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This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of lumacaftor in combination with ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the F508del-mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lumacaftor/Ivacaftor (LUM/IVA) | Experimental | Part A Cohort 1: Participants aged 6 through 8 years will receive LUM 200 milligram (mg) in fixed-dose combination with IVA 250 mg orally every 12 hours (q12h) for 14 days. Part A Cohort 2: Participants aged 9 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. Part B: Participants aged 6 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lumacaftor | Drug |
|
| |
| Ivacaftor |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 | 4 hours post-morning dose on Day 1 | |
| Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 | 4 hours post-morning dose on Day 14 | |
| Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) | The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval. | Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA) |
| Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose to Week 26 were considered treatment-emergent. | Day 1 up to Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | Day 1, Day 14 | |
| Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8474788 | Background | Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG Jr. Pulmonary function between 6 and 18 years of age. Pediatr Pulmonol. 1993 Feb;15(2):75-88. doi: 10.1002/ppul.1950150204. | |
| 37983082 | Derived | Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4. |
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The study was conducted in 2 parts - Part A and Part B. Part A consisted of 2 cohorts, in which participants aged 6 to 8 years were enrolled in Cohort 1 and participants aged 9 to 11 years were enrolled in Cohort 2. Part B consisted of a single cohort. Participants from Part A may have also participated in Part B of the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lumacaftor/Ivacaftor (LUM/IVA) | Part A Cohort 1: Participants aged 6 through 8 years received LUM 200 milligram (mg) in fixed-dose combination with IVA 250 mg orally every 12 hours (q12h) for 14 days. Part A Cohort 2: Participants aged 9 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. Part B: Participants aged 6 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A (14 Days) |
|
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| Drug |
|
|
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose through the end of Part A were considered treatment-emergent.
| Day 1 up to Day 28 |
| Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4 | Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Average of Day 15 and Week 4 measurements was taken and change was calculated as: Average (Day 15 and Week 4 measurement) minus Baseline measurement. | Baseline, Day 15 and Week 4 |
| Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 | Sweat samples were collected using an approved collection device. Change = Week 26 minus Week 24. | Week 24, Week 26 |
| Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2). | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24 | BMI was defined as weight in kg divided by height*height in m^2. z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts. | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in Weight at Week 24 | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24 | Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts. | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in Height at Week 24 | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24 | Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts. | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants 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. | Baseline, Week 24 |
| Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction. | Baseline, Week 24 |
| Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough and C3-6hr for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated. Ctrough was observed pre-dose concentration. C3-6hr was observed concentration at 3 to 6 hours post- dose. | For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4 |
| Tucson |
| Arizona |
| United States |
| Long Beach | California | United States |
| Palo Alto | California | United States |
| Aurora | Colorado | United States |
| Atlanta | Georgia | United States |
| Indianapolis | Indiana | United States |
| Boston | Massachusetts | United States |
| Kansas City | Missouri | United States |
| St Louis | Missouri | United States |
| Buffalo | New York | United States |
| Rochester | New York | United States |
| Syracuse | New York | United States |
| Charleston | South Carolina | United States |
| Austin | Texas | United States |
| Salt Lake City | Utah | United States |
| Norfolk | Virginia | United States |
| Seattle | Washington | United States |
| Milwaukee | Wisconsin | United States |
| Toronto | Ontario | Canada |
| 33331662 | Derived | Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. |
| 27805836 | Derived | Milla CE, Ratjen F, Marigowda G, Liu F, Waltz D, Rosenfeld M; VX13-809-011 Part B Investigator Group *. Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2017 Apr 1;195(7):912-920. doi: 10.1164/rccm.201608-1754OC. |
| Part A Cohort 1 (6 to 8 Years) |
|
| Part A Cohort 2 (9 to 11 Years) |
|
| COMPLETED |
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| NOT COMPLETED |
|
| Part B (24 Weeks) |
|
|
The Safety Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lumacaftor/Ivacaftor (LUM/IVA) | Part A Cohort 1: Participants aged 6 through 8 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. Part A Cohort 2: Participants aged 9 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. Part B: Participants aged 6 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Data were planned to be reported separately for Part A and Part B of the study. Here "n" signifies participants who were evaluable for specified part of the study. | Mean | Standard Deviation | years |
| ||||||||||||||||||||||||
| Sex/Gender, Customized | Data were planned to be reported separately for Part A and Part B of the study. Here "n" signifies participants who were evaluable for specified part of the study. | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 | The Pharmacokinetic (PK) Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | 4 hours post-morning dose on Day 1 |
|
|
| |||||||||||||||||||||||||||||||||
| Primary | Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 | The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable. | Posted | Mean | Standard Deviation | ng/mL | 4 hours post-morning dose on Day 14 |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) | The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval. | The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable. | Posted | Median | Full Range | ng*hr/mL | Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA) |
|
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| Primary | Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose to Week 26 were considered treatment-emergent. | The Safety Set included all participants who received any amount of Part B study drug | Posted | Number | participants | Day 1 up to Week 26 |
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| Secondary | Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 | The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable. | Posted | Mean | Standard Deviation | ng/mL | Day 1, Day 14 |
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| Secondary | Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose through the end of Part A were considered treatment-emergent. | The Safety Set included all participants who received at least 1 dose of study drug. Here "n" signifies those subjects who were evaluable for the specified cohort. | Posted | Number | participants | Day 1 up to Day 28 |
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| Secondary | Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4 | Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Average of Day 15 and Week 4 measurements was taken and change was calculated as: Average (Day 15 and Week 4 measurement) minus Baseline measurement. | The Full Analysis Set (FAS) included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | millimole per liter (mmol/L) | Baseline, Day 15 and Week 4 |
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| Secondary | Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 | Sweat samples were collected using an approved collection device. Change = Week 26 minus Week 24. | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | mmol/L | Week 24, Week 26 |
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| Secondary | Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 | BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2). | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kilogram per square meter (kg/m^2) | Baseline, Week 24 |
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| Secondary | Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24 | BMI was defined as weight in kg divided by height*height in m^2. z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts. | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | z-score | Baseline, Week 24 |
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| Secondary | Part B: Absolute Change From Baseline in Weight at Week 24 | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | kilograms (kg) | Baseline, Week 24 |
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| Secondary | Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24 | Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts. | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | z-score | Baseline, Week 24 |
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| Secondary | Part B: Absolute Change From Baseline in Height at Week 24 | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | centimeter (cm) | Baseline, Week 24 |
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| Secondary | Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24 | Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is, with range from -infinity to +infinity; where 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts. | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | z-score | Baseline, Week 24 |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 | The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants 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. | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline, Week 24 |
|
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| Secondary | Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 | The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction. | The FAS included all Part B enrolled participants who were exposed to any amount of Part B study drug. Here "Number of Participants" analyzed signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline, Week 24 |
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| Secondary | Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) | Ctrough and C3-6hr for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated. Ctrough was observed pre-dose concentration. C3-6hr was observed concentration at 3 to 6 hours post- dose. | The PK Set included all enrolled participants who received the study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here "n" signifies those participants who were evaluable at the specified time point for the given category. | Posted | Mean | Standard Deviation | ng/mL | For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4 |
|
|
Part A: Day 1 up to Day 28; Part B: Day 1 up to Week 26
For Part A: MedDRA 16.0 and For Part B: MedDRA 18.1 was used.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A Cohort 1: LUM/IVA | Participants aged 6 through 8 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. | 0 | 5 | 4 | 5 | ||
| EG001 | Part A Cohort 2: LUM/IVA | Participants aged 9 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. | 0 | 5 | 3 | 5 | ||
| EG002 | Part B: LUM/IVA | Participants aged 6 through 11 years received LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks. | 4 | 58 | 55 | 58 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Lower respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Increased viscosity of upper respiratory secretion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Nasal polyps | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Paranasal sinus hypersecretion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Respiration abnormal | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Rhonchi | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Sinus headache | Nervous system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Faecal volume increased | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Faeces soft | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pulmonary function test decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Mean cell haemoglobin concentration decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Blood bicarbonate decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Blood creatinine decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Crystal urine present | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Eosinophil count decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pseudomonas test positive | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Streptococcus test positive | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Forced Expiratory Volume Decreased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Hepatic Enzyme Increased | Investigations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Normochromic normocytic anaemia | Blood and lymphatic system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Application site erythema | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Application site urticaria | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Application site vesicles | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Vessel puncture site reaction | General disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Sunburn | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Otitis externa | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Gastroenteritis bacterial | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Impetigo | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Staphylococcal skin infection | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Tinea infection | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Increased appetite | Metabolism and nutrition disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| House dust allergy | Immune system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Mycotic allergy | Immune system disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Eye pruritus | Eye disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Attention deficit/hyperactivity disorder | Psychiatric disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Enuresis | Renal and urinary disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Dandruff | Skin and subcutaneous tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.0/18.1 | Systematic Assessment |
|
Due to limited sampling and instances of missing data, C4h was reported instead of Cmax as an approximation of maximum concentration. Sparse PK sampling scheme was optimized around parent compounds which limited the estimation of AUC for metabolites.
PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex Pharmaceuticals Incorporated | 617-341-6777 | medicalinfo@vrtx.com |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C569105 | lumacaftor |
| C545203 | ivacaftor |
Not provided
Not provided
Not provided
| Title | Measurements |
|---|---|
|
| Part A Cohort 2 (n=5): Female |
|
| Part A Cohort 2 (n=5): Male |
|
| Part B (n=58): Female |
|
| Part B (n=58): Male |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| LUM |
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| IVA |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
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| Title | Denominators | Categories | ||||
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