Effect Camostat for Kidney Protection in Chronic Kidney Disease
Phase: PHASE2
Conditions: Chronic Kidney Disease(CKD)
Sponsor: Odense University Hospital

CamKid 
 
EUCT: 2023-508516-34-00 
 
Clinical Trial Protocol 
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Date: 07.11.2024 
 
 
 
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Clinical Trial Protocol 
 
 
 
CamKid 
Effect of Camostat for Kidney Protection in 
Chronic Kidney Disease 
 
 
 
 
 
 
 
 
Sponsor: 
Claus Bistrup 
Department of Nephrology 
Odense University Hospital 
 
 
 
 
EU CT no.: 2023-508516-34-00 
 
 
 
Version: 2.1 
Date: 07.11.2024 

CamKid 
 
EUCT: 2023-508516-34-00 
 
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Date: 07.11.2024 
 
 
 
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1 TABLE OF CONTENTS 
1 
Table of Contents ....................................................................................................................... 2 
1 
General Information .................................................................................................................. 6 
1.1 
Title ...................................................................................................................................... 6 
1.2 
Sponsor......................................................................... Fejl! Bogmærke er ikke defineret. 
1.3 
Principal Investigator ................................................... Fejl! Bogmærke er ikke defineret. 
1.4 
Investigator................................................................... Fejl! Bogmærke er ikke defineret. 
1.5 
Collaborators ................................................................ Fejl! Bogmærke er ikke defineret. 
1.6 
Study Monitor .............................................................. Fejl! Bogmærke er ikke defineret. 
1.7 
Pharmacy ...................................................................... Fejl! Bogmærke er ikke defineret. 
1.8 
Guidelines .................................................................... Fejl! Bogmærke er ikke defineret. 
1.9 
Time Plan ............................................................................................................................. 6 
1.10 
Signature Page.............................................................. Fejl! Bogmærke er ikke defineret. 
1.11 
List of Abbreviations ........................................................................................................... 7 
2 
Background Information ........................................................................................................... 8 
2.1 
Background .......................................................................................................................... 8 
2.2 
Aim....................................................................................................................................... 9 
2.3 
Hypothesis ............................................................................................................................ 9 
2.4 
Treatment ........................................................................................................................... 10 
2.4.1 
Pharmacokinetics (PK) of Camostat Mesilate (CM) ................................................. 10 
2.4.2 
Safety Profile for Camostat Mesilate ......................................................................... 11 
2.4.3 
Potential Benefits ....................................................................................................... 12 
2.4.4 
Overall Benefit/Risk Conclusion ............................................................................... 12 
2.4.5 
Rationale for dose selection ....................................................................................... 13 
3 
Study purpose and objectives.................................................................................................. 13 
3.1 
Purpose ............................................................................................................................... 13 
3.2 
Primary objective ............................................................................................................... 13 
3.3 
Secondary objectives.......................................................................................................... 13 
4 
Study design .............................................................................................................................. 13 

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4.1 
Endpoints ........................................................................................................................... 13 
4.2 
Design ................................................................................................................................ 14 
4.3 
Intervention ........................................................................................................................ 14 
4.4 
Minimizing bias ................................................................................................................. 15 
4.5 
Recruitment ........................................................................................................................ 15 
4.6 
Screening ............................................................................................................................ 15 
4.7 
Duration/Follow-up ............................................................................................................ 16 
4.8 
End of study definition ....................................................................................................... 16 
4.9 
Discontinuation of Study ................................................................................................... 16 
4.10 
Source data ......................................................................................................................... 16 
5 
Selection and withdrawal of subjects ..................................................................................... 16 
5.1 
Patients ............................................................................................................................... 16 
5.1.1 
Inclusion criteria ........................................................................................................ 16 
5.1.2 
Exclusion criteria ....................................................................................................... 17 
5.2 
Healthy controls ................................................................................................................. 17 
5.2.1 
Inclusion criteria ........................................................................................................ 17 
5.2.2 
Exclusion criteria ....................................................................................................... 17 
5.3 
Screen failure ..................................................................................................................... 18 
5.4 
Subject withdrawal criteria ................................................................................................ 18 
5.4.1 
Subject Withdrawal from Study ................................................................................. 18 
5.4.2 
Subject Withdrawal from the Investigational Medicinal Product(s) (IMPs) ............. 18 
6 
Treatment of Subjects .............................................................................................................. 19 
6.1 
The Investigational Medicinal Product (IMP) - Camostat Mesilate .................................. 19 
6.2 
IMP dosing modifications .................................................................................................. 19 
6.3 
Drug Supplies, Packaging and Labelling ........................................................................... 19 
6.3.1 
Camostat Mesilate ...................................................................................................... 19 
6.4 
Drug Storage and Accountability ....................................................................................... 20 
6.5 
Drug administration ........................................................................................................... 21 
6.6 
Management of overdose ................................................................................................... 21 
6.7 
Concomitant Medications .................................................................................................. 21 
6.8 
Post-Study Care.................................................................................................................. 21 
7 
Assessments and procedures ................................................................................................... 21 

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For a detailed specification of study endpoints refer to Section 4.1 (Endpoints). ...................... 21 
7.1 
Primary Endpoint ............................................................................................................... 21 
7.2 
Secondary Endpoints.......................................................................................................... 22 
8 
Assessment of Safety ................................................................................................................ 22 
8.1 
Adverse Events (AE) ......................................................................................................... 23 
8.2 
Serious Adverse Events (SAE) and Serious Unexpected Suspected Adverse Events 
(SUSAR): ....................................................................................................................................... 23 
8.2.1 
Pregnancies ................................................................................................................ 24 
8.3 
Reporting of Adverse Events ............................................................................................. 24 
8.4 
Reporting of Serious Adverse Events (SAE) ..................................................................... 24 
8.5 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSAR) ..................... 24 
8.6 
Annual Safety Report ......................................................................................................... 24 
9 
Statistics .................................................................................................................................... 25 
9.1 
Statistical Methods ............................................................................................................. 25 
9.2 
Interim analysis .................................................................................................................. 25 
9.3 
Sample Size ........................................................................................................................ 25 
9.4 
Trial power ......................................................................................................................... 25 
9.5 
Level of Significance ......................................................................................................... 25 
9.6 
Reporting Deviations from the Statistical Plan .................................................................. 25 
9.7 
Selection of Subjects for Analyses..................................................................................... 25 
9.8 
End of study ....................................................................................................................... 25 
10 
Direct Access to Source Data/Documents .......................................................................... 26 
11 
Quality Control and Quality assurance ............................................................................. 26 
12 
Ethics ..................................................................................................................................... 26 
12.1 
Ethical Conduct of the Study ............................................................................................. 26 
12.2 
Informed Consent ............................................................................................................... 26 
12.3 
Access to data..................................................................................................................... 26 
12.4 
Ethical Considerations ....................................................................................................... 27 
13 
Data Handling and Record Keeping .................................................................................. 27 

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13.1 
Trial Master File and Source Data ..................................................................................... 27 
13.2 
Use of Case Report Forms (CRF) ...................................................................................... 27 
13.3 
Data handling ..................................................................................................................... 28 
13.4 
Computer Systems ............................................................................................................. 28 
13.5 
Data Entry .......................................................................................................................... 28 
13.6 
Data Validation .................................................................................................................. 28 
13.7 
Biological material ............................................................................................................. 28 
13.8 
Research biobank ............................................................................................................... 28 
14 
Financing and Insurance ..................................................................................................... 29 
15 
Publication Policy ................................................................................................................. 29 
16 
References ............................................................................................................................. 29 
 
 
 

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1 GENERAL INFORMATION 
1.1 
Title 
Protocol Title:  
Effect Camostat for Kidney Protection in Chronic Kidney Disease  
Short Title:  
CamKid 
Danish Title: 
 Camostat til beskyttelse af nyrefunktionen hos patienter med kronisk 
nyresygdom 
 
1.2 
Time Plan 
 
Month 
Year 
Protocol finished 
Approval from CTIS 
Approval from GCP-unit 
Inclusion of participants 
Completed inclusion of participants 
End of study 
Data analysis completed 
Manus completed 
Publication 
November  
February 
April 
August 
September 
October 
October 
February 
April 
2023 
2024 
2024 
2024 
2025 
2025 
2026 
2027 
2027 
 
 
 
 
 
 
 
 
 
 

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1.3 
List of Abbreviations 
 
ACEi 
Angiotensin Converting Enzyme inhibitor 
ARB 
Angiotensin II-receptor blocker 
CKD 
Chronic didney disease 
CM 
Camostat Mesilate 
eGFR 
Estimated Glomerular Filtration Rate 
ENaC 
Epithelial sodium channel 
IMP 
Investigated Medical Product 
NSAID 
Non-Steroidal Anti-Inflammatory Drugs 
NYHA 
New York Heart Association 
PK 
Pharmacokinetics 
SLGT-2 
Sodium Glucose Co Transporter-2 
TIA 
Transient Ischemic Attack 
U-ACR 
Urine Albumin/Creatine Ratio 
U-hCG 
Urine Human Choriogonadotropin 
uPA 
Urokinase-type plasminogen activator 
 
 

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2 BACKGROUND INFORMATION 
2.1 
Background 
Chronic kidney disease (CKD) affects 10-15 % of the global population. Prevalence and mortality 
have remained stable through the latest three decades in contrast to conditions like cardiovascular 
disease and cancer where the decrease in mortality rate has been substantial [1]. CKD is associated 
with increased risk of hypertension, cardiovascular disease, metabolic bone disease, and premature 
death. As CKD progresses to end-stage kidney disease, expensive renal replacement therapies like 
dialysis or kidney transplantation are needed. Proteinuria is an important prognostic factor for CKD 
progression and cardiovascular morbidity and mortality. Reduction of proteinuria is associated with 
slower disease progression [2]. While there are currently limited treatment options available to slow 
down progression of CKD, including ACE inhibitors (ACEi), angiotensin II receptor blockers (ARB), 
and SGLT2 inhibitors, there is a need for improved treatment alternatives in the fields of CKD. 
Patients with CKD and proteinuria have expanded extracellular volume [3], increased salt-sensitivity 
of blood pressure and respond to dietary sodium restriction suggesting impaired sodium excretion 
[4]. We propose a causal relation between proteinuria and progression of CKD. The common 
mediator is aberrant filtration of serine protease most significantly plasmin but also kallikrein and 
prostasin. They have in common the ability to proteolytically activate both the epithelial sodium 
channel (ENaC) and complement system precursors also aberrantly filtered. This unifying concept 
accounts for sodium retention and for continuous inflammatory input by complement system 
activation [5,6]. We suggest that these apparent different mechanisms are promoted by a common 
denominator: aberrant serine protease activity in tubular fluid and that they therefore can be 
attenuated pharmacologically. Inhibition of soluble serine proteases is hypothesized to slow down 
CKD progression in patients with proteinuria. 
 
Camostat Mesilate (CM) (Foipan®, Ono Pharmaceuticals, Japan) is a well-established broad serine 
protease inhibitor in use for decades to treat chronic pancreatitis and postoperative reflux esophagitis 
in Japan [7]. Preclinical data indicate that CM suppresses the proteolytic activation of ENaC and 
decreases blood pressure, reduces proteinuria and improves renal injury markers [8-10]. We propose 
that CM will mitigate CKD progression, hypertension, and cardiovascular disease in CKD patients 
with proteinuria. 
 
Research conducted by applicant lab has identified is aberrant filtration of urokinase-type 
plasminogen activator (uPA) and plasminogen from plasma to urine in various diseases with 
albuminuria (preeclampsia, diabetes, hypertension and kidney transplant glomerulopathy) [8,9]. In 
tubular fluid, plasminogen is activated to plasmin, which subsequently activates ENaC proteolytically 
in the distal nephron, impairing sodium excretion and free water clearance [10-13]. Probably, 
contributing to hypertension since ENaC inhibition by Amiloride mobilizes excess sodium and water 
and lowers blood pressure in patients with diabetes and albuminuria [14,15]. Sets of proteases have 
been identified in urine in proteinuria and many derive from complement and coagulation cascades 
[16], such as kallikrein, plasmin, prostasin, urokinase, MASPs (proteases in the lectin pathway of the 
complement system). Plasmin is the most abundant protease in proteinuria [17]. Plasmin may activate 

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complement factors at sites of coagulation [18]. We propose that continuous activation of these 
proteases in tubular fluid promotes inflammation and kidney injury in proteinuria. 
Our in vitro data show that plasmin in urine promotes formation of the anaphylatoxins C3a and C5a, 
C3b and membrane attack complex (sTCC, MAC, measured as C5b-9; Isaksson and Palarasah et al.). 
Deletion of C3a receptor protects against kidney fibrosis in murine models [19,20]. Deletion of 
plasminogen protects mice from kidney fibrosis [21]. Taken together, inhibition of proteases from 
these cascades may interrupt detrimental intratubular complement pathways in the kidney. Various 
drugs have been developed showing reversible inhibitory effects on trypsin, plasmin, plasma-
kallikrein, and thrombin. CM is an orally bioavailable synthetic serine protease inhibitor. CM is a 
registered drug in Japan available since 1985 for treatment of pancreatitis and reflux esophagitis. 
Upon oral administration, CM and its active metabolite (GBPA) inhibits trypsin, kallikrein, thrombin 
and plasmin, and C1r and C1 esterases in the complement system. CM and GBPA circulate at 10-30 
ng/ml 2 hours after intake of 100 mg in humans [22].  
 
Published available data on Camostat leading to the hypotheses 
CM lowered proteinuria in 20 patients with proteinuria from various etiologies [23]; in patients with 
nephrotic syndrome [24] and in patients with diabetes and nephrotic proteinuria [25,26]. No renal 
adverse effects were reported. In preclinical studies, CM prevents podocyte injury and lowers 
proteinuria in rats with metabolic syndrome [27]. Furthermore, CM lowered renal tissue plasmin 
activity [28], and showed natriuretic and antiproteinuric effect [22]. CM is eliminated in the urine 
(89-95 %, Pubchem). The studies on proteinuria are from Japan, they are explorative, open label and 
small scale. To our knowledge, pharmacodynamic mechanistic hypothesis-driven studies have not 
been conducted in CKD patients. Many registered ongoing trials test the efficacy of CM in Covid-19 
disease. A Danish study pioneered this and reported no adverse renal or cardiovascular effects [29].  
 
2.2 
Aim 
The overall aim of the project is to mitigate progression of CKD of any course and lower 
cardiovascular morbidity and mortality in CKD patients with proteinuria by repurposing a known 
pharmaceutical. The specific objectives are to test whether Camostat Mesilate, a serine protease 
inhibitor, possess previously undiscovered renoprotective effects by inhibiting serine protease 
activity and suppressing complement activation within the renal tubules. 
 
This will be accomplished through an initial interventional pilot study that will serve as the foundation 
of a future long-term clinical interventional study. This preliminary study is designed as an 
exploratory, non-randomized, interventional, pharmacodynamic study in CKD patients with 
proteinuria and healthy controls, aiming to evaluate the effect of Camostat Mesilate in CKD patients 
with proteinuria and in healthy controls. 
 
2.3 
Hypothesis 
In patients with CKD and proteinuria on a fixed normal sodium intake, administration of Camostat 
Mesilate (200 mg x3/day for 4 days) will enhance fluid excretion, mobilize body water, reduce body 
weight and extracellular volume, and increase sodium excretion compared to healthy controls. 

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Secondary, Camostat Mesilate will inhibit urinary protease activity, prevent aberrant proteolytic 
activation of the ENaC gamma subunit and the formation of soluble C5b-9 in urine, consequently 
leading to a reduction in albuminuria. 
 
2.4 
Treatment 
CM is an orally bioavailable synthetic serine protease inhibitor. It has been a registered drug in Japan 
since 1985, primarily used for the treatment of pancreatitis and reflux esophagitis. Notably, CM is 
very well tolerated and has no known drug-drug interactions [31]. 
 
2.4.1 Pharmacokinetics (PK) of Camostat Mesilate (CM) 
Upon oral administration, CM rapidly undergoes hydrolysis in plasma to 4-(4-guanidinobenzoyl-oxy) 
phenylacetic acid (GBPA), which is further degraded into 4-guanidinobenzoic acid (GBA). CM and 
GBPA have similar biological activity, while GBA is inactive [30]. The absorption fraction after oral 
dosing has not been documented. 
The Japanese Summary of Product Characteristics (SmPC) [31] references a study involving five 
healthy, fasting adults who received a single oral dose of 200 mg CM. In this study, GBPA had a Tmax 
of 40 minutes, Cmax of 87.1 ng/mL, AUC 10.400 ng*min/mL and T½ of 100 minutes. Another study 
of four patients with complete gastrectomy given a single dose of 100 mg CM showed similar plasma 
concentration changes, including a Cmax of 30 ng/mL. 
In another study, four healthy Caucasian males received a single dose of 40 mg CM as an intravenous 
infusion over 12 hours [32]. The parent compound was undetectable in plasma, suggesting rapid 
degradation. PK parameters for the active metabolite, GBPA, included a Tmax of 300 minutes (after 
infusion start), Cmax of 89.4 ng/mL, Css of 83.6 ng/mL, AUC of 966 ng*h/mL, and T½ of 1.0 hour. 
In a study assessing pancreatic function, twelve healthy individuals (6 males and 6 females, median 
age 24.5 years) were administered 500 mg of CM four times daily for four weeks. Css for GBPA at 
the end of week 1-4 were 19600 ng/ml, 18600 ng/ml, 19000 ng/ml and 14400 ng/ml [33]. 
An ongoing phase 1/2 trial is evaluating PK in 18 subjects following single oral doses of 100mg, 200 
mg and 300 mg of CM, respectively [34], however this paper states that doses up to 900 mg daily has 
been used previously. Specific data has yet to be published.   
CM is primarily metabolized to GBPA and then to GBA by carboxylesterase and arylesterase [31]. 
Neither the parent compound nor its metabolites affect the activity of CYP1A2, CYP2C9, CYP2C19, 
CYP2D6 or CYP3A4. GBA is mainly renally excreted (>95%).   
 
Kidney function 
The primary metabolites of CM are primarily excreted through the kidneys, with GBA being the 
predominant one and to a much lesser extent GBPA. After a single oral administration of 200 mg CM 
to five healthy adults, most of these metabolites were excreted within 5-6 hours [31]. No PK studies 
have been identified that included patients with CKD. However, the TACTIC trial, aimed at studying 
the effect of CM on chronic pancreatitis in a Western population, excluded patients with CKD stage 
IV (eGFR < 30 ml/min/1.73m2) [34]. This suggests that previous studies may have documented the 
safety of CM in patients with milder degrees of renal impairment. 
 

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Interactions with other drugs 
No interactions with other drugs have been reported for CM, GBA, or GBPA. These compounds are 
not metabolized by cytochrome P450 enzymes (CYP). 
 
2.4.2 Safety Profile for Camostat Mesilate 
CM is a serine protease inhibitor that seems to modulate the activity of ENaC. In patients with CKD 
and proteinuria, ENaC is proteolytically activated by serine proteases aberrantly filtered to tubular 
fluid. CM suppresses this proteolytic activation of ENaC, leading to reduced blood pressure, 
decreased proteinuria, and attenuation of renal injury progression [22-28].  
 
According to the SmPC [31], CM is indicated for remission of acute symptoms of chronic pancreatitis 
(600 mg/day) and postoperative reflux esophagitis (300 mg/day). A total of 3.806 patients were 
evaluated in the Drug Use Investigation, and the following adverse reactions were reported: 
• Abnormal laboratory test results (1.3-1.8 %) 
• Hepatic function abnormalities (elevated AST and ALT - 0.3 %) 
• Rash (0.4 %) 
• Pruritus (0.2 %) 
• Nausea (0.1-0.3 %) 
• Abdominal discomfort (0.2 %) 
• Diarrhea (0.2 %) 
 
Clinically significant adverse reactions (incidences unknown, but rare): 
• Shock and anaphylactic symptoms (decreased blood pressure, dyspnea, pruritus) 
• Thrombocytopenia  
• Hepatic function disorder or jaundice 
• Hyperkaliemia 
 
Reported adverse effect are rare (less than 3%) and generally mild, including symptoms like pruritus, 
increased thirst and appetite and lightheadedness) [34]. 
 
A phase 1/2 study in the United States investigated the safety of CM as a treatment for chronic 
pancreatitis [34]. The phase 1 study examined the pharmacokinetics and safety CM doses of 100, 200 
and 300 mg doses and demonstrated safety in 18 subjects. The phase 2 study was a double-blind, 
randomized, parallel-group, dose-ranging study currently ongoing to further assess safety and 
efficacy of CM compared to placebo. As of May 2019, 63 out of 78 subjects have completed the 
study, with only few serious adverse events (SAEs) reported, none of which were directly linked to 
treatment [34]. 
 
Two case reports have emerged, one involving autoimmune hepatitis possibly triggered by drug-
induced liver injury related to CM treatment. Discontinuation of the drug did not result in complete 
remission, but low-dose corticosteroids effectively treated the liver function [35]. Another case study 

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reported eosinophilic pneumonia, likely caused by a 10-day treatment with CM. Eosinophil levels in 
the blood and infiltration into alveolar space improved upon cessation of the drug [36]. 
 
Relevant monitoring of treatment should be based on the knowledge about the reported clinically 
significant adverse reactions, which include hyperkaliemia, hepatic function disorder or jaundice, 
thrombocytopenia, eosinophilic pneumonia, and shock/anaphylactic symptoms. 
 
Safety in patients with reduced renal function or end-stage renal disease 
Human data regarding CM treatment and renal insufficiency are limited but generally reassuring. 
Three studies have been identified that address the safety of CM administration in patients with 
varying degrees of renal insufficiency: 
 
1. Onbe et al. (J Diabet Complications 1991) [24] studied eight patients with nephrotic syndrome 
and diabetic nephropathy who received 600 mg of CM daily for four weeks. The study 
demonstrated reduced proteinuria, with stable creatinine clearance throughout the study. 
2. Ikeda et al. (J Diabetes Complications 1999) [25] examined three patients with nephrotic 
syndrome and diabetic nephropathy who were given 600 mg of CM daily for four weeks. The 
study reported reduced proteinuria with no reported side effects. 
3. Matsubara et al. (Clin Nephrol 1989) [23] conducted a study involving 17 patients with heavy 
proteinuri due to various nephropathies who received 600 mg of CM daily for four weeks. 
The study observed a reduction in urine protein excretion from the second week onwad, with 
no changes in serum creatinine during the study. 
 
