Alkalinization
Analgesics..
Antiandrogens..
Bromhexine
Budesonide
Cannabidiol
Colchicine
Conv. Plasma
Curcumin
Ensovibep
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Iota-carragee..
Ivermectin
Lactoferrin
Lifestyle..
Melatonin
Metformin
Molnupiravir
Monoclonals..
Nigella Sativa
Nitazoxanide
Nitric Oxide
Paxlovid
Peg.. Lambda
Povidone-Iod..
Quercetin
Remdesivir
Vitamins..
Zinc

Other
Feedback
Home
Home   COVID-19 treatment studies for Molnupiravir  COVID-19 treatment studies for Molnupiravir  C19 studies: Molnupiravir  Molnupiravir   Select treatmentSelect treatmentTreatmentsTreatments
Alkalinization Meta Lactoferrin Meta
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta Molnupiravir Meta
Cannabidiol Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Nitric Oxide Meta
Ensovibep Meta Paxlovid Meta
Famotidine Meta Peg.. Lambda Meta
Favipiravir Meta Povidone-Iod.. Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Iota-carragee.. Meta
Ivermectin Meta Zinc Meta

Other Treatments Global Adoption
All Studies   All Outcomes   Recent:  
0 0.5 1 1.5 2+ Recovery -33% Improvement Relative Risk Recovery (b) -100% Recovery (c) -100% Recovery (d) 0% Recovery (e) 0% Recovery (f) -50% Recovery (g) -200% Recovery (h) -50% c19early.org/m Khoo et al. NCT04746183 Molnupiravir RCT EARLY TREATMENT Is early treatment with molnupiravir beneficial for COVID-19? RCT 18 patients in the United Kingdom Trial underpowered to detect differences Khoo et al., J. Antimicrobial Chemotherapy, doi:10.1093/jac/dkab318 Favors molnupiravir Favors control

Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study

Khoo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkab318, NCT04746183 (history)
Khoo et al., Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label,.., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkab318, NCT04746183
Aug 2021   Source   PDF  
  Twitter
  Facebook
Share
  All Studies   Meta
Dose and safety study of molnupiravir with 18 participants, finding no serious adverse events in short-term followup. There was no significant difference in clinical outcomes. NCT04746183 (history).
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer [Hadj Hassine, Swanstrom]. See [Fountain-Jones, Sanderson, twitter.com] for analysis of variants potentially created by molnupiravir.
risk of no recovery, 33.3% higher, RR 1.33, p = 0.63, treatment 8 of 12 (66.7%), control 3 of 6 (50.0%), all dosages, symptomatic at day 15.
risk of no recovery, 100% higher, RR 2.00, p = 0.61, treatment 4 of 12 (33.3%), control 1 of 6 (16.7%), all dosages, symptomatic at day 29.
risk of no recovery, 100% higher, RR 2.00, p = 0.20, treatment 4 of 4 (100.0%), control 3 of 6 (50.0%), 800mg, symptomatic at day 15.
risk of no recovery, no change, RR 1.00, p = 1.00, treatment 2 of 4 (50.0%), control 3 of 6 (50.0%), 600mg, symptomatic at day 15.
risk of no recovery, no change, RR 1.00, p = 1.00, treatment 2 of 4 (50.0%), control 3 of 6 (50.0%), 300mg, symptomatic at day 15.
risk of no recovery, 50.0% higher, RR 1.50, p = 1.00, treatment 1 of 4 (25.0%), control 1 of 6 (16.7%), 800mg, symptomatic at day 29.
risk of no recovery, 200.0% higher, RR 3.00, p = 0.50, treatment 2 of 4 (50.0%), control 1 of 6 (16.7%), 600mg, symptomatic at day 29.
risk of no recovery, 50.0% higher, RR 1.50, p = 1.00, treatment 1 of 4 (25.0%), control 1 of 6 (16.7%), 300mg, symptomatic at day 29.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Khoo et al., 27 Aug 2021, Randomized Controlled Trial, United Kingdom, peer-reviewed, 38 authors, average treatment delay 4.0 days, trial NCT04746183 (history).
All Studies   All Outcomes   Submit Updates or Corrections
This PaperMolnupiravirAll
Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study
Saye H Khoo, Richard Fitzgerald, Thomas Fletcher, Sean Ewings, Thomas Jaki, Rebecca Lyon, Nichola Downs, Lauren Walker, Olana Tansley-Hancock, William Greenhalf, Christie Woods, Helen Reynolds, Ellice Marwood, Pavel Mozgunov, Emily Adams, Katie Bullock, Wayne Holman, Marcin D Bula, Jennifer L Gibney, Geoffrey Saunders, Andrea Corkhill, Colin Hale, Kerensa Thorne, Justin Chiong, Susannah Condie, Henry Pertinez, Wendy Painter, Emma Wrixon, Lucy Johnson, Sara Yeats, Kim Mallard, Mike Radford, Keira Fines, Victoria Shaw, Andrew Owen, David G Lalloo, Michael Jacobs, Gareth Griffiths
Objectives: AGILE is a Phase Ib/IIa platform for rapidly evaluating COVID-19 treatments. In this trial (NCT04746183) we evaluated the safety and optimal dose of molnupiravir in participants with early symptomatic infection. Methods: We undertook a dose-escalating, open-label, randomized-controlled (standard-of-care) Bayesian adaptive Phase I trial at the Royal Liverpool and Broadgreen Clinical Research Facility. Participants (adult outpatients with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset) were randomized 2:1 in groups of 6 participants to 300, 600 and 800 mg doses of molnupiravir orally, twice daily for 5 days or control. A dose was judged unsafe if the probability of 30% or greater dose-limiting toxicity (the primary outcome) over controls was 25% or greater. Secondary outcomes included safety, clinical progression, pharmacokinetics and virological responses. Results: Of 103 participants screened, 18 participants were enrolled between 17 July and 30 October 2020. Molnupiravir was well tolerated at 300, 600 and 800 mg doses with no serious or severe adverse events. Overall, 4 of 4 (100%), 4 of 4 (100%) and 1 of 4 (25%) of the participants receiving 300, 600 and 800 mg molnupiravir, respectively, and 5 of 6 (83%) controls, had at least one adverse event, all of which were mild ( grade 2). The probability of !30% excess toxicity over controls at 800 mg was estimated at 0.9%. Conclusions: Molnupiravir was safe and well tolerated; a dose of 800 mg twice daily for 5 days was recommended for Phase II evaluation.
Author contributions S.H.K., G.G., T.J., S.E., R.F. and P.M. contributed to study design. S.H.K., G.G., T.J., S.E., G.S., K.T., P.M. and H.P. contributed to data analysis and interpretation. R.F. led clinical conduct as the principal investigator of the clinical site. T.F., L.W., R.L. and M.D.B. participated in clinical assessment and data collection. K.F. participated in the management of pharmacovigilance. S.C., E.W., M.R. and L.J. contributed to the digital data collection and data management of the trial. M.R. led set-up of the randomization system. W.G., T.F., V.S., E.A., K.B. and C.H. contributed to study bioanalysis. A.C., N.D., E.M., O.T.-H., S.Y., H.R., J.C., R.L., C.W., J.L.G., A.O., M.J. and D.G.L. contributed to study management and execution. K.M. contributed to monitoring activities. W.P. and W.H. contributed preclinical and safety data on molnupiravir. S.H.K., G.G., M.J., A.O. and D.G.L. were involved in primary manuscript writing. All authors contributed to the final version of the manuscript. The statisticians S.E., G.S. and K.T. had full access to all the data in the study and S.H.K. and G.G. had final responsibility for the decision to submit for publication. Disclaimer The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Supplementary data Supplement S1 and Supplement S2 are available as Supplementary data at JAC Online.
References
Cevik, Tate, Lloyd, SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis, Lancet Microbe
Cox, Wolf, Plemper, Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets, Nat Microbiol
Griffiths, Fitzgerald, Jaki, AGILE-ACCORD: a randomized, multicentre, seamless, adaptive phase I/II platform study to determine the optimal dose, safety and efficacy of multiple candidate agents for the treatment of COVID-19: a structured summary of a study protocol for a randomised platform trial, Trials
Mozgunov, Jaki, Paoletti, Randomized dose-escalation designs for drug combination cancer trials with immunotherapy, J Biopharm Stat
Painter, Holman, Bush, Human safety, tolerability, and pharmacokinetics of a novel broad-spectrum oral antiviral compound, molnupiravir, with activity against SARS-CoV-2, Antimicrob Agents Chemother
Painter, Sheahan, Baric, Reduction in infectious SARS-CoV-2 in treatment study of COVID-19 with molnupiravir
Rosenke, Hansen, Schwarz, Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model, Nat Commun
Wahl, Gralinski, Johnson, SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801, Nature
Loading..
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit