Cystic Fibrosis
Conditions
Brief summary
This study will evaluate the safety and pharmacokinetics (PK) of lumacaftor (LUM) and ivacaftor (IVA) in participants 1 to less than 2 years of age with cystic fibrosis (CF), homozygous for F508del (F/F).
Interventions
DRUGLUM
Fixed Dose Combination (FDC) granules (LUM/IVA).
DRUGIVA
FDC granules (LUM/IVA).
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 23 Months
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants will be 1 to less than 2 years of age on day 1 of the relevant part of the study * Homozygous for F508del (F/F) Key
Exclusion criteria
* Any clinically significant laboratory abnormalities at the screening visit that would interfere with the study assessments or pose an undue risk for the participants * Solid organ or hematological transplantation Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 1 and Day 15 |
| Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Pre-dose at Day 8 and Day 15 |
| Part B : Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Week 26 |
Secondary
| Measure | Time frame |
|---|---|
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Day 25 |
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Pre-dose at Day 15, Week 4, Week 12 and Week 24 |
| Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Pre-dose at Day 8 and Day 15 |
| Part B: Absolute Change in Sweat Chloride | From Baseline at Week 24 |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study was conducted in participants with cystic fibrosis (CF) aged 1 through less than 2 years of age who are homozygous for F508del. A total of 61 participants were enrolled in Parts A and B of the study. One participant in Part B was enrolled but not dosed in this study. Therefore, data for 60 participants are reported in the participant flow and baseline characteristics sections.
Participants by arm
| Arm | Count |
|---|---|
| Part A: LUM/IVA Participants weighing 7 to less than(\<)10 kilograms (kg) at screening received lumacaftor (LUM) 75 milligrams (mg)/ ivacaftor (IVA) 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 10 to \<14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants weighing greater than or equal to (\>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. | 14 |
| Part B: LUM/IVA Participants weighing 7 to \<9 kg at screening received LUM 75 mg/ IVA 94 mg FDC q12h and those weighing 9 to \<14 kg received LUM 100 mg/IVA 125 mg q12h for 24 weeks. Participants weighing \>=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight. | 46 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal of Consent (not due to adverse event) | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: LUM/IVA | Part B: LUM/IVA | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 46 Participants | 60 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 37 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not collected per local regulations | 0 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 34 Participants | 48 Participants |
| Sex: Female, Male Female | 7 Participants | 24 Participants | 31 Participants |
| Sex: Female, Male Male | 7 Participants | 22 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 46 |
| other Total, other adverse events | 12 / 14 | 42 / 46 |
| serious Total, serious adverse events | 0 / 14 | 5 / 46 |
Outcome results
Primary
Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA
Time frame: Day 1 and Day 15
Population: Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here the Number Analyzed signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 1: LUM | 14600 nanograms per milliliter (ng/mL) | Standard Deviation 5560 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 1: IVA | 1620 nanograms per milliliter (ng/mL) | Standard Deviation 648 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 15: LUM | 16600 nanograms per milliliter (ng/mL) | Standard Deviation 9590 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 15: IVA | 718 nanograms per milliliter (ng/mL) | Standard Deviation 352 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 15: LUM | 13900 nanograms per milliliter (ng/mL) | Standard Deviation 5800 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 1: LUM | 12600 nanograms per milliliter (ng/mL) | Standard Deviation 7190 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 15: IVA | 496 nanograms per milliliter (ng/mL) | Standard Deviation 268 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 1: IVA | 1320 nanograms per milliliter (ng/mL) | Standard Deviation 804 |
Primary
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA
Time frame: Pre-dose at Day 8 and Day 15
Population: PK set included participants who received at least 1 dose of study drug. Here the Number Analyzed signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 8: LUM | 12000 ng/mL | Standard Deviation 8880 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 15: LUM | 8380 ng/mL | Standard Deviation 7790 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 8: IVA | 169 ng/mL | Standard Deviation 75.5 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 15: IVA | 78.9 ng/mL | Standard Deviation 19.1 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 15: IVA | 120 ng/mL | Standard Deviation 60.5 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 8: LUM | 12800 ng/mL | Standard Deviation 3900 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 8: IVA | 185 ng/mL | Standard Deviation 101 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Day 15: LUM | 10500 ng/mL | Standard Deviation 3070 |
Primary
Part B : Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 up to Week 26
Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period. The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part B: LUM/IVA arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part B : Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 44 participants |
| Part A: LUM 75 mg/IVA 94 mg | Part B : Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 5 participants |
Secondary
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA)
Time frame: Pre-dose at Day 8 and Day 15
