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

• Conditions: Biological Availability
• Interventions: Drug: Calcium Dobesilate

• Registration Number: NCT04922996
• Lead Sponsor: University Hospital, Geneva

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-15
• Primary Completion: 2021-05-26
• Status Verified: 2021-06
• Study First Submitted: 2021-06-03
• Study First Submitted QC: 2021-06-10
• Last Update Submitted: 2021-06-10
• Study First Posted: 2021-06-11
• Last Update Posted: 2021-06-11
• Study Completion: 2021-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
New	Calcium Dobesilate	Patients with approved indication for calcium dobesilate treatment but not already on treatment
Ongoing	Calcium Dobesilate	Patients already on calcium dobesilate treatment

Primary Outcome Measures

Name	Time	Method
CaD presence and concentration in nasal mucosa	Day 0	Nasal mucosa tissue of calcium dobesilate for patients on treatment as assessed by tandem mass spectrometry in ug/ml
CaD presence and concentration in saliva	Day 0	Saliva concentrations of calcium dobesilate for patients on treatment as assessed by tandem mass spectrometry in ug/ml

Secondary Outcome Measures

Name	Time	Method
Pharmakokinetic of CaD in plasma for patients starting treatment	Day 7- 8 hours after the morning dose	Calcium dobesilate plasma concentrations in ug/ml for patients starting treatment
Pharmakokinetic of CaD in plasma for patients on treatment	Day 0 - 8 hours after the morning dose	Calcium dobesilate plasma concentrations in ug/ml for patients on treatment
Correlation between nasal mucosal tissue and plasma concentration for patients on treatment	Day 0	Ratio in %
Correlation between oral tissue and plasma concentration for patients on treatment	Day 0	Ratio in %

Trial Locations

Locations (1)

HUG; 🇨🇭 Geneva, Switzerland