Table 3.
Summary of Safety During the Study Period
| AE Parameter | Simeprevir + Sofosbuvir | Simeprevir + Sofosbuvir + Ribavirin | Totala |
| All patients, n (%) | n = 291 | n = 17 | N = 315 |
| Any AE | 159 (54.6) | 13 (76.5) | 178 (56.5) |
| Any serious AE | 24 (8.2) | 2 (11.8) | 26 (8.3) |
| Any AE at least possibly related to simeprevir | 91 (31.3) | 5 (29.4) | 96 (30.5) |
| Grade ≥2 | 28 (9.6) | 2 (11.8) | 30 (9.5) |
| Any AE leading to permanent stop of ≥1 study medicationb | 3 (1.0) | 1 (5.9) | 4 (1.3) |
| Any fatal AE | 2 (0.7) | 0 | 2 (0.6) |
| Most common (>3% of patients) AEs | |||
| Headache | 39 (13.4) | 2 (11.8) | 41 (13.0) |
| Nausea | 34 (11.7) | 1 (5.9) | 35 (11.1) |
| Fatigue | 32 (11.0) | 6 (35.3) | 40 (12.7) |
| Insomnia | 15 (5.2) | 4 (23.5) | 21 (6.7) |
| Rash | 11 (3.8) | 1 (5.9) | 14 (4.4) |
| Abdominal pain | 10 (3.4) | 0 | 10 (3.2) |
| Diarrhea | 10 (3.4) | 0 | 10 (3.2) |
| Dyspnea | 8 (2.7) | 3 (17.6) | 11 (3.5) |
| Anemia | 7 (2.4) | 4 (23.5) | 13 (4.1) |
| Patients with cirrhosis, n (%) | n = 116 | n = 6 | n = 124 |
| Any AE | 68 (58.6) | 6 (100) | 76 (61.3) |
| Any serious AE | 15 (12.9) | 2 (33.3) | 17 (13.7) |
| Any AE at least possibly related to simeprevir | 38 (32.8) | 2 (33.3) | 40 (32.3) |
| Grade ≥2 | 12 (10.3) | 0 | 12 (9.7) |
| Patients without cirrhosis, n (%) | n = 175 | n = 11 | n = 191 |
| Any AE | 91 (52.0) | 7 (63.6) | 102 (53.4) |
| Any serious AE | 9 (5.1) | 0 | 9 (4.7) |
| Any AE at least possibly related to simeprevir | 53 (30.3) | 3 (27.3) | 56 (29.3) |
| Grade ≥2 | 16 (9.1) | 2 (18.2) | 18 (9.4) |
Abbreviation: AE, adverse event.
aIncludes 7 patients treated with simeprevir + peginterferon + ribavirin.
bThe 3 patients in the simeprevir + sofosbuvir group each discontinued both study medications; AEs leading to discontinuation were chronic kidney disease (serious AE, not related to simeprevir), renal impairment (not serious, not related to simeprevir), and thrombocytopenia (very likely related to both simeprevir and sofosbuvir). The 1 patient in the simeprevir + sofosbuvir + ribavirin group discontinued ribavirin only due to anemia (very likely related to ribavirin).