Cystic Fibrosis
Conditions
Brief summary
The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.
Interventions
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants with confirmed diagnosis of CF * Must have the F508del-CFTR mutation on at least 1 allele. * FEV1 greater than equal (\>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4) * Participant of child-bearing potential and who are sexually active must meet the contraception requirements
Exclusion criteria
* History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension). * An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug. * History of solid organ or hematological transplantation. * History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates. * Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout * Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception * Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3 * Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit * Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4 * Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21) | AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the 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. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21). |
| Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56) | Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56). |
| Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs | Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56) | AEs and SAEs are defined in Outcome Measure 1. |
| Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 | Cohort 1: Day 14, Day 21 | — |
| Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | Cohort 2 and 3: Day 28, Day 56 | — |
| Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56 | Cohort 4: Baseline, Day 56 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | Cohort 2 and 3: Day 28, Day 56 | FEV1 and ppFEV1 are defined in Outcome Measure 6. |
| Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Cohort 2 and 3: Baseline, Day 28 and 56 | FEV1 and ppFEV1 are defined in Outcome Measure 6. |
| Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Cohort 2 and 3: Baseline, Day 28 and 56 | FEV1 and ppFEV1 are defined in Outcome Measure 6. |
| Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56 | Cohort 4: Baseline, Day 56 | FEV1 and ppFEV1 are defined in Outcome Measure 6. |
| Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14 | Cohort 1: Baseline, Day 14 | — |
| Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56 | Cohort 4: Baseline, Day 56 | CFQ-R respiratory domain is defined in Outcome Measure 17. |
| Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56 | Cohort 4: Baseline, Day 56 | BMI was defined as weight in kilogram (kg) divided by height\*height in square meter (m\^2). |
| Cohort 4: Absolute Change From Baseline in Weight at Day 56 | Cohort 4: Baseline, Day 56 | — |
| Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | Cohort 2 and 3: Day 28, Day 56 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | Cohort 2: Baseline, Day 14 | — |
| Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56 | Cohort 4: Baseline, Day 56 | — |
| Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 | Cohort 1: Day 14, Day 21 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 | Cohort 1: Day 14, Day 21 | FEV1 and ppFEV1 are defined in Outcome Measure 6. |
| Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | Cohort 2 and 3: Day 28, Day 56 | FEV1 and ppFEV1 are defined in Outcome Measure 6. |
Countries
Australia, Belgium, France, Germany, New Zealand, United Kingdom, United States
Participant flow
Recruitment details
Participants in each cohort are mutually exclusive. A total of 312 participants were randomized of which one participant did not receive any treatment and a total of 311 participants were treated.
Pre-assignment details
Study included 4 cohorts which were studied in sequential manner. For results reporting, combined placebo arm was reported for Cohort 2 and 3 and results for these 2 cohorts are reported collectively.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Placebo Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21). | 21 |
| Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). | 20 |
| Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). | 21 |
| Cohort 2 and 3: Placebo (HO and HE) Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56). | 27 |
| Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). | 23 |
| Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). | 21 |
| Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). | 42 |
| Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). | 11 |
| Cohort 4: Placebo Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). | 63 |
| Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56). | 62 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Cohort 1: Placebo | Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h | Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h | Cohort 2 and 3: Placebo (HO and HE) | Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) | Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) | Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) | Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) | Cohort 4: Placebo | Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 20 Participants | 21 Participants | 27 Participants | 23 Participants | 21 Participants | 42 Participants | 11 Participants | 63 Participants | 62 Participants | 311 Participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 13 Participants | 9 Participants | 11 Participants | 9 Participants | 19 Participants | 5 Participants | 31 Participants | 29 Participants | 144 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 8 Participants | 18 Participants | 12 Participants | 12 Participants | 23 Participants | 6 Participants | 32 Participants | 33 Participants | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 41 | 14 / 20 | 12 / 20 | 12 / 21 | 15 / 21 | 17 / 23 | 18 / 21 | 37 / 42 | 6 / 11 | 23 / 27 | 12 / 21 | 15 / 20 | 26 / 38 | 10 / 11 | 20 / 27 | 53 / 63 | 51 / 62 |
| serious Total, serious adverse events | 0 / 41 | 0 / 20 | 0 / 20 | 0 / 21 | 0 / 21 | 2 / 23 | 0 / 21 | 3 / 42 | 2 / 11 | 1 / 27 | 0 / 21 | 1 / 20 | 4 / 38 | 1 / 11 | 4 / 27 | 5 / 63 | 9 / 62 |
Outcome results
Primary
Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
Time frame: Cohort 1: Day 14, Day 21
Population: Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 | -2.131 millimole per liter (mmol/L) |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 | -9.128 millimole per liter (mmol/L) |
| Cohort 1: Placebo - Period 2 | Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 | 0.548 millimole per liter (mmol/L) |
p-value: 0.26795% CI: [-7.484, 2.125]ANCOVA
p-value: <0.00195% CI: [-14.801, -4.551]ANCOVA
Primary
Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the 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. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).
Time frame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
Population: Cohort 1 Safety Set included all participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 12 participants |
| Cohort 1: Placebo - Period 1 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 29 participants |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Cohort 1: Placebo - Period 2 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 15 participants |
| Cohort 1: Placebo - Period 2 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 14 participants |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 12 participants |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
Primary
Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56
Time frame: Cohort 2 and 3: Day 28, Day 56
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | 0.321 mmol/L |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | -1.043 mmol/L |
| Cohort 1: Placebo - Period 2 | Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | -2.900 mmol/L |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | -1.240 mmol/L |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | -2.154 mmol/L |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 | 1.627 mmol/L |
p-value: 0.6895% CI: [-7.565, 4.953]ANCOVA
p-value: 0.40995% CI: [-9.053, 3.712]ANCOVA
p-value: 0.16195% CI: [-10.888, 1.835]ANCOVA
p-value: 0.39695% CI: [-9.543, 3.81]ANCOVA
p-value: 0.36595% CI: [-12.028, 4.467]ANCOVA
Primary
Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).
Time frame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
Population: Cohort 2 and 3 Safety Set included all participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 23 participants |
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 18 participants |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 2 participants |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 18 participants |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 37 participants |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 3 participants |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 2 participants |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 7 participants |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 4 participants |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 20 participants |
| Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 12 participants |
| Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 15 participants |
| Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 26 participants |
| Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 4 participants |
| Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with any AEs | 10 participants |
| Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 | Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) | Participants with SAEs | 1 participants |
Primary
Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.
Time frame: Cohort 4: Baseline, Day 56
Population: Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56 | -1.23 percent predicted of FEV1 | Standard Error 0.801 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56 | -0.62 percent predicted of FEV1 | Standard Error 0.829 |
p-value: 0.597895% CI: [-1.66, 2.86]Mixed Model Repeated Measure (MMRM)
Primary
Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
AEs and SAEs are defined in Outcome Measure 1.
Time frame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
Population: Cohort 4 Safety Set included all participants who received at least 1 dose of study drug in Cohort 4.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs | Participants with any AEs | 53 participants |
| Cohort 1: Placebo - Period 1 | Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs | Participants with SAEs | 5 participants |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs | Participants with any AEs | 52 participants |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs | Participants with SAEs | 9 participants |
Secondary
Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
Time frame: Cohort 1: Baseline, Day 14
Population: Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14 | -4.442 mmol/L |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14 | -1.668 mmol/L |
Secondary
Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: Cohort 1: Day 14, Day 21
Population: Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 | 0.128 liters |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 | 0.015 liters |
| Cohort 1: Placebo - Period 2 | Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 | -0.046 liters |
Secondary
Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 1: Day 14, Day 21
Population: Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 | 3.46 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 | 0.63 percent predicted of FEV1 |
| Cohort 1: Placebo - Period 2 | Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 | -1.44 percent predicted of FEV1 |
Secondary
Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Baseline, Day 28 and 56
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Here, n = participants evaluable for specified category for each arm, respectively. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | 0.21 percent predicted of FEV1 |
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 1.82 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -1.35 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 0.64 percent predicted of FEV1 |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -2.62 percent predicted of FEV1 |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 3.59 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -3.82 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | -1.68 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -4.52 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 2.16 percent predicted of FEV1 |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -0.03 percent predicted of FEV1 |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | -2.02 percent predicted of FEV1 |
Secondary
Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
Time frame: Cohort 2: Baseline, Day 14
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | -6.490 mmol/L |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | -5.901 mmol/L |
| Cohort 1: Placebo - Period 2 | Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | -9.442 mmol/L |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | -3.137 mmol/L |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | -9.179 mmol/L |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 | 0.048 mmol/L |
Secondary
Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: Cohort 2 and 3: Day 28, Day 56
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | 3.3 units on a scale |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | 7.9 units on a scale |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | 8.9 units on a scale |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | 5.5 units on a scale |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | 11.2 units on a scale |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 | -8.6 units on a scale |
Secondary
Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Day 28, Day 56
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | 1.96 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | 1.99 percent predicted of FEV1 |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | 6.15 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | 2.29 percent predicted of FEV1 |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | 6.09 percent predicted of FEV1 |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 | -1.57 percent predicted of FEV1 |
Secondary
Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Baseline, Day 28 and 56
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Here, n = participants evaluable for specified category for each arm, respectively. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | 0.24 percent change |
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 2.51 percent change |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -1.15 percent change |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 1.72 percent change |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -3.13 percent change |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 5.55 percent change |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -5.46 percent change |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | -2.34 percent change |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | -6.39 percent change |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | 2.96 percent change |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 28: (n= 21, 20, 20, 18, 11, 27) | 1.89 percent change |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 | Day 56: (n= 21, 20, 20, 17, 10, 24) | -2.42 percent change |
Secondary
Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 2 and 3: Day 28, Day 56
Population: Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | 3.13 percent change |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | 2.98 percent change |
| Cohort 1: Placebo - Period 2 | Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | 9.70 percent change |
| Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 | Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | 4.30 percent change |
| Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 | Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | 8.24 percent change |
| Cohort 2 and 3: Placebo (HO and HE) - Period 2 | Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 | -2.05 percent change |
Secondary
Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
BMI was defined as weight in kilogram (kg) divided by height\*height in square meter (m\^2).
Time frame: Cohort 4: Baseline, Day 56
Population: Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56 | 0.08 kg/m^2 | Standard Error 0.075 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56 | -0.04 kg/m^2 | Standard Error 0.077 |
Secondary
Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
CFQ-R respiratory domain is defined in Outcome Measure 17.
Time frame: Cohort 4: Baseline, Day 56
Population: Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56 | -0.82 units on a scale | Standard Error 1.802 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56 | 5.66 units on a scale | Standard Error 1.864 |
Secondary
Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
Time frame: Cohort 4: Baseline, Day 56
Population: Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56 | -0.78 mmol/L | Standard Error 1.23 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56 | -11.82 mmol/L | Standard Error 1.281 |
Secondary
Cohort 4: Absolute Change From Baseline in Weight at Day 56
Time frame: Cohort 4: Baseline, Day 56
Population: Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Absolute Change From Baseline in Weight at Day 56 | 0.16 kg | Standard Error 0.211 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Absolute Change From Baseline in Weight at Day 56 | -0.11 kg | Standard Error 0.216 |
Secondary
Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
FEV1 and ppFEV1 are defined in Outcome Measure 6.
Time frame: Cohort 4: Baseline, Day 56
Population: Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo - Period 1 | Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56 | -2.20 percent change | Standard Error 1.373 |
| Cohort 1: LUM 200 mg qd - Period 1 | Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56 | -0.69 percent change | Standard Error 1.423 |