A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03125395
• Collaborator: (none)
• Enrollment: 57
• Locations: 20
• Arm: 1
• Actual Duration (Months): 26.2
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Rollover Study to Evaluate the Safety of Long-term Treatment With Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
• Actual Study Start Date: May 12, 2017
• Actual Primary Completion Date: Jul 17, 2019
• Actual Study Completion Date: Jul 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LUM/IVA LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.	Drug: LUM/IVA; Participants received LUM/IVA every q12h.; Other Names: VX-809/VX-770 lumacaftor/ivacaftor

Outcome Measures

Primary Outcome Measures

1. Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to Week 98]

Secondary Outcome Measures

1. Absolute Change in Sweat Chloride [From Parent Study 115B Baseline at Week 96]

   Sweat samples were collected using an approved collection device.

2. Absolute Change in Body Mass Index (BMI) [From Parent Study 115B Baseline at Week 96]

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

3. Absolute Change in BMI-for-age Z-score [From Parent Study 115B Baseline at Week 96]

   BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. 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.

4. Absolute Change in Weight [From Parent Study 115B Baseline at Week 96]

5. Absolute Change in Weight-for-age Z-score [From Parent Study 115B Baseline at Week 96]

   Z-score is a statistical measure to describe whether a mean was above or below the standard. 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.

6. Absolute Change From Baseline in Stature (Height) [From Parent Study 115B Baseline at Week 96]

7. Absolute Change in Stature-for-age Z-score [From Parent Study 115B Baseline at Week 96]

   Z-score is a statistical measure to describe whether a mean was above or below the standard. 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.

8. Time-to-first Pulmonary Exacerbation [From Parent Study 115B Baseline through Week 96]

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

9. Number of Pulmonary Exacerbations (PEx) [From Parent Study 115B Baseline through Week 96]

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

10. Number of Cystic Fibrosis (CF) Related Hospitalizations [From Parent Study 115B Baseline through Week 96]

11. Absolute Change in Fecal Elastase-1 (FE-1) Levels [From Parent Study 115B Baseline at Week 96]

12. Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels [From Parent Study 115B Baseline at Week 96]

13. Number of Participants With Microbiology Culture Status (Positive or Negative) [Week 96]

    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.

14. Absolute Change in Lung Clearance Index (LCI) 2.5 [From Parent Study 115B Baseline at Week 96]

    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.

15. Absolute Change in Lung Clearance Index (LCI) 5.0 [From Parent Study 115B Baseline at Week 96]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects entering the Treatment Cohort must meet the following criteria:

• Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132)

• Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit

Subjects entering the Observational Cohort must meet 1 of the following criteria:

• Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort.

• Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort.

• Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required.

Exclusion Criteria (Treatment Cohort Only):

• Prematurely discontinued LUM/IVA treatment in Study 115B.

• History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering LUM/IVA to the subject

• History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor.

• Subjects with a history of allergy or hypersensitivity to LUM/IVA.

• Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified.

• QTc value at the completion of Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor

• History of poor compliance with LUM/IVA and/or procedures in Study 115B as deemed by the investigator.

• Participation in an investigational drug trial (including studies investigating LUM and/or IVA) other than Study 115B.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94305
2	Children's Hospital Colorado	Aurora	Colorado	United States	80045
3	Ann & Robert Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana	United States	46202
5	Boston Children's Hospital	Boston	Massachusetts	United States	02115
6	Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn	Minneapolis	Minnesota	United States	55404
7	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
8	The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo	Buffalo	New York	United States	14222
9	University of North Carolina Hospitals	Chapel Hill	North Carolina	United States	27514
10	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
11	University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
12	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
13	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
14	Medical University of South Carolina	Charleston	South Carolina	United States	29425
15	Texas Children's Hospital	Houston	Texas	United States	77030
16	Children's Hospital of the King's Daughters	Norfolk	Virginia	United States	23507
17	Seattle Children's Hospital	Seattle	Washington	United States	98105
18	British Columbia's Children's Hospital	Vancouver	British Columbia	Canada	V6H 3N1
19	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
20	McGill University Health Centre, Glen Site, Montreal Children's Hospital	Montreal	Quebec	Canada	H4A 3J1

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 10, 2016
• Statistical Analysis Plan - May 20, 2019

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03125395
• Other Study ID Numbers: VX16-809-116; 2019-003112-31
• First Posted: Apr 24, 2017
• Last Update Posted: Aug 7, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor

Study Results

Participant Flow

Recruitment Details	This study was planned to have 2 cohorts: Treatment Cohort and Observational Cohort. Only the Treatment Cohort is presented in results as there were no participants enrolled in the Observational Cohort.
Pre-assignment Detail	This study was conducted in participants with cystic fibrosis (CF) aged 2 years and older who participated in parent study VX15-809-115 Part B (NCT02797132).

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Period Title: Overall Study
STARTED	57
Study 115B FAS	60
Study 116 FAS	57
Study 116 LCI Substudy Set	31
COMPLETED	47
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Overall Participants	57
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	43.2 (12.17)
Sex: Female, Male (Count of Participants)
Female	28 49.1%
Male	29 50.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5.3%
Not Hispanic or Latino	54 94.7%
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	56 98.2%
More than one race	0 0%
Unknown or Not Reported	1 1.8%

Outcome Measures

1. Primary Outcome

Title	Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Day 1 up to Week 98

Outcome Measure Data

Analysis Population Description

Study 116 safety set included all participants dosed in study 115B who were exposed to any amount of study drug in current study 116 treatment cohort.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Participants with AEs	56 98.2%
Participants with SAEs	15 26.3%

2. Secondary Outcome

Title	Absolute Change in Sweat Chloride
Description	Sweat samples were collected using an approved collection device.
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 Full Analysis Set (FAS) included all participants who were enrolled and exposed to any amount of study drug in current study 116.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [millimole per liter (mmol/L)]	-29.6 (12.7)

3. Secondary Outcome

Title	Absolute Change in Body Mass Index (BMI)
Description	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [kg/m^2]	0.30 (1.21)

4. Secondary Outcome

Title	Absolute Change in BMI-for-age Z-score
Description	BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [z-score]	0.27 (0.73)

5. Secondary Outcome

Title	Absolute Change in Weight
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [kg]	6.0 (2.0)

6. Secondary Outcome

Title	Absolute Change in Weight-for-age Z-score
Description	Z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Error) [z-score]	0.23 (0.56)

7. Secondary Outcome

Title	Absolute Change From Baseline in Stature (Height)
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [centimeter]	16.1 (2.3)

8. Secondary Outcome

Title	Absolute Change in Stature-for-age Z-score
Description	Z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [z-score]	0.07 (0.39)

9. Secondary Outcome

Title	Time-to-first Pulmonary Exacerbation
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	From Parent Study 115B Baseline through Week 96

Outcome Measure Data

Analysis Population Description

Study 115B FAS included all participants who were enrolled and exposed to any amount of study drug in parent study 115B

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	60
Median (Inter-Quartile Range) [days]	600.0

10. Secondary Outcome

Title	Number of Pulmonary Exacerbations (PEx)
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	From Parent Study 115B Baseline through Week 96

Outcome Measure Data

Analysis Population Description

Study 115B FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	60
Number [pulmonary exacerbation events]	82

11. Secondary Outcome

Title	Number of Cystic Fibrosis (CF) Related Hospitalizations
Time Frame	From Parent Study 115B Baseline through Week 96

Outcome Measure Data

Analysis Population Description

Study 115B FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	60
Number [hospitalizations]	28

12. Secondary Outcome

Title	Absolute Change in Fecal Elastase-1 (FE-1) Levels
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [microgram per gram (mcg/g)]	132.6 (174.2)

13. Secondary Outcome

Title	Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels
Time Frame	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	57
Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	-108.5 (306.6)

14. Secondary Outcome

Title	Number of Participants With Microbiology Culture Status (Positive or Negative)
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	Week 96

Outcome Measure Data

Analysis Population Description

Study 116 FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this outcome at Week 96.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	46
Burkholderia (Positive)	0 0%
Burkholderia (Negative)	46 80.7%
MRSA (Positive)	4 7%
MRSA (Negative)	42 73.7%
MSSA (Positive)	15 26.3%
MSSA (Negative)	31 54.4%
P. Aeruginosa Mucoid (Positive)	0 0%
P. Aeruginosa Mucoid (Negative)	46 80.7%
P. Aeruginosa Non-Mucoid (Positive)	1 1.8%
P. Aeruginosa Non-Mucoid (Negative)	45 78.9%
P. Aeruginosa Small Colony Variant (Positive)	0 0%
P. Aeruginosa Small Colony Variant (Negative)	46 80.7%
Stenotrophomonas Maltophilia (Positive)	2 3.5%
Stenotrophomonas Maltophilia (Negative)	44 77.2%

15. Secondary Outcome

Title	Absolute Change in Lung Clearance Index (LCI) 2.5
Description	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	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 LCI substudy set included all participants who signed the informed consent/assent to the optional LCI substudy and were enrolled and exposed to any amount of study drug in current study 116.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	31
Mean (Standard Deviation) [lung clearance index]	-0.20 (1.55)

16. Secondary Outcome

Title	Absolute Change in Lung Clearance Index (LCI) 5.0
Description	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	From Parent Study 115B Baseline at Week 96

Outcome Measure Data

Analysis Population Description

Study 116 LCI substudy set.

Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Measure Participants	31
Mean (Standard Deviation) [lung clearance index]	0.11 (0.65)

Adverse Events

Time Frame	Day 1 up to Week 98
Arm/Group Title	LUM/IVA
Arm/Group Description	LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
All Cause Mortality
	LUM/IVA
	Affected / at Risk (%)	# Events
Total	0/57 (0%)
Serious Adverse Events
	LUM/IVA
	Affected / at Risk (%)	# Events
Total	15/57 (26.3%)
Gastrointestinal disorders
Constipation	1/57 (1.8%)
Haematemesis	1/57 (1.8%)
Pancreatitis	1/57 (1.8%)
Infections and infestations
Appendicitis	1/57 (1.8%)
Chronic sinusitis	1/57 (1.8%)
Gastritis viral	1/57 (1.8%)
Gastroenteritis adenovirus	1/57 (1.8%)
Gastroenteritis viral	1/57 (1.8%)
Infective pulmonary exacerbation of cystic fibrosis	6/57 (10.5%)
Pneumonia	2/57 (3.5%)
Respiratory tract infection viral	1/57 (1.8%)
Investigations
Alanine aminotransferase increased	1/57 (1.8%)
Aspartate aminotransferase increased	1/57 (1.8%)
Metabolism and nutrition disorders
Weight gain poor	1/57 (1.8%)
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome	1/57 (1.8%)
Other (Not Including Serious) Adverse Events
	LUM/IVA
	Affected / at Risk (%)	# Events
Total	55/57 (96.5%)
Ear and labyrinth disorders
Ear pain	3/57 (5.3%)
Gastrointestinal disorders
Abdominal pain	7/57 (12.3%)
Abdominal pain upper	4/57 (7%)
Constipation	7/57 (12.3%)
Diarrhoea	6/57 (10.5%)
Vomiting	17/57 (29.8%)
General disorders
Fatigue	5/57 (8.8%)
Pyrexia	23/57 (40.4%)
Vessel puncture site pain	4/57 (7%)
Infections and infestations
Conjunctivitis	4/57 (7%)
Ear infection	12/57 (21.1%)
Hand-foot-and-mouth disease	3/57 (5.3%)
Infective pulmonary exacerbation of cystic fibrosis	10/57 (17.5%)
Influenza	4/57 (7%)
Nasopharyngitis	8/57 (14%)
Otitis media	7/57 (12.3%)
Pharyngitis streptococcal	6/57 (10.5%)
Pneumonia	3/57 (5.3%)
Sinusitis	12/57 (21.1%)
Upper respiratory tract infection	13/57 (22.8%)
Viral upper respiratory tract infection	4/57 (7%)
Investigations
Alanine aminotransferase increased	10/57 (17.5%)
Aspartate aminotransferase increased	5/57 (8.8%)
Forced expiratory volume decreased	3/57 (5.3%)
Gamma-glutamyltransferase increased	4/57 (7%)
Pseudomonas test positive	9/57 (15.8%)
Staphylococcus test positive	12/57 (21.1%)
Metabolism and nutrition disorders
Decreased appetite	6/57 (10.5%)
Respiratory, thoracic and mediastinal disorders
Cough	47/57 (82.5%)
Dyspnoea	3/57 (5.3%)
Lower respiratory tract congestion	4/57 (7%)
Nasal congestion	25/57 (43.9%)
Nasal discharge discolouration	3/57 (5.3%)
Oropharyngeal pain	10/57 (17.5%)
Productive cough	5/57 (8.8%)
Rhinorrhoea	18/57 (31.6%)
Sinus congestion	3/57 (5.3%)
Sputum increased	5/57 (8.8%)
Upper respiratory tract congestion	3/57 (5.3%)
Wheezing	3/57 (5.3%)
Skin and subcutaneous tissue disorders
Rash	3/57 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.