Population: PK set included participants who received at least 1 dose of study drug. Here the Number Analyzed signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 8: M28-LUM | 1410 ng/mL | Standard Deviation 791 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M28-LUM | 1460 ng/mL | Standard Deviation 1060 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 8: M1-IVA | 606 ng/mL | Standard Deviation 298 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M1-IVA | 284 ng/mL | Standard Deviation 70.2 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 8: M6-IVA | 2380 ng/mL | Standard Deviation 843 |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M6-IVA | 1460 ng/mL | Standard Deviation 763 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 8: M6-IVA | 3290 ng/mL | Standard Deviation 1830 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 8: M28-LUM | 1470 ng/mL | Standard Deviation 365 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M1-IVA | 604 ng/mL | Standard Deviation 394 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M28-LUM | 1370 ng/mL | Standard Deviation 468 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M6-IVA | 2800 ng/mL | Standard Deviation 2300 |
| Part A: LUM 100 mg/IVA 125 mg | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 8: M1-IVA | 842 ng/mL | Standard Deviation 527 |
Secondary
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 up to Day 25
Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period. The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part A: LUM/IVA arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 participants |
| Part A: LUM 75 mg/IVA 94 mg | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 12 participants |
Secondary
Part B: Absolute Change in Sweat Chloride
Time frame: From Baseline at Week 24
Population: The Full Analysis Set (FAS) included all enrolled participants who were exposed to any amount of study drug in Part B.The pharmacodynamic analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part B: LUM/IVA arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part B: Absolute Change in Sweat Chloride | -29.1 Millimole per liter (mmol/L) | Standard Deviation 13.5 |
Secondary
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA)
Time frame: Pre-dose at Day 15, Week 4, Week 12 and Week 24
Population: PK set included participants who received at least 1 dose of study drug. Here the Number Analyzed signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: IVA | 286 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: LUM | 12100 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M1-IVA | 1420 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: IVA | 267 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: LUM | 11200 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M6-IVA | 1320 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M28-LUM | 1870 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M28-LUM | 1460 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M6-IVA | 4740 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M1-IVA | 1930 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M28-LUM | 1740 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M6-IVA | 3520 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M1-IVA | 256 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M1-IVA | 759 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: IVA | 213 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: LUM | 13500 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M28-LUM | 1570 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: IVA | 37.1 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: LUM | 21900 ng/mL | — |
| Part A: LUM 75 mg/IVA 94 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M6-IVA | 9090 ng/mL | — |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M6-IVA | 1970 ng/mL | Standard Deviation 1490 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: IVA | 112 ng/mL | Standard Deviation 68.3 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M1-IVA | 437 ng/mL | Standard Deviation 291 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M1-IVA | 466 ng/mL | Standard Deviation 359 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M1-IVA | 418 ng/mL | Standard Deviation 236 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: LUM | 9030 ng/mL | Standard Deviation 4390 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: LUM | 9370 ng/mL | Standard Deviation 5030 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: LUM | 9160 ng/mL | Standard Deviation 4400 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: LUM | 8930 ng/mL | Standard Deviation 5310 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M28-LUM | 1260 ng/mL | Standard Deviation 528 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M28-LUM | 1340 ng/mL | Standard Deviation 579 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M28-LUM | 1440 ng/mL | Standard Deviation 599 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M28-LUM | 1470 ng/mL | Standard Deviation 548 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: IVA | 112 ng/mL | Standard Deviation 82.9 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: IVA | 91.7 ng/mL | Standard Deviation 44.7 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: IVA | 144 ng/mL | Standard Deviation 296 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M1-IVA | 499 ng/mL | Standard Deviation 613 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M6-IVA | 1930 ng/mL | Standard Deviation 1460 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M6-IVA | 1950 ng/mL | Standard Deviation 1430 |
| Part A: LUM 100 mg/IVA 125 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M6-IVA | 1740 ng/mL | Standard Deviation 1130 |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M28-LUM | 569 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: IVA | 2.18 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: LUM | 887 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M6-IVA | 63.3 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M1-IVA | 18.3 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M1-IVA | 58.0 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M6-IVA | 46.5 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: M1-IVA | 18.5 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M1-IVA | 18.1 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M28-LUM | 602 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M6-IVA | 43.9 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: IVA | 2.86 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: M28-LUM | 501 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 24: LUM | 288 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: M28-LUM | 786 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Day 15: IVA | 3.68 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 12: LUM | 566 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: M6-IVA | 131 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: IVA | 11.4 ng/mL | — |
| Part B: LUM 150 mg/IVA 188 mg | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Week 4: LUM | 1000 ng/mL | — |