Collectively, these studies suggest the safety of CM administration in patients with varying degrees 
of renal insufficiency, with no evidence of harm to renal function or increased risk of adverse drug 
reactions. 
 
2.4.3 Potential Benefits 
Oral CM treatment is expected to significantly inhibit serine proteases and complement factors in 
tubular fluid in patients with CKD and proteinuria. This inhibition is anticipated to reduce salt and 
water retention and inflammation, ultimately slowing the progression of renal impairment and 
potentially improving cardiovascular outcomes in CKD patients. CM, although not on the European 
pharmaceutical market, has been used safely in Japan for decades. Repurposing CM for treatment of 
CKD patients represents a cost-effective and safe option compared to developing new medications. 
 
2.4.4 Overall Benefit/Risk Conclusion 
Currently, the available treatments to delay kidney disease progression include SGLT-2 inhibitors 
and ACEi/ARBs. CM is predicted to act additively by targeting a mechanism not addressed by 
ACEi/ARBs and SGLT-2 inhibitors. CM is expected to reduce proteinuria, reduce kidney tissue 
inflammation, and inhibit tubular complement activation by suppressing tubular serine protease 
activity. The primary risk of hyperkalemia, thrombocytopenia and hepatic functions abnormalities 
has been studied and appears manageable. 

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2.4.5 Rationale for dose selection 
The approved doses for CM are 100 mg three times daily for postoperative reflux esophagitis and 200 
mg three times daily for chronic pancreatitis symptoms.  
Some studies have employed much higher doses of CM without severe adverse effects, including 
nine patients with severe oral carcinomas who received up to 7.2 g daily for several months [37] and 
a study in healthy individuals using 2 g daily for four weeks [38]. 
 
Since there is limited data on CM use in patients with CKD, doses that are safe within the limits of 
the SmPC will be used. A dialy dose of 600 mg divided into three doses has been used in previous 
studies involving CKD patients. 
 
3 STUDY PURPOSE AND OBJECTIVES  
3.1 
Purpose 
The overall purpose of the study is to evaluate the potential benefits of Camostat Mesilate in CKD 
patients with proteinuria focusing on fluid balance, kidney injury markers, tubular protease activity 
and complement activation. 
 
3.2 
Primary objective 
• To evaluate salt and water excretion including total body water content and blood pressure.  
 
3.3 
Secondary objectives 
• To evaluate tubular serine protease activity and complement activation in patients CKD with 
proteinuria. 
• To evaluate whether proteolytic activation of ENaC plays a role in normal physiological 
regulation. 
 
4 STUDY DESIGN 
4.1 
Endpoints 
Primary endpoints 
Urine sodium excretion 
Water excretion 
BCM/weight 
Home blood pressure 
Secondary endpoints 
Tubular complement activation 
Urine C3a, MAC-sC5b-9, C3dg, MBL 
Urine protease activity  
Zymography 

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Protease activity assay 
 
Urine microvesicles:  
gammaENaC cleavage  
complement deposition (sC5b-9) 
 
24 hours Urine albumin excretion 
 
Plasma concentrations: 
Renin 
NT-proBNP 
Angiotensin II 
Aldosterone 
 
4.2 
Design 
This trial is a single-center, interventional, non-randomized, open-label pharmacodynamic study 
aiming to evaluate the effect of CM in both CKD patients with proteinuria and healthy controls. This 
approach has been chosen as the trial serves as a pilot study, aiming to investigate a novel treatment 
target in CKD patients. Including healthy control subjects allows for a comparison of the effect of CM 
on normal physiology versus CKD with proteinuria. By elucidating the differences in drug response 
between healthy individuals and CKD patients with proteinuria, a better understanding of the 
therapeutic potential and underlying mechanisms of CM in treating CKD can be gained. 
 
 
Experimental timeline 
 
 
 
 
 
 
 
 
 
 
 
 
Day 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   ---1 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
   End 
Blood sample 
 
 
 
 
 
 
 
 
 
 
 
24h urine sample 
 
 
 
 
 
 
 
 
 
 
 
Home blood pressure 
 
 
 
 
 
 
 
 
 
 
 
BCM + weight 
 
 
 
 
 
 
 
 
 
 
 
Salt standardized diet 
 
 
 
 
 
 
 
 
 
 
 
Camostat 200 mg x 3/day 
 
 
 
 
 
 
 
 
 
 
 
Figure 1: Main study design. BCM: body composition monitor. 
 
4.3 
Intervention 
The study will include a total of 20 patients with CKD and proteinuria and 20 healthy controls without 
proteinuria matched for age and gender. Both patients and controls will follow a standardized sodium 
diet of 150 mmol/day for a duration of 8 days. The diet is specified by a dietitian and prepared by the 
hospital kitchen. The diet will be distributed to the participants during Visit 2 and Visit 3. It will 
consist of five meals daily with different energy levels depending on the energy needs calculated from 
the Harris-Benedict formula. Participant are allowed only to drink tea or water in addition to the 
beverages included in the diet. On the fifth day of adhering to this diet (day 5), administration of oral 

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Camostat mesylate at a dose of 200 mg x3/day is initiated and will last for four days while the diet is 
continued. CKD patients will receive the IMP as an add-on to their current treatment regimen. 
Blood samples, 24-hour urine samples, home blood pressure, and body composition monitor (BCM) 
measurement will be obtained at baseline, after 4 days on the diet just before CM treatment (day 5) 
and on day 9 after completion of 4 days treatment with CM, after which the study is completed. 
 
4.4 
Minimizing bias 
To minimize potential bias, both CKD patients and healthy controls adhere to a standardized sodium 
diet, controlling for dietary influences on fluid balance and sodium excretion. This reduces variability 
and minimize bias associated with dietary sodium intake. Although the trial is open-label and non-
randomized, bias is minimized using completely objective measures for both primary and secondary 
endpoints. These measures include fluid balance, biomarkers, and blood pressure, ensuring an 
impartial assessment of outcomes.  Participants are recruited through specific criteria, and efforts are 
made to ensure eligibility. This controlled enrollment process helps maintain homogeneity within 
study groups. 
 
4.5 
Recruitment  
Patient recruitment will primarily take place at the Department of Nephrology at Odense University 
Hospital. The recruitment process will involve the following approaches: 
 
1. Identification of eligible patients: Patients meeting the inclusion criteria will be identified 
through the hospital's electronic patient records. During their routine visits in the outpatient 
clinic, the treating physician will assess their eligibility based on the inclusion and exclusion 
criteria outlined in the study protocol. Eligible patients will be provided with recruitment 
materials as part of their routine outpatient clinic visits. 
2. Recruitment of healthy controls: Healthy individuals of similar age and gender will be 
recruited through advertisements placed at local institutions and through social media 
platforms. Subjects of interest will be provided with recruitment material identical to the 
recruitment material provided to eligible patients. 
 
4.6 
Screening 
Participants who accept to take part in the study will be invited to attend a screening session. During 
this screening meeting, oral information will be provided, and written informational materials will be 
distributed. It is recommended that participants bring a relative with them to this meeting. The 
screening session will take place in a quiet room, free from disruptions. 
A minimum consideration time of 24 hours will be offered to participants; however, it is optional, 
and patients may choose to forgo this consideration period if they wish. No study-related procedures 
will be conducted until a signed, written informed consent form is obtained from the participants. 
A blood and urine sample and a pregnancy test (if relevant) will be collected to obtain current values. 
From these, inclusion and exclusion criteria are evaluated, and final eligibility are assessed. Only 
patients who understand and speak Danish will be included in the study. 
 

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4.7 
Duration/Follow-up 
The study period is 11 days. A follow-up visit will be offered one week after the end of the study 
period. It is optional for the participant to choose a telephone-visit instead. 
 
4.8 
End of study definition 
The end of the study is defined as the date of the last visit of the last participant in the study. 
 
4.9 
Discontinuation of Study 
Participants can withdraw from the study, or the IMP as outlined in section 5.4 Subject Withdrawal 
Criteria. 
 
The study may be prematurely discontinued due to regulatory decisions, changes in the Ethics 
Committee's opinion, or safety concerns regarding the drug. Additionally, the sponsor has the 
authority to temporarily suspend or terminate the study due to participant safety, ethical 
considerations, or serious recruitment challenges. 
 
4.10 Source data 
The following documents are defined as source data: 
• Informed consent (or power of attorney) 
• Prints of study visit notes/information from electronic patient records.  
o Note of each visit in the patient’s file 
o Biochemical measurements 
• SAE reports 
 
5 SELECTION AND WITHDRAWAL OF SUBJECTS 
5.1 
Patients 
5.1.1 Inclusion criteria 
Patients: 
1. Age  18 years. 
2. A clinical diagnosis of CKD of any course and meet the following criteria at screening: 
a. eGFR  30 ml/min/1.73m2 
b. U-ACR  300 mg/g. 
3. Stable antihypertensive treatment 2 weeks before start of investigated medical drug (IMP) and 
maintain this treatment throughout the study. 
4. Office blood pressure at the screening session should be >120/70 mmHg and <150/90 mmHg. 
5. Capable of providing a signed informed consent and comply with study requirements. 
6. Women with childbearing potential* must have a negative pregnancy test (urine hCG) at spot 
urine at the screening visit and should use contraception during the study and until one week 
after completion of study treatment. 
 

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5.1.2 Exclusion criteria 
1. Treatment with Amiloride, Spironolactone, Aldosterone, or analogues. 
2. Treatment with NSAIDs. 
3. Hyperkalemia > 5.0 mmol/L at screening. 
4. P-bilirubin > 25 umol/L at screening. 
5. Ongoing cancer treatment. 
6. Treatment with immunosuppressive therapy within 6 months prior to screening. 
7. History of organ transplantation. 
8. Evidence of current infection (CRP>50 or temperature > 38 C). 
9. Severe hepatic insufficiency classified as Child-Pugh C. 
10. Breastfeeding. 
11. Congestive heart failure NYHA class IV, unstable or acute congestive heart failure. 
12. Recent cardiovascular events < 2 months prior to screening: 
a. Coronary artery revascularization. 
b. Acute stroke or TIA. 
c. Acute coronary syndrome. 
13. Allergy or hypersensitivity to the IMP. 
14. Addison’s disease. 
15. Gastric bypass operation. 
16. Lactose intolerance since lactose serves as one of the inactive ingredients in the IMP. 
17. Participation in other clinical trials within the last 30 days. 
 
5.2 
Healthy controls 
5.2.1 Inclusion criteria 
1. Age  18 years. 
2. Good general health with no significant medical conditions or chronic illness (e.g., diabetes, 
hypertension, cardiovascular disease, autoimmune diseases, and cancer). 
3. Normal kidney function and no proteinuria at screening: 
a. eGFR > 90 ml/min/1.73m2 
b. U-ACR < 30 mg/g 
4. Office blood pressure at the screening < 140/90 mmHg. 
5. Capable of providing a signed informed consent and comply with study requirements. 
7. Women with childbearing potential* must have a negative pregnancy test (urine hCG) at spot 
urine at the screening visit and should use contraception during the study and until one week 
after completion of study treatment. 
 
5.2.2 Exclusion criteria 
1. Treatment with any prescription medication except oral contraceptives. 
2. Use of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) 
3. Hyperkalemia > 5.0 mmol/L at screening. 
4. P-bilirubin > 25 umol/L at screening. 

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5. Evidence of current infection (CRP>50 or temperature > 38 C). 
6. Breastfeeding. 
7. History of substance abuse including alcohol. 
8. Allergy or hypersensitivity to the IMP. 
9. Gastric bypass operation. 
10. Lactose intolerance since lactose serves as one of the inactive ingredients in the IMP. 
11. Participation in other clinical trials within the last 30 days. 
 
* Women are considered of childbearing potential following menarche and until becoming post-
menopausal (12 consecutive months without a menstrual period) unless permanently sterile. 
Permanent sterilization methods include hysterectomy, bilateral salpingectomy or bilateral 
oophorectomy (According to the Clinical Trial Facilitation Group, 2014-09-15). 
 
5.3 
Screen failure 
Screen failures are defined as patients who consent to participate in the clinical study and provide an 
informed consent at visit 1 but subsequently do not meet the inclusion and exclusion criteria. These 
participants may undergo re-screening once, with a minimum of 4 weeks from the initial visit 1. This 
process requires new informed and signed consent, a repeated assessment for the study, and a new 
participant identification number.  
 
5.4 
Subject withdrawal criteria 
5.4.1 Subject Withdrawal from Study 
Subject withdrawal is defined as any living subject who does not complete the final follow-up visit 
(visit 5) as outlined in this protocol. Reasons for withdrawal include, but are not limited to: 
• Subject's request (withdrawal of consent) 
• Adverse events (AE) or reactions 
• Conditions posing unacceptable risk as determined by Investigators or advisers. 
• Sponsor-initiated discontinuation of the study 
• Lost to follow-up. 
 
5.4.2 Subject Withdrawal from the Investigational Medicinal Product(s) (IMPs) 
Withdrawal from IMP is defined as discontinuation of study treatment with continued follow-up until 
completion at visit 5. Subjects withdrawing from IMP after at least one dose will undergo safety 
monitoring with a follow-up visit one week after IMP withdrawal. Reasons for withdrawal from IMP 
may include, but are not limited to: 
• Subject's request (withdrawal of consent) 
• Adverse events (AE) or reactions 
• Conditions posing unacceptable risk as determined by Investigators. 
 

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Investigators will attempt to reschedule visits for subjects who miss planned appointments. The eCRF 
will document the reason for withdrawal, withdrawal date, and the decision-maker (subject or 
Investigator).  
Subjects withdrawn before the end of intervention (visit 4) will not be included in statistical analyses. 
However, these participants will still be considered as part of the safety analysis for the study. 
Subjects only missing the final follow-up visit (visit 5) are included in the statistical analyses. 
 
6 TREATMENT OF SUBJECTS 
6.1 
The Investigational Medicinal Product (IMP) - Camostat Mesilate 
Camostat Mesilate will be provided as a film-coated tablet in press-through packages. Each tablet 
contains 100 mg of Camostat Mesilate. 
 
Chemical name: [4-[2-[2-(dimethylamino)-2-oxoethoxy]-2-oxoethyl]phenyl] 4-
(diaminomethylideneamino)benzoate;methanesulfonic acid 
International Nonproprietary Name (INN): Camostat 
Molecular formula: C20H22N4O5 · CH4O3S 
Molecular weight: 494,52 
Structural formula:  
 
 
 
 
6.2 
IMP dosing modifications 
No dosing modifications allowed. 
 
6.3 
Drug Supplies, Packaging and Labelling 
6.3.1 Camostat Mesilate 
The name of the drug is Foipan film-coated tablets 100 mg. It is imported from Japan.  
Foipan produced by the company: Ono Pharmaceutical Co., Ltd., 8-2, Kyutaromachi 1-chome, Chuo-
ku, Osaka, 541-8564 Japan.  
The Pharmacy at Odense University Hospital will make the imports to Denmark according to Danish 
law.       
If necessary, one of the following generic marketed products can be used: 
 
Brand Names 

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• 
Archiment 
Ohara Yakuhin, Japan 
• 
Camoent 
Tsuruhara Seiyaku Pharmaceutical, Japan 
• 
Camostat Mesilate 
Daito, Japan; Kyowa Yakuhin, Japan; Medisa Shinyaku, Japan; Nichi-Iko Pharmaceutical, 
Japan; Nihon Generic, Japan; Nipro, Japan; Ohara Yakuhin, Japan; Takeda Teva Pharma, 
Japan; Tatsumi Yakuhin, Japan; Towa Yakuhin, Japan; Tsuruhara Seiyaku Pharmaceutical, 
Japan 
• 
Camostate 
Nichi-Iko Pharmaceutical, Japan 
• 
Camoston 
Teva Seiyaku, Japan 
• 
Camotat 
Kobayashi Kako, Japan 
• 
Carmozacine 
Nipro Pharma Nipurofama, Japan 
• 
Foipan 
Ono Yakuhin, Japan 
• 
Kamostaal 
Towa Yakuhin, Japan 
• 
Leanac 
Maeda Yakuhin, Japan 
• 
Leseplon 
Tatsumi Kagaku, Japan 
• 
Libilister 
Takeda Teva Pharma, Japan 
• 
Mecilpan 
Choseido Pharmaceutical, Japan 
• 
Mospan 
Daito, Japan 
• 
Pancrel 
Kyowa Yakuhin, Japan 
• 
Raintat 
Koa Isei, Japan 
6.4 
Drug Storage and Accountability 
The Sponsor and Principal Investigator are responsible for secure and correct storage of the IMP after 
arrival at study site. The IMP will be stored in a locked medication room within the outpatient clinic 
at the Department of Nephrology, Odense University Hospital. The storage compartment will be 
monitored regularly. Records of received, used and remaining quantities of the IMP will be 
maintained. Any discrepancies must be solved and explained. 
Until dispensation to the study subjects, the IMP must be stored as follows: 
 
• Foipan (Camostat mesilate): store at temperature below 25° Celsius 
 
For the trial participants, the IMP should be stored at room temperature. 

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Participants are required to self-administer the IMP in the comfort of their own homes. The IMP batch 
provided to each participant is documented in the eCRF. To ensure compliance, participants will be 
encouraged to set an alarm on their mobile phones at the designated administration times and maintain 
a diary of the administration. At the final visit, participants will be questioned about their 
administration, and the investigator will verify by counting the returned tablets. Any deviations from 
the prescribed dosage regimen will be documented in the eCRF. Any returned IMP will be destroyed. 
 
6.5 
Drug administration 
CM will be administered from day 5 at a dose of 200 mg x3/day (e.g., at 6 AM, 2 PM, and 10 PM). 
The intervention period is 4 days. Total number of doses is 200 mg x3 x4 = 2400 mg (=24 tablets).  
 
6.6 
Management of overdose 
An overdose is characterized as any instance in which a participant has ingested a dose exceeding the 
maximum target dose specified in the protocol. The approach to managing an overdose should be 
based on clinical judgment based on symptoms and signs. 
In the event of an overdose, the investigator is responsible for: 
1. Contact the sponsor to report the overdose incident. 
2. Evaluate the participant's condition to determine whether it is necessary to interrupt the study 
intervention, 
3. Closely monitor the participant for any adverse events (AE) or serious adverse events (SAE) 
and assess laboratory abnormalities as clinically indicated. 
4. Record the amount and duration of the overdose eCRF. 
 
6.7 
Concomitant Medications 
All medications or vaccines that the participant is currently taking at the time of enrollment or receives 
during the study must be documented in the eCRF. Please refer to exclusion criteria for medications 
not allowed during the study. Also, it should be noticed, that all antihypertensive and diuretic 
medication should remain stable during the study period and 14 days before initiation the study. 
 
6.8 
Post-Study Care 
Following the termination of the study, there are no predefined post-study care. They will resume 
their routine appointments with their attending physician at the outpatient clinic as usual. 
 
7 ASSESSMENTS AND PROCEDURES 
For a detailed specification of study endpoints refer to Section 4.1 (Endpoints). 
 
7.1 
Primary Endpoint 
Data on the primary endpoint will be collected by the study personnel and/or investigators. 
 

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7.2 
Secondary Endpoints 
Data on the secondary endpoints will be collected by the study personnel and/or investigators. 
 
Schedule of Activities (SoA) 
Screening 
Preintervention 
Salt standardized diet 
Intervention period 
End of intervention 
End of study 
(1 week after visit 4) 
Study days 
-14 to 
-2 
0 
1-4 
5 
6-8 
9 
(18) 
Visit 
1 
2 
 
3 
 
4 
5 
Informed consent and eligibility 
Orally informed consent 
● 
 
 
 
 
 
 
Eligibility (in- and exclusion criteria) 
● 
 
 
 
 
 
 
Signed informed consent 
● 
 
 
 
 
 
 
Baseline characteristics 
Demographics 
 
● 
 
 
 
 
 
Medical history 
 
● 
 
 
 
 
 
Physical examination1 
 
● 
 
 
 
 
 
Anthropometric data 
Weight 
 
● 
 
● 
 
● 
 
Blood pressure (office) 
● 
 
 
 
 
 
 
Home blood pressure2 
 
● 
 
● 
 
● 
 
Body Composition Monitor 
 
● 
 
● 
 
● 
 
Laboratory evaluations 
u-HCG (if relevant) 
● 
 
 
 
 
 
 
Blood samples3 
● 
● 
 
● 
 
● 
 
Spot urine (albumin/creatine ratio) 
● 
 
 
 
 
 
 
24-hour urine4 
 
● 
 
● 
 
● 
 
100 mL spot-urine +20 mL for freeze5 
 
● 
 
● 
 
● 
 
Study intervention and safety 
Salt standardized diet 
 
 
● 
● 
● 
 
 
Study intervention 
 
 
 
● 
● 
 
 
Dispensation and return of IMP 
 
 
 
● 
 
● 
 
End of study phone call 
 
 
 
 
 
 
● 
AE/SAE/OE 
 
 
 
 
 
● 
● 
Table 1: Schedule of activities - Main study 
1. At a minimum assessment of cardiovascular and respiratory systems. 
2. Each participant will receive a calibrated blood pressure monitor and will be instructed to record their blood pressure three times in 
the morning and three times in the evening, following a 15-minute period of rest.  
3. Plasma: hemoglobin, leucocytes, platelet count, CRP, albumin, sodium, potassium, hydrogencarbonat, creatinine, carbamide, 
ALAT, LDH, bilirubin, renin, angiotensin, aldosteron   
4. Albumin, total protein, sodium, potassium, creatinine, creatinine clearance 
5. Tubular complement activation and urine protease activity 
8 ASSESSMENT OF SAFETY 
The safety of enrolled participants will be monitored continuously based on statements of Adverse 
Events (AE) and Serious Adverse Events (SAE). AEs and SAEs will be monitored and recorded from 
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after the final dose of the IMP. Following the occurrence of an AE or SAE, participants will receive 
appropriate follow-up and treatment based on standard guidelines. Adverse events will be reported 
by both the participant and the investigator, along with any qualified designees who are responsible 
for detecting, documenting, and recording events meeting the definition of an AE or SAE through in-
person visits and telephone contacts. Annually, a safety report will be uploaded into the CTIS. 
 
