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CAMOSTAT MESILATE

Camostat mesilate (also known as camostat mesylate) is a serine protease inhibitor that has gained significant attention in recent clinical research, particularly during the COVID-19 pandemic. Originally approved in Japan for treating conditions like chronic pancreatitis and reflux esophagitis, this drug has shown promise in preventing viral entry of SARS-CoV-2 into human cells by inhibiting the host cell serine protease TMPRSS2. This article explores the ongoing clinical trials investigating camostat mesilate across various conditions, with a primary focus on its potential as a treatment for COVID-19 and other medical conditions.

Table of Contents

What is Camostat Mesilate?

Camostat mesilate (also known as camostat mesylate or by the brand name Foipan®) is a medication that belongs to a class of drugs called serine protease inhibitors. It has been used clinically in Japan since 1985 for treating conditions such as chronic pancreatitis (inflammation of the pancreas) and postoperative reflux esophagitis (inflammation of the esophagus after surgery)[1]. The drug has a well-established safety record with more than 15 years of clinical experience in Japan[2].

Camostat mesilate may also be referred to by several synonyms including:

  • Camostat mesylate
  • Foipan® (brand name in Japan)
  • FOY-305 (research designation)

How Does Camostat Mesilate Work?

Camostat mesilate works by inhibiting certain enzymes called serine proteases. These enzymes are involved in various biological processes in the body. Specifically, camostat inhibits:

  • Pancreatic enzymes: In chronic pancreatitis, camostat reduces the activity of digestive enzymes that can damage the pancreas[2].
  • TMPRSS2: This is a serine protease found on the surface of certain cells. It has gained attention because it is needed for some viruses, including SARS-CoV-2 (the virus that causes COVID-19), to enter cells[2].

By blocking these enzymes, camostat mesilate can help reduce inflammation in the pancreas and potentially prevent certain viral infections by blocking their entry into cells[3].

Current Medical Uses

Camostat mesilate has been approved and used in Japan for several conditions:

  • Chronic pancreatitis: To treat pain and inflammation associated with ongoing inflammation of the pancreas[1].
  • Postoperative reflux esophagitis: To treat inflammation of the esophagus that can occur after surgery[1].
  • Acute exacerbations of chronic pancreatitis: To manage flare-ups of chronic pancreatic inflammation[2].

It’s important to note that while camostat mesilate is widely used in Japan, it may not be approved for these uses in other countries. Clinical trials are currently investigating its potential for other medical conditions[4].

Potential Use in COVID-19

One of the most actively researched potential applications for camostat mesilate is in the treatment of COVID-19. Here’s why researchers are interested in this drug for COVID-19 treatment:

  • Mechanism against viral entry: SARS-CoV-2, the virus that causes COVID-19, needs to bind to a receptor called ACE2 on human cells to gain entry. This process requires a serine protease called TMPRSS2. Camostat mesilate can inhibit TMPRSS2, potentially blocking viral entry into cells[2].
  • Laboratory evidence: Studies have shown that camostat mesilate can inhibit SARS-CoV-2 replication in laboratory settings (in vitro)[1]. Additionally, in previous research on related coronaviruses like SARS-CoV, camostat mesilate showed protective effects in mouse models, reducing mortality from 100% to 30-35%[5].
  • Clinical trials: Multiple clinical trials have been conducted to evaluate camostat mesilate’s effectiveness against COVID-19 in humans, both in hospitalized patients and outpatients with mild to moderate disease[6][7].

Clinical trials have investigated different aspects of camostat mesilate in COVID-19 treatment, including:

  • Reduction of viral load (amount of virus in the body)[1]
  • Shortening the duration of symptoms[6]
  • Preventing progression to severe disease requiring hospitalization[7]
  • Reducing COVID-19-associated blood clotting problems (coagulopathy)[8]
  • Combination therapy with other medications like hydroxychloroquine or bicalutamide[9][10]

While research continues, it’s important to understand that camostat mesilate is still considered investigational for COVID-19 treatment and has not been approved by regulatory agencies like the FDA for this purpose[11].

Dosage and Administration

The dosage of camostat mesilate varies depending on the condition being treated and the clinical trial protocol. Based on the available information from clinical studies:

  • For COVID-19 clinical trials: Various dosing regimens have been studied, including:
    • 200 mg taken orally 3-4 times daily (600-800 mg total daily dose)[1][6]
    • Treatment duration typically ranging from 5 to 14 days[6][7]
  • For chronic pancreatitis (in Japan): The typical dosage is 100 mg taken orally 3 times daily[12].

Camostat mesilate is typically administered as oral tablets. It’s important to note that dosing should always be determined by a healthcare provider, and patients should never self-medicate with camostat mesilate or adjust their dosage without medical supervision[12].

Safety Profile and Side Effects

Camostat mesilate has been used in Japan for several decades and generally has a good safety profile. However, like all medications, it can cause side effects in some people[2].

Common side effects may include:

  • Gastrointestinal symptoms (nausea, vomiting, diarrhea)[13]
  • Skin reactions[13]
  • Headache[13]
  • Fatigue[13]

In clinical trials for COVID-19, researchers carefully monitored participants for adverse events. The CLOCC trial, for example, was designed to evaluate both the efficacy and safety of hydroxychloroquine-camostat combination therapy compared to hydroxychloroquine plus placebo in hospitalized patients with moderate COVID-19 infection[3].

Several studies have collected safety data by monitoring:

  • Laboratory tests including liver function, kidney function, and blood counts[7]
  • ECG parameters to check for heart-related side effects[14]
  • Vital signs including blood pressure and oxygen saturation[7]

It’s important to discuss potential risks and benefits with your healthcare provider before starting any new medication, including camostat mesilate[13].

Ongoing Research

Research on camostat mesilate continues to evolve, particularly in the context of COVID-19 treatment. Several large-scale clinical trials have been conducted or are in progress:

  • The ACTIV-2 trial: A large platform trial testing multiple potential COVID-19 treatments, including camostat mesilate, in outpatients[15].
  • The CLOCC trial: Evaluated the efficacy and safety of hydroxychloroquine-camostat combination therapy compared to hydroxychloroquine plus placebo in hospitalized patients with moderate COVID-19[3].
  • The CAMOVID trial: A multicenter randomized trial to evaluate the efficacy and safety of camostat mesilate for the treatment of SARS-CoV-2 infection in ambulatory adult patients[7].
  • The COMBO trial: Studying camostat in combination with bicalutamide for COVID-19 treatment[10].

These studies are helping researchers better understand the potential benefits and limitations of camostat mesilate in COVID-19 treatment, as well as optimal dosing strategies and patient populations who might benefit most from this therapy[11].

Other Potential Applications

Beyond its established uses and COVID-19 research, camostat mesilate is being investigated for other medical conditions:

  • Protein-losing enteropathy after Fontan operation: A phase 2 clinical trial is evaluating camostat mesilate for treating protein-losing enteropathy (a condition where protein leaks from the intestines) in patients who have undergone a specific heart surgery called the Fontan operation[4].
  • Chronic kidney disease (CKD): Researchers are studying whether camostat mesilate might help protect kidney function in patients with chronic kidney disease and proteinuria (protein in the urine). By inhibiting serine protease activity and tubular complement activation, camostat may potentially mitigate progressive kidney injury[16].

These investigations highlight the versatility of camostat mesilate as a serine protease inhibitor with potential applications across multiple medical conditions[4][16].

Category Details
Primary Uses in COVID-19 Trials – Reducing viral load in respiratory samples
– Preventing disease progression in early/mild COVID-19
– Reducing hospitalization rates
– Shortening time to clinical improvement
– Treating COVID-19 outpatients with risk factors
Common Dosage Regimens – 200 mg three to four times daily (600-800 mg total daily dose)
– Treatment durations from 5-14 days
– Administered as oral tablets
– Some trials using 100 mg tablets, 2-3 per dose
Mechanism of Action – Inhibits host cell serine protease TMPRSS2
– Blocks SARS-CoV-2 viral entry into cells
– May reduce viral replication
– Demonstrated in vitro inhibition of SARS-CoV-2
Non-COVID Applications – Protein-losing enteropathy after Fontan operation
– Kidney protection in chronic kidney disease patients with proteinuria
– Historical use in Japan for chronic pancreatitis
– Treatment of postoperative reflux esophagitis
Trial Designs – Randomized, double-blind, placebo-controlled studies
– Phase II and III trials
– Both inpatient and outpatient settings
– Some trials combining camostat with other treatments
– Follow-up periods typically 14-90 days
Combination Therapies – Camostat + hydroxychloroquine
– Camostat + bicalutamide
– Camostat + niclosamide
– Comparison with other COVID-19 treatments
Safety Monitoring – Adverse events and serious adverse events
– Liver function tests (AST, ALT, ALP, GGT)
– Kidney function (creatinine, GFR)
– Blood parameters (platelets, potassium)
– Vital signs and ECG monitoring

FAQ

  • What is camostat mesilate and how does it work against COVID-19? Camostat mesilate is a serine protease inhibitor that was originally approved in Japan for treating conditions like chronic pancreatitis and reflux esophagitis. For COVID-19, it works by inhibiting the host cell serine protease TMPRSS2, which is needed to prime the viral spike protein for cell entry. By blocking this process, camostat may prevent SARS-CoV-2 from entering and infecting human cells. Laboratory studies have shown that camostat can inhibit SARS-CoV-2 replication in cell cultures, and it demonstrated protective effects in animal models of coronavirus infection.
  • What dosages of camostat mesilate are being studied in clinical trials? Across various clinical trials, camostat mesilate is being studied at different dosages. Common dosing regimens include 200 mg taken three to four times daily (600-800 mg total daily dose), with treatment durations typically ranging from 5 to 14 days. Some trials use 100 mg tablets taken 2-3 times per dose to reach the desired amount. In the COPPS trial, for example, the dosage was 200 mg (2 x 100 mg tablets) administered orally four times daily for a total daily dose of 800 mg, while other trials like CAMOVID used 600 mg per day (2 x 100 mg tablets every 8 hours).
  • What are the primary outcomes being measured in camostat mesilate COVID-19 trials? The primary outcomes in camostat mesilate COVID-19 trials vary but generally focus on several key areas: 1) Viral load reduction, measured as change in SARS-CoV-2 viral load from respiratory samples; 2) Clinical improvement, such as time to resolution of symptoms or discharge from hospital; 3) Prevention of disease progression, measured as rates of hospitalization, oxygen requirement, or mechanical ventilation; 4) Mortality rates; and 5) Safety and tolerability, assessed through adverse events reporting. For outpatient studies, researchers often focus on whether camostat can prevent the need for hospitalization, while inpatient studies may look at recovery time or progression to severe disease.
  • Besides COVID-19, what other conditions is camostat mesilate being studied for? While most recent trials focus on COVID-19, camostat mesilate is also being investigated for other conditions. One notable trial is studying its potential benefit for protein-losing enteropathy after Fontan operation, a cardiac surgical procedure. Another trial is investigating camostat's potential for kidney protection in chronic kidney disease patients with proteinuria. Historically, camostat has been used in Japan for treating chronic pancreatitis and postoperative reflux esophagitis. These diverse applications highlight the drug's potential versatility beyond antiviral properties.
  • What are the potential side effects or safety concerns with camostat mesilate? Camostat mesilate has been used in Japan for over 15 years with a generally safe clinical track record. In current clinical trials, researchers are carefully monitoring for adverse events, with special attention to potential effects on liver function, kidney function, and blood parameters. Some trials specifically monitor liver enzymes (AST, ALT, ALP, GGT), kidney function markers (creatinine, GFR), and electrolyte levels like potassium. The safety profile is being thoroughly evaluated through measurement of treatment-emergent adverse events, vital signs, ECG parameters, and laboratory tests. So far, no major safety concerns have been highlighted in the available trial information, but comprehensive results are still pending from many studies.

