Clinical Trials for Ages 4 Months to <2 Years
TRIAL 8 (ARRIVAL): KALYDECO® (ivacaftor) in patients with CF age 4 months to less than 2 years.1,2

ON THIS PAGE: Study Design | Safety ProfileSummary of Results

STUDY DESIGN1-4

 

  • Trial 8 was a Phase 3, 24-week, open-label, 2-part study of KALYDECO that included the following cohorts of patients with CF: Patients age 4 to <6 months (n=6), patients age 6 to <12 months (n=11) and patients age 12 to <24 months (n=19)1-3
    •  Patients were eligible if they had a G551D, G1244E, G1349D, G178R, G551S, R117H,a S1251N, S1255P, S549N, or S549R mutation1-4
  • Patients in the 4 to <6 months cohort received 25 mg of KALYDECO every 12 hours with fat-containing food, in addition to their prescribed CF therapies. Patients 6 months and older received KALYDECO every 12 hours based on weight: 5 kg to <7 kg: one 25 mg packet of oral granules; 7 kg to <14 kg: one 50 mg packet of oral granules; ≥14 kg: one 75 mg packet of oral granules1
  • Instruction was provided to administer KALYDECO oral granules mixed with 5 mL of an age-appropriate soft food or liquid, either orally with a syringe or with a spoon, every 12 hours along with a fat-containing food. Bottle use was not recommended5

 

Primary endpoint2,3: Safety, assessed by adverse events (AEs) and clinical laboratory assessments

Select secondary endpoint2,3: Absolute change from baseline in sweat chloride concentration through week 24

 

aPatients with the R117H mutation were only eligible to enroll in this study in the United States.


 

Trial 8 limitations2,3:

  • The study was open label and not placebo controlled; therefore, causality cannot be attributed to KALYDECO
  • All patients in the study knew they were on active drug, which may have introduced bias related to awareness of treatment

SAFETY PROFILE

.

The safety profile of patients in this trial is similar
to that observed in patients age 2 years and older.1

Transaminase elevations1,2

INCIDENCE OF
TRANSAMINASE ELEVATIONS1,2
ELEVATED ALT OR AST 4 TO <6 MONTHS COHORT n/N (%) 6 TO <12 MONTHS COHORT n/N (%) 12 TO <24 MONTHS COHORT n/N (%)
>3x ULN 0/6 (0.0) 1/11 (9.1) 5/18 (27.8)
>5x ULN 0/6 (0.0) 0/11 (0.0) 2/18 (11.1)
>8x ULN 0/6 (0.0) 0/11 (0.0) 2/18 (11.1)

ALT, alanine aminotransferase. AST, aspartate aminotransferase. ULN, upper limit of normal.
 

  • No patients in either cohort had elevations in total bilirubin, or discontinued ivacaftor treatment due to transaminase elevations1
     

Please see Important Safety Information for more information about transaminase elevations reported in patients with CF receiving KALYDECO.


SUMMARY OF RESULTS1-3

 

PHARMACODYNAMIC RESULTS1,2

Reduction in sweat chloride from baseline with KALYDECO in:

 

Patients age 4 to less than 6 months

sweat icon

-50.0 mmol/L
 

  • In the 4 to <6 months cohort (n=3), the mean absolute change from baseline in sweat chloride was -50.0 mmol/L (95% CI: -93.1, -6.9) at Week 24 (secondary endpoint)1

 

Patients age 6 to less than 12 months

sweat

-58.6 mmol/L
 

  • In the 6 to <12 months cohort (n=6), the mean absolute change from baseline in sweat chloride was -58.6 mmol/L (95% CI: -75.9, -41.3) at Week 24 (secondary endpoint)1,2

 

Patients age 12 to less than 24 months

sweat

-73.5 mmol/L
 

  • In the 12 to <24 months cohort (n=10), the mean absolute change from baseline in sweat chloride was −73.5 mmol/L (95% CI: −86.0, −61.0) at 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.

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