Cystic Fibrosis

Oral treatment with lumacaftor/ivacaftor tablets according to the prescribing information

Lumacaftor plus Ivacaftor

Justus-Liebig-University

Hannover Medical School

University of Heidelberg

ICM to Evaluate the Activation of p.Phe508del-CFTR by Lumacaftor in Combination With Ivacaftor

Intestinal Current Measurements (ICM) to Evaluate the Activation of Mutant CFTR in Subjects With Cystic Fibrosis Aged 12 Years and Older, Homozygous for the p.Phe508del-CFTR Mutation, Treated With Lumacaftor in Combination With Ivacaftor

ICM will be performed according to the Standard Operating Procedure ICM_EU001, version 2.7 (October 2011) 'Ion Transport in Rectal Biopsies for Diagnosis and Clinical Trials in Cystic Fibrosis of the European Cystic Fibrosis Society (ECFS) Diagnostic Working Group & Clinical Trials Network modified by in-house protocol adjustments at the CF electrophysiology laboratories in Hannover and Heidelberg as described by Graeber et al. (2015) [39]. Electronic files of the tracings will be evaluated on-site and at the CF Electrophysiology Laboratory at the University of Heidelberg.

Pre-bronchodilator spirometry will be performed using in-house equipment. Pre-bronchodilator spirometry is defined as spirometry testing performed for a subject who has
Withheld short-acting bronchodilators or anticholinergic agents for more than 4 hours before the spirometry assessment; and
Withheld their long-acting bronchodilator (e.g., salmeterol) more than 12 hours before the spirometry assessment; and
Withheld their once-daily, long-acting bronchodilator (e.g., tiotropium bromide) for more than 24 hours before the spirometry assessment.

NPD will be performed according to the Standard Operating Procedure NPD_EU001, version 1.7 (March 2013) 'Nasal Potential Difference (NPD) Measurement for Diagnosis and Clinical Trials in Cystic Fibrosis' of the European Cystic Fibrosis Society (ECFS) Diagnostic Working Group & Clinical Trials Network. Electronic files of the tracings will be evaluated on-site and at the CF Electrophysiology Laboratory of Hannover Medical School.

The sweat test will be performed according the Clinical and Laboratory Standards Institute guidelines (Clinical and Laboratory Standards Institute: Sweat Testing: Sample Collection and Quantitative Chloride Analysis; Approved Guideline-Third Edition, Volume CLSI document C34-A3. Wayne, PA, USA: Clinical and Laboratory Standards Institute; 2009). After stimulation of sweat production by pilocarpine iontophoresis and collection of sweat (Macroduct®; Wescor Inc., Logan, NV, USA), the sweat chloride concentration is determined in-house by original titration with a chloridometer.

Whole blood samples will be collected. Plasma will be assayed by HPLC.

Liver-related events (serum serum aspartate transaminase, serum alanine transaminase, gamma-glutamyl transpeptidase, total bilirubin), respiratory events (chest discomfort, dyspnea, and respiration abnormal) and elevation of blood creatine phosphokinase will be monitored according to the FDA-approved patient labeling and the prescribing information.

Individual participant data will be made available to study participant and parental guide and the physician treating the study participant

forskolin/krvarenje

ICM to Evaluate the Activation of p.Phe508del-CFTR by Lumacaftor in Combination With Ivacaftor

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