Healthy volunteers and patients with COVID - 19 MedDRA version: 23.0 Level: HLT Classification code 10084510 Term: Coronavirus infections System Organ Class: 100000004862
Conditions
Interventions
Product Name: Hydroxychloroquine Sulfate Solution for Nebulization
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Hydroxychloroquine
CAS Number: 118-42-3
Concentration unit: % (W/V) pe
Sponsors
Všeobecná fakultní nemocnice v Praze
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria healthy subjects 1. Healthy male volunteers = 18 and = 55 years old (date of ICF signature is decisive). 2. Non-smoker or past-smoker (who has stopped smoking at least 6 months before the first dosing). 3. Body Mass Index at screening = 18.5 and = 30.0 kg/m2. 4. Subject is available for the whole study and has provided his written informed consent. 5. With clinical history and physical examination results within normality. 6. All laboratory screening results within the normal range or deemed clinically insignificant by Investigator. 7. Acceptance of use of effective contraceptive measures during the whole study. 8. Screening Vital signs and ECG without significant deviations. 9. Czech citizenship. Inclusion criteria COVID-19 patients 1. Study subjects must be =18 years inclusive (male or female) 2. Hospitalized or admitted patients to hospital with COVID-19 pneumonia or respiratory symptoms confirmed with positive PCR or antigen test for SARS-CoV-2 virus 3. Moderate to severe disease with or without supplemental oxygen administration by nasal cannula, face mask and or noninvasive or mechanical ventilation (for the purpose of the study the patient conditions and treatment will be considered, please see the protocol section Study population specific information and procedures) etc 4. Capable of giving sSigned informed consent prior to performing study procedures (please see the protocol section Study population specific information and procedures) 5. For woman of childbearing potential use of contraceptive measures during the study up to follow-up call day 30 after the end of treatment and or later discharge from the hospital Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 137 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria healthy subjects 1. Known hypersensitivity to 4-aminoquinoline compounds and contraindication of HCQ use. 2. Medical history of retinal or visual field changes of any etiology. 3. Acute or chronic diseases and/or clinical findings e.g. several renal or liver impairment, which may interfere with the aims of the study or with the bioavailability and/or pharmacokinetics of the IMP. 4. Medical history of asthma bronchiale or bronchospasms or any allergies deemed clinically significant by Investigator. 5. Clinically significant illness within 4 weeks before the first dosing, including major surgery. 6. Vaccination with live vaccines less than 14 days prior to the first administration of IMP. 7. Use of an investigational drug within 2 months prior to dosing in this study. 8. Use of HCQ within 3 months prior to dosing in this study. 9. Any clinically significant laboratory abnormality, including positive results of HBsAg and/or HCV and/or HIV test during screening procedure. 10. Prolonged QT interval at baseline or at increased risk for arrhythmia. 11. Positive alcohol breath test. 12. Positive urinary drug screen test at check-in. 13. Serious mental disease or inability to cooperate with clinical team. 14. Sitting blood pressure is out of the range of 90 - 140 mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50-100 bpm at screening. 15. Body temperature 37.2°C at screening or baseline. 16. History of substance abuse including alcohol. 17. Donation or loss of = 500 mL of blood within 90 days prior to the first dosing. 18. Donation of plasma or platelets within 14 days prior to the first dosing. 19. Haemoglobin below 120 g/L for women and 130 g/L for men at Screening. 20. Leukocytosis, level of leukocytes above 9.00 * 109/L at Screening. 21. All prescription, over-the-counter and herbal medications are prohibited within 10 days prior to study dosing (with exception of paracetamol =1000 mg/day at the discretion of the Investigator). 22. Subject is not willing to keep contraceptive requirements (set in Inclusion criteria). 23. Employees of the Study Centers, Study personnel and relatives of study personnel Exclusion Criteria COVID-19 patients 1. Presence of retinal or visual field changes of any etiology 2. Known hypersensitivity to 4-aminoquinoline compounds and contraindication of HCQ or present peroral HCQ use 3. Prolonged QT interval at baseline or at increased risk for arrythmia 4. Use of HCQ contraindicated medications (e.g. citalopram) 5. Multi-organ system dysfunction as judged by the investigator to be of clinical relevance 6. Elevated liver enzymes or judged by the investigator to be of clinical relevance 7. Exclusion of patients with hypokalemia/hypomagnesemia 8. Sever renal impairment as judged by the investigator to be of clinical relevance 9. Medical history of asthma bronchiale or bronchospasms or any allergies deemed clinically significant by Investigator 10. Participation of study subject in any concurrently ongoing clinical investigation for COVID-19 treatment which could interfere with the study outcome 11. Pregnancy and breast feeding. 12. Employees of the Study Centers, Study personnel and relatives of study personnel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Assessment of pharmacokinetics of single dose hydroxychloroquine sulfate following inhalation delivery in an ascending dosing scheme. •Population pharmacokinetics after multiple dose administration ;Secondary Objective: •Evaluation of efficacy, safety and tolerability of multiple dose hydroxychloroquine sulfate following inhalation delivery of HCQ combined with standard of care versus standard of care only using oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) considering: •Change in SpO2/FiO2 ratio from baseline versus Day 7 or at release •Time to saturation =92% on room air •Duration of supplemental oxygen use •Time to fever resolution •Number of days without fever •X ray lungs – prior to the start of the therapy and at release (number of affected segments) •Change in quantitative SARS-CoV-2 virus evaluation prior start of the therapy orand Day 1, and at release (nasal swab/BAL/ELF and blood) •Time to progression to noninvasive or invasive mechanical ventilation or ECMO in patients on oxygen or high flow nasal oxygen (HFNO) •Time to weaning from noninvasive or invasive mechanical ventilation or ECMO in the patients on MV or ECMO •Time to release from the hospital •Mortality;Primary end point(s): Healthy: pharmacokinetics of hydroxychloroquine sulfate following inhalation delivery in an ascending dosing scheme Patients: Evaluation of efficacy, safety and tolerability of hydroxychloroquine sulfate following inhalation delivery of HCQ combined with standard of care versus standard of care only using oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) considering: •Change in SpO2/FiO2 ratio from baseline versus Day 7 or at release •Time to saturation =92% on room air •Duration of supplemental oxygen use •Time to fever resolution •Number of days without fever •X ray lungs – prior to the start of the therapy and at release (number of affected segments) •Change in quantitative SARS-CoV-2 virus evaluation prior start of the therapy or Da | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Healthy subjects • Evaluation of safety and tolerability of hydroxychloroquine sulfate following inhalation delivery of HCQ Patients • Assessment of pharmacokinetics of hydroxychloroquine sulfate following inhalation delivery in an ascending dosing scheme. • Population pharmacokinetics after multiple dose administration ;Timepoint(s) of evaluation of this end point: Healthy subjects: 5 days Patients: discharge from hospital | — |
Countries
Czech Republic
Contacts
Public ContactOndrej Slanar
General University Hospital in Prague
Outcome results
None listed