Clinical Trials for Ages 2 to <6 Years
TRIAL 6 (KIWI): Patients with CF age 2 to less than 6 years. KALYDECO® (ivacaftor): Safety consistent with patients age 6 years and older1,2
TRIAL 6 (KIWI): Patients with CF age 2 to less than 6 years. KALYDECO® (ivacaftor): Safety consistent with patients age 6 years and older1,2
ON THIS PAGE: Study Design | Summary of Results
Mutations Eligible for Study2 (mutations in bold were enrolled)
G551D, G1244E, G1349D, G178R, G551S, G970R*, S1251N, S1255P, S549N, or S549R
*KALYDECO is not indicated for use in patients with a G970R mutation1
STUDY DESIGN1,2
- Trial 6 was a 24-week, open-label trial (N=34) evaluating safety, pharmacokinetics, and pharmacodynamics in patients with CF age 2 to less than 6 years (mean age: 3 years)1
- Patients were eligible if they had either a G551D, G1244E, G1349D, G178R, G551S, G970R*, S1251N, S1255P, S549N, or S549R mutation2
- Of the 34 patients enrolled, 32 had the G551D mutation and 2 had the S549N mutation2
- Patients received KALYDECO every 12 hours with fat-containing food, in addition to their prescribed CF therapies, based on weight; 7 kg to <14 kg: One 50-mg packet of oral granules; ≥14 kg to <25 kg: One 75-mg packet of oral granules2
Primary outcome2: Safety, assessed by adverse events and clinical laboratory assessments
Select secondary outcome measure2: Absolute change from baseline in sweat chloride concentration at 24 weeks
Trial 6 limitations2
- The study was open label and not placebo controlled; therefore, causality cannot be attributed
- All patients in the study knew they were on active drug, which may have introduced a treatment bias
SUMMARY OF RESULTS1
Safety results and pharmacokinetics were similar to older patients1
- The safety profile for patients in Trial 6, including type and frequency of adverse reactions, was similar to that observed in Trials 1 and 2
- Transaminase elevations were more common in patients who had abnormal transaminases at baseline
- The incidence of patients experiencing transaminase elevations (ALT or AST) >3x ULN was 14.7% (5/34). All 5 patients had maximum ALT or AST levels >8x ULN, which returned to baseline levels following interruption of KALYDECO dosing. KALYDECO was permanently discontinued in 1 patient
- Ivacaftor exposure in patients age 2 to less than 6 years administered either 50 mg or 75 mg of KALYDECO oral granules every 12 hours was similar to that observed in older patients administered KALYDECO tablets
- KALYDECO oral granules (2 x 75 mg) had similar bioavailability as the 150-mg tablet when given with fat-containing food
The efficacy of KALYDECO in patients age 2 to less than 6 years
was extrapolated from patients age 6 years and older with support from
population pharmacokinetic analyses showing similar drug exposure levels in adults and
children age 2 to less than 6 years.1
Reduction in sweat chloride from baseline (pharmacodynamic measure) with KALYDECO1,†
†SD 24.3, P=.002 for patients who received 50 mg; SD 27.6, P<.0001 for patients who received 75 mg.2
- The mean absolute change from baseline in sweat chloride for patients age 2 to less than 6 years (n=34) was −45 mmol/L (95% CI: −53, −38) through Week 24 (secondary endpoint)1,3
- There was no direct correlation between decrease in sweat chloride levels and improvement in lung function (FEV1)1
CI, confidence interval; SD, standard deviation.
