Safety profile established in placebo-controlled
The overall safety profile of KALYDECO (ivacaftor) is based on pooled data from three placebo-controlled clinical trials conducted in 353 patients 6 years of age and older with CF who had a G551D mutation in the CFTR gene (Trials 1 and 2) or were homozygous for the F508del mutation (Trial 3).
- Of the 353 patients included in the pooled analyses of patients with CF who had either a G551D mutation or were homozygous for the F508del mutation in the CFTR gene, 50% of patients were female and 97% were Caucasian; 221 received KALYDECO, and 132 received placebo from 16 to 48 weeks
- KALYDECO is not effective in patients with CF who are homozygous for the F508del mutation
In addition, the following clinical trials have also been conducted:
- An 8-week crossover design trial (Trial 4) involving 39 patients between the ages of 6 and 57 years with a G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R mutation in the CFTR gene
- A 24-week placebo-controlled trial (Trial 5) involving 69 patients between the ages of 6 and 68 years with an R117H mutation in the CFTR gene
- A 24-week open-label trial (Trial 6) in 34 patients 2 to less than 6 years of age. Patients eligible for Trial 6 were those with the G551D, G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R mutation in the CFTR gene. Of 34 patients enrolled, 32 had the G551D mutation and 2 had the S549N mutation.
Transaminase elevations (Trials 1, 2, 3, and 6)1
In Trials 1, 2, and 3, the incidence of maximum transaminase (ALT or AST) >8, >5, or >3 x ULN was 2%, 2%, and 6% in patients treated with KALYDECO and 2%, 2%, and 8% in patients treated with placebo, respectively.
- Two patients (2%) on placebo and 1 patient (0.5%) on KALYDECO permanently discontinued treatment for elevated transaminases, all >8 x ULN
- Two patients treated with KALYDECO were reported to have serious adverse reactions of elevated liver transaminases compared to none on placebo
- Transaminase elevations were more common in patients with a history of transaminase elevations
During the 24-week open-label clinical study in 34 patients ages 2 to less than 6 years (Trial 6), where patients received either 50 mg (less than 14 kg) or 75 mg (14 kg or greater) ivacaftor granules twice daily, the incidence of patients experiencing transaminase elevations (ALT or AST) >3 x ULN was 14.7% (5/34). All 5 patients had maximum ALT or AST levels >8 x ULN, which returned to baseline levels following interruption of KALYDECO dosing. Transaminase elevations were more common in patients who had abnormal transaminases at baseline. KALYDECO was permanently discontinued in one patient.
Trials 4, 5, and 6 safety data1
The safety profiles for patients with a G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R mutation enrolled in Trial 4, for patients with an R117H mutation enrolled in Trial 5, and for patients ages 2 to less than 6 years enrolled in Trial 6 were similar to that observed in Trials 1 and 2.
ALT, alanine transaminase; AST, aspartate transaminase; ULN, upper limit of normal.