Table 3.
Adverse Events
| Z3P3 (n = 616) | Z6 (n = 613) | ||
|---|---|---|---|
| AE | n (%) | n (%) | p Value |
| General adverse events | |||
| Total subjects with any AE | 552 (89.61) | 552 (90.05) | 0.85 |
| Total subjects with any SAE | 168 (27.27) | 191 (31.16) | 0.15 |
| Total deaths | 18 (2.92) | 26 (4.24) | 0.22 |
| Total subjects discontinuing because of AE | 11 (1.79) | 14 (2.28) | 0.55 |
| Renal events | (n = 615) | (n = 612) | |
| Increase in serum creatinine >0.5 mg/dLa | 4 (0.65) | 18 (2.94) | 0.002 |
| Urinary protein dipstick >2+a | 1 (0.16) | 2 (0.33) | 0.62 |
| Calculated creatinine clearance <30 mL/minb | 21 (3.60) | 28 (4.86) | 0.31 |
| Most commonly occurring postdose symptoms (≤3 days)c | |||
| Pyrexia | 10 (1.62) | 19 (3.10) | 0.09 |
| Myalgia | 15 (2.44) | 19 (3.10) | 0.49 |
| Influenza-like illness | 5 (0.81) | 8 (1.31) | 0.42 |
| Headache | 16 (2.60) | 20 (3.26) | 0.50 |
| Arthralgia | 8 (1.3) | 10 (1.6) | 0.64 |
| Any of above (after year 4 infusion) | 29 (4.7) | 36 (5.9) | 0.38 |
| Any of above (after year 5 infusion) | 14 (2.3) | 24 (3.9) | 0.10 |
| Any of above (after year 6 infusion) | 7 (1.1) | 14 (2.3) | 0.13 |
| Cardiovascular AEs | |||
| Arrhythmiad | |||
| Any AE | 52 (8.4) | 60 (9.8) | 0.43 |
| SAE | 11 (1.8) | 20 (3.3) | 0.11 |
| Atrial fibrillation | |||
| Any AE | 13 (2.1) | 21 (3.4) | 0.17 |
| SAE | 7 (1.1) | 12 (2.0) | 0.26 |
| Strokee | |||
| SAE | 9 (1.5) | 19 (3.1) | 0.06 |
| Death from strokef | 0 (0.0) | 4 (0.7) | 0.06 |
| Myocardial infarction | |||
| Any AE | 4 (0.6) | 6 (1.0) | 0.55 |
| SAE | 4 (0.6) | 5 (0.8) | 0.75 |
| Hypertensiong | 93 (15.1) | 48 (7.8) | 0.0001 |
| Death from cardiovascular causesf | 3 (0.5) | 8 (1.3) | 0.14 |
AE = adverse event; SAE = serious adverse event.
For urinary protein dipstick >2 +, an extension criterion of baseline urinary protein dipstick ≤2+ is required. All increases in creatinine clearance were temporary and resolved with additional remeasurement. All patients with increased levels 9 to 11 days after dose had resolved and could be redosed at next annual visit (years 4 and 5).
For creatinine clearance <30 mL/min, an extension criterion of baseline creatinine clearance ≥30 mL/min is required.
The five most common AEs reported within 3 days of infusion in the ZOL group in the core study.
Arrthymia category includes AEs coded to MedDRA Arrthymia Higher Level Group term.
Twenty-eight women with 35 events. Category of stroke includes selected relevant terms within the MedDRA System Organ Classification of nervous system disorders, which had been predefined for reporting strokes for regulatory submissions. Specific MedDRA terms within this set (with ≥2 events): cerebrovascular accident or cerebral infarction (total = 11; Z3P3 = 5, Z6 = 6), transient ischemic attack (TIA) (total = 9; Z3P3 = 2, Z6 = 7), cerebral hemorrhage (total = 2; Z3P3 = 0, Z6 = 2). An analysis of baseline risk factors for stroke did not suggest that the nonsignificant imbalance in strokes during the study was because of an imbalance in any baseline risk factors.
Deaths by cause as reported by investigator before adjudication for underlying cause of death. Adjudicated causes could be assigned to 25 (57%) of 44 deaths. Among causes of death after adjudication, those the result of stroke were 1 (Z3P3) and 3 (Z6) and those the result of cardiovascular causes were 1 (Z3P3) and 0 (Z6). Cardiovascular deaths include any death in which the preferred term for the cause was in the MedDRA System Organ Classification of cardiac event.
Preferred term of hypertension (does not include related preferred terms).