Safety and Pharmacokinetics of a Novel Niclosamide Solution in Combination With Camostat (NIC-002)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Niclosamide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité Research Organisation GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part A: verum niclosamide; The SAD cohorts are planned as follows: Cohort A1: 200 mg (fasted conditions) Cohort A2: 600 mg (fasted conditions) Cohort A3: 1600 mg (fasted and fed conditions)	Drug: Niclosamide; Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
Placebo Comparator: Part A: placebo to niclosamide; The SAD cohorts are planned as follows: Cohort A1: placebo to niclosamide 200 mg (fasted conditions) Cohort A2: placebo to niclosamide 600 mg (fasted conditions) Cohort A3: placebo to niclosamide 1600 mg (fasted and fed conditions)	Drug: Placebo; placebo to the interventional drug
Active Comparator: Part B: verum as solution (niclosamide); Two different crossover designs are chosen. Both are randomized, open-label, two-sequence, two periods crossover designs comparing the new niclosamide solution with the marketed chewing tablets. Planned doses are 1600 mg once daily (oral solution), 2000 mg once daily (chewing tablets) and 500 mg three times daily of both dosage forms.	Drug: Niclosamide; Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
Active Comparator: Part B: verum as chewing tablet (niclosamide); Two different crossover designs are chosen. Both are randomized, open-label, two-sequence, two periods crossover designs comparing the new niclosamide solution with the marketed chewing tablets. Planned doses are 1600 mg once daily (oral solution), 2000 mg once daily (chewing tablets) and 500 mg three times daily of both dosage forms.	Drug: Niclosamide; Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
Active Comparator: Part C: verum (niclosamide and camostat); Subjects will receive the combination of niclosamide solution (planned 500 mg three times daily) + camostat (600 mg three times daily) or placebo over a treatment period of 7 days. The dose of the niclosamide solution depends on the safety and pharmacokinetic results of Part A and B but will not exceed 500 mg three times daily.	Drug: Niclosamide; Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
Placebo Comparator: Part C: placebo to niclosamide and camostat; Subjects will receive the combination of niclosamide solution (planned 500 mg three times daily) + camostat (600 mg three times daily) or placebo over a treatment period of 7 days. The dose of the niclosamide solution depends on the safety and pharmacokinetic results of Part A and B but will not exceed 500 mg three times daily.	Drug: Placebo; placebo to the interventional drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent number of Adverse Events	Assessment of severity of an AE will be based on CTCAE Version 5.0	up to 14 days
Maximum plasma concentration of niclosamide (µg/ml)	Measurement will start at Day 1	from predose until 24 hours after intervention
Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h]	Measurement will start at Day 1	from predose until 24 hours after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food effect on maximum plasma concentration of niclosamide (µg/ml)	Measurement will start at Day 1 after a standard high fat breakfast	from predose until 24 hours after intervention
Food effect on Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide (AUC0-last) [µg/ml*h]	Measurement will start at Day 1 after a standard high fat breakfast	from predose until 24 hours after intervention
Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing		from predose until Day 9
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

Collaborators and Investigators

• Sponsor: Charité Research Organisation GmbH
• Collaborators: Bayer
• Investigators: Principal Investigator: Maximilian Posch, Dr. med., Charité Research Organisation GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Actual): May 3, 2021
• Study Completion (Actual): May 3, 2021

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2021
• Last Update Submitted That Met QC Criteria: November 26, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Niclosamide
• Other Study ID Numbers: 201767

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No