Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

• Part A: Maximum observed concentration (Cmax) of VX-445, TEZ, and IVA metabolites[ Time Frame: from Day 1 through 15 ]
• Part A: Observed pre-dose concentration (Ctrough) of VX-445, TEZ, and IVA metabolites[ Time Frame: from Day 1 through 15 ]
• Part A: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ, and IVA metabolites[ Time Frame: from Day 1 through 15 ]
• Part A: Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs)[ Time Frame: from baseline through safety follow-up (28 Weeks) ]
• Part B: Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1)[ Time Frame: from baseline through Weeks 12 and 24 ]
• Part B: Absolute change in sweat chloride[ Time Frame: from baseline through Weeks 12 and 24 ]
• Part B: Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain score[ Time Frame: from baseline through Weeks 12 and 24 ]
• Part B: Absolute change in body mass index (BMI) and BMI for age-z-score[ Time Frame: from baseline at Week 24 ]
• Part B: Absolute change in weight and weight for age-z-score[ Time Frame: from baseline at Week 24 ]
• Part B: Absolute change in height and height for age-z-score[ Time Frame: from baseline at Week 24 ]
• Part B: Absolute change in the Modified Facial Hedonic Scale[ Time Frame: from baseline at Week 24 ]
• Parts B: Ctrough of VX-445, TEZ, IVA, and IVA metabolites[ Time Frame: Day 1 through Week 24 ]
• Part B: Absolute change in lung clearance index2.5 (LCI2.5)[ Time Frame: from baseline through Week 24 ]

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.

• Drug: VX-445
  Fixed dose combination (FDC) tablet (VX-445/TEZ/IVA)
• Drug: TEZ
  FDC tablet (VX-445/TEZ/IVA)
• Drug: IVA
  FDC tablet (VX-445/TEZ/IVA) and IVA mono tablet

• Experimental: Part A: Triple Combination
  Subjects will receive 100 mg VX-445/ 50 mg TEZ/ 75 mg IVA as an FDC tablet in the morning and 75 mg IVA as mono tablet in the evening.
• Experimental: Part B: Triple Combination
  Subjects will receive VX-445/TEZ/IVA as FDC tablet in the morning and IVA as mono tablet in the evening with the dose to be based on the outcome of Part A.