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Clinical Trial for Age 2 to <6 Years

Safety Evaluated in Patients Age 2 Through 5 Years Who Are Homozygous for the F508del-CFTR Mutation


Trial 6 | Phase 3, Open-Label Safety Study1-3

Trial 6 was a 24-week, Phase 3, open-label study assessing the safety, tolerability, and pharmacokinetics of ORKAMBI in 60 patients age 2 through 5 years with CF who were homozygous for the F508del-CFTR mutation. Patients received ORKAMBI granules (if <14 kg: lumacaftor 100 mg/ivacaftor 125 mg, or if ≥14 kg: lumacaftor 150 mg/ivacaftor 188 mg) mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food. All patients continued to take their prescribed CF therapies (including during the 2-week washout period). The primary endpoint was safety and tolerability up to Week 24.1,2


Trial 6 | Limitations2

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

Download the Clinical Brochure, including information from Trial 6 in patients age 2 through 5 years.


Safety Profile in Trial 6 Was Similar to That in Patients Age 6 Years and Older1 



The Primary Endpoint Was Safety and Tolerability up to Week 24.

Discontinuation and Serious Adverse Events1,2

  • 3 patients (5%) discontinued due to adverse events
  • 4 patients (6.7%) experienced serious adverse events (1 with gastroenteritis viral, 1 with constipation, and 2 with infective pulmonary exacerbations of CF)

Adverse Event (Preferred Term)

ORKAMBI Total, N=60 n(%)

Patients with any adverse event of special interest of respiratory symptoms

6 (10.0)


3 (5.0)


3 (5.0)

Respiration abnormal

1 (1.7)

  • Median time to onset for respiratory adverse events was 9 days and median duration was
    4.5 days2 
  • No respiratory events led to treatment interruption or discontinuation2

Elevated ALT or AST

ORKAMBI Total, N=60 n(%)

>3 x ULN

9 (15.0)

>3 x to ≤5 x ULN

2 (3.3)

>5 x to ≤8 x ULN

2 (3.3)

>8 x ULN

5 (8.3)

  • No elevations of bilirubin were observed during the study2
  • 3 patients discontinued lumacaftor/ivacaftor treatment permanently due to transaminase elevations1

Trial 6: Sweat Chloride Results (Pharmacodynamics)

Secondary Endpoint: Absolute Change in Sweat Chloride

Mean Absolute Within-Group Change in Sweat Chloride1

  • From baseline at Week 24: -31.7 mmol/L (95% CI -35.7, -27.6) 
  • After washout, from Week 24 to Week 26: +33.0 mmol/L (95% CI 28.9, 37.1)
  • There is no direct correlation between changes in sweat chloride levels and changes in lung function (percent predicted FEV1)

Trial 6: Results for BMI z-Score and BMI

Secondary Endpoint: Absolute Change in BMI z-Score
Secondary Endpoint: Absolute Change in BMI z-Score

Mean Absolute Within-Group Change in BMI z-Score and BMI2

  • For BMI z-Score, change from baseline at Week 24: +0.29 (95% CI 0.14, 0.45) 
  • For BMI, change from baseline at Week 24: +0.27 (95% CI 0.07, 0.47) 

ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; BMI, body mass index; CI, confidence interval; FEV1, forced expiratory volume in 1 second; LS, least squares; q12h, every 12 hours; ULN, upper limit of normal.