Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02797132
• Collaborator: (none)
• Enrollment: 62
• Locations: 20
• Arm: 1
• Actual Duration (Months): 16
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. Subjects who participate in Part A may participate in Part B, if they meet the eligibility criteria.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: LUM/IVA	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, 2-Part, Open-label Study to Evaluate the Safety and Pharmacokinetics of Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lumacaftor/Ivacaftor (LUM/IVA) Part A (<14 kg): Participants weighing less than (<) 14 kilograms (kg) at screening received LUM 100 milligram (mg)/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A. Part A (>=14 kg): Participants weighing greater than or equal to (>=) 14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A. Part B (<14 kg): Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B. Part B (>=14 kg): Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.

Drug: LUM/IVA; Other Names: Orkambi VX-809+VX-770

Outcome Measures

Primary Outcome Measures

1. Part A: Pre-dose Concentration (Ctrough) of LUM and IVA [Day 15]

2. Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to Week 26]

Secondary Outcome Measures

1. Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites [Day 15]

2. Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to Day 25]

3. Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 [Baseline, Week 24]

   Sweat samples were collected using an approved collection device.

4. Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 [Baseline, Week 24]

   BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).

5. Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24 [Baseline, Week 24]

   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 (BMI z-score).

6. Part B: Absolute Change From Baseline in Weight at Week 24 [Baseline, Week 24]

7. Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24 [Baseline, Week 24]

   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 (Weight z-score).

8. Part B: Absolute Change From Baseline in Stature (Height) at Week 24 [Baseline, Week 24]

9. Part B: Absolute Change From Baseline in Stature-for-Age Z-Score [Baseline, Week 24]

   z-score is a statistical measure to describe whether a mean was above or below the standard. Stature (height), adjusted for age and sex, was analyzed as Stature-for-age z-score (Stature z-score).

10. Part B: Number of Pulmonary Exacerbations [Through Week 24]

    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria.

11. Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24 [Through Week 24]

    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. Time to event data was not collected and instead, number of participants with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.

12. Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations [Through Week 24]

13. Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24 [Baseline, Week 24]

14. Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24 [Baseline, Through Week 24]

15. Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 [Baseline and Week 24]

    Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.

16. Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 [Baseline, Week 24]

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

17. Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 [Week 24, Week 26]

    Sweat samples were collected using an approved collection device.

18. Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale [Day 1]

    The acceptability and palatability of LUM/IVA granules was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). The assessment was conducted in 2 steps: assessment of approved food/liquid (Evaluation 1), and assessment of approved food/liquid with LUM/IVA granules (Evaluation 2).

19. Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24 [Baseline, Week 24]

    Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

20. Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24 [Baseline, Week 24]

    LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.

21. Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites [Week 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 5 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit

• Subjects with confirmed diagnosis of CF at the Screening Visit

• Subjects who are homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation

Exclusion Criteria:

• Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1

• A standard 12-lead ECG demonstrating QTc >450 millisecond (msec) at the Screening Visit.

• History of solid organ or hematological transplantation.

• Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit.

• History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination at the Screening Visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Palo Alto	California	United States
2		Aurora	Colorado	United States
3		Chicago	Illinois	United States
4		Indianapolis	Indiana	United States
5		Boston	Massachusetts	United States
6		Minneapolis	Minnesota	United States
7		Kansas City	Missouri	United States
8		Buffalo	New York	United States
9		Chapel Hill	North Carolina	United States
10		Cincinnati	Ohio	United States
11		Cleveland	Ohio	United States
12		Columbus	Ohio	United States
13		Philadelphia	Pennsylvania	United States
14		Charleston	South Carolina	United States
15		Houston	Texas	United States
16		Norfolk	Virginia	United States
17		Seattle	Washington	United States
18		Vancouver	British Columbia	Canada
19		Toronto	Ontario	Canada
20		Montréal		Canada

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 13, 2017
• Statistical Analysis Plan - Sep 23, 2016

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT02797132
• Other Study ID Numbers: VX15-809-115; 2016-001004-33
• First Posted: Jun 13, 2016
• Last Update Posted: Oct 30, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Vertex Pharmaceuticals Incorporated: CF
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details	The study was conducted in 2 parts, Part A and Part B. In Parts A and B, participants received doses of lumacaftor/ivacaftor (LUM/IVA) based on weight. Participants from Part A may have also participated in Part B.

Arm/Group Title	Lumacaftor/Ivacaftor (LUM/IVA)
Arm/Group Description	Part A (<14 kg): Participants weighing less than (<) 14 kilograms (kg) at screening received LUM 100 milligram (mg)/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A. Part A (>=14 kg): Participants weighing greater than or equal to (>=) 14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A. Part B (<14 kg): Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B. Part B (>=14 kg): Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Period Title: Part A (15 Days)
STARTED	12
Part A (<14 kg Weight)	4
Part A (>=14 kg Weight)	8
COMPLETED	11
NOT COMPLETED	1
Period Title: Part A (15 Days)
STARTED	60
Part B (<14 kg Weight)	19
Part B (>=14 kg Weight)	41
COMPLETED	57
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Lumacaftor/Ivacaftor (LUM/IVA)
Arm/Group Description	Part A (<14 kg): Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A. Part A (>=14 kg): Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A. Part B (<14 kg): Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B. Part B (>=14 kg): Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Overall Participants	62
Age (months) [Mean (Standard Deviation) ]
Part A (<14 kg Weight)	27.0 (6.00)
Part A (>=14 kg Weight)	48.0 (11.11)
Part B (<14 kg Weight)	31.6 (5.05)
Part B (>=14 kg Weight)	49.9 (10.63)
Sex: Female, Male (Count of Participants)
Female	2 3.2%
Male	2 3.2%
Female	2 3.2%
Male	6 9.7%
Female	9 14.5%
Male	10 16.1%
Female	20 32.3%
Male	21 33.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	4 6.5%
Unknown or Not Reported	0 0%
Hispanic or Latino	0 0%
Not Hispanic or Latino	8 12.9%
Unknown or Not Reported	0 0%
Hispanic or Latino	1 1.6%
Not Hispanic or Latino	18 29%
Unknown or Not Reported	0 0%
Hispanic or Latino	2 3.2%
Not Hispanic or Latino	39 62.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 6.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 12.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	18 29%
More than one race	0 0%
Unknown or Not Reported	1 1.6%
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	41 66.1%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Part A: Pre-dose Concentration (Ctrough) of LUM and IVA
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set for Part A included all participants who received at least 1 dose of LUM/IVA in Part A.

Arm/Group Title	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A.
Measure Participants	4	7
LUM	8710 (3590)	12300 (5960)
IVA	94.0 (67.0)	216 (185)

2. Primary Outcome

Title	Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Day 1 up to Week 26

Outcome Measure Data

Analysis Population Description

The Safety Set included all participants who received at least 1 dose of LUM/IVA in Part B.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	41
AEs	19 30.6%	40 NaN
SAEs	2 3.2%	2 NaN

3. Secondary Outcome

Title	Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The PK set for Part A included all participants who received at least 1 dose of LUM/IVA in Part A.

Arm/Group Title	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A.
Measure Participants	4	7
LUM Metabolite (M28 LUM)	1310 (590)	1370 (286)
IVA Metabolite (M1 IVA)	475 (384)	1240 (1180)
IVA Metabolite (M6 IVA)	1510 (1130)	3270 (2100)

4. Secondary Outcome

Title	Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Day 1 up to Day 25

Outcome Measure Data

Analysis Population Description

The Safety Set included all participants who received at least 1 dose of LUM/IVA in Part A.

Arm/Group Title	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part A (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A.
Measure Participants	4	8
AEs	4 6.5%	6 NaN
SAEs	0 0%	0 NaN

5. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
Description	Sweat samples were collected using an approved collection device.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	18	31
Mean (Standard Deviation) [millimole per liter (mmol/L)]	-33.5 (14.5)	-30.7 (14.0)

6. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Description	BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	38
Mean (Standard Deviation) [Kilogram per meter square (kg/m^2)]	0.22 (0.78)	0.29 (0.75)

7. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24
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 (BMI z-score).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	38
Mean (Standard Deviation) [Z-score]	0.36 (0.67)	0.26 (0.53)

8. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Weight at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	38
Mean (Standard Deviation) [Kilogram (kg)]	1.4 (0.7)	1.5 (1.0)

9. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24
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 (Weight z-score).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	38
Mean (Standard Deviation) [Z-score]	0.44 (0.52)	0.17 (0.36)

10. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Stature (Height) at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	38
Mean (Standard Deviation) [Centimeter (cm)]	4.1 (1.4)	3.4 (1.0)

11. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Stature-for-Age Z-Score
Description	z-score is a statistical measure to describe whether a mean was above or below the standard. Stature (height), adjusted for age and sex, was analyzed as Stature-for-age z-score (Stature z-score).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	38
Mean (Standard Deviation) [Z-score]	0.19 (0.32)	0.04 (0.19)

12. Secondary Outcome

Title	Part B: Number of Pulmonary Exacerbations
Description	Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria.
Time Frame	Through Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	41
Number [pulmonary exacerbations]	5	20

13. Secondary Outcome

Title	Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
Description	Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. Time to event data was not collected and instead, number of participants with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
Time Frame	Through Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	41
Count of Participants [Participants]	3 4.8%	15 NaN

14. Secondary Outcome

Title	Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations
Time Frame	Through Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	41
Number [hospitalizations]	1	3

15. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	12	23
Mean (Standard Deviation) [microgram per gram]	38.4 (76.1)	60.0 (94.0)

16. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24
Time Frame	Baseline, Through Week 24

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing less than 14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	17	38
Mean (Standard Deviation) [ng/mL]	-262.1 (343.1)	-71.1 (120.5)

17. Secondary Outcome

Title	Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24
Description	Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The FAS analysis set was used. Here "Number Analyzed" signifies those participants who were evaluated for this outcome at the specified time point..

Arm/Group Title	Part B: LUM 100 mg/IVA 125 mg	Part B: LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing less than <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	41
Negative	18 29%	37 NaN
Positive	0 0%	1 NaN
Negative	19 30.6%	36 NaN
Positive	0 0%	0 NaN
Negative	16 25.8%	33 NaN
Positive	2 3.2%	5 NaN
Negative	17 27.4%	35 NaN
Positive	2 3.2%	1 NaN
Negative	12 19.4%	26 NaN
Positive	6 9.7%	12 NaN
Negative	13 21%	26 NaN
Positive	6 9.7%	10 NaN
Negative	18 29%	37 NaN
Positive	0 0%	1 NaN
Negative	19 30.6%	35 NaN
Positive	0 0%	1 NaN
Negative	17 27.4%	35 NaN
Positive	1 1.6%	3 NaN
Negative	16 25.8%	34 NaN
Positive	3 4.8%	2 NaN
Negative	18 29%	38 NaN
Positive	0 0%	0 NaN
Negative	19 30.6%	36 NaN
Positive	0 0%	0 NaN
Negative	17 27.4%	37 NaN
Positive	1 1.6%	1 NaN
Negative	18 29%	36 NaN
Positive	1 1.6%	0 NaN

18. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Analysis population: participants >=3 years of age with data available for Baseline and Week 24. Only participants from "Part B (>=14 Kg Weight)" arm met the eligibility criteria for the specified time point and were included in the analysis.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	0	12
Mean (Standard Deviation) [percentage of predicted FEV1]	0.5 (11.6)

19. Secondary Outcome

Title	Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26
Description	Sweat samples were collected using an approved collection device.
Time Frame	Week 24, Week 26

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	17	31
Mean (Standard Deviation) [mmol/L]	34.4 (14.9)	32.2 (13.8)

20. Secondary Outcome

Title	Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale
Description	The acceptability and palatability of LUM/IVA granules was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). The assessment was conducted in 2 steps: assessment of approved food/liquid (Evaluation 1), and assessment of approved food/liquid with LUM/IVA granules (Evaluation 2).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled subjects in Part B who were exposed to any amount of LUM/IVA in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	18	38
Liked it Very Much	9 14.5%	30 NaN
Liked it a Little	4 6.5%	6 NaN
Not sure	3 4.8%	1 NaN
Disliked it a Little	0 0%	0 NaN
Disliked it Very Much	2 3.2%	1 NaN
Liked it Very Much	4 6.5%	6 NaN
Liked it a Little	2 3.2%	5 NaN
Not sure	4 6.5%	6 NaN
Disliked it a Little	3 4.8%	6 NaN
Disliked it Very Much	5 8.1%	15 NaN

21. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24
Description	Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The LCI Substudy Set included all participants who had signed informed consent (and assent, if applicable) to the optional LCI Substudy in Part B and enrolled and dosed in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	3	14
Mean (Standard Deviation) [ratio]	0.27 (0.48)	-0.76 (1.19)

22. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24
Description	LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The LCI Substudy Set included all subjects who had signed informed consent (and assent, if applicable) to the optional LCI Substudy in Part B and enrolled and dosed in Part B. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	3	14
Mean (Standard Deviation) [ratio]	0.24 (0.40)	-0.12 (0.69)

23. Secondary Outcome

Title	Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The PK set for Part B included all participants who received at least 1 dose of LUM/IVA in Part B. Here "Number Analyzed" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Part B (<14 kg Weight): LUM 100 mg/IVA 125 mg	Part B (>=14 kg Weight): LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.	Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Measure Participants	19	41
LUM	9060 (4060)	9390 (4830)
LUM Metabolite (M28 LUM)	1420 (846)	1510 (752)
IVA	108 (109)	110 (108)
IVA Metabolite (M1 IVA)	555 (560)	521 (478)
IVA Metabolite (M6 IVA)	2050 (1940)	1900 (1430)

Adverse Events

Time Frame	Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26
Arm/Group Title	Part A: LUM 100 mg/IVA 125 mg		Part A: LUM 150 mg/IVA 188 mg		Part B: LUM 100 mg/IVA 125 mg		Part B: LUM 150 mg/IVA 188 mg
Arm/Group Description	Participants weighing <14 kg at screening received LUM 100 milligram (mg)/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A.		Participants weighing >= 14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A.		Participants weighing less than <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.		Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hurs for 24 weeks in Part B.
All Cause Mortality
	Part A: LUM 100 mg/IVA 125 mg		Part A: LUM 150 mg/IVA 188 mg		Part B: LUM 100 mg/IVA 125 mg		Part B: LUM 150 mg/IVA 188 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/8 (0%)		0/19 (0%)		0/41 (0%)
Serious Adverse Events
	Part A: LUM 100 mg/IVA 125 mg		Part A: LUM 150 mg/IVA 188 mg		Part B: LUM 100 mg/IVA 125 mg		Part B: LUM 150 mg/IVA 188 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		2/41 (4.9%)
Gastrointestinal disorders
Constipation	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	0/4 (0%)		0/8 (0%)		0/19 (0%)		2/41 (4.9%)
Gastroenteritis viral	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Part A: LUM 100 mg/IVA 125 mg		Part A: LUM 150 mg/IVA 188 mg		Part B: LUM 100 mg/IVA 125 mg		Part B: LUM 150 mg/IVA 188 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		6/8 (75%)		19/19 (100%)		40/41 (97.6%)
Blood and lymphatic system disorders
Anaemia	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Lymphocytosis	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Cardiac disorders
Tachycardia	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Ventricular extrasystoles	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Endocrine disorders
Hypothyroidism	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		1/41 (2.4%)
Eye disorders
Eye irritation	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		1/41 (2.4%)
Lacrimation increased	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Gastrointestinal disorders
Faeces discoloured	1/4 (25%)		0/8 (0%)		0/19 (0%)		0/41 (0%)
Faeces soft	2/4 (50%)		0/8 (0%)		0/19 (0%)		0/41 (0%)
Flatulence	1/4 (25%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Vomiting	2/4 (50%)		0/8 (0%)		6/19 (31.6%)		11/41 (26.8%)
Constipation	0/4 (0%)		0/8 (0%)		3/19 (15.8%)		4/41 (9.8%)
Diarrhoea	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		4/41 (9.8%)
Abdominal pain	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		3/41 (7.3%)
Nausea	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		2/41 (4.9%)
Abdominal pain upper	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Haematochezia	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		1/41 (2.4%)
Oral discomfort	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Oral pain	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Post-tussive vomiting	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Steatorrhoea	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		1/41 (2.4%)
Dyschezia	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Frequent bowel movements	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Gastrooesophageal reflux disease	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
General disorders
Pyrexia	0/4 (0%)		0/8 (0%)		7/19 (36.8%)		10/41 (24.4%)
Fatigue	0/4 (0%)		0/8 (0%)		0/19 (0%)		2/41 (4.9%)
Chills	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		1/41 (2.4%)
Discomfort	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Pain	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Asthenia	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Hepatobiliary disorders
Hepatomegaly	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Immune system disorders
Seasonal allergy	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Hypersensitivity	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	0/4 (0%)		1/8 (12.5%)		0/19 (0%)		2/41 (4.9%)
Lice infestation	0/4 (0%)		1/8 (12.5%)		0/19 (0%)		0/41 (0%)
Lower respiratory tract infection viral	0/4 (0%)		1/8 (12.5%)		0/19 (0%)		0/41 (0%)
Upper respiratory tract infection	0/4 (0%)		0/8 (0%)		3/19 (15.8%)		7/41 (17.1%)
Ear infection	0/4 (0%)		0/8 (0%)		3/19 (15.8%)		4/41 (9.8%)
Otitis media	0/4 (0%)		0/8 (0%)		0/19 (0%)		4/41 (9.8%)
Sinusitis	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		3/41 (7.3%)
Conjunctivitis	0/4 (0%)		0/8 (0%)		0/19 (0%)		2/41 (4.9%)
Rhinitis	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		2/41 (4.9%)
Viral upper respiratory tract infection	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		2/41 (4.9%)
Impetigo	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Cellulitis	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Labyrinthitis	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Pharyngitis streptococcal	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		1/41 (2.4%)
Viral rash	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Vulvovaginal mycotic infection	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Candida nappy rash	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Gastroenteritis rotavirus	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Hand-foot-and-mouth disease	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		0/41 (0%)
Influenza	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Oral candidiasis	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Injury, poisoning and procedural complications
Joint dislocation	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Radial head dislocation	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Investigations
Respiratory rate increased	0/4 (0%)		1/8 (12.5%)		0/19 (0%)		0/41 (0%)
Alanine aminotransferase increased	0/4 (0%)		0/8 (0%)		3/19 (15.8%)		5/41 (12.2%)
Aspartate aminotransferase increased	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		4/41 (9.8%)
Forced expiratory volume decreased	0/4 (0%)		0/8 (0%)		0/19 (0%)		2/41 (4.9%)
Pseudomonas test positive	0/4 (0%)		0/8 (0%)		3/19 (15.8%)		2/41 (4.9%)
Activated partial thromboplastin time prolonged	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Burkholderia test positive	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Gamma-glutamyltransferase increased	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		1/41 (2.4%)
International normalised ratio increased	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Prothrombin time prolonged	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Pulmonary function test decreased	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Staphylococcus test positive	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Streptococcus test positive	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Bacterial test positive	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Blood creatine phosphokinase increased	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		0/41 (0%)
Blood iron decreased	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Blood creatinine increased	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Enterovirus test positive	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Respirovirus test positive	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Vitamin D decreased	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		2/41 (4.9%)
Dehydration	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		1/41 (2.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Musculoskeletal pain	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Nervous system disorders
Headache	0/4 (0%)		0/8 (0%)		0/19 (0%)		4/41 (9.8%)
Cognitive disorder	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Lethargy	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Psychiatric disorders
Enuresis	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Sleep terror	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		0/41 (0%)
Tearfulness	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		0/41 (0%)
Renal and urinary disorders
Urinary incontinence	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Cough	2/4 (50%)		3/8 (37.5%)		12/19 (63.2%)		26/41 (63.4%)
Rhinorrhoea	0/4 (0%)		2/8 (25%)		8/19 (42.1%)		7/41 (17.1%)
Nasal congestion	1/4 (25%)		0/8 (0%)		4/19 (21.1%)		6/41 (14.6%)
Oropharyngeal pain	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		3/41 (7.3%)
Dyspnoea	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		2/41 (4.9%)
Nasal discharge discolouration	0/4 (0%)		0/8 (0%)		0/19 (0%)		2/41 (4.9%)
Productive cough	0/4 (0%)		0/8 (0%)		2/19 (10.5%)		2/41 (4.9%)
Wheezing	0/4 (0%)		0/8 (0%)		1/19 (5.3%)		2/41 (4.9%)
Epistaxis	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Respiration abnormal	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Sinus congestion	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Sputum discoloured	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Tonsillar inflammation	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Upper respiratory tract congestion	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Skin and subcutaneous tissue disorders
Eczema	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Rash	0/4 (0%)		0/8 (0%)		3/19 (15.8%)		1/41 (2.4%)
Urticaria	0/4 (0%)		0/8 (0%)		0/19 (0%)		1/41 (2.4%)
Hyperhidrosis	1/4 (25%)		0/8 (0%)		0/19 (0%)		0/41 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.