Cystic Fibrosis
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).
Interventions
DRUGVX-121
Tablets for oral administration.
DRUGTEZ
TEZ tablet for oral administration.
DRUGVX-561
Tablets for oral administration.
DRUGTEZ/IVA
Fixed-dose combination tablets for oral administration.
DRUGIVA
Tablets for oral administration.
DRUGPlacebo
Placebos matched to VX-121, TEZ, and VX-561 for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Part 1: Heterozygous for F508del and an MF mutation (F/MF) * Part 2: Homozygous for F508del (F/F) * FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height Key
Exclusion criteria
* History of clinically significant cirrhosis with or without portal hypertension * Lung infection with organisms associated with a more rapid decline in pulmonary status * History of solid organ or hematological transplantation Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2) | — |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline Through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Sweat Chloride (SwCl) Concentrations | From Baseline Through Day 29 | Sweat samples were collected using an approved collection device. |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | From Baseline at Day 29 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Pre-dose at Day 15 and Day 29 | — |
Countries
Germany, Netherlands, Portugal, United Kingdom, United States
Participant flow
Recruitment details
Three parts were planned for this study, only Parts 1 (participants heterozygous for F508del and a minimal function mutation \[F/MF genotypes\]) and 2 (participants homozygous for F508del \[F/F genotypes\]) were conducted. Part 3 was optional and not conducted at sponsor's discretion.
Pre-assignment details
A total of 87 participants were enrolled in this study (58 participants in Part 1 and 29 participants in Part 2 run-in Period), 1 participant in Part 2 run-in period discontinued from the study and was not randomized in the treatment period. Therefore, results are presented for 86 participants in this study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period. | 10 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. | 9 |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. | 19 |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. | 20 |
| Part 2: TEZ/IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. | 10 |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. | 18 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 7 | 12 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: Placebo | Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Part 1: VX-121/TEZ/VX-561 TC - High Dose | Part 2: TEZ/IVA | Part 2: VX-121/TEZ/VX-561 TC - High Dose | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 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 |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants | 20 Participants | 10 Participants | 18 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 8 Participants | 19 Participants | 17 Participants | 8 Participants | 18 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) <40 percent | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 6 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) >=40 to <70 percent | 9 Participants | 6 Participants | 14 Participants | 17 Participants | 6 Participants | 11 Participants | 63 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) >=70 to <=90 percent | 0 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 9 Participants | 8 Participants | 18 Participants | 17 Participants | 9 Participants | 18 Participants | 79 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 3 Participants | 9 Participants | 2 Participants | 7 Participants | 27 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 16 Participants | 11 Participants | 8 Participants | 11 Participants | 59 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 19 | 0 / 20 | 0 / 10 | 0 / 18 |
| other Total, other adverse events | 9 / 10 | 8 / 9 | 16 / 19 | 20 / 20 | 8 / 10 | 16 / 18 |
| serious Total, serious adverse events | 2 / 10 | 1 / 9 | 1 / 19 | 0 / 20 | 0 / 10 | 0 / 18 |
Outcome results
Primary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline Through Day 29
Population: Full analysis set (FAS) included all randomized participants who carry the intended cystic fibrosis transmembrane conductance regulator gene (CFTR) allele mutation(s) and received at least 1 dose of study drug in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 1.9 percentage points |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 4.6 percentage points |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 14.2 percentage points |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 9.8 percentage points |
| Part 2: TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -0.1 percentage points |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 15.9 percentage points |
Primary
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 9 participants |
| Part 1: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 2 participants |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 8 participants |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 participants |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 16 participants |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 participants |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 20 participants |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part 2: TEZ/IVA | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 8 participants |
| Part 2: TEZ/IVA | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 16 participants |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
Secondary
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: From Baseline at Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 3.3 units on a scale |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 17.6 units on a scale |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 21.2 units on a scale |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 29.8 units on a scale |
| Part 2: TEZ/IVA | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | -5.0 units on a scale |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 19.4 units on a scale |
Secondary
Absolute Change in Sweat Chloride (SwCl) Concentrations
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Sweat Chloride (SwCl) Concentrations | 2.3 millimole per liter (mmol/L) |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Absolute Change in Sweat Chloride (SwCl) Concentrations | -42.8 millimole per liter (mmol/L) |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Absolute Change in Sweat Chloride (SwCl) Concentrations | -45.8 millimole per liter (mmol/L) |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Absolute Change in Sweat Chloride (SwCl) Concentrations | -49.5 millimole per liter (mmol/L) |
| Part 2: TEZ/IVA | Absolute Change in Sweat Chloride (SwCl) Concentrations | -2.6 millimole per liter (mmol/L) |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Absolute Change in Sweat Chloride (SwCl) Concentrations | -45.5 millimole per liter (mmol/L) |
Secondary
Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)
Time frame: Pre-dose at Day 15 and Day 29
Population: Pharmacokinetic (PK) set included all participants who received at least 1 dose study drug in the treatment period and for whom the PK data are considered sufficient and interpretable. Participants who received VX-121/TEZ/VX-561 TC in Parts 1 or 2 were to be analyzed for Ctrough. Overall participants in Part 1 were assessed for Ctrough, therefore data are reported in single Part 1: TC combined arm. The number analyzed signifies participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: VX-121 5 mg | 317 nanogram per milliliter (ng/mL) | Standard Deviation 119 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: VX-121 5 mg | 366 nanogram per milliliter (ng/mL) | Standard Deviation 130 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: VX-121 10 mg | 520 nanogram per milliliter (ng/mL) | Standard Deviation 214 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: VX-121 10 mg | 582 nanogram per milliliter (ng/mL) | Standard Deviation 342 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: VX-121 20 mg | 974 nanogram per milliliter (ng/mL) | Standard Deviation 500 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: VX-121 20 mg | 1160 nanogram per milliliter (ng/mL) | Standard Deviation 592 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: TEZ | 1890 nanogram per milliliter (ng/mL) | Standard Deviation 925 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: TEZ | 1920 nanogram per milliliter (ng/mL) | Standard Deviation 994 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: M1-TEZ | 4500 nanogram per milliliter (ng/mL) | Standard Deviation 1290 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: M1-TEZ | 4640 nanogram per milliliter (ng/mL) | Standard Deviation 1730 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: VX-561 | 475 nanogram per milliliter (ng/mL) | Standard Deviation 247 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: VX-561 | 510 nanogram per milliliter (ng/mL) | Standard Deviation 285 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: M1-VX-561 | 311 nanogram per milliliter (ng/mL) | Standard Deviation 141 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: M1-VX-561 | 336 nanogram per milliliter (ng/mL) | Standard Deviation 173 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: M6-VX-561 | 148 nanogram per milliliter (ng/mL) | Standard Deviation 98 |
| Part 1: Placebo | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: M6-VX-561 | 163 nanogram per milliliter (ng/mL) | Standard Deviation 128 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: M6-VX-561 | 174 nanogram per milliliter (ng/mL) | Standard Deviation 128 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: VX-121 20 mg | 1050 nanogram per milliliter (ng/mL) | Standard Deviation 414 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: VX-561 | 457 nanogram per milliliter (ng/mL) | Standard Deviation 264 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: VX-121 20 mg | 1030 nanogram per milliliter (ng/mL) | Standard Deviation 371 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: M1-VX-561 | 316 nanogram per milliliter (ng/mL) | Standard Deviation 188 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: TEZ | 1870 nanogram per milliliter (ng/mL) | Standard Deviation 675 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: VX-561 | 434 nanogram per milliliter (ng/mL) | Standard Deviation 257 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: TEZ | 2070 nanogram per milliliter (ng/mL) | Standard Deviation 1340 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: M6-VX-561 | 159 nanogram per milliliter (ng/mL) | Standard Deviation 94.6 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: M1-TEZ | 4550 nanogram per milliliter (ng/mL) | Standard Deviation 1200 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 15: M1-VX-561 | 326 nanogram per milliliter (ng/mL) | Standard Deviation 175 |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) | Day 29: M1-TEZ | 4440 nanogram per milliliter (ng/mL) | Standard Deviation 1680 |