Clinical trial NCT04644705: Safety and Pharmacokinetics of a Novel Niclosamide Solution in Combination With Camostat
Official title: A 3-part Study to Investigate the Safety and Pharmacokinetics of a Novel Niclosamide Solution as a Treatment Option for COVID-19 in Combination With Camostat
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Charité Research Organisation GmbH
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2020-11-25
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Treatment emergent number of Adverse Events
timeFrame: up to 14 days
measure: Maximum plasma concentration of niclosamide (µg/ml)
timeFrame: from predose until 24 hours after intervention
measure: Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h]
timeFrame: from predose until 24 hours after intervention
Secondary outcomes:
measure: Food effect on maximum plasma concentration of niclosamide (µg/ml)
timeFrame: from predose until 24 hours after intervention
measure: Food effect on Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide (AUC0-last) [µg/ml*h]
timeFrame: from predose until 24 hours after intervention
measure: Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing
timeFrame: from predose until Day 9
measure: 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
timeFrame: from predose until Day 9
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
Study officials:
affiliation: Charité Research Organisation GmbH
name: Maximilian Posch, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: