Table 7.
Incidence of Abnormal Renal Test Results in Randomized Placebo-Controlled Phase 2 or Phase 3 Population by Dose Group
| Phase 2 or phase 3 RCT | 2′MOE ASO dose (mg/week) | |||||||
|---|---|---|---|---|---|---|---|---|
| Event, n (%), confirmeda | Placebo (N = 642) | Total ASO (N = 1,366) | >0–75 (N = 76) | >75–175 (N = 175) | >175–275 (N = 793) | >275–375 (N = 225) | >375–475 (N = 85) | >475 (N = 12) |
| Serum chemistries | ||||||||
| Creatinine (mg/dL), n | 637 | 1,344 | 76 | 175 | 773 | 224 | 84 | 12 |
| ≥0.3 mg/dL (26.5 μM) increase from baseline or ≥1.5 × baseline | 11 (1.7) | 32 (2.4) | 2 (2.6) | 3 (1.7) | 20 (2.6) | 5 (2.2) | 2 (2.4) | 0 |
| ≥2 × baseline | 0 | 1 (0.1)b | 0 | 0 | 0 | 0 | 1 (1.2)b | 0 |
| eGFR (mL/min per 1.73 m2), n | 637 | 1,343 | 76 | 175 | 772 | 224 | 84 | 12 |
| <60 mL/min per 1.73 m2 | 22 (3.5) | 62 (4.6) | 2 (2.6) | 4 (2.3) | 43 (5.6) | 9 (4.0) | 4 (4.8) | 0 |
| <30 mL/min per 1.73 m2 | 0 | 1 (0.1) | 0 | 0 | 1 (0.1) | 0 | 0 | 0 |
| BUN (mg/dL), n | 637 | 1,344 | 76 | 175 | 773 | 224 | 84 | 12 |
| ≥2 × ULN or baseline if >ULN | 1 (0.2) | 1 (0.1) | 0 | 0 | 0 | 0 | 1 (1.2) | 0 |
| Albumin (g/dL), n | 637 | 1,344 | 76 | 175 | 773 | 224 | 84 | 12 |
| <LLN, or baseline if <LLN | 4 (0.6) | 8 (0.6) | 0 | 1 (0.6) | 2 (0.3) | 3 (1.3) | 1 (1.2) | 1 (8.3) |
| <2.5 g/dL | 0 (0.0) | 2 (0.1) | 0 | 0 | 1 (0.1) | 0 | 1 (1.2) | 0 |
| Serum electrolytes | ||||||||
| Potassium (mEq/L), n | 637 | 1,342 | 76 | 175 | 771 | 224 | 84 | 12 |
| <LLN or baseline if <LLN | 11 (1.7) | 17 (1.3) | 1 (1.3) | 4 (2.3) | 9 (1.2) | 1 (0.4) | 2 (2.4) | 0 |
| <3.0 mM | 1 (0.2) | 2 (0.1) | 0 | 0 | 1 (0.1) | 0 | 1 (1.2) | 0 |
| >ULN or baseline if >ULN | 31 (4.9) | 71 (5.3) | 11 (14.5) | 6 (3.4) | 43 (5.6) | 4 (1.8) | 3 (3.6) | 4 (33.3) |
| >5.5 mM | 5 (0.8) | 13 (1.0) | 3 (3.9) | 1 (0.6) | 7 (0.9) | 1 (0.4) | 0 | 1 (8.3) |
| Sodium (mEq/L), n | 637 | 1,344 | 76 | 175 | 773 | 224 | 84 | 12 |
| <LLN or baseline if <LLN | 33 (5.2) | 42 (3.1)* | 5 (6.6) | 2 (1.1) | 24 (3.1) | 6 (2.7) | 4 (4.8) | 1 (8.3) |
| <130 mM | 1 (0.2) | 3 (0.2) | 0 | 0 | 1 (0.1) | 1 (0.4) | 0 | 1 (8.3) |
| >ULN or baseline if >ULN | 21 (3.3) | 55 (4.1) | 3 (3.9) | 8 (4.6) | 37 (4.8) | 4 (1.8) | 3 (3.6) | 0 |
| >150 mM | 1 (0.2) | 2 (0.1) | 0 | 0 | 0 | 1 (0.4) | 1 (1.2) | 0 |
| Bicarbonate (mEq/L), n | 637 | 1,344 | 76 | 175 | 773 | 224 | 84 | 12 |
| <LLN or baseline if <LLN | 58 (9.1) | 99 (7.4) | 6 (7.9) | 23 (13.1) | 32 (4.1) | 19 (8.5) | 18 (21.4) | 1 (8.3) |
| Chloride (mEq/L), n | 637 | 1,344 | 76 | 175 | 773 | 224 | 84 | 12 |
| <LLN or baseline if <LLN | 9 (1.4) | 22 (1.6) | 0 | 5 (2.9) | 7 (0.9) | 5 (2.2) | 4 (4.8) | 1 (8.3) |
| >ULN or baseline if >ULN | 13 (2.0) | 46 (3.4) | 5 (6.6) | 8 (4.6) | 17 (2.2) | 10 (4.5) | 5 (6.0) | 1 (8.3) |
| Urine | ||||||||
| Blood, n | 636 | 1,338 | 76 | 175 | 772 | 220 | 83 | 12 |
| 2+ or ≥0.2 mg/dL or ≥2 mg/L | 2 (0.3) | 4 (0.3) | 0 | 1 (0.6) | 1 (0.1) | 1 (0.5) | 1 (1.2) | 0 |
| 3+ or ≥1.0 mg/dL or ≥10 mg/L | 2 (0.3) | 4 (0.3) | 0 | 1 (0.6) | 1 (0.1) | 1 (0.5) | 1 (1.2) | 0 |
| Protein, n | 636 | 1,338 | 76 | 175 | 772 | 220 | 83 | 12 |
| 1+ or ≥30 mg/dL or ≥0.3 g/L | 51 (8.0) | 143 (10.7) | 10 (13.2) | 12 (6.9) | 88 (11.4) | 24 (10.9) | 9 (10.8) | 0 |
| 2+ or ≥100 mg/dL or ≥1 g/L | 9 (1.4) | 22 (1.6) | 2 (2.6) | 3 (1.7) | 13 (1.7) | 4 (1.8) | 0 | 0 |
| 3+ or ≥300 mg/dL or ≥3 g/L | 1 (0.2) | 4 (0.3) | 0 | 0 | 4 (0.5) | 0 | 0 | 0 |
a
Confirmed event is defined as a consecutive abnormal laboratory value on next measurement after the initial observation. If there is no consecutive test to confirm, then the initial observation is presumed confirmed.
b
Patient postbaseline creatinine event was within the range of normal at 0.78 mg/dL.
*
P < 0.05, Fisher's exact test.
LLN, lower limit of normal; ULN, upper limit of normal.