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.