Open-label, Single-dose, Randomized, Two-way Crossover Study to Compare the Pharmacokinetics and Pharmacodynamics of Subcutaneous Injection of SCP-111 (Furosemide) vs Intravenous Injection of Furosemide in Healthy Volunteers
Phase: PHASE1
Conditions: Heart Failure, Fluid Overload
Sponsor: scPharmaceuticals, Inc.

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 1 of 56 
 
 
STUDY PROTOCOL 
 
Open-label, Single-dose, Randomized, Two-way (two-
period) Crossover Study to Compare the Pharmacokinetics 
and Pharmacodynamics of SCP-111 (furosemide injection) 
Administered as a Subcutaneous Injection vs Furosemide 
Administered as an Intravenous Injection in Healthy 
Volunteers 
 
 
IND Number: 
158047 
Protocol Number:  
scP-04-001 
Study Type: 
Phase I 
Investigational Drug-Device Combination:  
SCP-111 Autoinjector  
Original Protocol Date: 
04 February 2022 
Amendment 1 Date 
03 May 2022 
Amendment 2 Date 
18 November 2022 
Amendment 3 Date 
06 September 2023 
Amendment 4 Date 
29 November 2023 
 
 
CONFIDENTIAL STATEMENT 
The information contained in this document and all information provided to you is the 
confidential and proprietary information of scPharmaceuticals, Inc. (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 this protocol, provided such individuals agree to maintain the confidentiality of such 
information. 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 2 of 56 
SPONSOR CONTACT INFORMATION 
 
John Mohr, Pharm.D., FIDP 
Sr. Vice President Clinical Development and Medical Affairs 
25 Mall Road, Suite 203 
Burlington, MA 01803 
Phone: (781) 301-7220 
Cell: (281) 658-7949 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 3 of 56 
SUMMARY OF CHANGES 
Amendment 1:  The protocol has been amended to incorporate FDA recommended dosing regimen 
of 2 x 40 mg intravenous doses given 2 hours apart.  The PK sampling points and injection site pain 
assessment for IV dosing have been revised to account for new dosing regimen.  
Amendment 2:  The protocol has been amended to update IV furosemide dose administration 
description, details around Secondary Objectives and remove BD device references.  It also clarifies 
when subjects abstain from caffeine-containing products, the number of subjects enrolled, exclusion 
criteria and assessment details. Minor administrative changes were made for consistency. 
Amendment 3:  The protocol has been amended to update exclusion criteria based on FDA 
feedback. It also includes taking photographs of the injection site prior to injection (baseline) and 4 
hours post IV or 6 hours post SC administration and for any AE at injection site at time of event. 
Adverse event Investigational Product (IP) terminology has been updated to study treatment. A 
section for documenting AE/SAEs during the washout and Follow-up period has been added. Study 
drug and study device SCP-111 Autoinjector description updated current common terminology. 
Amendment 4:  The protocol has been amended to change the inclusion criteria age range to 45 to 
80 years of age, extend the study duration to 4 months and expand Introduction description. 
Version 
Date 
Page 
Change 
Reason for Change 
Original 
04 Feb 2022 
N/A 
Original Version 
New Document 
Amendment 1 
03 May 2022 
Synopsis, Study 
Objectives p. 6, 
Study Treatments p. 
8,  
Section 1.1. p. 15, 
Section 2. p. 16, 
Section 3.1. p. 17, 
Section 3.1.1. p. 18, 
Section 5.5. p. 23, 
Section 6.1.1. p. 24, 
Section 6.2.1.3.2. p. 
28, 
6.2.1.6.2. p. 29, 
Appendix 1 p. 49. 
Replaced Intravenous 
(IV) Furosemide 
injection 80 mg over 2 
minutes with dosing 
regimen of two 40 mg 
intravenous injections 
over two minutes, two 
hours apart. 
Updated to FDA 
recommended IV 
dosing regimen. 
Amendment 1 
03 May 2022 
Section 6.2.2.6. 
Pharmacokinetic 
Assessments – 
Plasma p. 31-32. 
Replaced “5, 15, 30, 
45 minutes and 1, 
1.25, 1.5, 2, 3, 4, 5, 6, 
8 and 12 hours after 
the IV injection” with 
First IV and Second 
IV 2-minute injection 
dose sampling points. 
Revised PK sampling 
points for IV dosing to 
account for new dosing 
regimen. 
Amendment 1 
03 May 2022 
Section 6.2.2.7. 
Assessment for 
Injection Site Pain p. 
32, 
Appendix 1 p. 49. 
Replaced 
“immediately after the 
dose and 15 and 30 
minutes and 6 and 12 
hours after the dose” 
with assessments 
following 1st and 2nd 
dose. 
Revised Pain 
assessment for IV 
dosing to account for 
new dosing regimen. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 4 of 56 
Version 
Date 
Page 
Change 
Reason for Change 
Amendment 2 
18 Nov 2022 
Multiple sections 
and pages 
Modified IV 
furosemide injection 
description to “one to 
two minutes” or “1 to 
2.”   
Updated to align with IV 
furosemide dose 
administration in 
approved labeling for 
Listed Drug. 
Amendment 2 
18 Nov 2022 
Multiple sections 
and pages 
Modified assessment  
“injection site 
pain/discomfort” to 
“injection site pain.” 
Updated to clarify 
intensity of pain being 
measured with rating 
scale. 
Amendment 2 
18 Nov 2022 
Synopsis, 
Secondary 
endpoints p. 9 
Section 3.2. p. 22 
Section 6.1.1. p. 27 
Added titles to 
Secondary Endpoints, 
specified time units to 
“hours”, 
added injection site 
pain assessment. 
Updated details around 
Secondary Endpoints. 
Amendment 2 
18 Nov 2022 
Multiple sections 
and pages 
Added subjects 
instructed to abstain 
from caffeine-
containing products 2 
days prior to 
admission through 
completion of 
Crossover Period 2.  
To clarify subjects need 
to maintain <2 gram 
sodium diet and abstain 
from caffeine containing 
products for PK 
sampling. 
Amendment 2 
18 Nov 2022 
Synopsis, Study 
Treatments p. 11 
Section 3.1.1. p. 20 
Figure 1 p. 22 
Section 5.2. p. 25 
Removed BD Intevia 
device references, 
description and figure. 
The autoinjector for the 
study is to be 
determined. 
Amendment 2 
18 Nov 2022 
Synopsis, Number 
of Subjects p. 11 
Section 8.1. p 42 
Updated 21 subjects 
will be enrolled to 
ensure  18 subjects 
complete the study 
through the Follow-up 
Phase. 
To clarify number of 
subjects enrolled. 
Amendment 2 
18 Nov 2022 
Synopsis, Subject 
Population p. 12 
Section 4.2. p. 23 
 
Removed Exclusion 
Criteria #13: 
“Moderate-to-severe 
hepatic dysfunction 
as determined by the 
investigator.” 
Removed because 
included within 
Exclusion Criteria #12: 
Reported history of liver 
disease, cirrhosis, or 
ascites. 
Amendment 2 
18 Nov 2022 
Synopsis, 
Pharmacokinetic 
and statistical 
analysis p. 13, 
Section 8.4 p. 42 
Removed “Phoenix® 
WinNonlin® V8.1 or 
higher” methods. 
 
The statistical analysis 
methods to be 
determined. 
Amendment 2 
18 Nov 2022 
Section 1.4. p. 19 
Replaced “electrolyte 
abnormalities” with 
”abnormal serum 
potassium levels.” 
To clarify subjects with 
abnormal serum 
potassium levels 
excluded at screening.  

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 5 of 56 
Version 
Date 
Page 
Change 
Reason for Change 
Amendment 2 
18 Nov 2022 
Section 3.2.2. p. 22 
Section 6.2.1.3.3. p. 
31 
Section 6.2.1.6.3. p. 
32 
Section 6.2.2.5. p. 
34 
Modified urine 
collection description. 
To provide additional 
details for urine 
collection. 
Amendment 2 
18 Nov 2022 
Section 6.2. p. 28 
Added assessments 
performed at same 
time as a PK sample 
can be performed just 
prior to PK sample 
collection. 
To provide flexibility for 
performing 
assessments 
scheduled at same time 
as PK sample 
collection. 
Amendment 2 
18 Nov 2022 
Section 6.2.1.2. p. 
30 
Section 6.2.1.5. p. 
31 
Section 11.1. 
Appendix 1. p. 51 
 
Added “Subjects will 
be monitored during 
the study to ensure a 
minimum of 100 mL 
of fluid consumed for 
every 300 mL of urine 
output.” 
To re-emphasize during 
Treatment Phase to 
monitor subjects’ fluid 
intake. 
Amendment 2 
18 Nov 2022 
Section 3.1.2. Study 
Schematic p. 21 
Section 6.2. p. 28 
Section 6.2.1.7. p. 
33 
Section 11.1. 
Appendix 1. p. 51 
Added “Follow-up visit 
should occur 24-48 
hours after discharge 
from CRU for 
Crossover Period 2.” 
To clarify timing of 
Follow-up visit.  
Amendment 2 
18 Nov 2022 
Section 9.1.12 p. 47 
Removed that all 
used study product 
will be returned from 
the Subject to the site 
for accountability. 
Removed incorrect 
accountability 
instruction. 
Amendment 2 
18 Nov 2022 
Multiple sections 
and pages 
Administrative 
changes 
Added abbreviations,  
further clarified 
assessments and 
modified language for 
consistency. 
Amendment 3 
06 Sep 2023 
Synopsis, Subject 
Population p. 14  
Section 4.2 p. 26 
Removed “ascites” 
from exclusion #12 
and updated 
exclusion #20 to 
include tromethamine 
and benzyl alcohol. 
Updated exclusion 
criteria to align with 
Prescribing Information 
based on FDA 
feedback. 
Amendment 3 
06 Sep 2023 
Synopsis, Study 
Design and 
Methodology, p. 12 
Section 3.1 p. 22 
Section 6.2.1.2 p.32 
Section 6.2.1.3.3 
p.33 
Section 6.2.1.6.1 p. 
34 
Added Photographs 
of injection site will be 
performed prior to IV 
and SC injection 
(baseline) and 4 
hours post IV or 6 
hours post SC 
administration and for 
AE at injection site.  
Updated to include 
photographs of the 
injection site to 
evaluate AEs related to 
injection site. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 6 of 56 
Version 
Date 
Page 
Change 
Reason for Change 
Section 6.2.1.6.3 p. 
34 
Section 6.2.2.8 p. 
38 
Section 7. p. 38 
Section 7.7.4. p.43 
Appendix 1 p. 53 
Amendment 3 
06 Sep 2023 
Multiples sections 
and pages 
Investigational 
Product (IP) replaced 
with Study Treatment. 
Updated terminology to 
clarify capture AEs for 
IV and SC Study 
Treatments.   
Amendment 3 
06 Sep 2023 
Section 7.7.8 p. 43 
Added a section for 
Adverse Events and 
Serious Adverse 
Events during the 
washout and Follow-
up period. 
Added to explain how 
AEs/SAEs during the 
washout and Follow-up 
period will be 
documented. 
Amendment 3 
06 Sep 2023 
Section 9.1.6 p. 47 
Revised document 
retention guidelines to 
reference clinical trial 
agreement. 
Updated to align with 
current processes. 
Amendment 3 
06 Sep 2023 
Synopsis, Study 
Design and 
Methodology, p. 11 
Section 3.1 p. 22 
Replaced “plasma” 
with “blood” samples. 
Clarified blood samples 
collected to measure 
furosemide plasma 
concentrations. 
Amendment 3 
06 Sep 2023 
Synopsis, Study 
Treatment, p. 12 
Section 5.2 p.27 
Added “isotonic” to 
describe SCP-111 
formulation. 
Updated to common 
terminology. 
Amendment 3 
06 Sep 2023 
Synopsis, Study 
Treatment, p. 12 
Section 3.3 p. 25 
Section 5.2 p.27 
Modified description 
for study device SCP-
111 Autoinjector. 
Updated to common 
terminology. 
Amendment 4 
29 Nov 2023 
Synopsis, Subject 
Population p. 13 
Section 4.1 p. 26 
Changed the 
inclusion criteria age 
range to 45 to 80 
years of age. 
Updated to correlate 
with intended use 
population. 
Amendment 4 
29 Nov 2023 
Synopsis, Study 
Duration p. 11 
Extended the study 
duration to 4 months. 
Updated to account for 
increased enrollment 
time due to change in 
age range. 
Amendment 4 
29 Nov 2023 
Introduction, p. 20  
Expanded 
Introduction 
description of 
treatment of fluid 
overload in certain 
chronic conditions. 
Updated to include 
background on water 
homeostasis and better 
align with proposed 
indication and use.  
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 7 of 56 
PROTOCOL APPROVAL PAGE 
Study Title: 
Open-label, Single-dose, Randomized, Two-way (two-
period) Crossover Study to Compare the 
Pharmacokinetics and Pharmacodynamics of SCP-111 
(furosemide injection) Administered as a Subcutaneous 
Injection vs Furosemide Administered as an Intravenous 
Injection in Healthy Volunteers 
Protocol Number: 
scP-04-001 
Original Protocol 
Date of Issue: 
04 February 2022 
Amendment 1 Date: 
03 May 2022 
Amendment 2 Date: 
18 November 2022 
Amendment 3 Date: 
06 September 2023 
Amendment 4 Date: 
29 November 2023 
Sponsor Name and 
Address: 
scPharmaceuticals, Inc. 
25 Mall Road, Suite 203 
Burlington, MA 01803 
I, the undersigned, have read and approve this protocol and agree on its content.  It 
is confirmed that the information and guidance given in this protocol complies with 
scientific principles, the guidelines of Good Clinical Practices, the Declaration of 
Helsinki in the latest relevant version, and the applicable legal and regulatory 
requirements. 
Approval Section 
 
Name/Title 
Signature / Date 
Reviewed and 
Approved by: 
John Mohr, Pharm D 
SVP, Clinical Development 
and Medical Affairs 
Approvals obtained through 
MasterControl 
Reviewed and 
Approved by: 
Barbara Cornelius 
Associate Director, Clinical 
Operations 
Approvals obtained through 
MasterControl 
Reviewed and 
Approved by: 
Jen Vandiver 
VP, Product Development 
and Engineering 
Approvals obtained through 
MasterControl 
Reviewed and 
Approved by: 
Eric Kendig 
VP, Head of Regulatory 
Affairs 
Approvals obtained through 
MasterControl 
Reviewed and 
Approved by: 
Michelle Whipple 
VP, Quality 
Approvals obtained through 
MasterControl 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 8 of 56 
INVESTIGATOR PROTOCOL AGREEMENT 
Protocol Title: 
Open-label, Single-dose, Randomized, Two-way (two-period) 
Crossover Study to Compare the Pharmacokinetics and 
Pharmacodynamics of SCP-111 (furosemide injection) 
Administered as a Subcutaneous Injection vs Furosemide 
Administered as an Intravenous Injection in Healthy 
Volunteers 
Protocol Number: scP-04-001 
Amendment 4 
 
By my signature, I  
• 
agree to conduct the study in accordance with the relevant, current protocol(s) and 
will only make changes in a protocol after notifying the Sponsor, except when 
necessary to protect the safety, rights, or welfare of Subjects.  
• 
agree to personally conduct or supervise the described investigation(s).  
• 
agree to inform any patients, or any persons used as controls, that the study 
treatment is being used for investigational purposes and I will ensure that the 
requirements relating to obtaining informed consent in 21 CFR Part 50 and 
institutional review board (IRB) review and approval in 21 CFR Part 56 are met.  
• 
agree to report to the Sponsor adverse experiences that occur during the 
investigation(s) in accordance with 21 CFR 312.64.  I have read and understand 
the information in the Investigator’s brochure, including the potential risks and side 
effects of the study treatment.  
• 
agree to ensure that all associates, colleagues, and employees assisting in the 
conduct of the study are informed about their obligations in meeting the above 
commitments.  
• 
agree to maintain adequate and accurate records in accordance with 21 CFR 
312.62 and to make those records available for inspection in accordance with 21 
CFR 312.68.  
• 
will ensure that an IRB that complies with the requirements of 21 CFR Part 56 will 
be responsible for the initial and continuing review and approval of the clinical 
investigation.  I also agree to promptly report to the IRB all changes in the research 
activity and all unanticipated problems involving risks to human subjects or others. 
Additionally, I will not make any changes in the research without consent from the 
Sponsor and will not institute those changes in the research protocol until after IRB 
approval, except where necessary to eliminate apparent immediate hazards to 
human subjects.  
• 
agree to comply with all other requirements regarding the obligations of clinical 
investigators and all other pertinent requirements in 21 CFR Part 312. 
 
 
 
Investigator's Signature 
 
Date 
Print Name 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 9 of 56 
STUDY SYNOPSIS 
SHORT TITLE 
SCP-111 PK/PD 
PROTOCOL TITLE 
Open-label, Single-dose, Randomized, Two-way (two-period) 
Crossover Study to Compare the Pharmacokinetics and 
Pharmacodynamics of SCP-111 (furosemide injection) 
Administered as a Subcutaneous Injection vs Furosemide 
Administered as an Intravenous Injection in Healthy Volunteers 
PROTOCOL 
NUMBER 
scP-04-001 
SPONSOR 
scPharmaceuticals, Inc. 
INVESTIGATIONAL 
PRODUCT 
SCP-111 (furosemide injection) 80 mg/1 mL for subcutaneous 
administration via an autoinjector  
STUDY 
OBJECTIVES 
Primary Objective: 
 
• To estimate the bioavailability of SCP-111 80 mg/1 mL 
administered as a subcutaneous injection via an 
autoinjector compared with an equivalent dose of 
furosemide administered as two 40 mg intravenous 
injections over one to two minutes, two hours apart.  
 
Secondary Objectives:  
 
• To describe the pharmacokinetics and pharmacodynamics 
of SCP-111 80 mg/1 mL administered as a subcutaneous 
injection via an autoinjector. 
 
• To describe the safety and tolerability of SCP-111 80 mg/1 
mL administered as a subcutaneous injection via an 
autoinjector. 
 
ENDPOINTS 
Primary Endpoints: 
 
• Logarithmic transformed geometric mean ratio between 80 
mg subcutaneous SCP-111 and 80 mg intravenous 
furosemide of the:  
o AUC from time 0 (pre-dose) to the last quantifiable 
time point (AUClast) 
o AUC from time 0 (pre-dose) extrapolated to infinity 
(AUCinf) 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 10 of 56 
Secondary Endpoints: 
 
Pharmacokinetics/pharmacodynamics 
 
The following pharmacokinetics (PK) parameters will be evaluated 
for subcutaneous and intravenous furosemide administration: 
 
• Maximum observed plasma concentration (Cmax)  
• Time to Cmax (Tmax) 
• Terminal phase elimination rate constant (λz), estimated by 
linear regression of logarithmically transformed 
concentration versus time data 
• Terminal elimination half-life (t½) estimated using the 
equation [ln(2)/λz] 
• Apparent systemic clearance (CL/F) 
• Systemic clearance (CL) 
• Apparent systemic volume of distribution (Vz/F) 
• Systemic volume of distribution (V) 
 
The following pharmacodynamics (PD) parameters will be 
evaluated for subcutaneous and intravenous furosemide 
administration: 
 
• Urine output (0-6, 0-8, and 0-12 hours)  
• Urinary sodium excretion (0-6, 0-8, and 0-12 hours)  
• Urinary potassium excretion (0-6, 0-8, and 0-12 hours)   
 
Safety and tolerability 
 
Safety 
 
Adverse Events (AEs) and Serious Adverse Events (SAEs) will be 
grouped by body system and summarized.  The incidence 
(number and percentage of subjects) of adverse events and 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 11 of 56 
serious adverse events will be presented overall and by MedDRA 
System Organ Class and Preferred Term.      
 
Injection Site Pain 
 
Injection site pain will be assessed using an 11-point scale where 
0 is equivalent to no pain and 10 is equivalent to the worst 
possible pain.  For IV administration, the 11-point pain scale will 
be performed pre-dose after IV needle placement, immediately 
after 1st dose and 15 and 30 minutes after 1st dose, immediately 
after 2nd dose and 15 and 30 minutes and 4 and 10 hours after the 
2nd dose.  For SC administration, the 11-point pain scale will be 
performed pre-dose, immediately after dose and 15 and 30 
minutes and 6 and 12 hours after dose.  Pain requiring treatment, 
withdrawal from the study or discontinuation of study drug will also 
be recorded as an adverse event (AE).  
STUDY DURATION 
4 months 
 
STUDY DESIGN & 
METHODOLOGY 
Study Design: 
 
This is an open-label, single-center, single-dose, randomized, two-
way (two-period) crossover study in healthy volunteers.  Each 
Subject will complete Screening, Baseline, Treatment, and Follow-
up Phases.  
 
The Screening Phase will be conducted on an outpatient basis 
between 14 and 3 days prior to the Baseline visit.  Subjects will be 
instructed to maintain a < 2-gram sodium diet and abstain from 
caffeine-containing products within 2 days prior to admission to 
the Clinical Research Unit (CRU).  On arrival to the CRU (Day 0), 
baseline and final qualification assessments will be performed. 
 
The Treatment Phase will be comprised of two crossover periods 
separated by a 3 ± 1 day washout period.  During each CRU 
admission and through the washout period, Subjects will continue 
a < 2-gram sodium diet and abstain from caffeine-containing 
products.  Subjects will be randomly assigned in a 1:1 ratio to 1 of 
2 treatment sequences to receive intravenous (IV) furosemide or 
subcutaneous (SC) SCP-111 in the abdomen in Crossover 
Periods (i.e., IV followed by SC or vice versa).  Blood samples will 
be collected to measure furosemide plasma concentrations at pre-
dose and for 12 hours post-dose.  Prior to dosing in each 
Treatment Phase, subjects will void their bladder completely and 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 12 of 56 
urine will be collected starting after the injection through 12 hours 
post injection to determine total urine output and urinary sodium 
and potassium excretion.  Assessment of injection site pain will be 
conducted for IV and SC administration using an 11-point pain 
scale.  Photographs of the injection site will be performed prior to 
the IV and SC injection (baseline) and 4 hours post IV 
administration and 6 hours post SC administration.  In addition, a 
photograph will be taken of the IV and SC injection site for any AE 
(i.e., erythema, edema, pruritus, bruising) that occurs at the site at 
the time of the event.  Subjects will remain domiciled in the CRU 
for each Treatment Phase through 12 hours after administration of 
study drug.  After final assessments are performed, subjects may 
be discharged from the CRU if safety parameters are acceptable 
to the Investigator.  
 
The Follow-up Phase will occur 24-48 hours (Day 5 ± 1) after 
discharge from the CRU following Crossover Period 2, completing 
Subjects’ study participation. 
STUDY 
TREATMENTS 
Study Drugs: 
 
 
• Intravenous Furosemide (IV Furosemide):  Hospira, 
furosemide injection, solution 10 mg/mL (NDA 018667) 
(total dose = 80 mg) administered intravenously 40 mg over 
1 to 2 minutes by IV injection followed by a second dose of 
40 mg over 1 to 2 minutes, 2 hours later (reference 
treatment). 
 
• SCP-111 (furosemide injection), 80 mg/1 mL for 
subcutaneous administration:  Total dose = 80 mg; 
administered as a subcutaneous injection (test treatment) 
via an autoinjector.  
 
 
Study Drug: SCP-111, (furosemide injection), 80 mg/1 mL is a 
proprietary furosemide formulation that is isotonic and buffered to 
a neutral pH for subcutaneous administration.  
 
Study Device: SCP-111 Autoinjector is an investigational single-
entity drug-device combination product consisting of a prefilled 
syringe containing 1 mL of SCP-111 (furosemide injection), 
preloaded into a fixed single dose, disposable, two step 
mechanical autoinjector designed to administer the full dose to the 
subcutaneous tissue. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 13 of 56 
NUMBER OF 
SUBJECTS 
21 subjects will be enrolled to ensure 18 subjects complete the 
study through the Follow-up Phase 
NUMBER OF SITES 
1 
PARTICIPATING 
COUNTRIES 
US 
SUBJECT 
POPULATION 
 
 
Subjects may be enrolled in the study only if all the inclusion 
criteria and none of the exclusion criteria are met. 
 
Inclusion Criteria:  
Female and male subjects are eligible for inclusion only if all the 
following criteria are met: 
1. An Institutional Review Board (IRB) approved informed 
consent is signed and dated prior to any study-related 
activities. 
2. Male and female subjects 45 to 80 years of age. 
3. Has the ability to understand the requirements of the study and 
is willing to comply with all study procedures. 
4. In the opinion of the Investigator, able to participate in the 
study. 
Exclusion Criteria:  
A Subject is not eligible for inclusion if any of the following criteria 
apply:  
1. Pregnant or lactating women or women of childbearing age 
who are not willing to use an adequate form of contraception. 
2. Systolic BP (SBP) < 90 mmHg at screening or baseline. 
3. Heart rate > 110 beats per minute (BPM) at screening or 
baseline.  
4. Temperature > 38°C (oral or equivalent). 
5. Serum potassium < 3.0 or > 5.5 mEq/L at screening. 
6. Other significant cardiac abnormalities which may interfere with 
study participation or study assessments. 
7. Current or planned treatment during the study with any IV 
therapies, including inotropic agents, vasopressors, 
levosimendan, nesiritide or analogues.  

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 14 of 56 
8. Presence of implanted ventricular assist device, cardiac 
defibrillator or pacemaker. 
9. Severely impaired renal function, defined as an estimated 
glomerular filtration rate (eGFR) at screening admission < 30 
mL/min/1.73m2, calculated using the simplified Modification of 
Diet in Renal Disease (sMDRD) equation. 
10. Urinary retention due to bladder emptying disorders and/or 
urethral narrowing. 
11. Presence or need for urinary catheterization. 
12. Reported history of hepatic cirrhosis. 
13. Administration of intravenous radiographic contrast agent 
within 72 hours prior to Screening. 
14. Concomitant or any use within past 30 days of drugs known to 
interact with furosemide (aminoglycoside antibiotics, ethacrynic 
acid, high doses of salicylates, cisplatin, tubocurarine, 
succinylcholine, chloral hydrate, phenytoin, methotrexate, 
indomethacin, or lithium).  
15. Administration of an investigational drug or implantation of 
investigational device, or participation in another interventional 
clinical trial, within 30 days prior to Screening. 
16. Any surgical or medical condition which in the opinion of the 
investigator may interfere with participation in the study or 
which may affect the outcome of the study. 
17. Positive urine drug screen at Screening or Baseline. 
18. Blood alcohol concentration > 2 mg/dL (0.02%) at Screening.  
19. Alcohol breath test > 2 mg/dL (0.02%) on admission to the 
CRU. 
20. History of severe allergic or hypersensitivity reactions to 
furosemide or any component of the SCP-111 formulation 
(tromethamine or benzyl alcohol). 
PHARMACOKINETIC 
AND STATISTICAL 
ANALYSIS 
Pharmacokinetic parameters will be estimated using 
noncompartmental methods.  Individual pharmacokinetic 
parameters for furosemide will be calculated using 
noncompartmental analysis and will be summarized using 
descriptive statistics.  Bioavailability of SCP-111 will be 
determined by the logarithmic transformed geometric mean ratios 
of the SCP-111 to IV furosemide AUClast and AUCinf and 90% 
Confidence Intervals for the geometric mean ratios (test/reference) 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 15 of 56 
will be determined and should be within 80% and 125% to 
establish bioequivalence.       
 
 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 16 of 56 
TABLE OF CONTENTS 
SPONSOR CONTACT INFORMATION .................................................................... 2 
SUMMARY OF CHANGES ....................................................................................... 3 
PROTOCOL APPROVAL PAGE............................................................................... 7 
INVESTIGATOR PROTOCOL AGREEMENT ........................................................... 8 
STUDY SYNOPSIS ................................................................................................... 9 
ABBREVIATIONS ................................................................................................... 18 
1. INTRODUCTION ............................................................................................... 20 
 Rationale for the Current Study ................................................................... 20 
 Potential Benefits of Participating in the Study ............................................ 21 
 Potential Risks of Participating in the Study ................................................ 21 
 Risk Management ....................................................................................... 21 
2. STUDY OBJECTIVES ....................................................................................... 21 
3. INVESTIGATIONAL PLAN ............................................................................... 22 
 Overall Study Design and Plan ................................................................... 22 
 Endpoints .................................................................................................... 25 
 SCP-111 Autoinjector.................................................................................. 26 
4. SELECTION OF STUDY POPULATION .......................................................... 26 
 Inclusion Criteria ......................................................................................... 26 
 Exclusion Criteria ........................................................................................ 26 
 Removal of Subjects from Therapy/Premature Discontinuation .................. 27 
5. TREATMENTS .................................................................................................. 27 
 Treatments Administered ............................................................................ 27 
 Identity of Investigational Product ............................................................... 28 
 Method of Assigning Subjects to Treatment Groups ................................... 28 
 Selection of Doses in the Study .................................................................. 28 
 Selection and Timing of Dose for Each Subject .......................................... 29 
 Procedures for Blinding ............................................................................... 29 
 Prior and Concomitant Therapy .................................................................. 29 
 Prohibited Medications ................................................................................ 29 
 Study Stopping Criteria ............................................................................... 29 
 Treatment Compliance .............................................................................. 30 
 Study Drug Accountability ......................................................................... 30 
6. STUDY PROCEDURES .................................................................................... 30 
 Study Measurements and Assessments ..................................................... 30 
 Study Phases and Procedures .................................................................... 30 
7. ADVERSE EVENTS .......................................................................................... 39 
 Definition of an Adverse Event .................................................................... 39 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 17 of 56 
 Definition of an Unexpected Adverse Event ................................................ 40 
 Definition of a Serious Adverse Event ......................................................... 40 
 Severity of Adverse Events and Serious Adverse Events ........................... 41 
 Outcome of Adverse Events and Serious Adverse Events ......................... 42 
 Assessment of Relatedness to Study Treatment ........................................ 42 
 Method, Frequency, and Time Period for Detecting Adverse Events and 
Serious Adverse Events .............................................................................. 43 
8. STATISTICS ..................................................................................................... 45 
 Determination of Sample Size ..................................................................... 45 
 Analysis Populations ................................................................................... 45 
 Baseline Characteristics and Subject Disposition ....................................... 45 
 Pharmacokinetic and Statistical Analysis .................................................... 45 
 Pharmacodynamic Analysis ........................................................................ 47 
 Safety and Tolerability Analysis .................................................................. 47 
9. RESPONSIBILITIES ......................................................................................... 47 
 Investigator Responsibilities ........................................................................ 47 
 Sponsor Responsibilities ............................................................................. 51 
 Joint Investigator and Sponsor Responsibilities .......................................... 51 
10. REFERENCES .................................................................................................. 52 
11. APPENDICES ................................................................................................... 53 
 Appendix 1.  Time and Event Schedule .................................................... 54 
 Appendix 2.  Assessment of Injection Site Pain ........................................ 56 
 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 18 of 56 
ABBREVIATIONS 
 
AE 
Adverse Event 
AUC 
Area Under the Curve 
AUCinf 
Area Under the Curve to infinity 
AUClast 
Area Under the Curve to last quantifiable time point 
βhCG 
Beta-human Chorionic Gonadotropin 
BMI 
Body Mass Index 
BPM 
Beats per minute 
BUN 
Blood Urea Nitrogen 
C 
Celsius 
CFR 
Code of Federal Regulations 
CL 
Systemic Clearance 
CL/F 
Apparent Systemic Clearance 
Cmax 
Maximum Plasma Concentration 
CRF 
Case Report Form 
CRU 
Clinical Research Unit 
CV 
Cardiovascular 
ECG 
Electrocardiogram 
ED 
Emergency Department 
eGFR 
Estimated Glomerular Filtration Rate 
EP 
European Pharmacopoeia 
F 
Fahrenheit 
FDA 
Food and Drug Administration  
GCP 
Good Clinical Practice 
HCP 
Healthcare Professional 
ICH 
International Conference on Harmonization 
IFU 
Instructions for Use 
IM 
Intramuscular 
IN 
Inches 
IND 
Investigational New Drug 
IP 
 
Investigational Product 
IRB/EC 
Institutional Review Board/Ethics Committee 
IV 
Intravenous 
lbs 
Pounds 
Mg/dL 
Milligrams per Deciliter 
Min 
Minute 
mL 
Milliliter 
mmHg 
Millimeters of mercury 
mEq/L 
Milliequivalent per Liter 
OTC 
Over-The-Counter 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 19 of 56 
SAE 
Serious Adverse Event 
SBP 
Systolic Blood Pressure 
SC 
Subcutaneous 
sMDRD 
Simplified Modification of Diet in Renal Disease 
USP 
United States Pharmacopeia 
V 
Systemic Volume 
Vz/F 
Apparent Systemic Volume of Distribution 
 
 
 
 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 20 of 56 
1.   
INTRODUCTION 
Water is a primary constituent of the human body and is responsible for many 
physiological processes.  The balance between fluid gains and fluid losses is 
regulated through various mechanisms such as neural regulation of thirst, hormonal 
regulation (vasopressin and natriuretic peptides), management through the skin, 
hemodynamic changes, and renal control of sodium and water excretion.  Chronic 
diseases that can lead to reduced functionality of organs such as the heart, kidney 
and liver can lead to an impaired ability to adequately regulate body water and 
electrolytes.  When this occurs, fluid can begin to slowly accumulate in the 
vasculature and tissues leading to symptoms such as weight gain, swelling, exercise 
intolerance, dyspnea and fatigue.  Diuretics are drugs that pharmacologically tilt the 
regulation of fluid in favor of the excretion of water and electrolytes by increasing the 
production and volume of urine and thus affecting water homeostasis.  Diuretics are 
the cornerstone of therapy for managing volume overload in patients with congestive 
heart failure, liver cirrhosis and kidney disease.   
Furosemide, a loop diuretic that was developed in the 1960’s, is an anthranilic acid 
derivative and is available for oral, intravenous (IV), intramuscular (IM) 
administration as well as a 5-houir subcutaneous infusion via an on-body Infusor.  Its 
mechanism of action is inhibition of the sodium-potassium-2 chloride co-transporter 
thus decreasing the reabsorption of sodium and chloride in the proximal and distal 
tubules and in the loop of Henle, thus promoting sodium and water excretion.  
However, on average, only 50% of an orally administered dose of furosemide is 
absorbed and oral bioavailability ranges from 10% to 100%, making it a matter of 
clinical judgement as to how much furosemide to dose in an individual patient, 
especially in patients with heart failure where absorption can become even further 
reduced and highly variable.  
In the event of worsening symptoms due to fluid overload, administration of IV loop 
diuretics that bypass the gastrointestinal tract, which are typically administered either 
in the hospital or an outpatient infusion center if available, are often needed to 
effectively decrease the excess fluid overload and the associated signs and 
symptoms.  Intravenous (IV) furosemide is indicated for the management of edema 
associated with heart failure, cirrhosis of the liver and renal disease, including 
nephrotic syndrome.   
SCP-111 (furosemide injection, 80 mg/1 mL) is a pH neutral formulation of 
furosemide that has been developed for subcutaneous injection. SCP-111 contains 
the inactive ingredients tromethamine (tris(hydroxymethyl)) aminomethane) and 
benzyl alcohol and is buffered to a neutral pH with sodium hydroxide and 
hydrochloric acid.  
 Rationale for the Current Study 
The proposed study aims to determine the bioavailability and describe the 
pharmacokinetics and pharmacodynamics of SCP-111 administered as a 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 21 of 56 
subcutaneous injection compared to two 40 mg injections of furosemide 
administered intravenously over one to two minutes, two hours apart.   
In a prior pharmacokinetic study conducted by scPharmaceuticals, the relative 
bioavailability of furosemide 80 mg/10 mL was 99.6% when administered as a 5-
hour, biphasic infusion compared to two 40 mg injections of furosemide administered 
over two minutes, two hours apart (Sica DA, et al. 2018).  The data from this study 
was used to construct a pharmacokinetic and pharmacodynamic model and 
simulations of a subcutaneous injection was performed.  These simulations 
demonstrated that subcutaneous injections of furosemide would likely achieve AUC 
ratios comparable to intravenous furosemide whereby the 90% confidence intervals 
would fall between 80 and 125% (scPharmaceuticals, Data on file). 
 Potential Benefits of Participating in the Study 
There are no potential benefits to Subjects beyond the contribution to the 
development and testing of SCP-111. 
 Potential Risks of Participating in the Study 
Furosemide is the most widely used diuretic globally and has been used clinically for 
over 50 years.  Intravenous, intramuscular and oral formulations are approved by the 
Food and Drug Administration.  Marked diuresis accompanied by dehydration or a 
reduction in blood pressure including orthostatic hypotension has been associated 
with administration of furosemide.  In addition, furosemide can cause electrolyte 
abnormalities (hyponatremia, hypokalemia and hypocalcemia).  Subcutaneous 
administration of furosemide, USP, which has an alkaline pH (8.5-9), has been 
associated with local skin irritation and infusion site reactions.  The furosemide 
formulation used in this study has been buffered to a neutral pH. 
 Risk Management 
Subjects will be monitored in the Clinical Research Unit (CRU) for at least 12 hours 
after dosing with the study treatment and monitored.  Subjects will be allowed liquid 
and solid oral intake ad libitum during the study with a minimum of 100 mL of fluid 
consumed for every 300 mL of urine output.  Subjects with abnormal serum 
potassium levels at screening will be excluded from the study.  Blood pressure and 
heart rate will be monitored during and after the injections.  
2.   
STUDY OBJECTIVES 
The primary objective of the study is: 
 
