Table.
Key efficacy and safety data in lumacaftor-ivacaftor trials for Phe-508del homozygous cystic fibrosis patients.
| Author (ref #) | Phase | Treatment | Duration | Mean absolute change in pp FEV1 vs placebo or baseline | Adverse effects |
|---|---|---|---|---|---|
| Flume (11) | II | IVA 150 mg q 12h | 16 week vs placebo 24 week open label extension |
+ 1.7 Not sustained during OLE |
Cough, nausea, rash and dermatitis similar in active and placebo Pulmonary exacerbation lower in active arm |
| Clancy (12) | II | LUM 25, 50, 100, 200 mg qd Or placebo |
28 days | 25 mg: −2.46 50 mg: −2.15 100 mg: + 0.3 200 mg: + 0.47 |
Cough, fatigue, pulmonary exacerbation, sinus congestion. musculoskeletal discomfort |
| Boyle (13) | II |
Cohor1: LUM 200 mg qd, followed by LUM 200 mg qd with IVA 150 or 250 mg q 12 h Or placebo Cohort 2: LUM 200, 400, 600 mg qd followed by LUM with IVA 250 mg q 12 h Or placebo Cohort 3: LUM 400 mg qd, followed by LUM 400 mg with IVA 250 mg q 12 h Or Placebo |
Cohort 1: 14 days of monotherapy followed by 7 days of combination therapy Cohorts 2 and 3: 28 days of monotherapy followed by 28 days of combination therapy |
Cohort 1: NS Cohort 2: LUM 600 mg qd and IVA +6.2 LUM 400 mg q 12 h and IVA + 6.1 Cohort 3: LUM 400 mg and IVA + 6.1 |
Cough Chest tightness and dyspnea higher during monotherapy with higher doses of LUM Pulmonary exacerbations |
| Wainwright (17) | III | LUM 600mg qd or 400 mg q 12 h with IVA 250 mg q 12 hrs Or placebo |
24 weeks vs placebo | +2.6 – 4.0 | Dyspnea, chest tightness Pulmonary exacerbations Elevation of CK, AST, ALT Hemoptysis Bronchospasms Hypertension |
| Konstan (18) | III | LUM 600 qd or 400 mg q 12 h with IVA 250 mg q 12 h | 96 weeks open label extension | +0.5 week 72, +0.5 week 96 in previously treated subjects |
Dyspnea Chest tightness Pulmonary exacerbation Hemoptysis Distal intestinal obstruction syndrome Elevation of AST and ALT Hypertension |
| Milla (19) | III | LUM 200 mg and IVA 250 mg q 12 h Open label 6–11 year olds |
24 weeks | + 2.5 (NS) | Elevation of AST, ALT Rash |
| Ratjen (20) | III | LUM 200 mg and IVA 250 mg q 12 h | 24 weeks | + 2.4 | Cough, increased sputum, nasal congestion Elevation of AST, ALT |
Abbreviations: LUM, lumacator; IVA, ivacaftor; CK, creatine phosphokinase; AST, aspartate aminotransferase; ALT, alanine aminotransferase