Table 2.
Summary of phase 2 (Boyle et al [49]) and phase 3 (Wainwright et al [52]) studies with ivacaftor-lumacaftor combination treatment in CF patients ages 12 and older who are homozygous for F508del-CFTR.
| Study | FEV1* | BMI† | CFQ-R‡ | Pulmonary exacerbations§ | Number of participants |
|---|---|---|---|---|---|
| Phase 2 study, 8 weeks [37] | |||||
| Lumacaftor 200 mg/day | 3.8 (−0.4 to 8.1) | 23 | |||
| Ivacaftor 250 mg twice/day | P= 0.077 | ||||
| Lumacaftor 400 mg/day | 2.7 (−1.7 to 7.0) | 21 | |||
| Ivacaftor 250 mg twice/day | P= 0.225 | ||||
| Lumacaftor 600 mg/day | 5.6 (1.2 to 10.0) | 21 | |||
| Ivacaftor 250 mg twice/day | P= 0.013 | ||||
| Lumacaftor 400 mg twice/day | 4.2 (−1.3 to 9.6) | 11 | |||
| Ivacaftor 250 mg twice/day | P= 0.132 | ||||
| Phase 3 study, 24 weeks [38] | |||||
| TRAFFIC | |||||
| Lumacaftor 600 mg/day | 4.0 (2.6 to 5.4) | 0.16 (−0.04 to 0.35) | 3.9 (0.7 to 7.1) | 0.72 (0.52 to 1.00) | 183 |
| Ivacaftor 250 mg twice/day | P< 0.001 | P= 0.11 | P= 0.02 | P= 0.05 | |
| Lumacaftor 400 mg twice/day | 2.6 (1.2 to 4.0) | 0.13 (−0.07 to 0.32) | 1.5 (−1.7 to 4.7) | 0.66 (0.47 to 0.93) | 182 |
| Ivacaftor 250 mg twice/day | P< 0.001 | P= 0.19 | P= 0.36 | P= 0.02 | |
| TRANSPORT | |||||
| Lumacaftor 600 mg/day | 2.6 (1.2 to 4.1) | 0.41 (0.23 to 0.59) | 2.2 (−0.9 to 5.3) | 0.69 (0.52 to 0.92) | 185 |
| Ivacaftor 250 mg twice/day | P< 0.001 | P< 0.001 | P= 0.17 | P= 0.01 | |
| Lumacaftor 400 mg twice/day | 3.0 (1.6 to 4.4) | 0.36 (0.17 to 0.54) | 2.9 (−0.3 to 6.0) | 0.57 (0.42 to 0.76) | 187 |
| Ivacaftor 250 mg twice/day | P< 0.001 | P< 0.001 | P= 0.07 | P< 0.001 | |
| TRAFFIC + TRANSPORT Pooled | |||||
| Lumacaftor 600 mg/day | 3.3 (2.3 to 4.3) | 0.28 (0.15 to 0.41) | 3.1 (0.8 to 5.3) | 0.70 (0.56 to 0.87) | 368 |
| Ivacaftor 250 mg twice/day | P< 0.001 | P< 0.001 | P= 0.007 | P= 0.001 | |
| Lumacaftor 400 mg twice/day | 2.8 (1.8 to 3.8) | 0.24 (0.11 to 0.37) | 2.2 (0.0 to 4.5) | 0.61 (0.49 to 0.76) | 369 |
| Ivacaftor 250 mg twice/day | P< 0.001 | P< 0.001 | P= 0.05 | P< 0.001 |
*
Difference versus placebo for absolute change in percentage predicted FEV1 (percentage points; 95% CI).
†
Difference versus placebo in absolute change from baseline BMI; mean (95% CI).
‡
Difference versus placebo in absolute change from baseline in CFQ-R respiratory domain; mean (95% CI). The minimal clinically important difference for stable patients on this scale is 4.0 points [53].
§
Rate ratio (95% CI)