Cystic Fibrosis
Conditions
Brief summary
This study is a multiple within participant crossover study to evaluate the effect of ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator (CFTR) function.
Detailed description
CFTR Mutations associated with residual function or defective messenger ribonucleic acid (mRNA) splicing include the following: R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G-\>A, 3849+10kbC-\>T, 3272-26A-\>G, 711+5G-\>A, 3120G-\>A, 1811+1.6kbA-\>G, 711+3A-\>G, 1898+3A-\>G, 1898+1G-\>A, 1717-1G-\>A, 1717-8G-\>A, 1342-2A-\>C, 405+3A-\>C, 1716G/A 1811+1G-\>C, 1898+5G-\>T, 3850-3T-\>G, IVS14b+5G-\>A, 1898+1G-\>T, 4005+2T-\>C, 621+3A-\>G, 621+1G-\>T.
Interventions
DRUGIvacaftor
150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
DRUGPlacebo-matched-to-ivacaftor tablet
Orally every 12 hours up to 4 weeks.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants with confirmed diagnosis of CF * Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (\<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (\>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing * FEV1 \>= 40 percent (%) * 12 years of age or older * Willing to agree to meet the contraception requirements * Able to swallow tablets
Exclusion criteria
* A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D * Unable to perform spirometry * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 * Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 | Open-label Baseline, Open-label Day 57 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation). |
| Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 | Open-label Baseline, Open-label Day 57 | LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity \[FRC\]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation). |
| Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms) | LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity \[FRC\]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation). |
| Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 | Open-label Baseline, Open-label Day 57 | Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From first dose of study drug through completion of follow-up visit (up to 26 weeks) | Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a Washout Period AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period. |
| Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 | Study Baseline, Open-label Day 57 | Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IPIP Detailed reporting group description is provided in Participant Flow module. | 5 |
| IPPI Detailed reporting group description is provided in Participant Flow module. | 6 |
| PIIP Detailed reporting group description is provided in Participant Flow module. | 7 |
| PIPI Detailed reporting group description is provided in Participant Flow module. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Cycle 1 Period 2 (2 Weeks) | Adverse Event | 0 | 0 | 0 | 1 |
| Cycle 2 Period 2 (2 Weeks) | Non-compliance with Study Drug | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | IPIP | IPPI | PIIP | PIPI | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 8.04 | 29.7 years STANDARD_DEVIATION 11.66 | 41.4 years STANDARD_DEVIATION 13.96 | 33.8 years STANDARD_DEVIATION 17.26 | 37.3 years STANDARD_DEVIATION 13.86 |
| Age, Customized 20 - 40 years | 1 participants | 4 participants | 3 participants | 2 participants | 10 participants |
| Age, Customized greater than (>) 40 years | 4 participants | 1 participants | 4 participants | 2 participants | 11 participants |
| Age, Customized less than (<) 20 years | 0 participants | 1 participants | 0 participants | 2 participants | 3 participants |
| Genotype mRNA Splice Site (Class V) Mutations | 3 participants | 3 participants | 2 participants | 2 participants | 10 participants |
| Genotype Residual Function Mutations | 2 participants | 3 participants | 5 participants | 4 participants | 14 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 24 | 18 / 24 | 20 / 21 |
| serious Total, serious adverse events | 0 / 24 | 1 / 24 | 0 / 21 |
Outcome results
Primary
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time frame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
Population: Full analysis set (FAS) population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and n signifies participants who were evaluable for the specified category in each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 1: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Overall (n=24, 24, 23, 23) | 0.5828 Percent predicted of FEV1 | Standard Deviation 3.67326 |
| Cycle 1: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Residual Function Mutations (n=14, 14, 14, 14) | 1.4069 Percent predicted of FEV1 | Standard Deviation 3.75842 |
| Cycle 1: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | -0.5710 Percent predicted of FEV1 | Standard Deviation 3.39739 |
| Cycle 1: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Overall (n=24, 24, 23, 23) | 2.0898 Percent predicted of FEV1 | Standard Deviation 4.63833 |
| Cycle 1: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Residual Function Mutations (n=14, 14, 14, 14) | 2.9971 Percent predicted of FEV1 | Standard Deviation 4.24124 |
| Cycle 1: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | 0.8196 Percent predicted of FEV1 | Standard Deviation 5.09161 |
| Cycle 2: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | 1.7132 Percent predicted of FEV1 | Standard Deviation 3.80933 |
| Cycle 2: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Overall (n=24, 24, 23, 23) | 0.8495 Percent predicted of FEV1 | Standard Deviation 4.20641 |
| Cycle 2: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Residual Function Mutations (n=14, 14, 14, 14) | 0.2942 Percent predicted of FEV1 | Standard Deviation 4.49056 |
| Cycle 2: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Overall (n=24, 24, 23, 23) | 3.6868 Percent predicted of FEV1 | Standard Deviation 6.13466 |
| Cycle 2: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | Residual Function Mutations (n=14, 14, 14, 14) | 4.7300 Percent predicted of FEV1 | Standard Deviation 7.27436 |
| Cycle 2: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | 2.0640 Percent predicted of FEV1 | Standard Deviation 3.55493 |
Comparison: This statistical analysis is for Overall category.95% CI: [0.383, 4.144]
Secondary
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity \[FRC\]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time frame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
Population: FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and n signifies participants who were evaluable for the specified category in each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 1: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Overall (n=23, 24, 23, 22) | 0.4596 ratio | Standard Deviation 1.97774 |
| Cycle 1: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Residual Function Mutations (n=13, 14, 14, 13) | 0.4808 ratio | Standard Deviation 2.06279 |
| Cycle 1: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | 0.4321 ratio | Standard Deviation 1.9714 |
| Cycle 1: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Overall (n=23, 24, 23, 22) | 0.2822 ratio | Standard Deviation 3.54741 |
| Cycle 1: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Residual Function Mutations (n=13, 14, 14, 13) | 0.8628 ratio | Standard Deviation 4.34252 |
| Cycle 1: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | -0.5306 ratio | Standard Deviation 1.91374 |
| Cycle 2: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | 1.0568 ratio | Standard Deviation 2.12093 |
| Cycle 2: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Overall (n=23, 24, 23, 22) | 0.4111 ratio | Standard Deviation 2.3992 |
| Cycle 2: Placebo | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Residual Function Mutations (n=13, 14, 14, 13) | -0.0039 ratio | Standard Deviation 2.54929 |
| Cycle 2: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Overall (n=23, 24, 23, 22) | 0.0770 ratio | Standard Deviation 1.98188 |
| Cycle 2: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | Residual Function Mutations (n=13, 14, 14, 13) | 0.3475 ratio | Standard Deviation 2.0699 |
| Cycle 2: Ivacaftor | Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9) | -0.3136 ratio | Standard Deviation 1.89562 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a Washout Period AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.
Time frame: From first dose of study drug through completion of follow-up visit (up to 26 weeks)
Population: Safety set included all participants who received at least 1 dose of study drug. Here, number of participants analyzed signifies participant evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cycle 1: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 17 participants |
| Cycle 1: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Cycle 1: Ivacaftor | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 18 participants |
| Cycle 1: Ivacaftor | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
| Cycle 2: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 20 participants |
| Cycle 2: Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Secondary
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity \[FRC\]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time frame: Open-label Baseline, Open-label Day 57
Population: FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and n signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 | Overall (n=21) | -1.5687 ratio | Standard Deviation 2.27137 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 | mRNA Splice Site(ClassV)Mutations (n=9) | -1.3459 ratio | Standard Deviation 2.88447 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 | Residual Function Mutations (n=12) | -1.7358 ratio | Standard Deviation 1.80502 |
Secondary
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time frame: Open-label Baseline, Open-label Day 57
Population: FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and n signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 | Overall (n=21) | 4.6815 Percent predicted of FEV1 | Standard Deviation 4.17934 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 | mRNA Splice Site(ClassV)Mutations (n=9) | 4.3072 Percent predicted of FEV1 | Standard Deviation 2.93624 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 | Residual Function Mutations (n=12) | 4.9622 Percent predicted of FEV1 | Standard Deviation 5.02864 |
Secondary
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57
Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time frame: Open-label Baseline, Open-label Day 57
Population: FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and n signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 | Overall (n=21) | 1.77 kilograms (kg) | Standard Deviation 1.906 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 | mRNA Splice Site(ClassV)Mutations (n=9) | 2.32 kilograms (kg) | Standard Deviation 2.111 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 | Residual Function Mutations (n=12) | 1.35 kilograms (kg) | Standard Deviation 1.71 |
Secondary
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time frame: Study Baseline, Open-label Day 57
Population: FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and n signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 1: Placebo | Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 | Overall (n=19) | -15.74 millimole per liter (mmol/L) | Standard Deviation 14.781 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 | mRNA Splice Site(ClassV)Mutations (n=8) | -14.13 millimole per liter (mmol/L) | Standard Deviation 8.254 |
| Cycle 1: Placebo | Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 | Residual Function Mutations (n=11) | -16.91 millimole per liter (mmol/L) | Standard Deviation 18.493 |