Ongoing Clinical Trials on CAMOSTAT MESILATE

  • Study on the Effects of Camostat Mesilate for Kidney Protection in Patients with Chronic Kidney Disease and Proteinuria

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Denmark

Glossary

  • Camostat Mesilate: A serine protease inhibitor drug that has been used in Japan since 1985 for treating conditions like chronic pancreatitis and reflux esophagitis. In COVID-19 research, it's being studied for its ability to inhibit SARS-CoV-2 viral entry into cells.
  • TMPRSS2: Transmembrane Serine Protease 2, a protein on the surface of human cells that is needed to prime the SARS-CoV-2 spike protein for cell entry. Camostat mesilate works by inhibiting this enzyme.
  • Serine Protease Inhibitor: A class of drugs that block the action of serine proteases, which are enzymes that cut protein chains at specific sites. In the case of camostat, it inhibits proteases involved in viral entry and other biological processes.
  • COVID-19 Associated Coagulopathy (CAC): Abnormal blood clotting associated with COVID-19 infection that can lead to serious complications. Some studies are investigating whether camostat mesilate might help reduce this coagulation disorder.
  • Viral Load: The amount of virus present in the body, typically measured from samples like nasal swabs. Many COVID-19 trials measure viral load reduction as a primary outcome to assess treatment effectiveness.
  • RT-PCR: Reverse Transcription-Polymerase Chain Reaction, a laboratory technique used to detect SARS-CoV-2 genetic material in patient samples. It's commonly used in clinical trials to measure viral load.
  • Clinical Deterioration: Worsening of a patient's health status, often measured using standardized scales like the WHO COVID-19 ordinal scale. Prevention of clinical deterioration is a key outcome in many camostat trials.
  • Cycle Threshold (Ct): In PCR testing, the number of amplification cycles required for the target virus to be detected. Lower Ct values indicate higher viral loads, while higher values indicate lower viral loads.
  • Protein-losing Enteropathy: A condition where excessive protein is lost from the digestive tract, leading to low blood protein levels. Camostat is being studied for this condition specifically after Fontan operation (a cardiac procedure).
  • WHO Ordinal Scale: A standardized scale developed by the World Health Organization to assess clinical status of COVID-19 patients, ranging from 0 (uninfected) to 8 (death). Many trials use this to measure disease progression and improvement.
  • Pharmacokinetics (PK): The study of how drugs move through the body, including absorption, distribution, metabolism, and excretion. Several trials measure PK parameters of camostat's active metabolite, GBPA.
  • GBPA: 4-(4-Guanidinobenzoyloxy)Phenylacetic Acid, the active metabolite of camostat mesilate that is measured in pharmacokinetic studies to understand how the drug works in the body.
  • AUC (Area Under the Curve): A pharmacokinetic measurement that represents the total exposure to a drug over time. Several trials measure this for camostat's active metabolite to understand drug exposure.

References

  1. https://clinicaltrials.gov/study/NCT04353284
  2. https://clinicaltrials.gov/study/NCT04455815
  3. https://clinicaltrials.gov/study/NCT04338906
  4. https://clinicaltrials.gov/study/NCT05474664
  5. https://clinicaltrials.gov/study/NCT04321096
  6. https://clinicaltrials.gov/study/NCT04583592
  7. https://clinicaltrials.gov/study/NCT04608266
  8. https://clinicaltrials.gov/study/NCT04435015
  9. https://clinicaltrials.gov/study/NCT04355052
  10. https://clinicaltrials.gov/study/NCT04652765
  11. https://clinicaltrials.gov/study/NCT04662073
  12. https://clinicaltrials.gov/study/NCT04730206
  13. https://clinicaltrials.gov/study/NCT04625114
  14. https://clinicaltrials.gov/study/NCT04451083
  15. https://clinicaltrials.gov/study/NCT04518410
  16. https://clinicaltrials.gov/study/NCT06794593