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

NCT04922996 | Unknown FDA Drug

• 1 other identifier: 2020-03050
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Biological Availability

Keywords

Calcium dobesilate; Biological Availability; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (17)

• Pharmakokinetic of CaD in plasma for patients on treatment

  Day 0 - before the morning dose

• Pharmakokinetic of CaD in plasma for patients on treatment

  Day 0 - 4 hours after the morning dose

• Pharmakokinetic of CaD in plasma for patients on treatment

  Day 0 - 8 hours after the morning dose

• Pharmakokinetic of CaD in plasma for patients starting treatment

  Day 0 - before the morning dose

• Pharmakokinetic of CaD in plasma for patients starting treatment

  Day 0- 4 hours after the morning dose

Study Arms (2)

Ongoing

Patients already on calcium dobesilate treatment

Drug: Calcium Dobesilate

New

Patients with approved indication for calcium dobesilate treatment but not already on treatment

Drug: Calcium Dobesilate

Interventions

Calcium Dobesilate DRUG

Dosage of calcium dobesilate in different tissues

Also known as: Biological samples

New; Ongoing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients already on CaD treatment according to the approved indication of treatment, or patients meeting conditions for CaD treatment

You may qualify if:

• 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.
• Male or female
• Aged ≥18 years
• Subject has provided the appropriate written informed consent. Subject must provide written informed consent before any study-specific procedures are performed

You may not qualify if:

• Known sensitivity to calcium dobesilate
• 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
• Currently treated with a nasal or an oral product, or any treatment with the same active substance as in CaD (e.g., doxiproct, dicynone)
• Current participation in any other investigational drug study
• Only for patients already on CaD treatment: treatment with CaD initiated within last 7 days only
• Only for patients starting CaD treatment: treatment with CaD within last 30 days

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

HUG

Geneva, 1205, Switzerland

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples Saliva samples Nasal mucosa samples

MeSH Terms

Interventions

Calcium Dobesilate

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 11, 2021
• Study Start: April 15, 2021
• Primary Completion: May 26, 2021
• Study Completion: August 1, 2021
• Last Updated: June 11, 2021

Record last verified: 2021-06

Locations

CH (1)