Oral formulations
Of the 12 Phase 2/3 trials (Table 2), nine trials are investigating oral
formulations of niclosamide with seven using the marketed oral tablet
form of niclosamide (also known under the tradename Yomesan), one
utilising capsules and one a novel suspension. However, one of these is
registered as suspended due to the ongoing pandemic.
Niclosamide in a chewable tablet form is being investigated in moderate
COVID-19 patients with gastrointestinal signs and symptoms at a dose of
400mg orally TDS for 14 days (NCT04542434, NCT04858425). Mortality,
adverse event rate, faecal virus clearance and several clinical features
have been listed as outcome measures. Niclosamide in a chewable tablet
form is also being investigated (in addition to SoC) in
asymptomatic/mild outpatient cases at 500mg orally BD for 7-14 days
(CTRI/2020/04/024949), mild-moderate cases at 2g orally QDS for seven
days (NCT04399356), moderately ill hospitalized COVID-19 cases with
gastrointestinal symptoms (NCT04436458), and mild-severe patients
receiving a 2g loading dose + 1g every 12 hours on day one and then 1g
TDS for seven days (NCT04753619). The last trial was recently published
(Abdulamir et al., 2021). This randomized, open label, controlled trial
included 75 mild-severe COVID-19 patients treated with SoC plus
niclosamide (tablet) orally versus 75 patients receiving SoC only. Each
group consisted of 25 mild, 25 moderate and 25 severe cases (defined
according to WHO classification criteria). In moderate and severe, but
not mild COVID-19 patients receiving “niclosamide + SoC” time to
recovery was significantly lower, especially in patients with
comorbidities compared to SoC only. Survival was not significantly
increased. The small sample size in each disease severity group and the
open label nature of the study have limited any robust conclusions being
drawn from the study.
A niclosamide suspension is currently being tested in moderate
hospitalized COVID-19 patients receiving 200mg/10mL niclosamide TDS for
five days (in addition to SoC), with time from admission to clinical
recovery as the primary outcome measure. Another trial utilizes four
250mg niclosamide capsules BD for seven consecutive days in moderate-
severe cases defining safety and median time to hospital discharge as
the primary outcome measures. Efficacy readouts of the other clinical
trials investigating oral niclosamide preparations across the full
COVID-19 disease spectra are awaited.