Subjects not continuing in the study (%) 1 (8.3) 2 0 2 5 Reason for not continuing in the study (%) Adverse event 0 1 (8.3) 0 0 1 (2.1) Lost to follow-up 0 1 (8.3) 0 1 (9.1) 2 (4.3) Poor/non-compliance 0 0 0 1 (9.1) 1 (2.1) Subject request to discontinue study treatment 1 (8.3) 0 0 0 1 (2.1) 1 Subjects completing or not completing the on-treatment period; 2 Subjects who continued into or did not continue the follow-up period. Table 4B: End of treatment period – Stage 2 – Treated subjects ASV 200 mg BD PBO Total Subjects 177 61 238 Subjects completing the period 1 (%) 153 (86.4) 41 (67.2) 194 (81.5) Subjects not completing the period 1 (%) 24 (13.6) 20 (32.8) 44 (18.5) Reason for not completing the period 1 (%) Lack of efficacy 7 (4.0) 11 (18.0) 18 (7.6) Adverse event 10 (5.7) 3 (4.9) 13 (5.5) Subject withdrew consent 2 (1.1) 1 (1.6) 3 (1.3) Death 1 (0.6) 0 1 (0.4) Lost to follow-up 1(0.6) 1 (1.6) 2 (0.8)
AST 0 1 (8.3) 2 (16.7) 0 Haemoglobin 0 0 2 (16.7) 1 (9.1) TBIL 1 (8.3) 1 (8.3) 1 (8.3) 0 Lipase 0 1 ( 8.3) 0 0 Platelets 0 0 1 (8.3) 0 ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; WBC, white blood cell. Serious adverse events Deaths: There were no deaths reported in Stage 1. Other SAEs: 5 subjects reported SAEs, 2 (16.7%) subjects each in the ASV 200 mg BD and ASV 600 mg QD groups and 1 in the ASV 600 mg BD group. No SAEs led to discontinuation of study therapy. Table 9: Study AI447016: Other serious adverse events. Stage 1 – enrolled subjects Treatment Group Preferred to Study Therapy a Onset and Duration 200-mg BD ASV 54 year old male Grade 3 Not related Onset: OT Week 32 Duration: 266 days Study drug not interrupted, treatment required 50 year old male Abdominal Pain/Grade 2 Not related OT Week 1 Duration: 8 days Study drug not interrupted, treatment required 600-mg BD ASV 54 year old Black female Goitre/Grade 2 Not related Onset: OT Week 48 Duration: 56 days drug not interrupted, treatment required 600-mg QD ASV 69 year old White male Hepatocellular injury/Grade 3 Related Onset: OT Week 6 Duration: 42 days Study drug not interrupted, treatment not required
40 year old White female Acute Psychosis b/Grade 2 Related Onset: OT Week 2 Duration: continuing Study drug discontinued, treatment required 57 year old White female Epistaxis/Grade 3 Not related Onset: OT Week 10 Duration: 48 hours drug interrupted, treatment required 45 year old White male Chest Pain/Grade 1 Syncope/ Grade 1 Not related Onset: OT Week 16 Duration: 3 days drug not interrupted, treatment not required 55 year old White female Bacteraemia/Grade 3 3 3 Related Onset: OT Week 16 Duration: 6 days Study drug not interrupted, treatment required 50 year old White male Urinary Tract Infection/Grade 1 Not related Onset: OT Week 32 Duration: 2 days Study drug not interrupted, treatment required 29 year old Egyptian male Suicide Attempt b/Grade 4 Related Onset: OT Week 4 Duration: 6 days Study drug discontinued, treatment required 63 year old White male Dizziness/Grade 3 Not related Onset: OT Week 6 Duration: 4 days Study drug not interrupted, treatment required 53 year old White female 2 Not related Onset: OT Week 16 Duration: 18.7 hours Study drug not interrupted, treatment required
SVR24 155/203 (76.4) f NA NA NA RVR 168/203 (82.8) NA NA NA cEVR 191/203 (94.1) NA NA NA EOTR 189/203 (93.1) NA NA NA SVR4 181/203 (89.2) NA NA NA Ineligible/intolerants SVR12 194/235 (82.6) [77.7 , 87.4] 119/135 (88.1) [82.7 , 93.6] 14/22 (63.6) [43.5, 83.7] SVR24 168/235 (71.5) g 118/135 (87.4) 14/22 (63.6) NA RVR 159/235 (67.7) 114/135 (84.4) 19/22 (86.4) NA cEVR 205/235 (87.2) 125/135 (92.6) 20/22 (90.9) NA EOTR 204/235 (86.8) 129/135 (95.6) 19/22 (86.4) NA SVR4 198/235 (84.3) 126/135 (93.3) 15/22 (68.2) NA Prior non-responders SVR12 169/205 (82.4) [77.2 , 87.6] 70/87 (80.5) [72.1, 88.8] 10/11 (90.9) (73.9, 100.0] 15/18 (83.3) [66.1 , 100] SVR24 152/205 (74.1) f 70/87 (80.5) 10/11 (90.9) 16/18 (88.9)