Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661 in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

    Summary
    EudraCT number
    		 2017-001164-38
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    11 Sep 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Mar 2020
    First version publication date
    12 Mar 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VX15-661-113
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02953314
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States,
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617 341 6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617 341 6777, medicalinfo@vrtx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001640-PIP01-14
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Sep 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Sep 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Sep 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the Pharmacokinetics (PK) of Tezacaftor (TEZ) and Ivacaftor (IVA) after administration of multiple doses of TEZ in combination with IVA in Part A and to evaluate the safety and tolerability of TEZ in combination with IVA through Week 24 in Part B.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Council on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Nov 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 77
    Country: Number of subjects enrolled
    Canada: 6
    Worldwide total number of subjects
    83
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    83
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study consisted of 2-parts (Part A and B). The planned primary analysis was designed to assess overall treatment arm “TEZ/IVA”, irrespective of weight-based dosing regimen. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus analysis is presented for the single treatment arm “TEZ/IVA”.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part A
    Arm description
    		 Subjects weighing <25 kg received TEZ 50 mg/IVA 75 mg for 14 days. Subjects weighing ≥25 kg received TEZ 50 mg/IVA 150 mg for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TEZ
    Investigational medicinal product code
    VX-661
    Other name
    Tezacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ 50 mg once daily.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA 75 mg or 150 mg every 12 hours.

    Arm title
    		 Part B
    Arm description
    		 Subjects weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination in the morning and IVA 75 mg in the evening for 24 weeks. Subjects weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination in the morning and IVA 150 mg in the evening for 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TEZ/IVA
    Investigational medicinal product code
    VX-661/VX-770
    Other name
    Tezacaftor/Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ/IVA as fixed dose combination orally once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA as mono tablet once daily in the evening.

    Number of subjects in period 1
    		Part A Part B
    Started
    13
    70
    Completed
    13
    67
    Not completed
    0
    3
         Adverse Event
    -
    1
         Withdrawal of consent (not due to AE)
    -
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part A
    Reporting group description
    		 Subjects weighing <25 kg received TEZ 50 mg/IVA 75 mg for 14 days. Subjects weighing ≥25 kg received TEZ 50 mg/IVA 150 mg for 14 days.

    Reporting group title
    Part B
    Reporting group description
    		 Subjects weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination in the morning and IVA 75 mg in the evening for 24 weeks. Subjects weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination in the morning and IVA 150 mg in the evening for 24 weeks.

    Reporting group values
    		 Part A Part B Total
    Number of subjects
    		 13 70 83
    Age categorical
    Units: Subjects
        <=18 years
    		 13 70 83
        Between 18 and 65 years
    		 0 0 0
        >=65 years
    		 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 7 34 41
        Male
    		 6 36 42
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 3 3
        Not Hispanic or Latino
    		 13 67 80
        Unknown or Not Reported
    		 0 0 0
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 1 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 0 1
        White
    		 12 68 80
        More than one race
    		 0 1 1
        Unknown or Not Reported
    		 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Part A
    Reporting group description
    		 Subjects weighing <25 kg received TEZ 50 mg/IVA 75 mg for 14 days. Subjects weighing ≥25 kg received TEZ 50 mg/IVA 150 mg for 14 days.

    Reporting group title
    Part B
    Reporting group description
    		 Subjects weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination in the morning and IVA 75 mg in the evening for 24 weeks. Subjects weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination in the morning and IVA 150 mg in the evening for 24 weeks.

    Primary: Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA

    		 Close Top of page
    End point title
    		 Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA [1] [2]
    End point description
    Pharmacokinetic (PK) set included subjects who received at least 1 dose of study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here “n” signifies those subjects who were evaluable for this endpoint at specified time points and "99999" represents "Not Applicable" as data for geometric coefficient of variation could not be calculated for the category with n=1 subject.
    End point type
    Primary
    End point timeframe
    Day 1 and Day 14
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this primary PK endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part A.
    End point values
    		 Part A
    Number of subjects analysed
    13
    Units: nanogram per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Day 1: TEZ (<25 Kg) (n= 2)
    6630 ± 10.3
        Day 1: TEZ (≥25 Kg) (n= 11)
    4310 ± 42.6
        Day 14: TEZ (<25 Kg) (n= 2)
    6300 ± 10.3
        Day 14: TEZ (≥25 Kg) (n= 10)
    5340 ± 49.0
        Day 1: IVA (<25 Kg) (n= 1)
    656 ± 99999
        Day 1: IVA (≥25 Kg) (n= 9)
    1010 ± 64.3
        Day 14: IVA (<25 Kg) (n= 2)
    578 ± 60.4
        Day 14: IVA (≥25 Kg) (n= 10)
    1490 ± 105
    No statistical analyses for this end point

    Primary: Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA

    		 Close Top of page
    End point title
    		 Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA [3] [4]
    End point description
    PK set was used. Here “n” signifies those subjects who were evaluable for this endpoint at specified time points and "99999" represents "Not Applicable" as data could not be calculated for the category with n=0 subject.
    End point type
    Primary
    End point timeframe
    Day 1 and Day 14
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this primary PK endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part A.
    End point values
    		 Part A
    Number of subjects analysed
    13
    Units: hour*nanogram per milliliter (hr*ng/mL)
    geometric mean (geometric coefficient of variation)
        Day 1: TEZ (<25 Kg) (n= 2)
    54300 ± 16.2
        Day 1: TEZ (≥25 Kg) (n= 11)
    41600 ± 36.2
        Day 14: TEZ (<25 Kg) (n= 2)
    66500 ± 30.5
        Day 14: TEZ (≥25 Kg) (n= 10)
    71600 ± 61.1
        Day 1: IVA (<25 Kg) (n= 0)
    99999 ± 99999
        Day 1: IVA (≥25 Kg) (n= 0)
    99999 ± 99999
        Day 14: IVA (<25 Kg) (n= 2)
    5050 ± 49.1
        Day 14: IVA (≥25 Kg) (n= 10)
    12400 ± 118
    No statistical analyses for this end point

    Primary: Part B: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Part B: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [5] [6]
    End point description
    Safety set included all subjects who received at least 1 dose of study drug. The planned analysis was designed to assess overall treatment arm, irrespective of weight-based dosing regimen. The aim of weight-based dosing is to achieve similar exposures in children of different weights, thus analysis is presented for the single treatment arm.
    End point type
    Primary
    End point timeframe
    Day 1 up to Week 28
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this primary safety endpoint.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: Subjects
        Subjects with AEs
    65
        Subjects with SAEs
    6
    No statistical analyses for this end point

    Secondary: Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)

    		 Close Top of page
    End point title
    		 Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA) [7]
    End point description
    PK set. Here “Number Analyzed” signifies those subjects who were evaluable for this outcome measure at specified time points and "99999" represents "Not Applicable" as data for geometric coefficient of variation could not be calculated for the category with n=1 subject.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 14
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part A.
    End point values
    		 Part A
    Number of subjects analysed
    13
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1: M1-TEZ (<25 kg)(n=2)
    1720 ± 3.29
        Day 1: M1-TEZ (≥25 kg)(n=11)
    1530 ± 22.0
        Day 14: M1-TEZ (<25 kg)(n=2)
    8360 ± 22
        Day 14: M1-TEZ (≥25 kg)(n=10)
    5930 ± 19.9
        Day 1: M2-TEZ (<25 kg)(n=2)
    1130 ± 4.36
        Day 1: M2-TEZ (≥25 kg)(n=11)
    922 ± 25.8
        Day 14: M2-TEZ (<25 kg)(n=2)
    6180 ± 27.2
        Day 14: M2-TEZ (≥25 kg)(n=10)
    5350 ± 27.2
        Day 1: M1-IVA (<25 kg)(n=1)
    2320 ± 99999
        Day 1: M1-IVA (≥25 kg)(n=9)
    2430 ± 57.1
        Day 14: M1-IVA (<25 kg)(n=2)
    1460 ± 34.6
        Day 14: M1-IVA (≥25 kg)(n=10)
    3420 ± 72.7
        Day 1: M6-IVA (<25 kg)(n=1)
    849 ± 99999
        Day 1: M6-IVA (≥25 kg)(n=9)
    1070 ± 55.7
        Day 14: M6-IVA (<25 kg)(n=2)
    1090 ± 31.4
        Day 14: M6-IVA (≥25 kg)(n=10)
    2720 ± 59.2
    No statistical analyses for this end point

