To evaluate the efficacy of ivacaftor treatment, as measured by lung clearance index (LCI), in subjects with cystic fibrosis (CF) who have a specified CF transmembrane conductance regulator (CFTR) gating mutation
Name: ivacaftor
Type: DrugPart 1-Sequence 1 Part 1 - Sequence 2 Part 2: ivacaftor
Name: Placebo
Type: DrugPart 1-Sequence 1 Part 1 - Sequence 2
Description: LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Measure: Absolute Change From Baseline in Lung Clearance Index (LCI2.5) Through 8 Weeks of Treatment (Average of Week 4 and Week 8 LCI2.5) Time: Baseline Through Week 8 for each treatment period, Up to 24 WeeksDescription: Serum samples were collected for evaluation of change in immunoreactive trypsinogen levels at Week 8.
Measure: Absolute Change From Baseline in Immunoreactive Trypsinogen Levels at Week 8 Time: Baseline and Week 8 of each treatment period, Up to 24 WeeksDescription: Fecal elastase-1 was used clinically to diagnose pancreatic exocrine insufficiency in participants with cystic fibrosis.
Measure: Absolute Change From Baseline in Fecal Elastase-1 Levels at Week 8 Time: Baseline and Week 8 of each treatment period, Up to 24 WeeksDescription: BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Measure: Absolute Change From Baseline in Body Mass Index (BMI) at Week 8 Time: Baseline and Week 8 of each treatment period, Up to 24 WeeksAllocation: Randomized
Crossover Assignment
There are 9 SNPs
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E --- --- S1251N --- --- S1255P --- --- G1349D ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E --- --- S1251N --- --- S1255P --- --- G1349D ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E --- --- S1251N ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E --- --- S1251N ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E --- --- S1251N --- --- S1255P ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G1244E --- --- S1251N --- --- S1255P ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N ---
Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R ---
Exclusion Criteria: - An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 - Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator) - Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin - History of solid organ or hematological transplantation - Any clinically significant "non-CF-related" illness within 2 weeks before Day 1 - Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 - Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening Inclusion Criteria: - Male or female with confirmed diagnosis of CF. - Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. --- G551D --- --- G178R --- --- S549N --- --- S549R ---