Healthy Volunteers
Conditions
Brief summary
Niclosamide is a well-established substance that is a promising candidate for a repurposing approach to treat COVID-19. Niclosamide is currently marketed as a chewing tablet for the treatment of intestinal worm infections. The marketed formulation is optimized for minimal drug substance absorption. A niclosamide solution has been developed that is expected to release the drug substance more readily and more reproducibly. Camostat is approved for oral treatment of chronic pancreatitis and reflux oesophagitis in Japan. Camostat has been shown to effectively block viral replication in a SARS-CoV-2 animal model. Since the mechanisms of actions are different, it was hypothesized that a combination of both substances might have an additive or even synergistic effect in the treatment of COVID-19 patients. This 3-part study is designed to investigate (1) safety and pharmacokinetics of single ascending doses of the new niclosamide solution after fasted and fed conditions, (2) the relative bioavailability of the niclosamide solution compared to the chewing tablet, and (3) safety and pharmacokinetics of the combination of niclosamide solution and camostat after multiple doses in healthy volunteers.
Interventions
DRUGNiclosamide
Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
DRUGPlacebo
placebo to the interventional drug
Sponsors
Bayer
Charité Research Organisation GmbH
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This three part study has double-blinded (placebo-controlled) and open-label parts.
Intervention model description
Part A is a randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study with 3 planned cohorts. Part B consists of two randomized, open-label, two-sequence, two-period crossover cohorts comparing the new niclosamide solution with the marketed chewing tablets. Part C is a randomized, double-blinded, placebo-controlled multiple dose study investigating the safety and pharmacokinetics of the combination of niclosamide solution and camostat over a treatment period of 7 days.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects in good health as determined by past medical history * physical examination, vital signs and safety lab at screening * between 18 to 45 years of age
Exclusion criteria
* Significant illness * pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment emergent number of Adverse Events | up to 14 days | Assessment of severity of an AE will be based on CTCAE Version 5.0 |
| Maximum plasma concentration of niclosamide (µg/ml) | from predose until 24 hours after intervention | Measurement will start at Day 1 |
| Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h] | from predose until 24 hours after intervention | Measurement will start at Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Food effect on maximum plasma concentration of niclosamide (µg/ml) | from predose until 24 hours after intervention | Measurement will start at Day 1 after a standard high fat breakfast |
| Area Under the Plasma Concentration Time Curve between two dosing intervals (AUC tau ss) of niclosamide [µg/ml*h] at steady state after multiple dosing | from predose until Day 9 | — |
| Food effect on Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide (AUC0-last) [µg/ml*h] | from predose until 24 hours after intervention | Measurement will start at Day 1 after a standard high fat breakfast |
| Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing | from predose until Day 9 | — |
Countries
Germany
Outcome results
None listed