    Secondary: Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)

    		 Close Top of page
    End point title
    		 Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA) [8]
    End point description
    PK set. Here “Number Analyzed” signifies those subjects who were evaluable for this outcome measure at specified time points. “Number Analyzed=0” signified no subjects were evaluated for the specified parameter at that time point and "99999" represents "Not Applicable" as data for geometric mean and geometric coefficient of variation could not be calculated for the category with n=0 subject.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 14
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part A.
    End point values
    		 Part A
    Number of subjects analysed
    13
    Units: hr*ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1: M1-TEZ (<25 kg)(n=2)
    36500 ± 5.80
        Day 1: M1-TEZ (≥25 kg)(n=11)
    27400 ± 26.3
        Day 14: M1-TEZ (<25 kg)(n=2)
    160000 ± 15.5
        Day 14: M1-TEZ (≥25 kg)(n=10)
    121000 ± 17.1
        Day 1: M2-TEZ (<25 kg)(n=2)
    14200 ± 12.3
        Day 1: M2-TEZ (≥25 kg)(n=11)
    11100 ± 25.9
        Day 14: M2-TEZ (<25 kg)(n=2)
    137000 ± 32.7
        Day 14: M2-TEZ (≥25 kg)(n=10)
    119000 ± 27.7
        Day 1: M1-IVA (<25 kg)(n=0)
    99999 ± 99999
        Day 1: M1-IVA (≥25 kg)(n=0)
    99999 ± 99999
        Day 14: M1-IVA (<25 kg)(n=2)
    13700 ± 52.1
        Day 14: M1-IVA (≥25 kg)(n=10)
    30300 ± 81.1
        Day 1: M6-IVA (<25 kg)(n=0)
    99999 ± 99999
        Day 1: M6-IVA (≥25 kg)(n=0)
    99999 ± 99999
        Day 14: M6-IVA (<25 kg)(n=2)
    10200 ± 58.5
        Day 14: M6-IVA (≥25 kg)(n=10)
    26000 ± 70.6
    No statistical analyses for this end point

    Secondary: Part A: Number of Subjects With AEs and SAEs

    		 Close Top of page
    End point title
    		 Part A: Number of Subjects With AEs and SAEs [9]
    End point description
    Safety set. The planned analysis was designed to assess overall treatment arm, irrespective of weight-based dosing regimen. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus analysis is presented for the single treatment arm.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 28
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part A.
    End point values
    		 Part A
    Number of subjects analysed
    13
    Units: subjects
        Subjects with AEs
    12
        Subjects with SAEs
    0
    No statistical analyses for this end point

    Secondary: Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA)

    		 Close Top of page
    End point title
    		 Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA) [10]
    End point description
    PK set. Here “Overall Number of subjects Analyzed” signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    69
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        TEZ (<40 kg)(n=62)
    4800 ± 33.7
        TEZ (≥40 kg)(n=7)
    5870 ± 46.5
        M1-TEZ (<40 kg)(n=62)
    5310 ± 36.0
        M1-TEZ (≥40 kg)(n=7)
    5440 ± 61.5
        M2-TEZ (<40 kg)(n=62)
    4170 ± 47.4
        M2-TEZ (≥40 kg)(n=7)
    5210 ± 55.0
        IVA (<40 kg)(n=62)
    725 ± 56.9
        IVA (≥40 kg)(n=7)
    886 ± 58.7
        M1-IVA (<40 kg)(n=62)
    1560 ± 54.8
        M1-IVA (≥40 kg)(n=7)
    1870 ± 50.2
        M6-IVA (<40 kg)(n=62)
    870 ± 69.2
        M6-IVA (≥40 kg)(n=7)
    1120 ± 29.5
    No statistical analyses for this end point

    Secondary: Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA )

    		 Close Top of page
    End point title
    		 Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA ) [11]
    End point description
    PK set. Here “Number Analyzed” signifies those subjects who were evaluable for this outcome measure at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    69
    Units: hr*ng/mL
    geometric mean (geometric coefficient of variation)
        TEZ (<40 kg)(n=61)
    50300 ± 36.3
        TEZ (≥40 kg)(n=6)
    60900 ± 50.6
        M1-TEZ (<40 kg)(n=61)
    104000 ± 44.2
        M1-TEZ (≥40 kg)(n=6)
    100000 ± 87.2
        M2-TEZ (<40 kg)(n=61)
    88400 ± 57.0
        M2-TEZ (≥40 kg)(n=6)
    93600 ± 46.5
        IVA (<40 kg)(n=59)
    5330 ± 62.2
        IVA (≥40 kg)(n=6)
    7410 ± 53.8
        M1-IVA (<40 kg)(n=59)
    12700 ± 55.9
        M1-IVA (≥40 kg)(n=6)
    17200 ± 40.4
        M6-IVA (<40 kg)(n=59)
    8140 ± 70.2
        M6-IVA (≥40 kg)(n=6)
    11100 ± 39.4
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [12]
    End point description
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FAS: subjects who carry the intended CFTR mutations and received at least 1 dose of study drug. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline through Week 24
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: percentage points
        least squares mean (confidence interval 95%)
    0.9 (-0.6 to 2.3)
    No statistical analyses for this end point

    Secondary: Part B: Relative Change in ppFEV1

    		 Close Top of page
    End point title
    		 Part B: Relative Change in ppFEV1 [13]
    End point description
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline through Week 24
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: percent change
        least squares mean (confidence interval 95%)
    1.4 (-0.4 to 3.1)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Weight

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Weight [14]
    End point description
    FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 24
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: kg
        least squares mean (confidence interval 95%)
    1.7 (1.3 to 2.0)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Weight-for-age Z-Score

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Weight-for-age Z-Score [15]
    End point description
    z-score is a statistical measure to describe whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher weight. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 24
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: z-score
        least squares mean (confidence interval 95%)
    0.00 (-0.05 to 0.05)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Height

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Height [16]
    End point description
    FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 24
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: centimeter (cm)
        least squares mean (confidence interval 95%)
    2.7 (2.4 to 2.9)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Height-for-age z-Score

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Height-for-age z-Score [17]
    End point description
    z-score is a statistical measure to describe whether a mean was above or below the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher height. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 24
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: z-score
        least squares mean (confidence interval 95%)
    0.00 (-0.05 to 0.05)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Body Mass Index (BMI)

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Body Mass Index (BMI) [18]
    End point description
    BMI was defined as weight in kg divided by height in square meter (m^2). FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 24
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: kg/m^2
        least squares mean (confidence interval 95%)
    0.23 (0.06 to 0.40)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in BMI-for-age z-Score

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in BMI-for-age z-Score [19]
    End point description
    BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 24
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: z-score
        least squares mean (confidence interval 95%)
    -0.03 (-0.10 to 0.04)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Sweat Chloride

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Sweat Chloride [20]
    End point description
    Sweat samples were collected using an approved collection device. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline through Week 4
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: millimole per liter (mmol/L)
        least squares mean (confidence interval 95%)
    -13.0 (-16.2 to -9.9)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Sweat Chloride

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Sweat Chloride [21]
    End point description
    Sweat samples were collected using an approved collection device. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline through Week 24
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: mmol/L
        least squares mean (confidence interval 95%)
    -14.5 (-17.4 to -11.6)
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

