brief narrative of the event.  If the 
patient died, the report should include the cause of death and whether or not the death was related 
to the study drug, as well as any autopsy findings, if available.  Please note that relationship to 
study drug/causality is very important and must be included in the initial report as it may impact 
expedited regulatory reporting requirements for the event.  Do not, however, delay reporting of an 
SAE in order to obtain additional information.  Additional information may be reported as a 
follow-up report as described in Section 7.6.8. 
Complete SAE/SADE information should be reported in compliance with the Sponsor’s Safety 
Management Plan for this study. 
There may be instances when copies of medical records for certain cases are requested.  However, 
it is not acceptable for the Investigator to send photocopies of the patients’ medical records 
in lieu of completion of the appropriate AE/SAE pages.  If medical records are submitted, all 
patient personal identifiers must be completely and thoroughly redacted prior to submission. 
7.6.4. 
SAE/SADE Reporting Contact Information 
Individual sites should report SAEs to NorthAmerica_Medical@parexel.com based on the 
timeframes given in Section 7.6.2. 
7.6.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
TEAEs and SAEs 
The Investigator should exercise his or her medical and scientific judgment in deciding whether 
an abnormal laboratory finding or other abnormal assessment is clinically relevant. 
Abnormal laboratory findings (e.g., clinical chemistry, hematology) or other abnormal 
assessments (e.g., vital signs) that are judged by the Investigator as clinically relevant must be 
recorded in the medical history or as TEAEs or SAEs if they meet the definition of an adverse 
event.  Clinically relevant abnormal laboratory findings or other abnormal assessments that are 
detected after the first inhalation of LIQ861, or that are present before administration of LIQ861 
but worsen after the first inhalation of LIQ861, should be assessed for AE criteria. 
7.6.6. 
Documenting SAEs/SADEs 
A separate set of SAE pages should be used for each SAE.  However, if at the time of initial 
reporting, multiple SAEs are present that are temporally and/or clinically related, they may be 
reported on the same SAE page. 
The Investigator should attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information.  In such cases, the diagnosis should be documented as the TEAE 
and/or SAE term. 
7.6.7. 
Regulatory/Ethics reporting requirement  
The Investigator must comply with the applicable local regulatory requirements related to the 
reporting of SAEs to the Sponsor.  Additionally, the Investigator will be responsible for submitting 
SAE reports to the IRB/EC. 
The Sponsor, or designee, will be responsible for submitting SAE reports to applicable regulatory 
authorities. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 44 of 67 
7.6.8. 
Follow-up of TEAEs and SAEs 
All TEAEs and SAEs documented at a previous visit/contact that are designated as ongoing will 
be reviewed at subsequent visits/contacts.  TEAEs and SAEs will be followed until resolution, 
until the condition stabilizes, or until the patient is lost to follow-up.  Once resolved, the 
appropriate TEAE/SAE eCRF page(s) will be updated.  If a patient dies during participation in the 
study or during a recognized follow-up period, a copy of any post-mortem findings, including 
histopathology, should be obtained, if available, and forwarded to the Sponsor, or designee.  New 
or updated information will be recorded on the originally completed SAE Report Form with all 
changes signed and dated by the Investigator, or designee.   
8. 
STATISTICS  
An integrated statistical and PK analysis plan (SAP) will provide details of planned analyses and 
summary documents, such as tables, listings and figures.  An overview of the planned analyses is 
provided here.  However, final analyses may not be limited to the summaries described herein. 
8.1. 
Determination of Sample Size 
Safety Study: Approximately 130 patients will be enrolled in the Main Study to ensure that at 
least 100 patients are evaluated for safety.    
PK Sub-Study: The PK Sub-Study will enroll at least 18 PAH patients to evaluate the comparative 
bioavailability of treprostinil from LIQ861 to treprostinil from Tyvaso.  The number of patients 
enrolled is sufficient to support such pharmacokinetic analyses.        
8.2. 
Analysis Populations 
The analysis populations are defined as follows: 
• Safety Population will include all patients who receive at least one inhalation of LIQ861 and 
provide at least one post-Baseline safety assessment. 
• Pharmacokinetic Population (PK Population) will include all patients in the PK Sub-Study 
who have not had any adverse events or protocol violations deemed to impact the PK, and have 
sufficient quantifiable samples collected for estimation of pharmacokinetic parameters from 
Day 1 of the crossover. 
Safety endpoints will be reported for patients in the Safety Population.  PK analyses will be 
performed on patients in the PK population.  Inclusion of various populations in specific 
exploratory analyses will be defined in the SAP.  
8.3. 
Baseline Characteristics and Patient Disposition 
Overall Baseline and demographic data will be summarized using descriptive statistics.  Patient 
disposition (e.g., the number of patients enrolled, completed, and discontinued) will be 
summarized and medical history data will be listed.   
8.4. 
Hypothesis 
No formal hypothesis testing is planned. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 45 of 67 
8.5. 
Exploratory Analyses 
All analyses for the exploratory endpoints described in Section 3.2.4 will be described in the 
SAP.  
8.6. 
Noncompartmental Pharmacokinetic Analyses (PK sub-study) 
Treprostinil concentrations will be summarized, by treatment, using descriptive statistics 
(including sample size (N), mean, standard deviation (SD), coefficient of variation (CV%), 
median, minimum, and maximum) for each treatment.  Concentrations below the limit of 
quantification (BLQ) will be treated as zero for the computation of descriptive statistics and for 
construction of mean concentration-time profiles.  Concentrations assigned a value of missing will 
be omitted from the calculation of descriptive statistics.  
For pharmacokinetic analysis, treprostinil concentrations below the limit of quantification (BLQ) 
will be assigned a value of zero when they precede quantifiable samples in the initial portion of 
the profile.  Following Cmax, BLQ values embedded between two quantifiable data points will be 
treated as missing when calculating area under the curve.  BLQ values occurring at the end of the 
collection interval (after the last quantifiable concentration) will be treated as missing data.  When 
consecutive BLQ concentrations follow quantifiable concentrations in the terminal portion of the 
concentration curve, these quantified values will be excluded from the PK analysis by assigning 
them a value of missing, unless otherwise warranted by the concentration-time profile. 
The PK parameters in Table 1 will be estimated by noncompartmental methods from plasma 
samples.  Actual elapsed time from dosing will be used to estimate all individual PK parameters.  
The final list of PK parameters reported will be described in the SAP. 
Table 1.  
Pharmacokinetic Parameters 
Cmax 
Maximum observed plasma concentration 
Tmax 
Time of maximum concentration (h), obtained directly 
from the observed concentration versus time data. 
AUClast 
Area under the plasma concentration-time curve from time 
0 to time of last measurable plasma concentration  
AUCinf 
Area under the plasma concentration-time curve from 0-
time extrapolated to infinity 
AUCext 
The percentage of the AUC that is extrapolated beyond 
the last measurable concentration 
λz 
Apparent plasma terminal-phase elimination rate constant 
t½ 
Terminal-phase half life 
Vz/F 
Apparent volume of distribution, terminal phase 
CL/F 
Apparent systemic clearance 
MRT 
Mean residence time 
Frel 
Relative Bioavailability in % 
Derived plasma PK descriptive statistics will be tabulated by treatment and reported with summary 
statistics.  Descriptive statistics for PK parameters (Cmax, Tmax, AUClast, AUCinf, λz, t1/2, Vz/F, 
CL/F, Frel) will include the arithmetic and geometric mean (for Cmax, AUClast, and AUCinf, 
only), CV%, SD of the arithmetic mean, median, minimum, maximum, and N.   
Relative bioavailability (Frel) will be calculated for all patients that complete both days of the PK 
sub-study assessments using the following formula: 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 46 of 67 
𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹= 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐿𝐿𝐿𝐿𝐿𝐿861
𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇
 × 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑜𝑜
𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐿𝐿𝐿𝐿𝐿𝐿861
 
8.7. 
Safety Analyses 
Extent of Exposure, Adverse Events, Adverse Device Effects, Clinical Laboratory Assessments, 
and Vital Signs will be summarized with descriptive statistics. 
8.7.1. 
Prior and Concomitant Medications 
Medications taken after the patient receives study drug through Study Termination or Follow-up 
to Early Termination will be listed by treatment, dose level, and patient. 
9. 
RESPONSIBILITIES 
9.1. 
Investigator Responsibilities 
9.1.1. 
Good Clinical Practice 
The Investigator will ensure that this study is conducted in full compliance with the principles of 
the “Declaration of Helsinki”, ICH guidelines, or with the laws and regulations of the country in 
which the research is conducted, whichever affords the greater protection to the study patient.  For 
studies conducted under a United States IND, such as this study, the Investigator will ensure that 
the basic principles of “Good Clinical Practice,” as outlined in 21 CFR 312, subpart D, 
“Responsibilities of Sponsors and Investigators,” 21 CFR, part 50 and 21 CFR, part 56 are adhered 
to.  The PK sub-study study is also subject to and will be conducted in compliance with 21 CFR, 
part 320, “Retention of Bioavailability and Bioequivalence Testing Samples.” 
9.1.2. 
Institutional Review Board (IRB)/Ethics Committee (EC) Approval 
This protocol and any accompanying material to be provided to the patient (such as advertisements, 
patient information sheets, or descriptions of the study used to obtain informed consent) will be 
reviewed and approved by the governing IRB/EC of the participating center prior to study 
initiation.  Approval from the IRB/EC should be documented in a letter to the Investigator 
specifying the protocol number, protocol version, documents reviewed, and date on which the 
committee met and granted the approval. 
Any modifications or amendment to documents originally submitted for review must also be 
submitted to the IRB/EC for approval prior to implementation.  Additionally, the IRB/EC must be 
informed of any serious or unexpected AEs, new information that may adversely affect the safety 
of the patients or the conduct of the study, annual updates and/or requests for re-approval, and 
when the study has been completed. 
9.1.3. 
Informed Consent 
It is the responsibility of the Investigator or designee to obtain written informed consent from each 
individual participating in this study after adequate explanation of the aims, methods, objectives, 
and potential hazards of the study and prior to undertaking any study-related procedures.  The 
Investigator, or designee, must utilize an IRB-approved consent form for documenting written 
informed consent.  Each informed consent will be appropriately signed and dated by the patient 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 47 of 67 
and the person obtaining consent.  A copy of the signed consent form will be provided to the patient 
and the original will be maintained with the patient’s records. 
9.1.4. 
Conflicts of Interest 
The Investigator will be paid by the Sponsor of this study for study-related expenses, but will not 
profit from results, whether positive or negative, with regard to the product being evaluated.  The 
Investigator will disclose any financial conflicts of interest to the Sponsor, should they arise, as 
required in 21 CFR part 54. 
9.1.5. 
Confidentiality 
The Investigator must assure that patients’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties.  Only patient initials and an identification code 
(i.e., not names) should be recorded on any form submitted to the sponsor and IRB.  The 
Investigator must keep a patient log showing codes, names, and addresses for all patients screened 
and for all patients enrolled in the trial. 
9.1.6. 
Study Files and Retention of Records 
The Investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified.  These documents should 
be classified into 2 separate categories (although not limited to) the following (1) Investigator’s 
study file, and (2) patient clinical source documents. 
The Investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/EC approval with correspondence, informed consent, drug records, staff curriculum vitae and 
authorization forms, and other appropriate documents and correspondence. 
Patient clinical source documents can include (although is not limited to) the following:  patient 
hospital/clinic records, physician’s and nurse’s notes, appointment book, original laboratory 
reports, electrocardiogram (ECG), electroencephalogram (EEG), X-ray, pathology and special 
assessment reports, consultant letters, screening and enrollment log, etc.   
All clinical study documents must be retained by the Investigator until at least two years after the 
last approval of a marketing application in an International Conference on Harmonization (ICH) 
region (i.e., United States, Europe, or Japan) and until there are no pending or contemplated 
marketing applications in an ICH region; or, until two years after the IND is discontinued and 
regulatory authorities have been notified.  The Investigator must notify the Sponsor prior to 
destroying any clinical study records. 
Should the Investigator wish to move study records to another location, arrangements must be 
made to store these in sealed containers so that they can be returned sealed to the Investigator in 
case of a regulatory audit.  Where source documents are required for the continued care of the 
patient, appropriate copies should be made for storage outside of the site. 
9.1.7. 
Case Report Forms 
For each patient who receives study drug, an eCRF must be completed and signed by the principal 
Investigator or sub-Investigator within a reasonable time period after data collection.  This also 
applies to records for those patients who fail to complete the study.  If a patient withdraws from 
the study, the reason must be noted on the eCRF.  If a patient is withdrawn from the study because 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 48 of 67 
of a treatment-limiting adverse event, thorough efforts should be made to clearly document the 
outcome. 
9.1.8. 
Drug Accountability 
The Investigator, or designee (i.e., pharmacist), is responsible for ensuring adequate accountability 
of all used and unused study drug.  This includes acknowledgment of receipt of each shipment of 
study product (quantity and condition), inventory at the site, distribution to, collection from, use 
by patient, and the destruction or return of unused study medication to the Sponsor.  Dispensing 
records will document quantities received and quantities dispensed to patients, including lot 
number, date dispensed, patient identifier number, patient initials, and the initials of the person 
dispensing the medication.  The Investigator will assure that the study medication and records 
described in this section will be stored in a locked cabinet suitable for storage of pharmaceutical 
products and in accordance with the conditions specified in the Investigator’s Brochure.  
Investigators must also assure that study medication and records will be available for examination 
by the study monitor during periodic visits. 
During the study, the investigator will be notified of any expiry dates or retest date extensions of 
study drug supplies.  If an expiry date notification is received during the study, the site must 
complete all instructions outlined in the notification, including segregation of expired clinical 
study material for destruction or return to the Sponsor or its designee. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for study drug 
disposal/destruction in order to ensure that it complies with study requirements.  Accountability 
records and inventory will be inspected during periodic visits throughout the study.  Drug 
reconciliation may also be performed by a monitor during periodic visits, and the site may return 
used drug kits after reconciliation has been completed.  At the Study Termination Visit, following 
final drug reconciliation by the monitor, the study site will be instructed by the Sponsor or its 
designee to return all unused study drug supplies, including empty containers. 
9.1.9. 
Inspections 
The Investigator will provide access to source documents and all study records for this trial to 
appropriately qualified personnel from the Sponsor, or its representatives, and to regulatory 
authority inspectors. 
9.2. 
Sponsor Responsibilities 
9.2.1. 
Study Materials and Instructions 
It is the sponsor’s responsibility to ensure that the Investigator is provided with the documents and 
other study materials necessary to conduct the study.  Examples of those materials include, but are 
not limited to: protocol, Investigator’s Brochure, study drug, eCRF, SAE collection forms, logs, 
etc.  The sponsor will also provide training and oversight through site and medical monitoring. 
9.2.2. 
Protocol Modifications 
Protocol modifications, except those intended to reduce immediate risk to study patients, will be 
made by Sponsor-initiated amendment.  IRB/EC approval must be obtained before changes can be 
implemented. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 49 of 67 
9.3. 
Joint Investigator/Sponsor Responsibilities 
9.3.1. 
Access to Information for Monitoring 
In accordance with International Conference on Harmonization Good Clinical Practice (ICH E6 
(R2)) guidelines, study monitors must have direct access to the Investigator’s source 
documentation in order to verify the data recorded in the eCRFs for consistency. 
The monitors, both central and field monitors, are responsible for routine review of the eCRFs at 
regular intervals throughout the study, to verify adherence to the protocol, and the completeness, 
consistency and accuracy of the data being entered on them.  The monitors should have access to 
any patient records needed to verify the entries on the eCRFs.  The Investigator agrees to cooperate 
with the monitors to ensure that any problems detected in the course of these monitoring activities 
are resolved. 
9.3.2. 
Study Discontinuation 
Both the sponsor and the Investigator reserve the right to terminate the study at any time.  Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies) and IRBs/ECs.  In terminating the study, the Sponsor and the Investigator 
will assure that adequate consideration is given to the protection of the patients’ interests. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 50 of 67 
10. REFERENCES 
American Thoracic Society Committee on Proficiency Standards for Clinical Pulmonary 
Function Laboratories (2002). "ATS statement: guidelines for the six-minute walk test." Am J 
Respir Crit Care Med 166(1): 111-117. 
Babu, A. S., R. Padmakumar, A. G. Maiya, A. K. Mohapatra and R. L. Kamath (2016). "Effects 
of Exercise Training on Exercise Capacity in Pulmonary Arterial Hypertension: A Systematic 
Review of Clinical Trials." Heart Lung Circ 25(4): 333-341. 
Badesch, D. B., S. H. Abman, G. Simonneau, L. J. Rubin and V. V. McLaughlin (2007). 
"Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical 
practice guidelines." Chest 131(6): 1917-1928. 
CDER (2010). FDA Guidance for Industry - Pharmacokinetics in Patients with Impaired Renal 
Function - Study Design, Data Analysis and Impact on Dosing and Labeling. Silver Spring, MD, 
FDA. 
Channick, R. N., R. Voswinckel and L. J. Rubin (2012). "Inhaled treprostinil: a therapeutic 
review." Drug Des Devel Ther 6: 19-28. 
McLaughlin, V. V., R. L. Benza, L. J. Rubin, R. N. Channick, R. Voswinckel, V. F. Tapson, I. 
M. Robbins, H. Olschewski, M. Rubenfire and W. Seeger (2010). "Addition of inhaled 
treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical 
trial." J Am Coll Cardiol 55(18): 1915-1922. 
Miller-Davis, C., S. Marden and N. K. Leidy (2006). "The New York Heart Association Classes 
and functional status: what are we really measuring?" Heart Lung 35(4): 217-224. 
Rector, T. S. and J. N. Cohn (1992). "Assessment of patient outcome with the Minnesota Living 
with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, 
placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group." Am Heart J 
124(4): 1017-1025. 
Simonneau, G., M. A. Gatzoulis, I. Adatia, D. Celermajer, C. Denton, A. Ghofrani, M. A. 
Gomez Sanchez, R. Krishna Kumar, M. Landzberg, R. F. Machado, H. Olschewski, I. M. 
Robbins and R. Souza (2013). "Updated clinical classification of pulmonary hypertension." J Am 
Coll Cardiol 62(25 Suppl): D34-41. 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 51 of 67 
APPENDIX 1.  TIME AND EVENTS SCHEDULES 
TIME AND EVENTS SCHEDULE FOR THE STUDY 
 
Event 
Screening 
Baseline a 
Treatment 
Follow-ups 
 
Visit 1 
Visit 2 
Visit 3  
Visits 4 & 5  
Visits 6+  
 
Day –28 
to 1 
Baseline 
Day 1 
Week 2 
 (± 2 day)  
Months 1 & 2 
(± 3 days) 
In Clinic at Month 4 
and Every 4 Months 
thereafter until Study 
Termination Visit b 
(± 7 days) 
Phone Visits at 
Month 6 and Every 4 
Months thereafter 
until Study 
Termination Visit b 
(± 3 days) 
Study Termination 
Visit c 
Informed Consent 
X 
 
 
 
 
 
 
Confirmation of eligibility  
X 
X 
 
 
 
 
 
Medical History & Demographics 
X 
 
 
 
 
 
 
Physical Examination d 
X 
X 
 
X e 
X f 
 
X c 
Weight/Height Measurement  
X 
X g 
 
 
X f 
 
X 
Vital Signs h 
X 
X 
X 
X 
X f 
 
X 
Clinical Labs (blood) i 
X 
X 
X 
X 
X f 
 
X 
NT-proBNP (blood) i 
X 
X 
X 
X 
X 
 
X 
Serum Pregnancy Test for Females j 
X 
 
 
 
 
 
 
Urine Pregnancy Test for Females j 
 
X 
 
 
 
 
 
Infectious Disease Screen 
X 
 
 
 
 
 
 
6MWT & Functional Class 
X 
X 
X 
X 
X 
 
X 
Pulmonary Function Testing 
X 
 
 
 
 
 
 
Inhalation Device User Survey k 
 
X 
X 
 
X f 
 
X 
MLWHF questionnaire 
 
X 
 
X e 
X f 
 
X 
Patient DPI Training l 
 
X 
X 
X 
X 
 
 
Record Last Dose of Inhaled 
Treprostinil 
 
X 
X 
X 
X 
 
X 
LIQ861 Administration m 
 
X 
X 
X 
X 
 
 
Treatment-Emergent Adverse Events n 
 
X 
X 
X 
X 
X 
X 
Prior Medication Assessment 
X 
X 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
X 
X 
X 
Assess PAH Symptoms 
 
X 
X 
X 
X 
X 
X 
Consider and Record Dose 
Adjustments 
 
 
X 
X 
X 
X 
 
Collect Unused Study Drug 
 
 
X 
X 
X 
 
X  
Dispense Study Drug  
 
X 
X 
X 
X o 
 
 
Schedule Next Visit 
X 
X 
X 
X 
X o 
X 
 
a. This table is for assessments for all subjects not participation in the PK Sub-Study.  For Day 1 and Day 2 assessments in the PK Sub-Study see the PK Sub-Study T&E Table 
(below). 
b. Patients will continue on 4-month periodic follow-up visits from the completion of Visit 6 until the Study Termination Visit. 
c. Study Termination Visit should be completed within 1 month of drug approval or study termination or when a patient is discontinued from the study.   

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 52 of 67 
d. A full PE will be conducted at Visit 1, at Visit 6 and every 12 months thereafter, and at Study Termination; a brief PE will be conducted during Visit 2 & Visit 5.   
e. Assessment is to be conducted at Visit 5 (Month 2) only. 
f. Assessment is to be conducted at Visit 6 and every 12 months thereafter. 
g. Height does not need to be assessed at Visit 2.   
h. Vital signs, temperature, blood pressure, respiratory rate, and heart rate (blood pressure, respiratory rate, and heart rate will be measured after the patient has been upright 
and rested for at least 5 minutes).  
i. Obtain venous blood for clinical laboratory tests before study drug administration. 
j. Females of childbearing potential only. 
k. The Inhalation Device User Survey should only be administered to Tyvaso Transition patients. 
l. Patients should receive device training prior to the first dose of LIQ861.  Patients should be retrained at each remaining visit until the Study Termination Visit. 
m. Refer to instructions for use.  For Tyvaso transition patients at Baseline, and all patients at post-Baseline visits, time of LIQ861 administration should be at least 4 hours after 
the last dose of inhaled treprostinil (Tyvaso or LIQ861). 
n. Only treatment-emergent AEs will be collected. 
o. The next Phone Visit and In Clinic Follow-up Visit should both be scheduled before the end of an in-clinic visit.  During Phone Visits, the timing of the following In Clinic 
Follow-up visit should be confirmed. 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 53 of 67 
TIME AND EVENTS SCHEDULE FOR THE PK SUB-STUDY 
Event 
Screening 
 
Baseline a 
 
Treatment 
 
Treatment through Follow-Up 
Visit 1 
 
Visit 2 
 
Visits 3+ 
Day –28 
to 0 
 
Day 1 
(Starting Hour) 
 
Day 2 
(Starting Hour) 
 
Week 1 through 
 
-1 
0 
1 
2 
3 
4 
 
-1 
0 
1 
2 
3 
4 
 
Follow-Up 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Proceed to Visit 3 in 
Main Study T&E Table 
(above) 
Confirmation of eligibility  
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Medical History & Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination b 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Weight/Height Measurement c 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Vital Signs d 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Clinical Labs (blood) e 
X 
 
X 
 
 
 
 
X f 
 
X 
 
 
 
 
X f 
 
NT-proBNP 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Serum Pregnancy Test for Females g 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test for Females g 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious Disease Screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6MWT & Functional Class 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary Function Testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inhalation Device User Survey h 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
MLWHF questionnaire  
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Patient DPI Training i 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
Record Last Dose of Inhaled Treprostinil 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Tyvaso Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
LIQ861 Administration  
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
Plasma for Pharmacokinetics j 
 
 
X 
X 
X 
X 
X 
X f 
 
X 
X 
X 
X 
X 
X f 
 
Treatment-Emergent Adverse Events k 
 
 
 
 
 
 
 
X 
 
Continuous 
 
Prior Medication Assessment 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
 
 
Continuous 
 
Continuous 
 
Assess PAH Symptoms 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense Study Drug  
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Schedule Next Visit 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
a. This table is for assessments in the PK Sub-Study.  For Day 1 assessments for patients that are not in the PK Sub-Study, see the Study T&E Table (above) 
b. A full PE will be conducted on Visit 1; a brief PE will be conducted during Visit 2. 
c. Height does not need to be assessed at Visit 2.   
d. Vital signs, temperature, blood pressure, respiratory rate, and heart rate (blood pressure, respiratory rate, and heart rate will be measured after the patient has been upright 
and rested for at least 5 minutes).  
e. Obtain venous blood for clinical laboratory tests at predose and 4 hours post-dose on Day 1 and Day 2.   
f. Blood for clinical labs and PK collected in the 4th hour after dosing should be obtained prior to administration of the first dose of LIQ861 on Day 1 and prior to 
administration of the second dose of LIQ861 on Day 2. 
g. Females of childbearing potential only. 
h. The Inhalation Device User Survey should be administered after administration of LIQ861. 
i. Patients should receive device training prior to the first dose of LIQ861 on Day 1 and Day 2.  Timing in relation to dose administration is not critical. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 54 of 67 
j. For PK sub-study only: Collect blood for measurement of treprostinil concentrations predose (within 30 minutes before dosing), and at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 
and 180 minutes and 4 hours after study drug administration.  Record actual times of blood collection for each timepoint. 
k. Adverse events will be collected after administration of Tyvaso. 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 55 of 67 
APPENDIX 2.  GUIDANCE FOR LIQ861 DOSE SELECTION AND TITRATION 
Dose Titration 
Titration to a higher dose of treprostinil in LIQ861 should be governed by patient’s degree of 
symptomatic relief, not to tolerance of PGI2 side effects.  If there are no symptoms of PGI2 excess, 
doses of LIQ861 may be increased in 25 µg treprostinil strength increments according to the 
following guidelines up to the Maximum Allowed Dose of 150 µg treprostinil strength.   
Dosing in excess of 150 µg treprostinil strength has not been previously studied and should not be 
implemented without consent from the sponsor.   
Selection of Initial Dose in LIQ861 Add-on Patients 
Start the patient on LIQ861 QID at the 25 µg treprostinil capsule strength. 
1. After initial administration of LIQ861, supervise the patient’s condition for a minimum post-
dose observation period of 1 hour and discharge at the discretion of the Investigator. 
2. Patients should be called between Day 5 and Day 7 post-dose to assess symptomatic relief 
and tolerance of LIQ861 therapy and a decision should be made whether to maintain the 
patient at the same dose or to increase to 50 µg LIQ861, administered as a single capsule 
QID.   
3. At the Week 2 Visit, or after 2 weeks of stable LIQ861 QID administration, if the patient is 
experiencing sufficient symptomatic relief AND is tolerating the treatment, that dose should 
be maintained unless symptoms worsen.   
a. If the patient is not experiencing sufficient symptomatic relief OR is not tolerating 
the treatment, LIQ861 may be increased or decreased by 25 µg treprostinil strength 
increments, respectively. 
4. Additional dosing increases may be implemented at 25 µg increments per week, however 
dose escalations are limited to a maximum of 150 µg as dosing in excess of 150 µg 
treprostinil strength has not been previously studied and should not be implemented without 
consent of the Sponsor.  Prior to any dose titration the Investigator should contact the patient 
by phone to assess degree of symptomatic relief and tolerance and need/desire to adjust the 
LIQ861 dose.   
Selection of Initial Dose in Tyvaso Transition Patients  
If the patient is transitioning from Tyvaso, determine the appropriate LIQ861 starting dose from 
Table 2 below: 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 56 of 67 
Table 2.  
Starting LIQ861 dose based upon Tyvaso Dose  
Tyvaso Dose1 
Starting LIQ861 Dose 
Estimated Treprostinil 
Breaths of Tyvaso 
Capsule Strength 
≤ 30 µg 
≤ 5  
25 µg 
≥ 36 µg and ≤ 48 µg 
≥ 6 and ≤ 8 
50 µg 
≥ 54 µg and ≤ 66 µg 
≥ 9 and ≤ 11 
75 µg 
≥ 72 µg and ≤ 84 µg 
≥ 12 and ≤ 14 
100 µg 
≥ 90 µg and ≤ 102 µg 
≥ 15 and ≤ 17 
125 µg 
≥ 108 µg 
≥ 18  
150 µg 
1Tyvaso doses up to 54 µg are consistent with the label.  However, it is understood that physicians may choose to 
dose in excess of 54 µg and it is important to explore transitioning these patients given that LIQ861 was well 
tolerated up to 150 µg in healthy volunteers. 
After initial administration of LIQ861 on Day 1, supervise the patient’s condition for a minimum 
post-dose observation period of 4 hours.   
For the second and third dose on Day 1, titrate LIQ861 dose in increments of 25 µg treprostinil 
strength based on clinical observations, patient feedback, and Investigator discretion.  The patient 
should be observed for a minimum of 1 hour after the second dose of LIQ861 and may be 
discharged at the discretion of the Investigator. 
At the Week 2 Visit, or after 2 weeks of QID administration of LIQ861, if the patient is 
experiencing sufficient symptomatic relief AND is tolerating the treatment, that dose should be 
maintained unless symptoms worsen.   
a. If the patient is not experiencing sufficient symptomatic relief OR is not tolerating 
the treatment, LIQ861 may be increased or decreased by 25 µg treprostinil strength 
increments, respectively. 
Additional dosing increases may be implemented at 25 µg increments per week, however dose 
escalations are limited to a maximum of 150 µg, unless agreed to by the Sponsor.  Prior to any 
dose titration the Investigator should contact the patient by phone to assess degree of symptomatic 
relief and tolerance and need/desire to adjust the LIQ861 dose.   
Tyvaso Transition Patients – PK Sub-Study Procedures 
If the patient is transitioning from Tyvaso and is enrolled in the PK Sub-Study, the patient’s final 
dose of Tyvaso on Day 1 of the study, and the starting dose for LIQ861 should be administered as 
described in Table 3.  In the event that a patient’s prescribed Tyvaso dose is not a multiple of 3 
breaths, the dose administered on Day 1 for PK assessments will be selected as described in Table 
3. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 57 of 67 
Table 3.  
Tyvaso and LIQ861 Dosing for Patients in the PK Sub-Study  
Prescribed Tyvaso Dose1 
PK Sub-Study Dosing 
Estimated 
Treprostinil 
Breaths of 
Tyvaso 
Day 1: Breaths of 
Tyvaso 
Day 2: LIQ861 
Capsule 
≤ 30 µg 
≤ 5  
3 
25 µg 
≥ 36 µg and ≤ 48 µg 
≥ 6 and ≤ 8 
6 
50 µg 
≥ 54 µg and ≤ 66 µg 
≥ 9 and ≤ 11 
9 
75 µg 
≥ 72 µg and ≤ 84 µg 
≥ 12 and ≤ 14 
12 
100 µg 
≥ 90 µg and ≤ 102 µg 
≥ 15 and ≤ 17 
15 
125 µg 
≥ 108 µg  
≥ 18  
18 
150 µg 
1Prescribed Tyvaso Dose is the dose on which the patient has been stable in concordance with the study eligibility 
criteria. 
Day 1 
1. PK samplings will be collected over a 4 hour period after administration of the final Tyvaso 
dose.  LIQ861 should be administered at the appropriate starting dose beginning with the 
second dose on Day 1. 
a. If the starting dose of LIQ861 is not tolerated, the next dose of LIQ861 may be 
decreased by 25 µg treprostinil strength. 
b. If the starting dose does not appear to be providing similar efficacy to the patient’s 
Tyvaso treatment, the next dose of LIQ861 may be increased by 25 µg and the 
patient should be observed for at least an hour after the increase prior to discharge 
from the clinic at the Investigator’s discretion. 
Day 2 
1. For the first dose on Day 2, LIQ861 should be administered at the same dose as the last 
tolerated dose taken on Day 1, and PK samples should be collected over a 4 hour period.  After 
completion of the PK sampling, the patient may be discharged at the discretion of the 
Investigator. 
2. At the Week 2 Visit, or after 2 weeks of QID administration of LIQ861, if the patient is 
experiencing sufficient symptomatic relief AND is tolerating the treatment, that dose should 
be maintained unless symptoms worsen.   
b. If the patient is not experiencing sufficient symptomatic relief OR is not tolerating 
the treatment, LIQ861 may be increased or decreased by 25 µg treprostinil 
strength increments, respectively. 
3. Additional dosing increases may be implemented at 25 µg increments per week up to a 
maximum of 150 µg.  Prior to any dose titration the Investigator should contact the patient by 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 58 of 67 
phone to assess degree of symptomatic relief and tolerance and need/desire to adjust the 
LIQ861 dose.   
Management of Side Effects 
If symptoms of PGI2 excess are observed, further dose increases of LIQ861 should be avoided 
until these symptoms subside. 
If side effects cannot be tolerated or medically managed, one or more of the following strategies 
may be employed: 
• 
Reduction of LIQ861 in 25 µg treprostinil strength increments until symptoms subside 
• 
Discontinuation of LIQ861 
Employment of any of the above strategies for mitigation of non-tolerated side effects should be 
documented in the eCRFs. 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 59 of 67 
APPENDIX 3.  INHIBITORS AND INDUCERS OF CYP2C8  
In addition to any medications listed in the Investigator’s Brochure that are excluded from 
concomitant use, the following inhibitors and inducers of CYP2C8 should not be taken by patients 
receiving LIQ861: 
CYP2C8 Inhibitors 
• Gemfibrozil 
• Ketoconazole 
• Trimethoprim 
• Clopidogrel 
• Deferasirox 
• Teriflunomide 
• Telithromycin 
• Phenelzine 
• Montelukast 
• Quercetin 
CYP2C8 Inducers  
• Rifampin 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 60 of 67 
APPENDIX 4.  PK SAMPLE COLLECTION, PROCESSING, AND SHIPMENT  
Sample Collection and Processing 
• One (1) 3 mL Vacutainer tube containing (K2) EDTA (lavender-top blood collection tubes, 
13 x 75 mm, BD Vacutainer catalog # 367856 or equivalent) will be collected for PK 
analysis at each of the time points specified in Section 6.4 of the protocol.  Fill tube as 
completely as possible to ensure sufficient sample volume for the required tests. 
• Immediately after the sample is drawn, gently invert the tube 5 to 10 times to thoroughly 
mix the anticoagulant and place the tube at room temperature.  Samples can be stored at 
room temperature for up to 60 minutes prior to completing the processing procedure. 
• Centrifuge the sample at room temperature at 2500 to 3000 rpm (approximately 650 to 
1450 x g) for 10 to 15 minutes to achieve a clear plasma layer over the red cells.  The speed 
and time may be varied according to the make and model of centrifuge used.   
• Immediately transfer (approximately) equal portions of the plasma to two (2) properly 
labeled polypropylene sample storage tubes (Sarstedt 3.5 mL tubes, P/N 60.549 or 
equivalent), cap and freeze samples at -20°C until shipment. 
Note:  Use of gel separation blood collection tubes is not recommended for PK sample analysis, 
as drug may be absorbed by the barrier gel. 
Sample Collection and Processing 
• All sample shipments should be preceded by a phone call or fax prior to their receipt.   All 
HIV positive or other known infectious sample shipments must be preceded by a phone 
call or facsimile prior to their receipt. 
• Detailed sample inventory information must accompany the samples.   Lack of paperwork 
or illegible information will delay sample login and project initiation.   Samples that are 
unclearly or incompletely labeled may be subject to additional handling fees.   Submission 
of sample inventory information in electronic form is encouraged. 
• Frozen samples should be shipped via overnight courier with an adequate amount of dry 
ice Monday through Wednesday to the following: 
ACM Global Laboratory 
Attn: Clinical Trials Specimen Management 
150 Elmgrove Park 
Rochester, NY 14624 
• Notify ACM by e-mail, facsimile, or telephone that a shipment is leaving your location.   
Upon arrival, the shipment will be unpacked and the contents verified and documented.   If 
requested, the individual responsible at the shipment point of origin will be notified of 
sample disposition. 
• Backup samples should be stored frozen at the Investigational site until successful receipt 
of initial shipment is confirmed by ACM. 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 61 of 67 
APPENDIX 5.  INHALATION DEVICE USER SURVEY 
Inhalation Device User Survey 
1. How long have you been using the RS00 Model 8 Dry Powder Inhaler (DPI) 
with LIQ861 (circle the most accurate)? 
Less than 
1 week 
 
Less than 
1 month 
 
Less than 6 
months 
 
Less than 
1 year 
 
More than 
1 year 
 
 
 
 
 
2. How would you rate the RS00 Model 8 DPI compared to the Tyvaso 
Inhalation System you were previously using (circle 1)? 
0 
 
1 
 
2 
 
3 
 
4 
Strongly 
Prefer the 
Old 
Device 
 
Prefer the 
Old 
Device 
 
No 
Preference 
 
Prefer the 
New 
Device 
 
Strongly 
Prefer the 
New 
Device 
 
 
For Investigational Site Personnel Only: 
 
  
  
  
Site Number 
 
Patient ID 
 
Date Administered 
 
Investigator/Coordinator 
Initials 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 62 of 67 
APPENDIX 6.  ASSESSMENT OF HEPATIC AND RENAL IMPAIRMENT 
Evidence of severe hepatic impairment will be assessed by simply documenting the patient’s 
history or presence of ascites and encephalopathy.  A patient will be considered to have severe 
hepatic impairment if the patient both: 
• has evidence of ascites, AND 
• has been diagnosed with or has evidence of encephalopathy grade of 1 or higher based on 
the West Haven Criteria. 
Any patient fitting this profile should be excluded from the study. 
 
Renal impairment will be assessed by calculating estimated glomerular filtration rate (eGFR) using 
Modification of Diet in Renal Disease (MDRD) equation (CDER 2010):  
eGFR = 175 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742,𝑖𝑖𝑖𝑖 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓) × (1.212,𝑖𝑖𝑖𝑖 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴) 
Where Serum Creatinine is measured in mg/dL, Age is measured in years, and eGFR is measured 
in mL/min/1.73m2.  Subjects with eGFR less than 45 will be excluded from the PK sub-study and 
subjects with eGFR of less than 30 will be excluded altogether. 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 63 of 67 
APPENDIX 7.  6MWT INSTRUCTIONS AND WORKSHEET 
The following instructions on performing a 6MWT are reproduced from the guidelines published 
by the American Thoracic Society (ATS 2002).  A sample data collection worksheet and Borg 
Scale are provided at the end of the instructions (below). 
Safety Considerations 
Testing should be performed in a location where a rapid, appropriate response to an emergency is 
possible. The appropriate location of a crash cart should be determined by the physician 
supervising the facility. 
Supplies that must be available include: 
• 
oxygen,  
• 
sublingual nitroglycerine,  
• 
aspirin, and  
• 
albuterol (metered dose inhaler or nebulizer).  
A telephone or other means should be in place to enable a call for help. 
The technician should be certified in cardiopulmonary resuscitation with a minimum of Basic 
Life Support by an American Health Association–approved cardiopulmonary resuscitation 
course. Advanced cardiac life support certification is desirable. Training, experience, and 
certification in related health care fields (registered nurse, registered respiratory therapist, 
certified pulmonary function technician, etc.) are also desirable. A certified individual should be 
readily available to respond if needed. 
Physicians are not required to be present during all tests. The physician ordering the test or a 
supervising laboratory physician may decide whether physician attendance at a specific test is 
required. 
If a patient is on chronic oxygen therapy, oxygen should be given at their standard rate or as 
directed by a physician or a protocol. 
Reasons for immediately stopping a 6MWT include the following:  
• 
chest pain, 
• 
intolerable dyspnea, 
• 
leg cramps, 
• 
staggering, 
• 
diaphoresis, and  
• 
pale or ashen appearance. 
Technicians must be trained to recognize these problems and the appropriate responses. If a test 
is stopped for any of these reasons, the patient should sit or lie supine as appropriate depending 
on the severity or the event and the technician's assessment of the severity of the event and the 
risk of syncope. The following should be obtained based on the judgment of the technician: 
• 
blood pressure,  
• 
pulse rate,  
• 
oxygen saturation, and 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 64 of 67 
• 
physician evaluation. 
Oxygen should be administered as appropriate. 
Technical Requirements and Equipment 
The 6MWT should be performed indoors, along a long, flat, straight, enclosed corridor with a 
hard surface that is seldom traveled.  The walking course must be 30 m in length; a 100-ft 
hallway is, therefore, required. The length of the corridor should be marked every 3 m. The 
turnaround points should be marked with a cone (such as an orange traffic cone). A starting line, 
which marks the beginning and end of each 60-m lap, should be marked on the floor using 
brightly colored tape. 
The following equipment is required to conduct the assessment: 
• 
Countdown timer (or stopwatch) 
• 
Mechanical lap counter 
• 
Two small cones to mark the turnaround points 
• 
A chair that can be easily moved along the walking course 
• 
Worksheets on a clipboard 
• 
A source of oxygen 
• 
Sphygmomanometer 
• 
Telephone 
• 
Automated electronic defibrillator 
In preparation for the assessment, patients should: 
• 
Wear comfortable clothing and appropriate shoes for walking, 
• 
Use their usual walking aids, such as a cane or walker, 
• 
Continue their usual medical regimen 
• 
Not have exercised vigorously within 2 hours of the beginning of the test. 
Additionally, a light meal is acceptable before early morning or early afternoon exams. 
Instructions for Conducting the 6MWT 
1. Repeat testing should be performed about the same time of day to minimize intraday 
variability. 
A “warm-up” period before the test should not be performed. 
The patient should sit at rest in a chair, located near the starting position, for at least 10 minutes 
before the test starts. During this time, check for contraindications, measure pulse and blood 
pressure, and make sure that clothing and shoes are appropriate. Compete the Patient Information 
portion of the data collection worksheet (below). 
Pulse oximetry is optional. If it is performed, measure and record baseline heart rate and oxygen 
saturation (SpO2) and follow manufacturer's instructions to maximize the signal and to minimize 
motion artifact. Make sure the readings are stable before recording. Note pulse regularity and 
whether the oximeter signal quality is acceptable. 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 65 of 67 
a. The SpO2 should not be used for constant monitoring during the exercise. The 
technician must not walk with the patient to observe the SpO2. If worn during the 
walk, the pulse oximeter must be lightweight (less than 2 pounds), battery 
powered, and held in place (perhaps by a “fanny pack”) so that the patient does 
not have to hold or stabilize it and so that stride is not affected. 
Have the patient stand and rate their baseline dyspnea and overall fatigue using the Borg scale 
provided below. 
Set the lap counter to zero and the timer to 6 minutes. Assemble all necessary equipment (lap 
counter, timer, clipboard, Borg Scale, worksheet) and move to the starting point. 
Instruct the patient as follows: 
“The object of this test is to walk as far as possible for 6 minutes. You will walk 
back and forth in this hallway. Six minutes is a long time to walk, so you will be 
exerting yourself. You will probably get out of breath or become exhausted. You 
are permitted to slow down, to stop, and to rest as necessary. You may lean against 
the wall while resting, but resume walking as soon as you are able. 
You will be walking back and forth around the cones. You should pivot briskly 
around the cones and continue back the other way without hesitation. Now I'm 
going to show you. Please watch the way I turn without hesitation.” 
Demonstrate by walking one lap yourself. Walk and pivot around a cone briskly. 
“Are you ready to do that? I am going to use this counter to keep track of the number 
of laps you complete. I will click it each time you turn around at this starting line. 
Remember that the object is to walk AS FAR AS POSSIBLE for 6 minutes, but 
don't run or jog. 
Start now, or whenever you are ready.” 
Position the patient at the starting line. You should also stand near the starting line during 
the test. Do not walk with the patient. As soon as the patient starts to walk, start the timer. 
Do not talk to anyone during the walk. Use an even tone of voice when using the standard 
phrases of encouragement. Watch the patient. Do not get distracted and lose count of the 
laps. Each time the participant returns to the starting line, click the lap counter once (or 
mark the lap on the worksheet). Let the participant see you do it. Exaggerate the click using 
body language, like using a stopwatch at a race. 
After the first minute, tell the patient the following (in even tones): “You are doing well. 
You have 5 minutes to go.” 
When the timer shows 4 minutes remaining, tell the patient the following: “Keep up the 
good work. You have 4 minutes to go.” 
When the timer shows 3 minutes remaining, tell the patient the following: “You are doing 
well. You are halfway done.” 
When the timer shows 2 minutes remaining, tell the patient the following: “Keep up the 
good work. You have only 2 minutes left.” 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 66 of 67 
When the timer shows only 1 minute remaining, tell the patient: “You are doing well. You 
have only 1 minute to go.” 
Do not use other words of encouragement (or body language to speed up). 
If the patient stops walking during the test and needs a rest, say this: “You can lean against 
the wall if you would like; then continue walking whenever you feel able.” Do not stop the 
timer. If the patient stops before the 6 minutes are up and refuses to continue (or you decide 
that they should not continue), wheel the chair over for the patient to sit on, discontinue the 
walk, and note on the worksheet the distance, the time stopped, and the reason for stopping 
prematurely. 
When the timer is 15 seconds from completion, say this: “In a moment I'm going to tell 
you to stop. When I do, just stop right where you are and I will come to you.” 
When the timer rings (or buzzes), say this: “Stop!” Walk over to the patient. Consider 
taking the chair if they look exhausted. Mark the spot where they stopped by placing a bean 
bag or a piece of tape on the floor. 
When the timer is 15 seconds from completion, say this: “In a moment I'm going to tell 
you to stop. When I do, just stop right where you are and I will come to you.” 
When the timer rings (or buzzes), say this: “Stop!” Walk over to the patient. Consider 
taking the chair if they look exhausted. Mark the spot where they stopped by placing a bean 
bag or a piece of tape on the floor. 
After the test record the postwalk Borg dyspnea and fatigue levels and ask this: “What, if 
anything, kept you from walking farther?” 
If using a pulse oximeter, measure SpO2 and pulse rate from the oximeter and then remove the 
sensor. 
Record the number of laps from the counter (or tick marks on the worksheet). 
Record the additional distance covered (the number of meters in the final partial lap) using the 
markers on the wall as distance guides. Calculate the total distance walked, rounding to the 
nearest meter, and record it on the worksheet. 
Congratulate the patient on good effort and offer a drink of water. 
 
 
 
 
 

Liquidia Technologies, Inc. 
 
Protocol LTI-301 
 Amendment 3 (20-Mar-19) 
CONFIDENTIAL 
Page 67 of 67 
Data Collection Worksheet for Conducting a Six-Minute Walk Test 
Lap Counter:  _ _ _ _ _   _ _ _ _ _   _ _ _ _ _   _ _ _ _ _   _ _ _ _ _    
Date:   
Technician ID: 
Walk #: 
 
Patient Information 
Patient Name: 
 
Race:   
☐ White    
Medications Before Test 
(Medication, Dose, Time) 
Patient ID #: 
 
☐ Black or African American 
Age: 
____years 
☐ Asian 
Height: 
 
____ft ____in, 
____ meters 
☐ Native Hawaiian or Other 
      Pacific Islander 
Weight: 
 
____ lbs,  
____ kg 
☐ American Indian or Alaska 
      Native 
Blood Pressure: 
____ / ____ 
Ethnicity: 
☐ Hispanic  ☐ Not Hispanic    
 
Test Information 
 
Baseline 
End of Test 
Stopped or 
Paused before 
6 minutes? 
☐ No  
Lap Distance: ____ meters 
Time: 
___:___ 
___:___ 
☐ Yes, Reason? 
Total Laps: ____ laps  
Heart Rate: 
___ 
___ 
Final Partial Lap: ____ meters  
Dyspneaa : 
___ (Borg) 
___ (Borg) 
Other 
symptoms at 
end of test? 
☐ Angina 
6MWDd :  ____ meters 
Fatigueb : 
___ (Borg) 
___ (Borg) 
☐ Dizziness 
Predicted distance: ___ meters 
SpO2c : 
___% 
___% 
☐ Hip, Leg, or 
     Calf Pain 
Percent predicted: ___ % 
Technician Comments and Interpretation (including comparison with a pre-LIQ861 6MWD): 
 
 
 
 
 
 
a. 
The patient should rate baseline dyspnea using the Borg Scale (below).  At the end of the test, the patient should be reminded of their 
baseline score before recording the End of Test score. 
b. 
The patient should rate baseline fatigue using the Borg Scale (below).  At the end of the test, the patient should be reminded of their 
baseline score before recording the End of Test score. 
c. 
Collection of SpO2 is optional.  If recorded, the device must be lightweight (less than 2 lbs) and should not be continuously monitored. 
d. 
6MWD = (Total Laps × Lap Distance) + Final Partial Lap 
The Borg Scale 
 
0 
Nothing at All 
 
0.5 
Very, Very slight (just noticeable) 
 
1 
Very slight 
 
2 
Slight (light) 
 
3 
Moderate 
 
4 
Somewhat severe 
 
5 
Severe (heavy) 
 
6 
 
 
7 
Very Severe 
 
8 
 
 
9 
 
 
10 
Very, very severe (maximal)