Clinical trial NCT04922996: Bioavailability and Pharmacokinetics of Calcium Dobesilate (Doxium®) in the Nasal Mucosal Tissue, Saliva and Blood of Treated Patients
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Biological Availability
Keywords: Calcium dobesilate
Biological Availability
Pharmacokinetics
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2021-06-11
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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

Primary outcomes:
measure: CaD presence and concentration in nasal mucosa
timeFrame: Day 0
measure: CaD presence and concentration in saliva
timeFrame: Day 0
Secondary outcomes:
measure: Pharmakokinetic of CaD in plasma for patients on treatment
timeFrame: Day 0 - before the morning dose
measure: Pharmakokinetic of CaD in plasma for patients on treatment
timeFrame: Day 0 - 4 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients on treatment
timeFrame: Day 0 - 8 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 0 - before the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 0- 4 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 0 - 8 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 1 - before the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 1 - 4 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 1- 8 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 3- before the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 3 - 4 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 3- 8 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 7- before the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 7 - 4 hours after the morning dose
measure: Pharmakokinetic of CaD in plasma for patients starting treatment
timeFrame: Day 7- 8 hours after the morning dose
measure: Correlation between nasal mucosal tissue and plasma concentration for patients on treatment
timeFrame: Day 0
measure: Correlation between oral tissue and plasma concentration for patients on treatment
timeFrame: Day 0
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: HUG
Study officials:
References: