. 2021 Oct 30;15(6):102329. doi: 10.1016/j.dsx.2021.102329

Table 1.

A. Published and unpublished (interim results), B. Stopped, and C. Ongoing studies with molnupiravir in COVID-19.

Study, First author	CTRL/CTRI identifier, Eponyms	N; Types of study	Severity of COVID-19	Arms (n)	Results	Side effects	Strength/Limitations
*A. Published and unpublished interim results*
Phase 1 studies
Painter et al.¹⁴	NCT04392219	130; DBRPC	NA	i) SD 50–1600 mg MOLNU or PBO (64) ii) MD 50–800 mg BID MOLNU or PBO (56) iii) 200 mg MOLNU (10) – Food effect	A range from 50 to 800 mg twice daily dosing for 5.5 days and a single dose up to 1600 mg was found to be safe and well tolerated	A greater proportion of patients in placebo arm had higher adverse events compared to molnupiravir in both single (43.8% vs. 35.4%, respectively) and multiple ascending doses (50.0% vs. 42.9%, respectively) arm. While headache was the most frequently reported adverse event in single ascending doses study (placebo arm had proportionately higher headache compared to molnupiravir [18.8% vs. 12.5%, respectively]), diarrhea was the most frequently reported adverse event noted in multiple ascending dose study (7.1% each in placebo and molnupiravir).	Peer reviewed, Published
Khoo et al.¹⁵	NCT04746183, AGILE	18; R, OL	Mild or moderate	i) 300 mg MOLNU BID (4) ii) 600 mg MOLNU BID (4) iii) 800 mg MOLNU BID (4) iv) SOC (6)	Primary outcome – dose-limiting toxicity	All (4/4, 100%) patients receiving 300 and 600 mg, 1/4 (25%) patients receiving 800 mg, and 5/6 patients (83%) receiving SOC were found to have mild adverse events. This finds highest dose of 800 mg twice daily had a 0.9% probability of having 30% excess toxicity over the controls, and therefore molnupiravir was safe and well tolerated with a plasma concentration within the target range.	Peer reviewed, Published
Phase 2 studies
Fischer et al.¹⁶	NCT04405570	202; DBRPC	Mild or moderate	i) 300 mg MOLNU BID (23) ii) 400 mg MOLNU BID (62) iii) 800 mg MOLNU BID (55) iv) PBO (62)	Time to clearance (RNA negativity) - the primary outcome - was significantly reduced in the molnupiravir 800 mg arm twice daily compared to the placebo (log-rank p value = 0.013, median: 14 days). Moreover, reduction in time to clearance of viral RNA was also greater and significant when compared to placebo (median: 14 days vs. 27 days; p value = 0.01).	Very few adverse events were noted in this study and was found to be lowest in molnupiravir 800 mg twice daily group. Headache, insomnia and increased levels of alanine aminotransferase (ALT) were the only adverse events reported by more than 4 participants and 5% and 8.1% of molnupiravir and placebo groups, respectively showed grade 3 level of adverse events. Two (2/140, 1.4%) as compared to one (1/62, 1.6%) adverse event led to discontinuation in molnupiravir and placebo groups respectively	Peer reviewed, Published
Phase 3 studies
–	NCT04575597, MOVe-OUT^18-20	775; DBRPC	Mild to moderate with 1 risk factor	i) MOLNU (385^a) ii) PBO (377^a)	Study found 7.3% of patients (28/385) on molnupiravir as compared to 14.1% of patients on placebo (53/377) had either been admitted to hospital or died suggesting a significant reduction in the risk of hospital admission or death by 50% (p = 0.0012) at day 29. No death was reported in the molnupiravir group as compared to 8 deaths in the placebo group on day 29.	The incidence of any adverse events (35% vs. 40% in molnupiravir vs. placebo arm, respectively) and drug-related adverse events (12% vs. 11% in molnupiravir vs. placebo arm, respectively) were found to be similar in both molnupiravir and placebo arm. Fewer people in the molnupiravir arm discontinued treatment as compared to the placebo arm (1.3% vs. 3.4%, respectively).	Limitations: Interim report, not peer reviewed and unpublished.
–	CTRI/2021/05/033739²⁴	741; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	i) Earlier clinical improvement (2-point decrease in WHO Clinical Progression Scale) in molnupiravir vs. SOC at day 5 (63.4% vs. 22.3%, respectively; p < 0.0001), day 10 (79.0% vs 49.5%, respectively; p < 0.0001) and day 14 (81.6% vs. 73.2%, respectively; p = 0.02). ii) Faster time to clinical improvement in molnupiravir vs. SOC (median time 8 days vs. 12 days, respectively; p = 0.0001). iii) Higher RT-PCR negativity (all p < 0.0001) in molnupiravir vs. SOC at day 5 (77.4% vs. 26.1%, respectively), day 10 (94.0% vs. 57.2%, respectively) and day 14 (97.0% vs. 85.2%, respectively). iv) Significantly fewer hospital admissions in molnupiravir vs. SOC alone (1.9% vs. 6.2% respectively; p = 0.003) over 14 days. No death reported in either group.	Nausea, diarrhea and headache were most common side effect reported – all with mild severity. No one discontinued from the trial.	Limitations: Interim report, not peer reviewed and unpublished. Trial still undergoing.
–	CTRI/2021/06/033992²⁵	353- FIA, OL, R, OC 403- SIA; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	i) The first interim results on 353 patients have shown higher RT-PCR negativity in molnupiravir arm vs. SOC alone (78.3% vs. 48.4%, respectively; p = not reported) on day 5. ii) Second interim results from 403 patients showed – a. significant increase in RT-PCR negativity with molnupiravir vs. SOC alone at day 5 (77.4% vs. 51.5%, p < 0.0001) and day 10 (99.5% vs. 69.5% respectively; p < 0.0001), although no difference noted at day 14 (99.5% vs. 98.5%; p = 0.62). b. Faster clinical improvement (at least one-point improvement from baseline on WHO ordinal scale) was also observed in molnupiravir vs. SOC at both day 5 (79.0% vs. 51.3%, respectively; p < 0.0001) and day 10 (97.8% vs. 82.3% respectively; p < 0.0001). However, no difference was noted at day 14. c. There have been 1 hospitalization in molnupiravir arm compared to 3 in SOC.	6.5% subjects in molnupiravir arm had adverse events compared to 8.9% in SOC group. Serious adverse events were reported in 1 subject in molnupiravir arm compared to 3 in SOC.	Limitations: Interim report, not peer reviewed and unpublished. Trial still undergoing.
*B. Stopped phase 3 studies due to futility*
–	NCT04575584, MOVe-IN^{21, 22}	304; DBRPC	Severe, Hospitalized	NR	Stopped due to futility	–	Limitations: Interim report, not peer review and unpublished.
–	CTRI/2021/05/033864²⁷	NA; OL, R, PC	Moderate	NR	Stopped due to futility	–	Limitations: Interim report, not peer review and unpublished.
–	CTRI/2021/08/035424²⁷	100; OL, R, PC	Moderate	NR	Stopped due to futility	–	Limitations: Interim report, not peer review and unpublished.
*B. Ongoing phase 2 and 3 studies*
–	NCT04405739, END-COVID¹⁷	96; DBRPC	Mild to moderate but hospitalized	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessing virological clearance.	Being assessed	–
–	NCT04939428, MOVe-AHEAD²³	1332; DBRPC	Non-COVID	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessing prevention with molnupiravir as a post-exposure prophylaxis.	Being assessed	First prevention trial
–	CTRI/2021/05/033736²⁶	1282, OL, R, PC	Moderate	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessing proportion of clinical improvement at day 14 as a primary outcome. Secondary outcome assessment includes proportion of clinical improvement at day 28, mortality rate at day 28; viral negativity at day 10, day 14 and day 28.	Being assessed	–
–	CTRI/2021/06/034220²⁶	1282, OL, R, PC	Moderate	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessing proportion of clinical improvement at day 14 as a primary outcome. Secondary outcome assessment includes proportion and time to clinical improvement at day 28, mortality rate at day 28; viral load at day 10, day 15 and day 28.	Being assessed	–
–	CTRI/2021/07/034588²⁶	1220; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessment of rate of hospitalization^# from randomization up to day 14 as a primary outcome. Secondary outcome assessment includes rate of hospitalization up to day 28; and proportion of clinical improvement at day 10, day 14 and day 28.	Being assessed	–
–	CTRI/2021/05/033693²⁶	1218; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessment of rate of hospitalization^# from randomization up to day 14 as a primary outcome. Secondary outcome assessment includes rate of hospitalization up to day 28; mortality rate at day 14; RT-PCR negativity at day 10 and day 15; time to clinical improvement at day 14; and proportion of clinical improvement at day 10, day 14 and day 28.	Being assessed	–
–	CTRI/2021/05/033904²⁶	1218; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessment of rate of hospitalization^# from randomization up to day 14 as a primary outcome. Secondary outcome assessment includes rate of hospitalization up to day 28; proportion of clinical improvement at day 10, day 14 and day 28; time to clinical improvement up to day 14; and change in viral load up to EOT.	Being assessed	–
–	CTRI/2021/06/034130²⁶	1218; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessment of rate of hospitalization^b from randomization up to day 14 as a primary outcome. Secondary outcome assessment includes rate of hospitalization up to day 28; proportion of clinical improvement at day 10, day 14 and day 28; time to clinical improvement up to day 14; and mortality rate at day 14 and day 28.	Being assessed	–
–	CTRI/2021/06/033938²⁶	1218; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessment of rate of hospitalization^# from randomization up to day 14 as a primary outcome. Secondary outcome assessment includes rate of hospitalization up to day 28; proportion of clinical improvement at day 10, day 14 and day 28; time to clinical improvement up to day 14; rate of viral negativity at day 10, day 15 and day 28; and mortality rate at day 14 and day 28.	Being assessed	–
–	CTRI/2021/06/034015²⁶	1220; OL, R, PC	Mild	i) MOLNU 800 mg BID + SOC (NA) ii) SOC (NA)	Assessment of rate of hospitalization^# from randomization up to day 14 as a primary outcome. Secondary outcome assessment includes rate of hospitalization up to day 28; proportion of clinical improvement at day 10, day 14 and day 28; time to clinical improvement up to day 14; and mortality rate at day 14 and day 28	Being assessed	–

Completed the trial.

Hospitalization is defined as hospital admission for >24 h with RR ≥ 24/minute and SpO2 ≤ 93% in room air requiring O2 supplementation; DBRPC: Double-blind, randomized, placebo-controlled; OL: Open-label; R: Randomized; PC; Placebo-controlled; SOC: Standard of care; MOLNU: Molnupiravir; PBO; Placebo; RT-PCR: Reverse transcriptase polymerase chain reaction; NA: Not applicable/available; NR; Not retrievable; BID: Twice daily; FIA: First interim analysis; SIA: Second interim analysis.