Table 3.
Summary of Primary and Secondary Efficacy Measures for the Pharmacodynamic (PD) Population and Susceptible Subpopulation, by Cohort and Treatment Group
| Efficacy Result, by Population | QD3HF | BID3HF | QD1HF | QD3STD | Overall | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pocapavir | Placebo | P | Pocapavir | Placebo | P | Pocapavir | Placebo | P | Pocapavir | Placebo | P | Pocapavir | Placebo | P | |
| PD population | |||||||||||||||
| Subjects, no. | 23 | 12 | 24 | 12 | 23 | 12 | 23 | 12 | 93 | 48 | |||||
| Subjects with drug-resistant virus, no. (%) | 5 (22) | 2 (17) | 12 (50) | 1 (8) | 15 (65) | 0 (0) | 8 (35) | 2 (17) | 41 (44) | 5 (10) | |||||
| Primary: time to virus clearance, d, median (95% CI) | 7(5.0–10.0) | 13.5(9.0–18.0) | .0039 | 10(5.0–12.0) | 11.5(9.0–18.0) | .1221 | 14(12.0–18.0) | 14(11.0–18.0) | .7168 | 10(6.0–18.0) | 13(9.0–22.0) | .1714 | 10(9.0–12.0) | 13(11.0–14.0) | .0019 |
| Secondary: percentage reduction in excreted virus (95% CI)a | 84.9 (32.45–6.62) | … | 50.26(−120.09 – 88.76) | … | 43.48(−152.79–87.36) | … | 75.5 (−9.58–94.52) | … | … | … | |||||
| Least squares mean (CCID50 × 106) (95% CI) | 65.8(27.37–58.17) | 435.82(129.41–1467.75) | .0138 | 106.76(45.24–251.94) | 214.62(63.73–722.79) | .3547 | 192.79(80.20–463.43) | 341.07(101.27–1148.63) | .4526 | 291.8(121.39–701.44) | 1190.91(353.62–4010.73) | .0655 | … | … | |
| Susceptible subpopulation | |||||||||||||||
| Subjects, no. | 18 | 10 | 11 | 11 | 8 | 12 | 15 | 10 | 52 | 43 | |||||
| Primary: time to virus clearance, d, median (95% CI) | 6(4.0–8.0) | 12(9.0–14.0) | .0012 | 5(3.0–7.0) | 12(9.0–18.0) | .0003 | 7(4.0–14.0) | 14(11.0–18.0) | .0128 | 6(5.0–10.0) | 13.5(7.0–22.0) | .0017 | 5.5(5.0–7.0) | 13(11.0–14.0) | <.0001 |
| Secondary: percentage reduction in excreted virus (95% CI)a | 94.3(70.79–8.87) | … | 79.17(−26.48–96.23) | … | 76.29(−55.50–96.38) | … | 87.68(33.74–97.71) | … | … | … | |||||
| Least squares mean (CCID50 × 106) | 29.89(11.32–78.95) | 519.74(141.22–1912.79) | .0008 | 48.52(14.01–168.05) | 222.28(64.17–769.91) | .0887 | 80.87(18.84–347.11) | 341.07(64.17–769.91) | .1319 | 159.19(54.94–461.27) | 1291.87(351.03–4754.42) | .0153 | … | … | |
Subjects received placebo or 1600 mg of pocapavir (8 capsules) per day according to the following 4 dosing regimens: once-daily dosing after consuming a high-fat meal (fat content, 60–75 g), starting 72 hours after monovalent oral poliovirus type 1 vaccine (mOPV1) exposure (QD3HF); twice-daily dosing (800 mg each) after a high-fat meal, starting 72 hours after mOPV1 exposure (BID3HF); once-daily dosing after a high-fat meal, starting 24 hours after mOPV1 exposure (QD1HF); and once-daily dosing after a standard meal (fat content, <25 g) starting 72 hours after mOPV1 exposure (QD3STD).
Abbreviations: CCID50, median cell culture infective dose; CI, confidence interval.
aCompared with cohort-matched placebo recipients.