8.1 
Adverse Events (AE) 
An AE is defined as any untoward medical occurrence in a trial subject receiving a pharmaceutical 
product, even if there may not necessarily be a causal relationship with the treatment. An AE can 
therefore be any undesirable and/or unintended sign or symptom (including deviation from usual 
laboratory findings) temporally associated with the use of the IMP, regardless of whether a causal 
link to the IMP is evident. 
Abnormal laboratory values or test results are classified as AEs only if they result in clinical signs or 
symptoms, are considered clinically significant, or require investigation or intervention. Repeated 
tests will be conducted until deviations from usual laboratory findings return to normal, stabilize, or 
are no longer clinically significant. If an abnormal test result is determined to be an error, it need not 
be reported as an adverse event. Such determinations will be made based on the scientific and medical 
judgment of the investigator (MD).  
 
All AEs will be recorded and assessed in accordance with the principles of Good Clinical Practice 
(GCP) and the latest requirements of the Medicines for Human Use (Clinical Trials) Regulations. 
 
Each AE must be assessed and categorized according to the Common Terminology Criteria for 
Adverse Events (CTCAE, version 5.0). These details will be recorded on the AE form within the 
CRF, providing the following information: 
1. The severity grade (mild, moderate, severe) 
2. Its relationship to the IMP (suspected or not suspected) 
3. Duration (including start and end dates, or indication if the AE is ongoing at the final examination) 
4. Whether it qualifies as a Serious Adverse Event (SAE) 
5. Actions taken in response to the IMP 
6. Outcome 
 
8.2 
Serious Adverse Events (SAE) and Serious Unexpected Suspected Adverse Events 
(SUSAR): 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence or effect that, at any 
dose, meets any of the following criteria: 
- Results in death. 
- Is life-threatening. 
- Requires hospitalization or prolongation of existing hospitalization. 
- Results in a congenital anomaly or birth defect. 
- Results in persistent or significant disability or incapacity. 
 

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Some medical events may place the patient at risk or require intervention to prevent any of the above-
mentioned consequences. Such events are referred to as "important medical events" and should also 
be categorized as "serious" in accordance with the definition. The decision of whether an event is 
"serious" is made by the investigator based on medical judgment. The investigator must assess 
causality independently, considering factors such as timing and other relevant information. A planned 
hospitalization will not be considered an SAE. To determine whether a serious adverse related event 
(SAR) is unexpected and, therefore, qualifies as a Suspected Unexpected Serious Adverse Reaction 
(SUSAR), the most recent product summary for Foipan (Camostat mesilate) is used. An adverse event 
is unexpected if its specificity and severity are not described in the latest product summary. 
 
8.2.1 Pregnancies 
Pregnancy, although not itself a serious adverse event, will also be reported on a SAE form and be 
followed up to determine outcome, including spontaneous or voluntary termination, details related to 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. All information pertaining to pregnancy should be recorded on a 
dedicated Clinical Trial Pregnancy Form. 
 
8.3 
Reporting of Adverse Events 
All adverse events will be reported and assessed in the appropriate eCRF. 
 
8.4 
Reporting of Serious Adverse Events (SAE) 
Throughout the entire study period, all serious adverse events/reactions will be reported and assessed. 
Participants will be questioned at each visit/telephone call after initiation of IMP administration. The 
investigator is required to report all SAEs to the sponsor within 24 hours of becoming aware of their 
occurrence. The initial report will be followed by detailed written reports. 
 
8.5 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSAR) 
The sponsor will ensure that all relevant information about SUSARs that are fatal or life-threatening 
is promptly recorded and reported to the EudraVigilance database, and in any case no later than seven 
days after the sponsor becomes aware of such a case. For other serious SUSARs, this information 
will be reported within 15 days. Additionally, any follow-up inquiries from authorities will be 
addressed within eight days. 
 
8.6 
Annual Safety Report 
An annual Safety Report will be submitted through CTIS. This safety report will adhere to the format 
of the Development Safety Update Report (DSUR). It will specify the reporting timeframe and 
provide a concise summary of all documented serious events, including both Serious Adverse Events 
(SAEs) and Serious Unexpected Suspected Adverse Reactions (SUSARs). Furthermore, the safety 
report will include an up-to-date benefit/risk evaluation. 

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9 STATISTICS 
9.1 
Statistical Methods 
The statistical methods employed will include descriptive statistics, such as means and standard 
deviations, for continuous variables, and frequencies and percentages for categorical variables. 
Inferential statistical tests will be used to compare outcomes between groups. 
 
9.2 
Interim analysis 
Interim analyses are not planned for this study. 
 
9.3 
Sample Size 
The total number of subjects planned to be enrolled is 20 CKD patients with proteinuria and 20 
healthy controls. The sample size is chosen based on feasibility and the availability of eligible 
participants. This study is primarily designed as a pilot study exploring the effects and 
pharmacodynamic features of the IMP, and the sample size is not determined by statistical power 
calculations. However, the selected sample size is considered sufficient to observe potential trends 
and provide preliminary insights into the effects of the intervention. 
 
9.4 
Trial power 
Since this study is designed as a pilot and not powered to detect specific effect sizes or differences 
between groups, it may have limited statistical power to detect smaller, yet potentially clinically 
relevant, effects. Therefore, it should be interpreted with this limitation in mind. 
 
9.5 
Level of Significance 
The level of significance to be used for hypothesis testing is set at p < 0.05. A p-value of less than 
0.05 will be considered statistically significant. 
 
9.6 
Reporting Deviations from the Statistical Plan 
Any deviations from the original statistical plan will be documented and justified in the final study 
report. The protocol may also be updated to reflect these deviations if necessary. 
 
9.7 
Selection of Subjects for Analyses 
The selection of subjects to be included in the analyses will be of all participants who have completed 
the study according to the prescribed protocol until the end of intervention (visit 4). This includes 
both CKD patients with proteinuria and healthy control subjects. This approach ensures that all 
relevant data are included in the analysis, providing a comprehensive assessment of the intervention's 
effects within the study population. 
 
9.8 
End of study 
The trial will be completed when 20 CKD patients and 20 healthy controls are included in the trial. 
Withdrawn participants will not be replaced. 
 

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10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Based on approval from the regional Ethics Committee, the Sponsor hereby affirms that the 
Investigators and the involved institutions in the clinical trial will permit trial-related monitoring, 
auditing, and inspection by regulatory authorities. This includes granting direct access to source data 
and study documents for review by The Danish Medicines Agency, The Ethics Committee, and their 
collaborators. 
 
11 QUALITY CONTROL AND QUALITY ASSURANCE 
The clinical trial will be conducted in accordance with the trial protocol, the Regulation, and the 
principles of Good Clinical Practice (ICH-GCP). 
The Investigator holds the responsibility for ensuring the study's conduction, documentation, and 
completion in accordance with the protocol. The study is monitored by the GCP-Unit at Odense 
University Hospital. 
 
12 ETHICS 
12.1 Ethical Conduct of the Study 
The study will be reported to the Clinical Trials Information System (CTIS). All necessary approvals 
from regulatory authorities will be awaited before initiating the study. The study will adhere to the 
approved protocol, and any deviations from the protocol will be documented and reported as required. 
The study will be conducted in accordance with the Declaration of Helsinki, principles of Good 
Clinical Practice (GCP), the Regulation (EU) No. 536/2014, and national ethical guidelines and law. 
 
12.2 Informed Consent 
The investigator is responsible to provide each potential participant with information about the 
background, purpose and potential risks of the study. Additionally, participants will be informed 
about their rights to privacy including protecting their personal information. To confirm that the 
participants have understood the provided information, they will be asked to recap their 
understanding. After appropriate consideration time, the investigator will obtain written informed 
consent from each participant. A copy of the Informed Consent Form (ICF) will be provided to the 
participant, and the original signed copy of the ICF will be maintained by the investigator.  And 
subject to inspection as needed. Furthermore, participants will be explicitly informed that they have 
the right to withdraw their consent at any time. 
 
12.3 Access to data 
To identify eligible participants, a review of laboratory data stored in the Electronic Patient Journal 
(EPJ) will be conducted, focusing on data related to eGFR and urine albumin/creatinine ratio. These 
data will be used to assess the eligibility of potential participants based on patient lists within the 
outpatient clinic. Once signed informed consent has been obtained, the Sponsor, Investigator, the 
GCP unit, Ethics Committees, and regulatory authorities will be allowed access to the source data. 
 

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12.4 Ethical Considerations 
The IMP, Camostat mesilate (CM), is not currently marketed in the EU, but has been used safely in 
Japan for decades. CM is known to be a safe and well-tolerated medication, with the most common 
side effects reported as abnormal biochemistry (1-2%), rash (0.4%), nausea (0.3%), pruritus (0.2%), 
and abdominal discomfort (0.2-0.4%). Furthermore, existing evidence from CM administration in 
patients with varying degrees of renal insufficiency suggests no harm to renal function or an increased 
risk of adverse drug reactions. 
During the study, participants will undergo the collection of several blood and urine samples, which 
may cause minor discomfort and inconvenience. Additionally, participants in the main study will be 
required to commit significant time and adhere to clinical visits, 24-hour urine collection, 24-hour 
blood pressure measurements, and compliance with a standardized sodium diet. However, 
participants will benefit from closer doctor contact compared to standard outpatient clinic visits. 
Currently, available treatment options to delay progression CKD are limited. This study may 
contribute valuable knowledge regarding the efficacy and safety of the IMP in a disease area that 
needs improved treatment options and a deeper understanding of disease mechanisms. As the target 
mechanism of CM is not yet fully explored, any beneficial effects discovered could be additive to 
existing pharmacological treatments. Regardless of the study results, it will contribute with important 
knowledge on the efficacy of the IMP and contribute to the broader understanding of disease 
mechanisms in CKD. 
 
13 DATA HANDLING AND RECORD KEEPING 
13.1 Trial Master File and Source Data 
According to requirements from the GCP-unit, a Trial Master File will be created, containing source 
data including the protocol and its amendments, all correspondence with regulatory authorities 
including the Danish Medicines Agency, the Ethics Committee, and the Danish Data Protection 
Agency, informed consent documents, staff curriculum vitae, forms, delegation logs, and other 
relevant documents and correspondence. All source documentation will be securely stored under the 
responsibility of the Principal Investigator. The Principal Investigator will maintain complete and 
accurate records to ensure comprehensive documentation of the trial's execution and enable 
subsequent data verification. 
 
13.2 Use of Case Report Forms (CRF) 
The Sponsor is responsible for maintaining an updated and accurate electronic CRF (eCRF) designed 
to accurately record all study-related observations and data using the REDCap database. Recording 
in the eCRF should generally occur following each study visit. Data entry into the eCRF should be 
done comprehensively and carefully to ensure correct data interpretation. The eCRF have a logging 
system that logs the date, time, and action taken in the eCRF, and the person responsible for this 
action. If any corrections are introduced, previous text or data will remain logged in the eCRF logging 
system for transparency and traceability. The eCRF will only be considered complete once all data, 
including any missing, incorrect, or inconsistent entries, have been accounted for. 
 

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13.3 Data handling 
All personal data and study materials are protected in compliance with national law, the EU General 
Data Protection Regulation (GDPR), and the Data Protection Agency. Blood samples and subject-
specific documents are supplied with a unique study identification code to prevent direct subject 
identification. After study completion, Study data will be stored in coded form for a duration of 25 
years in accordance with the recommendations of CTR nr. 536/2014. After this period, the data will 
be securely destroyed. 
 
13.4 Computer Systems 
Data processing will be conducted using a validated computer system that complies with regulatory 
requirements. For this study, source data will be sourced from medical records. Laboratory results 
(blood and urinary samples) will be extracted from the electronic medical record and added to the 
eCRF. Data regarding blood pressure, body water measurements, body weight, height, medication 
administration, and side effects will be directly recorded in the eCRF. 
 
13.5 Data Entry 
To enter, review, or correct study data, all personnel must log into the RedCap computer system using 
their confidential username and password. 
 
13.6 Data Validation 
Validation will be performed via review of the data in the eCRF to ensure accurate and reliable data. 
The CRF will be reviewed and signed by the investigator. 
 
13.7 Biological material 
Throughout the study, participants will undergo blood sampling four times, with a maximum of 50 
mL blood distributed in 6 sample tubes at each blood sampling session. The total blood volume 
collected throughout the study will not exceed 200 mL. Additionally, four fresh urine samples, each 
approximately 120 mL, will be collected, totaling a maximum of 500 mL. Moreover, there will be a 
total of three instances of 24-hour urine collection. 
 
13.8 Research biobank 
In collaboration with Open Patient Data Explorative Network (OPEN), a research biobank will be 
established. This biobank will house blood and urine samples collected from study participants. Most 
of these samples will undergo immediate analysis, while some will be stored for later analysis during 
the study period.  
Sample analysis will be conducted at the laboratories of Odense University Hospital (OUH), the 
Department of Cardiovascular and Renal Research at the University of Southern Denmark or the 
Department of Clinical Pharmacology, Aarhus University Hospital. 
Any surplus biological material remaining after the study’s conclusion will be securely stored for a 
period of 15 years. The storage is for potential use in future research studies. Access to the research 
biobank will be regulated by the principal investigator. 

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The biological samples will be stored in the biobank at Department of Clinical Biochemistry at OUH. 
The samples will be pseudonymized and the sample code list (code key) will be securely stored 
separately from the samples and will be under the custody of the sponsor and principal investigator. 
They will be responsible for maintaining the link between the pseudonymized samples and their 
original participant identities. 
For analysis samples will be transferred in pseudonymized form to laboratories with restricted access 
where they will be analyzed. Remaining material will be brought back for storage in the biobank. 
The primary objective of this biobank is to support research directly related to the objectives of this 
trial. However, it will also serve as a resource for potential future, unspecified research, after approval 
from the Danish Ethics Committee and renewed informed consent of the participants. Participants 
will receive information about this biobank during the oral information session and will be provided 
with written materials.  
14 FINANCING AND INSURANCE 
The study is initiated by the sponsor. Non-commercial funding finances the medication. There is no 
involvement from industry partners in the project. There will not be any remuneration during the 
project, however travel expenses will be refunded.  
In accordance with the relevant national regulations, subjects enrolled in the study are under The 
Danish Patient Insurance that covers all study subjects as guaranteed by The Danish Act on the Right 
to Complain and Receive Compensation within the Health Service administered by The Patient 
Assurance Association. 
 
15 PUBLICATION POLICY 
Following the completion of the study, the trial results, regardless of whether they are positive, 
negative, or inconclusive, will be published promptly and in a professionally responsible manner. 
This publication will be conducted in compliance with the Act on Processing of Personal Data. In 
cases where the results cannot be published in a journal, they will be published in another way. It is 
the responsibility of the investigator to maintain the confidentiality of study data ant to consult with 
the sponsor prior to the submission of any study data for publication. 
At this stage, a final list of authors cannot be determined; however, all researchers who have met the 
Vancouver criteria for authorship will be included in the final publication. 
Furthermore, the summary of the results must be submitted to the CTIS portal without undue delay 
and no later than one year after the trial has concluded.  
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