Table 3.
Summary of adverse events and changes in hemoglobin and total bilirubin levels across all treatment groups (safety population)
| n (%) | SMV12/PR24 50 mg (n = 27) | SMV24/PR24 50 mg (n = 13) | SMV12/PR24 100 mg (n = 26) | SMV24/PR24 100 mg (n = 13) | All SMV (n = 79) | PR48 (n = 13) |
|---|---|---|---|---|---|---|
| Adverse events | ||||||
| Discontinuation of all treatment due to adverse eventa | 1 (4) | 3 (23) | 3 (12) | 1 (8) | 8 (10) | 2 (15) |
| Discontinuation of simeprevir only due to adverse event | 1 (4) | 0 | 3 (12) | 2 (15) | 6 (8) | |
| Dose modification of PegIFNα-2a or RBV due to adverse event | 17 (63) | 8 (62) | 21 (81) | 12 (92) | 58 (73) | 11 (85) |
| Any serious adverse event | 0 | 1 (8) | 3 (12) | 1 (8) | 5 (6) | 0 |
| Deathb | 0 | 0 | 1 (8) | 0 | 1 (1) | 0 |
| Common adverse eventsc | ||||||
| White blood cell count decreased | 16 (59) | 10 (77) | 15 (58) | 12 (92) | 53 (67) | 10 (77) |
| Malaise | 17 (63) | 8 (62) | 16 (62) | 7 (54) | 48 (61) | 8 (62) |
| Neutrophil count decreased | 12 (44) | 10 (77) | 14 (54) | 12 (92) | 48 (61) | 9 (69) |
| Rash | 17 (63) | 8 (62) | 15 (58) | 8 (62) | 48 (61) | 6 (46) |
| Pyrexia | 18 (67) | 7 (54) | 10 (39) | 7 (54) | 42 (53) | 7 (54) |
| Headache | 14 (52) | 8 (62) | 13 (50) | 6 (46) | 41 (52) | 8 (62) |
| Hemoglobin decreased | 8 (30) | 7 (54) | 12 (46) | 7 (54) | 34 (43) | 6 (46) |
| Arthralgia | 9 (33) | 6 (46) | 7 (27) | 5 (39) | 27 (34) | 2 (15) |
| Alopecia | 11 (41) | 5 (39) | 6 (23) | 3 (23) | 25 (32) | 6 (46) |
| Anemia | 8 (30) | 5 (39) | 6 (23) | 5 (39) | 24 (30) | 5 (39) |
| Protocol predefined rash/cutaneous reactionsd | 21 (78) | 8 (62) | 18 (69) | 8 (62) | 55 (70) | 8 (62) |
| Grade 1 or 2 | 21 (78) | 8 (62) | 18 (69) | 8 (62) | 55 (70) | 8 (62) |
| Grade 3 or 4e | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin and total bilirubin levels by gradef | ||||||
| Hemoglobin levels | ||||||
| Grade 1 (9.5–10.5 g/dL) | 9 (33) | 4 (31) | 9 (35) | 5 (39) | 27 (34) | 8 (62) |
| Grade 2 (8.0–9.4 g/dL) | 5 (19) | 4 (31) | 8 (31) | 6 (46) | 23 (29) | 3 (23) |
| Grade 3 (6.5–7.9 g/dL) or 4 (<6.5 g/dL) | 0 | 0 | 0 | 0 | 0 | 0 |
| Total bilirubin levels | ||||||
| Grade 1 (1.2–1.5 mg/dL) | 10 (37) | 4 (31) | 10 (39) | 6 (46) | 30 (38) | 2 (15) |
| Grade 2 (1.6–2.5 mg/dL) | 3 (11) | 3 (23) | 8 (31) | 2 (15) | 16 (20) | 1 (8) |
| Grade 3 (2.6–5.0 mg/dL) | 1 (4) | 0 | 2 (8) | 0 | 3 (4) | 0 |
| Grade 4 (>5.0 mg/dL) | 0 | 0 | 0 | 1 (8) | 1 (1) | 0 |
All randomized patients who received any amount of investigational drug
PegIFNα-2a peginterferon alpha-2a, RBV ribavirin
aPatients who discontinued PegIFNα-2a/RBV treatment regardless of completion or discontinuation of simeprevir
bThere was one death by cerebral infarction in the SMV12/PR24 100 mg group, which occurred 3 weeks after the end of treatment and was considered to be unrelated to the study medication
cCommon adverse events were those classified as occurring with an incidence of >30 % of patients in all the simeprevir groups
dRash/cutaneous reaction (except for pruritus without visible skin finding), which is considered to have a relationship of causality to any medication
eRashes with some characteristics, such as vesiculation, moist desquamation or ulceration were categorized as grade 3. Exfoliative dermatitis, mucous membrane involvement, erythema multiforme exudativum, Stevens–Johnson syndrome or toxic epidermal necrosis were categorized as grade 4
fAccording to modified World Health Organization toxicity grades. The worst grade during the treatment period for each patient was identified