Bioavailability and Pharmacokinetics of Calcium Dobesilate (Doxium®) in the Nasal Mucosal Tissue, Saliva and Blood of Treated Patients

Biological Availability Clinical Trial

— CaDoBio  

Official title:

CaDoBio (Calcium Dobesilate Bioavailability): a Bioavailability and Pharmacokinetics Research Project to Measure the Concentrations of Calcium Dobesilate (Doxium®) in the Nasal Mucosal Tissue, Saliva and Blood of Treated Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04922996
• Other study ID #: 2020-03050
• Status: Active, not recruiting
• Start date: April 15, 2021
• Est. completion date: August 2021

Study information

• Verified date: June 2021
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Calcium dobesilate (CaD) has been shown to have potential antiviral effects, mediated via its interaction with the heparansulfate (HS) binding site of the viral SARS-CoV-2 spike protein (direct action), necessary for interation with the ACE-2 receptor on human cells. Preliminary pre-clinical results using viral pseudotyped particles demonstrated that CaD reduces the uptake of SARS-CoV-2 spike protein in cultured endothelial cells by more than 50%. Moreover, CaD is a well-established vasoactive and angioprotective drug improving endothelial dysfunction with a good tolerability profile. CaD strengthens vessels integrity and improves blood flow by acting on multiple parameters, like cytokines levels and signaling by FGF and VEGF. All these parameters may be dysregulated at some stage of Covid-19 pathological evolution, and acting on these could potentially reduce the progression toward severe disease. Based on these data, we hypothesize that CaD could be used as an early treatment for SARS-CoV-2 positive outpatients. However, bioavailability data and pharmacokinetics of CaD are not well known, outside of old data on animal models. Being able to show that the drug is present in nasal mucosae and saliva, where the virus is likely to start the infection of the host, would be a first step before studying a possible effect on the disease course on infected patients. Therefore this project plans to include between 6 and 10 patients, treated with CaD, for whom different nasal, saliva and blood sample will be taken at different timepoints before and after the daily dose of the treatment. Samples will be then analysed to detect and quantify the presence of CaD.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: August 2021
• Est. primary completion date: May 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients treated with calcium dobesilate (1000-2000mg/day), at any time on treatment or for whom initiation of treatment has been prescribed, for one of its Swiss

indications:

• Microangiopathies, in particular diabetic retinopathy.
• Clinical symptoms of chronic venous insufficiency of the legs (pains, cramps, paraesthesia, oedemas, stasis dermatitis), superficial thrombophlebitis in adjuvant treatment.
• Haemorrhoidal syndrome, post-thrombotic syndrome, microcirculatory disorders of arteriovenous origin.

2. Male or female

3. Aged =18 years

4. Subject has provided the appropriate written informed consent. Subject must provide written informed consent before any study-specific procedures are performed

Exclusion Criteria:

1. Known sensitivity to calcium dobesilate

2. Currently suffering from or treated for a nasal condition, e.g., a runny, congested nose, nasal infection, or an oral condition, e.g., oral infection, including suspected SARS-CoV-2 infection

3. Currently treated with a nasal or an oral product, or any treatment with the same active substance as in CaD (e.g., doxiproct, dicynone)

4. Current participation in any other investigational drug study

5. Only for patients already on CaD treatment: treatment with CaD initiated within last 7 days only

6. Only for patients starting CaD treatment: treatment with CaD within last 30 days

Related Conditions & MeSH terms

• Biological Availability

Intervention

Drug:
• Calcium Dobesilate
Dosage of calcium dobesilate in different tissues

Locations

Country	Name	City	State
Switzerland	HUG	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CaD presence and concentration in nasal mucosa	Nasal mucosa tissue of calcium dobesilate for patients on treatment as assessed by tandem mass spectrometry in ug/ml	Day 0
Primary	CaD presence and concentration in saliva	Saliva concentrations of calcium dobesilate for patients on treatment as assessed by tandem mass spectrometry in ug/ml	Day 0
Secondary	Pharmakokinetic of CaD in plasma for patients on treatment	Calcium dobesilate plasma concentrations in ug/ml for patients on treatment	Day 0 - before the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients on treatment	Calcium dobesilate plasma concentrations in ug/ml for patients on treatment	Day 0 - 4 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients on treatment	Calcium dobesilate plasma concentrations in ug/ml for patients on treatment	Day 0 - 8 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 0 - before the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 0- 4 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 0 - 8 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 1 - before the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 1 - 4 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 1- 8 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 3- before the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 3 - 4 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 3- 8 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 7- before the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 7 - 4 hours after the morning dose
Secondary	Pharmakokinetic of CaD in plasma for patients starting treatment	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment	Day 7- 8 hours after the morning dose
Secondary	Correlation between nasal mucosal tissue and plasma concentration for patients on treatment	Ratio in %	Day 0
Secondary	Correlation between oral tissue and plasma concentration for patients on treatment	Ratio in %	Day 0