1.) To estimate the bioavailability of SCP-111 80 mg/1 mL administered as a 
subcutaneous injection via an autoinjector compared with an equivalent 
dose of furosemide administered as two 40 mg intravenous injections over 
one to two minutes, two hours apart. 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 22 of 56 
The secondary objectives of the study are: 
 
1.) To describe the pharmacokinetics and pharmacodynamics of SCP-111 80 
mg/1 mL administered as a subcutaneous injection via an autoinjector. 
2.) To describe the safety and tolerability of SCP-111 80 mg/1 mL 
administered as a subcutaneous injection via an autoinjector. 
3.   
INVESTIGATIONAL PLAN 
 Overall Study Design and Plan 
This is an open-label, single-center, single-dose, randomized, two-way (two-period) 
crossover study in healthy volunteers.  Each Subject will complete Screening, 
Baseline, Treatment, and Follow-up Phases.  
The Screening Phase will be conducted on an outpatient basis between 14 and 3 
days prior to the Baseline visit.  Subjects will be instructed to maintain a < 2-gram 
sodium diet and abstain from caffeine-containing products within 2 days prior to 
admission to the CRU.  On arrival to the CRU (Day 0), baseline and final 
qualification assessments will be performed. 
 
The Treatment Phase will be comprised of two crossover periods separated by a 3 ± 
1 day washout period.  During each CRU admission and through the washout 
period, Subjects will continue a < 2-gram sodium diet and abstain from caffeine-
containing products.  Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 
treatment sequences to receive IV furosemide and SC SCP-111 in the abdomen in 
Crossover Periods (ie, IV followed by SC or vice versa).  Blood samples will be 
collected to measure plasma furosemide concentrations at pre-dose and for 12 
hours post-dose.  Prior to dosing in each Treatment Phase, subjects will void their 
bladder completely and urine will be collected starting after the injection through 12 
hours post injection to determine total urine output and urinary sodium and 
potassium excretion.  Assessment of injection site pain will be conducted for IV and 
SC administration using an 11-point pain scale.  Photographs of the injection site will 
be performed prior to the IV and SC injection (baseline) and 4 hours post IV 
administration and  6 hours post SC administration.  In addition, a photograph will be 
taken of the IV and SC injection site for any AE (i.e., erythema, edema, pruritus, 
bruising) that occurs at the site at the time of the event.  Subjects will remain 
domiciled in the CRU for each Crossover Period during the Treatment Phase 
through 12 hours after administration of study drug.  After final assessments are 
performed, Subjects may be discharged from the CRU if safety parameters are 
acceptable to the Investigator.  
The Follow-up Phase will occur 24-48 hours (Day 5 ± 1) after discharge from the 
CRU following Crossover Period 2, completing Subjects’ study participation. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 23 of 56 
3.1.1.   
Study Treatment 
Study Drugs: 
• Furosemide Injection 10 mg/mL, USP:  Hospira, furosemide injection, 
solution 10 mg/mL (NDA 018667), administered intravenously 40 mg over 1 
to 2 minutes by IV injection followed by a second dose of 40 mg administered 
over 1-2 minutes, 2 hours later (reference treatment). 
• SCP-111 (furosemide injection 80 mg/1 mL):  SCP-111 80 mg/1 mL for 
subcutaneous administration, (total dose = 80 mg dose) administered as a 
subcutaneous injection (test treatment) via an autoinjector.   
Study drug will be administered at time zero (0) for the purpose of documenting drug 
administration, PK plasma sampling, urine collection, and AE monitoring according 
to the Time and Event Schedule.  Serial sampling of venous blood for quantitation of 
furosemide in plasma will be collected over 12 hours according to the schedule of 
procedures.  Urine will be collected from spontaneous voids in 1-hour increments for 
the first 8 hours and in 2-hour increments up to 12 hours post-dose, for the purpose 
of determining the total urine volume and urinary sodium and potassium 
concentration over 12 hours.  Plasma samples will be processed and stored 
according to the instructions in the protocol and assayed using validated 
bioanalytical methods. 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 24 of 56 
3.1.2.   
Study Schematic 
 
 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 25 of 56 
 Endpoints 
3.2.1.   
Pharmacokinetic Endpoints 
Individual pharmacokinetic parameters for furosemide will be summarized with 
descriptive statistics.  Pharmacokinetic parameters including the maximum observed 
plasma concentration (Cmax), the area under the plasma concentration versus time 
curve from time 0 (pre-dose) to the last quantifiable time point (AUClast), the AUC 
from time 0 (pre-dose) to time infinity (AUCinf), the time to Cmax (Tmax), the terminal 
phase elimination rate constant (λz), the terminal elimination half-life (t½) for both 
SC SCP-111 (test) and IV furosemide (reference), the apparent systemic clearance 
(CL/F) for SC SCP-111 and systemic clearance (CL) for IV furosemide, the apparent 
systemic volume of distribution (Vz/F) for SC SCP-111 and systemic volume of 
distribution (V) for IV furosemide will be calculated using noncompartmental 
analysis.  Bioavailability of SC SCP-111 will be determined based on the logarithmic 
transformation of the geometric mean ratios of AUClast and AUCinf of IV furosemide 
(reference) and SC SCP-111 (test) and 90% confidence intervals will be calculated.  
Compartmental modeling of the pharmacokinetic data may be conducted. 
3.2.2.   
Pharmacodynamic Endpoints 
Urine will be collected from spontaneous voids in 1-hour increments for the first 8 
hours and in 2-hour increments up to 12 hours post-dose.  Total urine output for 
each time period ((0-1), (1-2), (2-3), (3-4), (4-5), (5-6), (6-7), (7-8), (8-10) and (10-12) 
hours after initiation of dosing) will be recorded.  The 6-hour, 8-hour and 12-hour 
urine output for IV furosemide and SC SCP-111 will be compared using appropriate 
statistical tests.  In addition, an aliquot of urine will be used from each time period 
((0-1), (1-2), (2-3), (3-4), (4-5), (5-6), (6-7), (7-8), (8-10) and (10-12) hours after 
initiation of dosing) for quantification of urinary sodium and urinary potassium. The 6-
hour, 8-hour and 12-hour urinary sodium and potassium excretion will be determined 
and compared for IV furosemide and SC SCP-111 using appropriate statistical tests.  
3.2.3.   
Safety and Tolerability Endpoints 
 Safety 
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) grouped by 
body system for IV furosemide (reference) and SC SCP-111 (test). 
Changes in pre-dose clinical labs, blood pressure and heart rate through CRU 
discharge will be summarized for IV furosemide (reference) and SC SCP-111 (test). 
 Injection Site Pain 
Injection site pain will be assessed using an 11-point scale where 0 is equivalent to 
no pain and 10 is equivalent to the worst possible pain for IV administration and for 
SC administration.  Pain requiring treatment, withdrawal from the study or 
discontinuation of study drug will also be recorded as an adverse event (AE) 
(Appendix 2). 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 26 of 56 
 SCP-111 Autoinjector 
The SCP-111 Autoinjector is an investigational single-entity, drug-device 
combination product containing SCP-111 (furosemide injection), 80 mg/1 mL for 
subcutaneous use, prefilled in a 1 mL long borosilicate type 1 glass syringe with a 
29-gauge, ½ inch stainless steel staked needle, a rigid needle shield, and a 
FluroTec™ coated butyl rubber stopper, preloaded into a commercially available 
fixed single dose, disposable, two step, mechanical autoinjector that administers a 
full dose of drug product into the subcutaneous tissue of the abdomen.  It is intended 
for use by patients, caregivers, or a healthcare professional (HCP) at home or in a 
clinic setting.  
4.   
SELECTION OF STUDY POPULATION 
 Inclusion Criteria 
Female and male subjects are eligible for inclusion only if all the following criteria are 
met: 
1. An Institutional Review Board (IRB) approved informed consent is signed and 
dated prior to any study-related activities. 
2. Male and female subjects 45 to 80 years of age. 
3. Has the ability to understand the requirements of the study and is willing to 
comply with all study procedures. 
4. In the opinion of the Investigator, able to participate in the study. 
 
 Exclusion Criteria 
A Subject is not eligible for inclusion if any of the following criteria apply:  
1. Pregnant or lactating women or women of childbearing age who are not 
willing to use an adequate form of contraception. 
2. Systolic BP (SBP) < 90 mmHg at screening or baseline. 
3. Heart rate > 110 beats per minute (BPM) at screening or baseline.  
4. Temperature > 38°C (oral or equivalent). 
5. Serum potassium < 3.0 or > 5.5 mEq/L at screening. 
6. Other significant cardiac abnormalities which may interfere with study 
participation or study assessments. 
7. Current or planned treatment during the study with any IV therapies, including 
inotropic agents, vasopressors, levosimendan, nesiritide or analogues.  
8. Presence of implanted ventricular assist device, cardiac defibrillator or 
pacemaker. 
9. Severely impaired renal function, defined as an estimated glomerular filtration 
rate (eGFR) at screening admission < 30 mL/min/1.73 m2, calculated using 
the simplified Modification of Diet in Renal Disease (sMDRD) equation. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 27 of 56 
10. Urinary retention due to bladder emptying disorders and/or urethral 
narrowing. 
11. Presence or need for urinary catheterization. 
12. Reported history of hepatic cirrhosis.  
13. Administration of intravenous radiographic contrast agent within 72 hours 
prior to Screening.  
14. Concomitant or any use within past 30 days of drugs known to interact with 
furosemide (aminoglycoside antibiotics, ethacrynic acid, high doses of 
salicylates, cisplatin, tubocurarine, succinylcholine, chloral hydrate, phenytoin, 
methotrexate, indomethacin or lithium). 
15. Administration of an investigational drug or implantation of investigational 
device, or participation in another interventional clinical trial, within 30 days 
prior to Screening. 
16. Any surgical or medical condition which in the opinion of the investigator may 
interfere with participation in the study or which may affect the outcome of the 
study. 
17. Positive urine drug screen at Screening or Baseline. 
18. Blood alcohol concentration > 2 mg/dL (0.02%) at Screening. 
19. Alcohol breath test > 2 mg/dL (0.02%) on admission to the CRU. 
20. History of severe allergic or hypersensitivity reactions to furosemide or any 
component of the SCP-111 formulation (tromethamine or benzyl alcohol). 
 
 Removal of Subjects from Therapy/Premature Discontinuation 
Subjects will be encouraged to complete the study and all assessments; however, 
subjects may voluntarily withdraw at any time.     
A Subject will be discontinued from the study for the following medical or 
administrative reasons: 
• Subject request  
• Pregnancy  
• Significant non-compliance with study procedures 
The Investigator may discontinue individual subjects from the study at any time.   
5.   
TREATMENTS 
 Treatments Administered 
Study drugs will be administered by qualified research staff in accordance with the 
procedures described in this protocol and in the Instructions for Use. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 28 of 56 
 Identity of Investigational Product 
Study Drug:  SCP-111 (furosemide injection), 80 mg/1 mL is a proprietary 
furosemide formulation that is isotonic and buffered to a neutral pH for subcutaneous 
administration. 
 
SCP-111 (furosemide injection), 1 mL buffered furosemide solution (80 mg/1 mL), is 
manufactured by Ajinomoto Althea, Inc., 11040 Roselle Street, San Diego, CA 
92121, USA, under good manufacturing practice conditions.  Each 1 mL of SCP-111 
contains 80 mg of furosemide and the following inactive ingredients: 9.7 mg 
Tromethamine, and 35 mg Benzyl Alcohol and also contains Sodium Hydroxide and 
Hydrochloric Acid for pH adjustment (pH range: 7.4 to 8.0). 
  
Study Device:  SCP-111 Autoinjector is an investigational single-entity drug-device 
combination product consisting of a prefilled syringe containing 1 mL of SCP-111 
(furosemide injection), preloaded into a fixed single dose, disposable, two step 
mechanical autoinjector designed to administer the full dose to the subcutaneous 
tissue.  
5.2.1.   
Labeling 
80 mg SCP-111 Autoinjector will bear labels that meet applicable laws for an 
investigational drug-device combination, which may include, but is not limited to, the 
following information: 
 
• Federal law statement 
• Batch number 
• Storage information 
 
The Instructions for Use for the SCP-111 Autoinjector as it exists at the time of the 
study will be available for the Investigator and study staff.  
5.2.2 
Storage and Handling 
Store SCP-111 Autoinjector at controlled room temperature between 20°C and 25°C 
(68°F and 77°F).  Excursions permitted between 15°C and 30°C (59°F and 86°F).  
Do not refrigerate or freeze.  Do not remove the autoinjector from the carton until 
ready for use.  Protect from Light. 
 Method of Assigning Subjects to Treatment Groups 
Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences to 
receive both IV furosemide and SC SCP-111 in the abdomen in Crossover Periods 
(ie, IV followed by SC or vice versa).    
 Selection of Doses in the Study 
The dose of 80 mg was selected based in part on the recommended dosage of 
furosemide injection, 10 mg/mL, USP for the treatment of edema associated with 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 29 of 56 
congestive heart failure, renal disease and liver cirrhosis.  The usual initial dose of 
furosemide IV is 20 to 40 mg given as a single dose slowly over 1 to 2 minutes.  If 
needed, another dose may be administered in the same manner 2 hours later. 
 Selection and Timing of Dose for Each Subject 
• Furosemide injection 10 mg/mL, USP:  Hospira furosemide injection, 
solution 10 mg/mL, (NDA 018667), administered intravenously 40 mg over 1 
to 2 minutes by IV injection followed by a second dose of 40 mg administered 
over 1 to 2 minutes, 2 hours later (reference treatment). 
• SCP-111 (furosemide injection 80 mg/1 mL):  SCP-111, furosemide 
injection 80 mg/1 mL for subcutaneous administration, (total dose = 80 mg 
dose) administered as a subcutaneous injection (test treatment) via an 
autoinjector.  
 Procedures for Blinding 
This is an open label study. 
 Prior and Concomitant Therapy 
Prior and concomitant therapy will include all prescription and non-prescription 
medications including over-the-counter (OTC) weight loss medications and 
nutritional supplements seven (7) days prior to enrollment.  All information on prior 
and concomitant therapy will be recorded in the Subject’s source and on the 
Subject’s electronic case report form (eCRF).  Requisite details will include the name 
of the therapy or drug and duration of the treatment (start and stop dates) and 
reason for use. 
 Prohibited Medications 
Concomitant or any use within past 30 days of drugs known to interact with 
furosemide, including aminoglycoside antibiotics, ethacrynic acid, salicylates, 
cisplatin and nephrotoxic drugs, paralytic agents, lithium, angiotensin converting 
enzyme inhibitors or angiotensin II receptor blockers, antihypertensive drugs, 
adrenergic blocking drugs or peripheral adrenergic blocking drugs, norepinephrine, 
chloral hydrate, methotrexate and other drugs undergoing renal tubular secretion, 
cephalosporin, cyclosporine, thyroid hormones, phenytoin, or indomethacin is not 
permitted.   
If a Subject is receiving oral furosemide, bumetanide or torsemide, the Subject must 
discontinue the therapy for 24 hours prior to being dosed with the reference or test 
treatment.   
 Study Stopping Criteria 
The study may be stopped if the Investigator, Independent Medical Monitor, Sponsor 
or IRB determines that Subject safety may be compromised by continuing in the 
study. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 30 of 56 
 Treatment Compliance 
Study drug will be administered in accordance with the procedures outlined in this 
protocol.  All study medication will be administered by designated study personnel 
and all information regarding study drug administration will be documented. 
 Study Drug Accountability 
Only authorized site personnel may supply or administer study drug and only 
Subjects enrolled in the study may receive study drug, in accordance with applicable 
regulatory requirements.   
Study staff authorized to handle and store the study drug will keep an accurate 
accounting of the receipt and disposition of the study drugs received from the 
Sponsor.  Drug accountability will be assessed by the study monitor during periodic 
monitoring visits.  At the end of the study, following final product reconciliation by the 
monitor, the study site will be instructed by the Sponsor as to disposition of used and 
unused study drug and supplies. 
6.   
STUDY PROCEDURES 
 Study Measurements and Assessments 
6.1.1.   
Assessment of Efficacy 
Efficacy of the SCP-111 autoinjector combination product is being assessed based 
on the determination of bioavailability of a subcutaneous injection of SCP-111 80 mg 
compared to furosemide 80 mg administered intravenously as two 40 mg injections 
over 1 to 2 minutes, 2 hours apart.  Urine output and urinary sodium and potassium 
excretion from time 0-6, 0-8 and 0-12 hours will also be assessed. 
6.1.2.   
Assessment of Safety 
Subjects will be monitored for adverse events which will be recorded and reported 
on the eCRF according to guidelines specified by the United States FDA and 
detailed in Section 7. Adverse Events.  Blood pressure, heart rate, clinical chemistry 
labs will be collected throughout both treatment phases as outlined in Section 6.2. 
Study Phases and Procedures.  Injection site pain will be assessed as described in 
Section 6.2.2.7.  
 
 Study Phases and Procedures 
The Time and Event Schedule outlining study phases and procedures is provided in 
Appendix 1. 
The Screening Phase will be conducted on an outpatient basis between 14 and 3 
days prior to Baseline.  Subjects will be instructed to maintain a  < 2 gram sodium 
diet and abstain from caffeine-containing products within 2 days prior to Baseline.  
Baseline/CRU Admission will occur on Day 0.  Study drug will be administered on 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 31 of 56 
Day 0 and Day 3 (± 1 day) with a 3 ± 1 day outpatient fluid washout phase between 
doses.  Subjects will be instructed to continue a < 2-gram sodium diet and abstain 
from caffeine-containing products through Day 0, the washout phase and Day 3 
study drug administration. Follow-up visit will occur 24-48 hours after discharge from 
the CRU for Crossover Period 2.     
Collection of the PK samples should occur as close to the scheduled time point as 
possible.  The actual times of PK sample collections will be recorded.  Assessments 
that are to be performed at the same time as a PK sample is to be drawn may be 
performed just prior to the collection of PK sample.  
6.2.1.   
Study Phases 
 Screening (Day -14 through -3) 
Subjects can be pre-screened ahead of enrollment by telephone and invited to the 
research center.  Upon arrival to the research center, the study procedures will be 
explained.  All Subjects who sign the informed consent form and satisfy the 
inclusion/exclusion criteria will be enrolled into the study.   
The initial Screening visit will be conducted between 14 and 3 days prior to 
Baseline/CRU Admission on Day 0.  The following procedures/assessments will be 
performed at Screening:   
1. Informed consent (must be done prior to any of the following procedures, 
including asking subjects to discontinue prohibited medications) 
2. Eligibility review 
3. Medical history and demographics 
o Date of birth 
o Sex 
o Race 
o Ethnicity 
o Height (in) 
o Weight (lbs) 
o BMI (calculated from height and weight) 
o Medical History (self-reported; include onset dates) 
 Heart Failure 
 Hypertension 
 Stroke 
 Myocardial infarction 
 Unstable angina 
 Atrial fibrillation/flutter 
 Presence of implanted ventricular assist device, cardiac 
defibrillator, CardioMEMS™ or pacemaker 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 32 of 56 
 Chronic obstructive pulmonary disease 
 Diabetes mellitus 
 Hepatic/liver disease 
 Chronic Kidney disease (If yes, stage) 
• Stage 1: Normal kidney function (GFR >90 
mL/min/1.73 m2 with urine findings, structural 
abnormalities, or genetic traits) 
• Stage 2: Mildly reduced kidney function (GFR (60-89 
mL/min/1.73 m2) 
• Stage 3a: Moderately reduced kidney function (GFR 
(45-59 mL/min/1.73 m2 
• Stage 3b: Moderately reduced kidney function (GFR 
30-44 mL/min/1.73 m2 
• Stage 4: Severe reduced kidney function (GFR 15-29 
mL/min/1.73 m2) 
• Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m2 or 
dialysis) 
 Depression 
 Hyperlipidemia 
 Obstructive sleep apnea 
 Current Smoker (not current smoker if stopped smoking for 
at least 12 months) 
4. Complete/full physical examination as described in Section 6.2.2.1 
5. Temperature 
6. Blood pressure 
7. Heart rate 
8. Screening labs will be performed to measure sodium, potassium, calcium, 
chloride, magnesium, carbon dioxide, blood urea nitrogen, serum creatinine, 
glucose, hemoglobin, hematocrit and blood alcohol.  
9. Urine drug screen  
10. Serum pregnancy test (for females of child-bearing potential) 
11. 12-Lead ECG as described in 6.2.2.2 
12. Prior medication assessment 
o If a Subject is receiving oral furosemide, bumetanide or torsemide, 
the Subject must discontinue the therapy for 24 hours prior to 
Baseline/CRU admission. 
13. Schedule next study visit (Baseline/CRU admission) 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 33 of 56 
 Baseline Assessment (Day 0)  
Subjects will be admitted to the CRU on Day 0 (the day of study drug administration) 
for Baseline assessment and procedures.  Low sodium diet (< 2 gram per day) and 
fluid intake ad libitum consisting of water, juice and caffeine free beverages are 
permitted while domiciled in the CRU.  Subjects will be monitored during the study to 
ensure a minimum of 100 mL of fluid consumed for every 300 mL of urine output.   
The following assessments will be completed at Baseline upon CRU admission: 
1. Eligibility re-review  
2. Limited physical examination as described in Section 6.2.2.1 
3. Prior medication assessment  
o Time and date of last dose of oral loop diuretic (if receiving) 
4. Weight measurement 
5. Temperature 
6. Blood pressure 
7. Heart rate 
8. Clinical laboratory tests as described in Section 6.2.2.3  
9. Alcohol breath test 
10. Urine drug screen 
11. Urine pregnancy test as applicable 
12. Randomization to treatment sequence 
13. Photograph of Injection Site as described in Section 6.2.2.8 
 
 Treatment Crossover Period 1 (Day 0) 
All subjects will remain domiciled in the CRU through the 12-hour post-dose PK 
sample.  Subjects will be discharged from the CRU if safety parameters are 
acceptable to the Investigator.       
 Pre-dose 
The following assessments will be completed prior to dosing: 
1. Void bladder immediately before dosing and discard as described in Section 
6.2.2.5 
2. Plasma sample for pharmacokinetics as described in Section 6.2.2.6 
3. Assessment of injection site pain as described in Section 6.2.2.7 
 
 Dosing  
For the purpose of assessments and pharmacokinetic sampling times, Day 0, Hour 0 
will be defined as the point at which study drug dose is initiated/administered.  IV 
furosemide or SC SCP-111 should be administered according to the randomization 
schedule.  IV furosemide is administered via IV injection as a 40 mg dose over 1 to 2 
minutes followed by a second dose of 40 mg over 1 to 2 minutes, 2 hours after the 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 34 of 56 
start of the initial IV dose.  SC SCP-111 is administered as a single 80 mg dose via 
the autoinjector. 
 
 Post-Dose (Hour 0-12) 
The following assessments will be completed beginning after the initial dose: 
 
1. Blood pressure (15, 30 minutes and Hour 1, 2, 2.5, 3, 4, 6, 8 and 12) 
2. Heart rate (15, 30 minutes and Hour 1, 2, 2.5, 3, 4, 6, 8 and 12)  
3. Plasma sample for pharmacokinetics as described in Section 6.2.2.6 
4. Clinical laboratory tests as described in Section 6.2.2.3 (Hour 12) 
5. Urine collection from spontaneous voids for time periods (0-1), (1-2), (2-3), (3-
4), (4-5), (5-6), (6-7), (7-8), (8-10) and (10-12) hours post-dose for urine 
volume and urinary sodium and potassium as described in Section 6.2.2.5 
6. Food, snack and fluid intake and recording as per Time and Event Schedule 
7. Assessment of injection site pain as described in Section 6.2.2.7 
8. Adverse events 
9. Concomitant medications  
10. Limited physical examination as described in Section 6.2.2.1 (Hour 12) 
11. Weight measurement (Hour 12) 
12. Photograph of Injection Site (4 hours post IV administration or 6 hours post 
SC administration) as described in Section 6.2.2.8 
13. Schedule next study visit 
14. Discharge from the CRU if safety parameters are acceptable to the 
investigator (Hour 12) 
    
 Washout (Days 3 ± 1) 
1. Adverse events 
2. Concomitant medications 
3. Low sodium diet and abstain from caffeine-containing products 
 
 Pre-Period 2 Assessment (Day 3 ± 1) 
Subjects will present to the CRU on Day 3 ±1 for Pre-Period 2 assessment and 
procedures.  Low sodium diet and fluid intake ad libitum consisting of water, juice 
and caffeine free beverages are permitted while domiciled in the CRU.  Subjects will 
be monitored during the study to ensure a minimum of 100 mL of fluid consumed for 
every 300 mL of urine output.   
The following assessments will be completed at the Pre-period 2 assessment upon 
CRU admission: 
1. Limited physical examination as described in Section 6.2.2.1 
2. Concomitant medication assessment  

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 35 of 56 
a. Time and date of last dose of oral loop diuretic (if receiving) 
3. Weight measurement 
4. Temperature 
5. Blood pressure 
6. Heart rate 
7. Clinical laboratory tests as described in Section 6.2.2.3 
8. Alcohol breath test 
9. Urine drug screen 
10. Urine pregnancy test as applicable 
11. Adverse events 
 
 Treatment Crossover Period 2 (Day 3 ± 1) 
All subjects will remain domiciled in the CRU through the 12-hour post-dose PK 
sample.  Subjects will be discharged from the CRU if safety parameters are 
acceptable to the Investigator.        
 Pre-dose 
The following assessments will be completed prior to dosing: 
1. Void bladder immediately before dosing and discard as described in Section 
6.2.2.5 
2. Plasma sample for pharmacokinetics as described in Section 6.2.2.6 
3. Assessment of injection site pain as described in Section 6.2.2.7 
4. Photograph of Injection Site as described in Section 6.2.2.8 
5. Adverse events 
 
 Dosing 
For the purpose of assessments and pharmacokinetic sampling times, Day 3, Hour 0 
will be defined as the point at which study drug dose is initiated/administered.  IV 
furosemide or SC SCP-111 should be administered according to the randomization 
schedule.  IV furosemide is administered via IV injection as a 40 mg dose over 1 to 2 
minutes followed by a second dose of 40 mg over 1 to 2 minutes, 2 hours  after the 
start of the initial IV dose.  SC SCP-111 is administered as a single 80 mg dose via 
the autoinjector. 
 
 Post-Dose (Hour 0-12) 
The following assessments will be completed beginning after the initial dose: 
 
1. Blood pressure (15, 30 minutes and Hour 1, 2, 2.5, 3, 4, 6, 8 and 12) 
2. Heart rate (15, 30 minutes and Hour 1, 2, 2.5, 3, 4, 6, 8 and 12)  
3. Plasma sample for pharmacokinetics as described in Section 6.2.2.6 
4. Clinical laboratory tests as described in Section 6.2.2.3 (Hour 12) 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 36 of 56 
5. Urine collection from spontaneous voids for time periods (0-1), (1-2), (2-3), (3-
4), (4-5), (5-6), (6-7), (7-8), (8-10) and (10-12) hours post-dose for urine 
volume and urinary sodium and potassium as described in Section 6.2.2.5 
6. Food, snack and fluid intake and recording as per Time and Event Schedule 
7. Assessment of injection site pain as described in Section 6.2.2.7 
8. Adverse events 
9. Concomitant medications  
10. Limited physical examination as described in Section 6.2.2.1 (Hour 12) 
11. Weight measurement (Hour 12) 
12. Photograph of Injection Site (4 hours post IV administration or 6 hours post 
SC administration) as described in Section 6.2.2.8 
13. Schedule next study visit 
14. Discharge from the CRU if safety parameters are acceptable to the 
investigator (Hour 12) 
 
 Follow-Up (Day 5 ± 1) 
Follow-up visit should occur 24-48 hours after discharge from CRU for Crossover 
Period 2. 
 
1. Complete/full physical examination as described in Section 6.2.2.1 
2. Weight measurement 
3. Blood pressure 
4. Heart rate 
5. Adverse events 
6. Concomitant medications 
 
6.2.2.   
Study Procedures 
 Physical Examination 
At Screening and Follow-up, a complete/full physical examination should be performed.  At 
Baseline assessment Day 0 and on Day 3 a limited physical examination may be performed 
consisting of assessments of the skin, lungs/chest, heart, extremities, abdomen and any other 
abnormalities detected during the study period.  Post-dose physical examination on Day 0 
and Day 3 should be performed 12 hours after the study drug is administered. 
 
 12-lead ECG 
At Screening a 12-lead ECG will be performed after the Subject has rested quietly for at least 
5 minutes in a supine position.      
 Clinical Laboratory Tests 
All clinical samples will be analyzed by a licensed clinical laboratory.  The clinical 
laboratory tests are as follows:  

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 37 of 56 
6.2.2.3.1 
Screening: 
Blood Clinical Chemistry:  sodium, potassium, calcium, chloride, magnesium, 
carbon dioxide, blood urea nitrogen, serum creatinine, glucose, hemoglobin, 
hematocrit, and blood alcohol.  
Serum pregnancy test in females of childbearing potential:  beta hCG  
Urine Drug Screen:  Subjects with positive urine drug screen test results will be 
excluded from the study. 
6.2.2.3.2 
Pre-Dose and Post-Dose  
Blood Clinical Chemistry:  sodium, potassium, calcium, chloride, magnesium, 
carbon dioxide, blood urea nitrogen, serum creatinine, glucose, hemoglobin, 
hematocrit. 
Post-dose clinical labs on Day 0 and Day 3 should be performed 12 hours after the 
study drug is administered.  
The Investigator is responsible for determining if out of range laboratory values are 
clinically significant or not.  All clinically significant values will be followed until 
stabilization, resolution, or loss to follow-up. 
 Temperature, Blood Pressure and Heart Rate 
Temperature (oral or equivalent) will be taken.  Blood pressure (mmHg) and heart 
rate (bpm) will be measured in the supine position after the Subject has rested 
comfortably for at least 5 minutes. 
Height and weight will be collected and BMI will be calculated.  Height collected at 
Screening only. 
 Urine Collection 
Subjects will be instructed to void in order to empty their bladder immediately before 
dosing (pre-dose urine).  The pre-dose urine will be discarded.  Dosing should not 
commence if the Subject has not emptied their bladder in the previous 60 minutes.  
Urine from spontaneous voids during the post-dose phases will be collected and 
pooled, measured, recorded for time periods (0-1), (1-2), (2-3), (3-4), (4-5), (5-6), (6-
7), (7-8), (8-10) and (10-12) hours after initiation of dosing.  Urine for each collection 
period must be collected in a single vessel and refrigerated until the end of the 
collection period.  An aliquot of urine from each time period will be collected and sent 
for urinary sodium and urinary potassium.  Urinary sodium and urinary potassium 
concentration for each collection interval over the 12-hour urine collection period will 
be analyzed by standard lab biochemistry test.  The 6-hour, 8-hour and 12-hour 
urinary sodium and potassium excretion will be determined and compared for each 
treatment group. Total urine output volume will be documented for each collection 
period. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 38 of 56 
 Pharmacokinetic Assessments – Plasma 
PK blood samples will be obtained by either direct venipuncture or use of an 
indwelling catheter.  Collection of PK samples should occur as close to the 
scheduled time point as possible.  The actual time of PK sample collection will be 
recorded.  
For IV administration of furosemide injection, USP (reference), PK blood samples 
will be collected as follows: 
• First IV 1 to 2-minute injection dose 
o Pre-dose 
o 5, 15, 30, 45 minutes and 1, 1.5, 2 hours after start of first IV dose.  
The sample taken at 2 hours will be drawn immediately prior to the 
start of the second IV dose.  
• 
Second IV 1 to 2-minute injection dose (new clock for PK sampling starts 
upon the start of administration of second IV dose):  
o 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8 and 10 hours after start 
of second IV dose.   
For the SC administration of SCP-111 (test), PK blood samples will be collected as 
follows: 
• Pre-dose  
• 5, 15, 30, 45 minutes and 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours after the 
SC injection 
 
A minimum of 2 mL of blood will be collected in pre-labeled tubes.  Blood samples 
will be processed into plasma and the plasma samples will be stored in appropriately 
labeled cryotubes at minus 70˚C until shipped to the bioanalytical laboratory.  
Plasma samples will be assayed for furosemide using a validated LC-MS/MS 
analytical method.  
Blood samples will be drawn and processed for plasma as described in a separate 
document supplied to the CRU.  The plasma samples will be split into two aliquots 
after processing, and one shipped to the bioanalytical laboratory.  The other plasma 
aliquot will be stored at the site at minus 70˚C.  
 Assessment for Injection Site Pain 
Pain will be assessed using an 11-point scale where 0 is equivalent to no pain and 
10 is equivalent to the worst possible pain. (Appendix 2) 
For IV administration of furosemide injection, USP (reference), assessment of 
injection site pain will be conducted pre-dose, after placement of the IV needle, 
immediately after the 1st dose,15 and 30 minutes after the 1st dose, immediately 
after the 2nd dose and 15 and 30 minutes and 4 and 10 hours after the 2nd dose. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 39 of 56 
For the SC administration of SCP-111 (test), assessment of injection site pain will be 
conducted pre-dose, immediately after the dose and 15 and 30 minutes and 6 and 
12 hours after the dose.  
 Photograph of Injection Site 
Photographs of the injection site will be performed prior to the IV and SC injection 
(baseline) and 4 hours post IV administration or 6 hours post SC administration.  In 
addition, a photograph will be taken of the IV and SC injection site for any AE (i.e., 
erythema, edema, pruritus, bruising) that occurs at the site at the time of the event. 
 Alcohol and Caffeine 
Subjects will abstain from alcohol and caffeine-containing products (including 
decaffeinated coffee), from 2 days prior to the Baseline visit, during both Crossover 
Periods and the washout period and until completion of procedures in Crossover 
Period 2.  Subjects will undergo an alcohol breath test at each CRU admission. 
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.  AEs will be 
assessed continuously through the last study visit unless the nature of the AE or 
SAE requires continued monitoring.  All AEs are recorded as mild, moderate or 
severe, and as Not Related, Possibly Related, Probably Related, or Definitely 
Related to the Study Treatment.  A photograph will be taken of the IV and SC 
injection site for any AE (i.e., erythema, edema, pruritus, bruising) that occurs at the 
site at the time of the event.   
 Definition of an Adverse Event 
An Adverse Event (AE) is any untoward medical occurrence associated with the use 
of a Study Treatment or Study Drug (refer Section 3.1.1 for study treatment 
definitions) in humans, whether considered related to the Study Treatment. An 
adverse event (also referred to as an adverse experience) can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a Study Treatment and 
does not imply any judgment about causality.  An adverse event can arise with any 
use of the Study Treatment (e.g., off-label use, use in combination with another 
drug) and with any route of administration, formulation, or dose, including an 
overdose. 
A “pre-existing” condition is one that is present prior to administration of study 
treatment and is reported as part of the Subject’s medical history.  Pre-existing 
conditions should be reported as AEs only if the frequency, intensity, or character of 
the pre-existing condition worsens during the study. 
Laboratory or functional test abnormalities generally are not considered AEs unless 
they are associated with clinical signs or symptoms or require medical intervention. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 40 of 56 
A laboratory abnormality (e.g., a clinically significant change detected on clinical 
chemistry, hematology, urinalysis) or functional test abnormality (e.g., a clinically 
significant change detected on ECG, pulse oximetry, or spirometry) that is 
independent from a known underlying medical condition and that requires medical or 
surgical intervention, or leads to  treatment interruption or discontinuation, must be 
considered an AE. 
All AEs judged to be clinically significant, including clinically significant laboratory 
results, ECG and functional test abnormalities, will be followed until resolution or 
return to baseline or until no further improvement is expected. 
An AE 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 treatment placement and/or drug 
administration even though it may have been present prior to the start of the 
study. 
• Continuous persistent disease or symptoms present at baseline that worsen 
following the start of the study. 
An AE 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. 
• Pre-existing diseases or conditions present or detected at the start of the study 
that do not worsen. 
• 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. 
 Definition of an Unexpected Adverse Event 
An adverse event is considered “unexpected” if it is not listed in the investigator 
brochure, product labeling or is not listed at the specificity or severity that has been 
observed. 
 Definition of a Serious Adverse Event 
An SAE is any AE occurring at any dose that results in any of the following 
outcomes: 
a. Death. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 41 of 56 
b. A life-threatening AE. 
• NOTE: Life-threatening means that the Subject was, in the view of the 
Investigator, at immediate risk of death from the event as it occurred. 
This definition does not include an event that, had it occurred in a more 
severe form, might have caused death. 
c. Inpatient hospitalization or prolongation of existing hospitalization. 
• NOTE: Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization, the event is an SAE. 
• NOTE: “Inpatient” hospitalization means the Subject 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 disability/incapacity. 
• NOTE: The term disability means a substantial disruption of a person’s 
ability to conduct normal life functions.  This definition is not intended 
to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
accidental trauma (ie, 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 Subject who received drug. 
f. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered an SAE when, based upon 
appropriate medical judgment, they may jeopardize the Subject and may 
require medical or surgical intervention to prevent one of the outcomes listed 
in this definition. 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 Subject 
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. 
 Severity of Adverse Events and Serious Adverse Events 
Severity (mild, moderate, or severe) of each AE/SAE must be assessed by the 
Investigator or designee.  The following criteria should be considered when 
assessing severity: 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 42 of 56 
  Outcome of Adverse Events and Serious Adverse Events 
• Not Recovered/Not Resolved:  One of the possible results of an adverse 
event outcome that indicates that the event has not improved or recuperated.   
• Recovered/Resolved:  One of the possible results of an adverse event 
outcome that indicates that the event has improved or recuperated.  
• Recovered/Resolved with Sequelae:  One of the possible results of an 
adverse event outcome where the Subject recuperated but retained 
pathological conditions resulting from the prior disease or injury.  
• Recovering/Resolving:  One of the possible results of an adverse event 
outcome that indicates that the event is improving.  
• Unknown:  Not known, not observed, not recorded, or refused. 
• Fatal:  The termination of life as a result of an adverse event 
 Assessment of Relatedness to Study Treatment 
The Investigator will assess each AE and SAE for causality based on their best 
medical judgment, the observed symptoms associated with the event, and the 
available information on the study treatment.  The relatedness guidance provided 
below can be used to assist in determining the relationship of the study treatment to 
the AE or SAE.  However, it is ultimately the investigator’s responsibility to determine 
the relationship based on their best medical judgment, knowledge, and experience. 
 
• Not Related:  Based upon available information regarding Subject history, 
disease process, relationship of adverse event to dosing and drug 
pharmacology, there is no reasonable relationship between the study 
treatment and the adverse event. 
• Possibly Related:  Relationship exists between the adverse event and study 
treatment, when the adverse event follows a reasonable sequence from the 
time of the study treatment administration, but could also have been produced 
by the Subject’s clinical state or by other drugs administered to the patient. 
• Probably Related:  Relationship exists between the adverse event and the 
study treatment when the adverse event follows a reasonable sequence from 
the time of the study treatment administration, follows a known response 
• Mild 
The symptom is barely noticeable to the Subject and does 
not influence performance or functioning.   
• Moderate 
The symptom is of sufficient severity to make the Subject 
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. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 43 of 56 
pattern of the drug class, is confirmed by improvement on stopping the study 
treatment and the study treatment is the most likely of all causes. 
• Definitely Related:  Relationship exists between the adverse event and the 
study treatment when the adverse event follows a reasonable sequence from 
the time of the study treatment administration, follows a known response 
pattern of the drug class, is confirmed by improvement on stopping the study 
treatment and no other reasonable cause exists. 
 Method, Frequency, and Time Period for Detecting Adverse 
Events and Serious Adverse Events 
At appropriate intervals, Subjects should be assessed for AEs and SAEs as in 
Section 6.2.  
7.7.1.   
Timeframes for Reporting Serious Adverse Events 
Prompt notification of the sponsor regarding SAEs is essential so that ethical and 
regulatory responsibilities and legal obligations can be satisfied.  The Investigator 
must report SAEs according to the following time frames:    
• Initial notification of all SAEs based on the available information must be 
provided to the sponsor or designee within 24 hours of the investigational site 
learning of the event.  (Initial notification within 24 hours of Death and life-
threatening events is extremely important).  
o Follow-up information when available must be sent to the sponsor 
or designee within 48 hours of receipt of the information by the 
investigational site.  
7.7.2.   
Serious Adverse Event Information to Report 
At a minimum, SAE reports must contain the Subject ID, the serious adverse event 
term, onset date, relationship to study treatment, and a brief narrative of the event. 
Please note that relationship to study treatment/causality is very important and 
must be included in the initial report as it may impact expedited regulatory reporting 
requirements for the event. 
Copies of medical records will be requested.  However, it is not acceptable for the 
Investigator to send photocopies of the Subject’s medical records in lieu of 
completion of the appropriate AE/SAE pages.  For medical records submitted, all 
Subject personal identifiers must be completely and thoroughly redacted prior to 
submission. 
7.7.3.   
Clinical Laboratory Abnormalities and Other Abnormal Assessments 
as Adverse Events and Serious Adverse Events 
The Investigator should exercise his or her medical and scientific judgment in 
deciding whether an abnormal laboratory finding, or other abnormal assessment is 
clinically significant. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 44 of 56 
Abnormal laboratory findings (e.g., clinical chemistry, hematology, and urinalysis) or 
other abnormal assessments (e.g., vital signs) that are judged by the Investigator as 
clinically significant must be recorded as AEs or SAEs if they meet the definition of 
an adverse event.  Clinically significant abnormal laboratory findings or other 
abnormal assessments that are detected after study treatment administration or that 
are present before study treatment administration but worsen after study treatment 
administration should be assessed for AE criteria. 
7.7.4.   
Documenting Adverse Events and Serious Adverse Events 
All adverse events, including SAEs that occur after dosing of study treatment must 
be documented in the Subject's medical records and on the CRF.   
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 AE and/or SAE term. 
A photograph will be taken of the IV and SC injection site for any AE (i.e., erythema, 
edema, pruritus, bruising) that occurs at the site at the time of the event.   
7.7.5.   
Regulatory Ethics and Reporting Requirements 
The Investigator must comply with the applicable local regulatory requirements 
related to the reporting of SAEs to the IRB. 
7.7.6.   
Follow-up of Adverse Events and Serious Adverse Events 
All AEs and SAEs documented at a previous visit/contact that are designated as 
ongoing will be reviewed at subsequent visits/contacts.  AEs and SAEs will be 
followed until the last study visit unless the nature of the AE or SAE requires 
continued monitoring.  If a Subject 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 scPharmaceuticals 
or designee.  New or updated information will be recorded on the originally 
completed SAE Report Form with all changes electronically signed/dated by the 
Investigator or designee.   
7.7.7.   
Post-study Adverse Events and Serious Adverse Events 
Should the Investigator learn of an AE or SAE occurring within 30 days after a 
Subject completes the study, the event should be reported if it is considered related  
to study treatment.     
7.7.8.   
Adverse Events and Serious Adverse Events during the Washout 
and Follow-up Period 
If AEs emerge during the washout or Follow-up period, the causal relationship will be 
assessed in relation to the study treatment administered in the time preceding the 
washout or Follow-up period. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 45 of 56 
7.7.9.   
Medical Monitor 
SAEs and other medical matters can be discussed with the Medical Monitor.   
8.   
STATISTICS 
 Determination of Sample Size 
In one study, the average coefficient of variation for furosemide AUCinf following a 20 
mg dose by the intravenous, oral, and sublingual routes of administration were 50%, 
25%, and 33%, respectively (Haegeli, et al. 2007).  In another study, the coefficient 
of variation for AUCinf following 2-40 mg intravenous doses 2-hours apart was 31.6% 
and 30.6% for an 80 mg, 5-hour subcutaneous infusion (Sica DA, et al. 2018).     
Assuming an intra-subject variability is approximately ½ of total variability for the 
primary pharmacokinetic parameter AUCinf and the test reference would fall within 
95% to 105% at a significance level of 0.05, a minimum sample size of 18 subjects 
would be required to establish bioequivalence between test and reference products 
(defined as 90% CI for AUCinf Geometric mean ratio SC injection to IV injection of 
furosemide within 80-125% interval) with a priori statistical power of at least 90%.  
21 subjects will be enrolled to ensure 18 subjects complete the study through the 
Follow-up Phase. 
 Analysis Populations 
Three analysis populations will be defined as follows: 
• PK Population will include all randomized subjects who receive full 80 mg dose 
of furosemide study drug AND have sufficient samples collected for estimation of 
pharmacokinetic parameters. 
• Bioavailability Population will include all subjects in the PK population who 
have a sufficient number of samples collected for estimation of pharmacokinetic 
parameters after receiving BOTH IV furosemide and SC SCP-111. 
• Safety Population will include all randomized subjects who received at least 
1 dose of either study drug and provided at least 1 post-baseline safety 
assessment. 
 Baseline Characteristics and Subject Disposition 
Overall Baseline and demographic data will be summarized using descriptive 
statistics.  Subject disposition (e.g., the number of subjects enrolled, completed, and 
discontinued) will be summarized and medical history data will be listed.   
 Pharmacokinetic and Statistical Analysis 
Pharmacokinetic parameters will be estimated using noncompartmental methods.  
Compartmental modeling of the pharmacokinetic data may be conducted. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 46 of 56 
Furosemide concentrations will be summarized using descriptive statistics (including 
N, mean, standard deviation (SD), coefficient of variation (CV%), median, minimum, 
and maximum) for each treatment.  
The following PK parameters in table below will be estimated by noncompartmental 
methods from plasma samples.  Actual elapsed time from dosing will be used to 
estimate all individual PK 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, 
for SCP-111 
V 
Systemic volume of distribution, terminal phase, 
for IV furosemide 
CL/F 
Apparent systemic clearance for SCP-111 
CL 
Systemic clearance for IV furosemide 
F 
Bioavailability ([AUCinf / Dose SC SCP-111] / 
[AUCinf / Dose IV furosemide]) 
 
Derived plasma PK descriptive statistics will be tabulated by dosing group and 
summary statistics.   Descriptive statistics for PK parameters (Cmax, Tmax, AUClast, 
AUCinf, λz, t½, V, Vz/F, CL and CL/F) will include the arithmetic and geometric mean 
(for Cmax, AUClast, and AUCinf, only), CV%, SD of the arithmetic mean, median, 
minimum, maximum, and N. 
Bioavailability of SC SCP-111 will be determined by the logarithmic transformation of 
the geometric mean ratios of the SC SCP-111 to IV furosemide AUClast and AUCinf 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 47 of 56 
and 90% Confidence Intervals will be determined and should be within 80% and 
125% to establish bioequivalence. 
 Pharmacodynamic Analysis 
Total urine output, total urinary sodium excretion and total urinary potassium 
excretion from times 0-6, 0-8 and 0-12 hours will be tabulated and compared using 
descriptive statistical analysis stratified by treatment group. 
 Safety and Tolerability Analysis 
Adverse events, clinical laboratory assessments, blood pressure and heart rate will 
be summarized with descriptive statistics.  
Injection site pain assessments will be conducted as described in 6.2.2.7.  All 
findings will be tabulated and assessed using descriptive statistical analysis stratified 
by treatment group; incidence rates will also be analyzed and reported in the final 
clinical study report. 
9.   
RESPONSIBILITIES 
 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” (as amended in Edinburgh, Tokyo, Venice, 
Hong Kong, and South Africa), 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 Subject. For studies conducted under a United States IND, 
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, 1998, and 21 CFR, part 56, 1998, are adhered to.  
9.1.2.   
Institutional Review Board and Independent Ethics Committee 
Approval 
This protocol and any accompanying material to be provided to the Subject (such as 
advertisements, Subject information sheets, or descriptions of the study used to 
obtain informed consent) will be submitted, by the Investigator, to an IRB [or] EC.  
Approval from the IRB/EC must be obtained before starting the study and 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 the protocol must also be submitted to the 
IRB/EC for approval prior to implementation. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 48 of 56 
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 Subject and the 
person obtaining consent. A copy of the signed consent form will be provided to the 
Subject. 
9.1.4.   
Confidentiality 
All information about the nature of the proposed investigation provided by the 
Sponsor or study monitor to the Principal Investigator (with the exception of 
information required by law or regulations to be disclosed to the IRB, the Subject, or 
the appropriate regulatory authority) must be kept in confidence by the Principal 
Investigator. 
The Investigator must assure that Subjects’ anonymity will be strictly maintained and 
that their identities are protected from unauthorized parties.  Only Subject 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 Subject log showing codes and, 
names, for all enrolled in the trial. 
9.1.5.   
Compensation, Insurance and Indemnity 
Information regarding compensation, insurance, and indemnity is addressed in the 
Clinical Trial Research Agreement. 
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 including 
(although not limited to) the following: (1) Investigator’s study file, and (2) Subject 
clinical source documents. 
The Investigator’s study file will contain the protocol/amendments, IRB/EC approval, 
informed consent, drug accountability records, staff curriculum vitae, medical 
licenses as applicable, financial disclosure forms, local laboratory documentation, 
screening and enrollment log, and other appropriate documents and 
correspondence. 
Subject clinical source documents would include (although is not limited to) the 
following: Subject hospital/clinic records, physician’s and nurse’s notes, laboratory 
reports, worksheets, consultant letters, etc.   

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 49 of 56 
All clinical study documents must be retained by the Investigator until the number of 
years specified in the clinical trial agreement.  The Investigator must notify 
scPharmaceuticals 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 Subject, appropriate copies 
should be made for storage outside of the site. 
9.1.7.   
Case Report Forms 
For each Subject who signs informed consent, a CRF must be completed and 
signed (or electronically signed if eCRF) by the principal Investigator or sub-
Investigator within a reasonable time period after data collection.  This also applies 
to records for those Subjects who fail to complete the study.  If a Subject withdraws 
from the study, the reason must be noted on the CRF.  If a Subject is withdrawn 
from the study because of a treatment-limiting AE, thorough efforts should be made 
to clearly document the outcome. 
9.1.8.   
Protocol Deviations 
Neither the Investigator nor the Sponsor is permitted to intentionally deviate from the 
protocol without proper notification to the FDA or to other relevant regulatory 
authorities in the form of a protocol amendment.  Protocol deviations that occur 
during the study must be documented. 
The Investigator will not alter this study protocol without obtaining the written 
agreement from the sponsor.  Once the study has started, amendments should be 
made only in exceptional cases.  The changes then become part of the study 
protocol and will require re-approval of the Institutional Review Board 
(IRB/Independent Ethics Committee (IEC). 
9.1.9.   
Disclosure of Data 
The Principal Investigator agrees by his/her participation that the results of this study 
may be used for submission to national and/or international registration and 
supervising authorities.  If required, these authorities will be provided with the name 
of the Principal Investigator, their addresses, qualifications and extent of 
involvement.  It is understood that the Principal Investigator is required to provide 
scPharmaceuticals with all study data, complete reports, and access to all study 
records.  
Data generated by this study must be available for inspection by the US FDA and 
other regulatory authorities, by scPharmaceuticals and its designees, and the IRB as 
appropriate.  At a Subject’s request, medical information may be given to his or her 
personal physician or other appropriate medical personnel responsible for his or her 
welfare.  Subject medical information obtained during this study is confidential and 
disclosure to third parties other than those noted above is prohibited. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 50 of 56 
9.1.10.   
Financial Disclosure 
The US FDA Financial Disclosure by Clinical Investigators (21 CFR 54) regulations 
require Sponsors to obtain certain financial information from Investigators 
participating in covered clinical studies; each Principal Investigator and Sub-
investigator is required to provide the required financial information and to promptly 
update scPharmaceuticals with any relevant changes to their financial information 
throughout the course of the clinical study and for up to 1 year after its completion. 
This rule applies to all Principal Investigators and Sub-investigators participating in 
covered clinical studies to be submitted to the FDA in support of an application for 
market approval. 
9.1.11.   
Study Completion 
scPharmaceuticals requires the following data and materials before a study can be 
considered complete or terminated: 
1. All clinical data and special test results from screening through the end of the 
study. 
2. eCRFs properly completed by appropriate study personnel and signed and dated 
by the Principal Investigator. 
3. Complete Product Accountability records. 
4. Copies of protocol amendments and IRB approval/notification/closure if 
appropriate. 
9.1.12.   
Drug and Device Product Accountability 
The Investigator or designee (pharmacist) is responsible for ensuring adequate 
accountability of all used and unused study treatment.  This includes 
acknowledgment of receipt of each shipment of study treatment (quantity and 
condition) and Subject dispensing records and return.  Dispensing records will 
document quantities received and quantities dispensed to Subjects, including lot 
number, date dispensed, Subject identifier number and the initials of the person 
dispensing the medication.   
At the end of the study, following final product reconciliation by the monitor, the 
Sponsor will instruct the study site the handling of all used and unused study drugs 
and materials.  
9.1.13.   
Inspections 
The Investigator will provide access to source documents and all study records for 
this trial to appropriately qualified personnel from scPharmaceuticals or its 
representatives, and to regulatory authority inspectors. 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 51 of 56 
 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 
treatments, CRF, logs, etc.  The Sponsor or designee 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 
Subjects, will be made by Sponsor-initiated amendment.  IRB approval must be 
obtained before changes can be implemented. 
 Joint Investigator and Sponsor Responsibilities 
9.3.1.   
Access to Information for Monitoring 
In accordance with International Conference on Harmonization Good Clinical 
Practice (ICH-GCP) guidelines, the study monitor must have direct access to the 
Investigator’s source documentation in order to verify the data recorded in the CRFs 
for consistency. 
The monitor is responsible for routine review of the CRFs at regular intervals 
throughout the study, to verify adherence to the protocol, and the completeness, 
consistency and accuracy of the data being entered.  The monitor should have 
access to any Subject records needed to verify the entries on the CRFs. The 
Investigator agrees to cooperate with the monitor to ensure that any problems 
detected during these monitoring visits 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), IRBs and IECs.  In terminating 
the study, the Sponsor and the Investigator will assure that adequate consideration 
is given to the protection of the Subjects’ interests. 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 52 of 56 
10.   REFERENCES 
 
Haegeli, Laurent; Brunner-La Rocca, Hans Peter; Wenk, Markus; Pfisterer, Matthias; 
Drewe, Jurgen; Krahenbuhl, Stephan (2007): Sublingual administration of furosemide: 
new application of an old drug. In British journal of clinical pharmacology 64 (6), pp. 
804–809. DOI: 10.1111/j.1365-2125.2007.03035.x. 
 
Sica, D. A., Muntendam, P., Myers, R. L., Ter Maaten, J. M., Sale, M. E., de Boer, R. A., 
& Pitt, B. (2018). Subcutaneous Furosemide in Heart Failure: Pharmacokinetic 
Characteristics of a Newly Buffered Solution. JACC Basic Transl Sci, 3(1), 25-34. 
doi:10.1016/j.jacbts.2017.10.001  
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
Confidential  
 
Page 53 of 56 
11.   APPENDICES 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
 
 
 
 
Confidential  
 
Page 54 of 56 
 Appendix 1.  Time and Event Schedule 
 
 
Screening 
Phase  
Day –14 to –3 
 
Baseline Phase 
Assessment 
Day 0 
 
Treatment Phase 
 
Follow-Up Phase 
 
Crossover Period 1 
Washout 
Period 
 (3 + 1 
Days)  
Pre-Period 2 
Assessment 
Day 3 ± 1 
Crossover Period 2 
 
 
Day 0 
Day 3 ± 1 
 
Day  5 ± 114  
Pre-dose 
Dosing 
Post-dose  
Pre-dose 
Dosing 
Post-Dose  
 
 
Sign Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of Eligibility 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Med History & Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Complete Physical Examination1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Limited Physical Examination1 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
 
Screening Labs for Eligibility2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight  
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
Height (Screening only)3   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Alcohol Test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol Breath Test 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Temperature 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Blood Pressure and Heart Rate 
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
Clinical Laboratory Tests4 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
 
Urine Drug Screen 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Serum Pregnancy Test5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test5 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
12-lead ECG  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to CRU 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Randomization to Treatment Sequence 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Study Treatment Administration6 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
Plasma for Pharmacokinetics7 
 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
 
Void Bladder8 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
Urine Collection8 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Food and Fluid intake9 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Assessment of Injection Site Pain10 
 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
 
Photograph of Injection Site11 
 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
 
Adverse Events12 
 
 
 
 
 
 
X 
X 
X 
X 
 
X 
 
X 
Prior Medication Assessment 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
 
 
 
 
 
X 
X 
X 
 
 
X 
X 
Schedule Next Study Visit 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
 
 
 
 
Confidential  
 
Page 55 of 56 
 
 
Discharge from CRU13 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
1 A complete/full physical examination should be performed at Screening and Follow-up.  On Days 0 and 3 a limited physical examination may be performed consisting of assessments of the skin, 
lungs/chest, heart, extremities and abdomen and any other abnormalities detected during the study period.  Post-dose physical examination on Day 0 and Day 3 should be performed 12 hours after the 
study drug is administered. 
2 Screening labs include sodium, potassium, calcium, chloride, magnesium, carbon dioxide, blood urea nitrogen (BUN), serum creatinine, glucose, hemoglobin, hematocrit and blood alcohol. 
3 Height and weight collected for calculation of BMI.  Height collected at Screening only. 
4 Clinical labs include sodium, potassium, calcium, chloride, magnesium, carbon dioxide, blood urea nitrogen (BUN), serum creatinine, glucose, hemoglobin, and hematocrit. Post-dose clinical labs on Day 
0 and Day 3 should be performed 12 hours after the study drug is administered.  
5  Pregnancy test for females of child-bearing potential. 
6 Intravenous furosemide is administered as 40 mg over 1 to 2 minutes followed by a second dose of 40 mg over 1 to 2 minutes, 2 hours apart by IV injection. SCP-111 is administered as a single, 80-mg 
dose by subcutaneous injection via an autoinjector.  
7 Pharmacokinetic sampling per instructions in 6.2.2.6 
8 Subjects will be instructed to void immediately before dosing (pre-dose urine) and this sample will be discarded.  Urine from spontaneous voids during post-dose phases will be collected and pooled, 
measured, recorded for time periods (0-1), (1-2), (2-3), (3-4), (4-5), (5-6), (6-7), (7-8), (8-10) and (10-12) hours after initiation of dosing.  Urine from each collection period must be collected in a single 
vessel and refrigerated until the end of the collection period.  Urinary sodium and urinary potassium concentrations for each collection interval over the 12-hour urine collection period will be analyzed by 
standard lab biochemistry test. Total urine output volume will be documented for each collection period. 
9 Low sodium snacks and meals as well as water, juice, and caffeine free beverages will be allowed ad libitum, and the amount measured and recorded over the post-dose phases. Subjects will be 
monitored to ensure a minimum of 100 mL of fluid consumed for every 300 mL of urine output.  
10 Assessment of injection site pain for IV administration performed pre-dose after IV needle placement, immediately after 1st dose and 15 and 30 minutes after 1st dose, immediately after 2nd dose and 15 
and 30 minutes and 4 and 10 hours after the 2nd dose.  For SC administration, injection site pain conducted pre-dose, immediately after dose and 15 and 30 minutes and 6 and 12 hours after dose. 
11 Photographs of the injection site will be performed prior to the IV and SC injection (baseline) and 4 hours post IV administration or 6 hours post SC administration.  In addition, a photograph will be 
taken of the IV and SC injection site for any AE (i.e., erythema, edema, pruritus, bruising) that occurs at the site at the time of the event.    
12 AEs will be assessed continuously during administration of study drug and during the post-dose phase. AEs and SAEs will be followed until resolution if the nature of the AE or SAE requires continued 
monitoring at the discretion of the Investigator. 
13 Discharge from the CRU after the last assessment per protocol if safety parameters acceptable to Investigator. 
14 Follow-up should occur 24-48 hours after discharge from CRU for Crossover Period 2. 
 
 
 

scPharmaceuticals, Inc. 
SCP-111 PK/PD Study 
Protocol Number: scP-04-001 
 
 
 
 
 
 
 
 
Confidential  
 
Page 56 of 56 
 Appendix 2.  Assessment of Injection Site Pain 
 
 
INJECTION SITE PAIN ASSESSMENT SCALE 
 
 
 
 
 
Verbally indicate the number on the Numeric Rating Scale that best 
represents the intensity of pain at or around the injection site NOW, with 
0 being None and 10 being the worst possible pain.