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

Charité Research Organisation GmbH

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: Niclosamide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04644705

201767

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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28 participants in 6 patient groups, including a placebo group

Part A: verum niclosamide

Active Comparator group

Description:

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)

Treatment:

Drug: Niclosamide

Part A: placebo to niclosamide

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo

Part B: verum as solution (niclosamide)

Active Comparator group

Description:

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.

Treatment:

Drug: Niclosamide

Part B: verum as chewing tablet (niclosamide)

Active Comparator group

Description:

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.

Treatment:

Drug: Niclosamide

Part C: verum (niclosamide and camostat)

Active Comparator group

Description:

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.

Treatment:

Drug: Niclosamide

Part C: placebo to niclosamide and camostat

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo