Table 3.
Overview of safety during the study, including safety follow-up period
| Placebo (n = 66) | Revusiran (n = 140) | |
|---|---|---|
| Number of patients (%) | ||
| Event | ||
| Any AE | 62 (93.9) | 136 (97.1) |
| Any severe AE | 19 (28.8) | 55 (39.3) |
| Any SAE | 34 (51.5) | 83 (59.3) |
| Any AE leading to discontinuation of trial regimen | 1 (1.5) | 20 (14.3) |
| Any AE leading to withdrawal from the trial | 0 | 9 (6.4) |
| Death | 7 (10.6) | 23 (16.4) |
| SAEs occurring in ≥ 5% patients in either treatment arm | ||
| Cardiac failure | 9 (13.6) | 25 (17.9) |
| Cardiac failure acute | 9 (13.6) | 15 (10.7) |
| Cardiac failure congestive | 4 (6.1) | 9 (6.4) |
| Atrial fibrillation | 2 (3.0) | 7 (5.0) |
| Neuropathy peripheral | 0 | 7 (5.0) |
| Atrial flutter | 4 (6.1) | 2 (1.4) |
| AEs occurring in ≥ 15% patients in either treatment arm | ||
| Cardiac failure | 12 (18.2) | 31 (22.1) |
| Cough | 10 (15.2) | 25 (17.9) |
| Neuropathy peripheral | 6 (9.1) | 25 (17.9) |
| Edema peripheral | 12 (18.2) | 25 (17.9) |
| Injection site pain | 4 (6.1) | 23 (16.4) |
| Constipation | 11 (16.7) | 21 (15.0) |
| Dizziness | 13 (19.7) | 18 (12.9) |
| Safety areas of interest | ||
| Cardiac events* | 36 (54.5) | 82 (58.6) |
| Severe cardiac events | 15 (22.7) | 35 (25.0) |
| Serious cardiac events | 25 (37.9) | 56 (40.0) |
| Hepatic events† | 9 (13.6) | 48 (34.3) |
| Severe hepatic events | 0 | 7 (5.0) |
| Serious hepatic events | 0 | 8 (5.7) |
| Renal events‡ | 7 (10.6) | 31 (22.1) |
| Severe renal events | 3 (4.5) | 6 (4.3) |
| Serious renal events | 3 (4.5) | 6 (4.3) |
| Peripheral neuropathy events§ | 8 (12.1) | 28 (20.0) |
| Severe peripheral neuropathy events | 1 (1.5) | 3 (2.1) |
| Serious peripheral neuropathy events | 0 | 7 (5.0) |
| ISR events‖ | 7 (10.6) | 54 (38.6) |
| Severe ISRs | 0 | 0 |
| Serious ISRs | 0 | 0 |
| Myopathy events** | 5 (7.6) | 4 (2.9) |
| Severe myopathy events | 0 | 0 |
| Serious myopathy events | 0 | 1 (0.7) |
| Lactic acidosis events†† | 4 (6.1) | 15 (10.7) |
| Severe lactic acidosis events | 0 | 0 |
| Serious lactic acidosis events | 0 | 1 (0.7) |
*Cardiac events include AEs mapping to the SOC “cardiac disorders”.†Hepatic events include AEs mapping to the SMQ “drug-related hepatic disorders”.‡Renal events include AEs mapping to the SMQ “acute renal failure”.§Peripheral neuropathy events include AEs mapping to the HLT “peripheral neuropathy”.‖Injection site reaction events include AEs mapping to the HLT “injection site reaction”.**Myopathy events include AEs mapping to the SMQ “myopathy” (narrow terms) and additional PTs of “biopsy muscle abnormal”, “electromyogram abnormal”, “muscle disorder”, and “muscular weakness”.††Lactic acidosis events include AEs mapping to the SMQ “lactic acidosis” (e.g., “blood lactate increased”, “lactic acidosis”, “blood bicarbonate decreased”)
AE adverse event, HLT high-level term, ISR injection site reaction, PT preferred term, SAE serious adverse event, SMQ standardized Medical Dictionary for Regulatory Affairs query, SOC system organ class