    		 Close Top of page
    End point title
    		 Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [22]
    End point description
    The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. FAS was used. The aim of weight based dosing is to achieve similar exposures in children of different weights, thus the planned analysis is presented for the single treatment arm irrespective of weight-based dosing regimen.
    End point type
    Secondary
    End point timeframe
    From Baseline through Week 24
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is reporting data only for Part B.
    End point values
    		 Part B
    Number of subjects analysed
    70
    Units: units on a scale
        least squares mean (confidence interval 95%)
    3.4 (1.4 to 5.5)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Part A: Day 1 up to Day 28; Part B: Day 1 up to Week 28
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Part A
    Reporting group description
    		 Subjects weighing <25 kg received TEZ 50 mg/IVA 75 mg for 14 days. Subjects weighing ≥25 kg received TEZ 50 mg/IVA 150 mg for 14 days.

    Reporting group title
    Part B
    Reporting group description
    		 Subjects weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination in the morning and IVA 75 mg orally in the evening for 24 weeks. Subjects weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination in the morning and IVA 150 mg in the evening for 24 weeks.

    Serious adverse events
    		 Part A Part B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 13 (0.00%)
    6 / 70 (8.57%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Gastrointestinal disorders
    Breath odour
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Snoring
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure to thrive
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A Part B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 13 (92.31%)
    62 / 70 (88.57%)
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    6 / 70 (8.57%)
         occurrences all number
    0
    6
    International normalised ratio increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Prothrombin time prolonged
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Pallor
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 13 (23.08%)
    6 / 70 (8.57%)
         occurrences all number
    3
    10
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 13 (7.69%)
    13 / 70 (18.57%)
         occurrences all number
    1
    14
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 13 (0.00%)
    10 / 70 (14.29%)
         occurrences all number
    0
    11
    Abdominal pain upper
         subjects affected / exposed
    0 / 13 (0.00%)
    5 / 70 (7.14%)
         occurrences all number
    0
    5
    Constipation
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 70 (2.86%)
         occurrences all number
    1
    2
    Vomiting
         subjects affected / exposed
    0 / 13 (0.00%)
    7 / 70 (10.00%)
         occurrences all number
    0
    8
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 13 (23.08%)
    25 / 70 (35.71%)
         occurrences all number
    4
    37
    Nasal congestion
         subjects affected / exposed
    2 / 13 (15.38%)
    10 / 70 (14.29%)
         occurrences all number
    2
    12
    Oropharyngeal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    6 / 70 (8.57%)
         occurrences all number
    1
    6
    Productive cough
         subjects affected / exposed
    0 / 13 (0.00%)
    6 / 70 (8.57%)
         occurrences all number
    0
    7
    Rhinorrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    7 / 70 (10.00%)
         occurrences all number
    0
    7
    Sputum increased
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 70 (4.29%)
         occurrences all number
    1
    3
    Skin and subcutaneous tissue disorders
    Rash erythematous
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Pain in extremity
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 70 (2.86%)
         occurrences all number
    1
    2
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    Ear infection
         subjects affected / exposed
    1 / 13 (7.69%)
    5 / 70 (7.14%)
         occurrences all number
    1
    5
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 13 (0.00%)
    15 / 70 (21.43%)
         occurrences all number
    0
    20
    Influenza
         subjects affected / exposed
    0 / 13 (0.00%)
    5 / 70 (7.14%)
         occurrences all number
    0
    5
    Nasopharyngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    6 / 70 (8.57%)
         occurrences all number
    1
    7
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    6 / 70 (8.57%)
         occurrences all number
    0
    9
    Urinary tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    4 / 70 (5.71%)
         occurrences all number
    0
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 70 (2.86%)
         occurrences all number
    1
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Apr 2017
    - Revised target enrollment, revised inclusion criteria
    19 Jul 2017
    - Defined dose for Part B

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 03:43:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA