Trial Outcomes & Findings for Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del (NCT NCT02797132)

NCT ID: NCT02797132

Last Updated: 2018-10-30

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

62 participants

Primary outcome timeframe

Day 15

Results posted on

2018-10-30

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Part A (15 Days) STARTED	12
Part A (15 Days) Part A (<14 kg Weight)	4
Part A (15 Days) Part A (>=14 kg Weight)	8
Part A (15 Days) COMPLETED	11
Part A (15 Days) NOT COMPLETED	1
Part B (24 Weeks) STARTED	60
Part B (24 Weeks) Part B (<14 kg Weight)	19
Part B (24 Weeks) Part B (>=14 kg Weight)	41
Part B (24 Weeks) COMPLETED	57
Part B (24 Weeks) NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Part A (15 Days) Adverse Event	1
Part B (24 Weeks) Adverse Event	3

Baseline Characteristics

Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lumacaftor/Ivacaftor (LUM/IVA) n=62 Participants 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.
Age, Continuous Part A (<14 kg Weight)	27.0 months STANDARD_DEVIATION 6.00 • n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Continuous Part A (>=14 kg Weight)	48.0 months STANDARD_DEVIATION 11.11 • n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Continuous Part B (<14 kg Weight)	31.6 months STANDARD_DEVIATION 5.05 • n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Age, Continuous Part B (>=14 kg Weight)	49.9 months STANDARD_DEVIATION 10.63 • n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part A (<14 kg Weight) · Female	2 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part A (<14 kg Weight) · Male	2 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part A (>=14 kg Weight) · Female	2 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part A (>=14 kg Weight) · Male	6 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part B (<14 kg Weight) · Female	9 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part B (<14 kg Weight) · Male	10 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part B (>=14 kg Weight) · Female	20 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Sex: Female, Male Part B (>=14 kg Weight) · Male	21 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (<14 kg Weight) · Hispanic or Latino	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (<14 kg Weight) · Not Hispanic or Latino	4 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (<14 kg Weight) · Unknown or Not Reported	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (>=14 kg Weight) · Hispanic or Latino	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (>=14 kg Weight) · Not Hispanic or Latino	8 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part A (>=14 kg Weight) · Unknown or Not Reported	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (<14 kg Weight) · Hispanic or Latino	1 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (<14 kg Weight) · Not Hispanic or Latino	18 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (<14 kg Weight) · Unknown or Not Reported	0 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (>=14 kg Weight) · Hispanic or Latino	2 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (>=14 kg Weight) · Not Hispanic or Latino	39 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Ethnicity (NIH/OMB) Part B (>=14 kg Weight) · Unknown or Not Reported	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · American Indian or Alaska Native	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · Asian	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · Native Hawaiian or Other Pacific Islander	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · Black or African American	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · White	4 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · More than one race	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (<14 kg Weight) · Unknown or Not Reported	0 Participants n=4 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · American Indian or Alaska Native	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · Asian	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · Native Hawaiian or Other Pacific Islander	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · Black or African American	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · White	8 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · More than one race	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part A (>=14 kg Weight) · Unknown or Not Reported	0 Participants n=8 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · American Indian or Alaska Native	0 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · Asian	0 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · Native Hawaiian or Other Pacific Islander	0 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · Black or African American	0 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · White	18 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · More than one race	0 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (<14 kg Weight) · Unknown or Not Reported	1 Participants n=19 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · American Indian or Alaska Native	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · Asian	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · Native Hawaiian or Other Pacific Islander	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · Black or African American	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · White	41 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · More than one race	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.
Race (NIH/OMB) Part B (>=14 kg Weight) · Unknown or Not Reported	0 Participants n=41 Participants • Data were planned to be reported separately for Part A and Part B of the study. Here "number analyzed" signifies participants who were evaluable for specified part of the study.

PRIMARY outcome

Timeframe: Day 15

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=4 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=7 Participants 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 A: Pre-dose Concentration (Ctrough) of LUM and IVA LUM	8710 nanogram per milliliter (ng/mL) Standard Deviation 3590	12300 nanogram per milliliter (ng/mL) Standard Deviation 5960
Part A: Pre-dose Concentration (Ctrough) of LUM and IVA IVA	94.0 nanogram per milliliter (ng/mL) Standard Deviation 67.0	216 nanogram per milliliter (ng/mL) Standard Deviation 185

PRIMARY outcome

Timeframe: Day 1 up to Week 26

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=41 Participants 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: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	19 Participants	40 Participants
Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 15

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=4 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=7 Participants 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 A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites LUM Metabolite (M28 LUM)	1310 ng/mL Standard Deviation 590	1370 ng/mL Standard Deviation 286
Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites IVA Metabolite (M1 IVA)	475 ng/mL Standard Deviation 384	1240 ng/mL Standard Deviation 1180
Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites IVA Metabolite (M6 IVA)	1510 ng/mL Standard Deviation 1130	3270 ng/mL Standard Deviation 2100

SECONDARY outcome

Timeframe: Day 1 up to Day 25

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=4 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=8 Participants 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 A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	0 Participants
Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: 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.

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=18 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=31 Participants 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: Absolute Change From Baseline in Sweat Chloride at Week 24	-33.5 millimole per liter (mmol/L) Standard Deviation 14.5	-30.7 millimole per liter (mmol/L) Standard Deviation 14.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: 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.

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24	0.22 Kilogram per meter square (kg/m^2) Standard Deviation 0.78	0.29 Kilogram per meter square (kg/m^2) Standard Deviation 0.75

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24	0.36 Z-score Standard Deviation 0.67	0.26 Z-score Standard Deviation 0.53

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Weight at Week 24	1.4 Kilogram (kg) Standard Deviation 0.7	1.5 Kilogram (kg) Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24	0.44 Z-score Standard Deviation 0.52	0.17 Z-score Standard Deviation 0.36

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Stature (Height) at Week 24	4.1 Centimeter (cm) Standard Deviation 1.4	3.4 Centimeter (cm) Standard Deviation 1.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Stature-for-Age Z-Score	0.19 Z-score Standard Deviation 0.32	0.04 Z-score Standard Deviation 0.19

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=41 Participants 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: Number of Pulmonary Exacerbations	5 pulmonary exacerbations	20 pulmonary exacerbations

SECONDARY outcome

Timeframe: Through Week 24

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

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.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=41 Participants 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: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24	3 Participants	15 Participants

SECONDARY outcome

Timeframe: Through Week 24

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=41 Participants 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: Number of Cystic Fibrosis (CF)-Related Hospitalizations	1 hospitalizations	3 hospitalizations

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=12 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=23 Participants 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: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24	38.4 microgram per gram Standard Deviation 76.1	60.0 microgram per gram Standard Deviation 94.0

SECONDARY outcome

Timeframe: Baseline, Through Week 24

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=17 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24	-262.1 ng/mL Standard Deviation 343.1	-71.1 ng/mL Standard Deviation 120.5

SECONDARY outcome

Timeframe: Baseline and Week 24

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

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.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=41 Participants 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: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: Stenotrophomonas Maltophilia · Negative	18 Participants	36 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: Stenotrophomonas Maltophilia · Positive	1 Participants	0 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: Burkholderia · Negative	18 Participants	37 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: Burkholderia · Positive	0 Participants	1 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: Burkholderia · Negative	19 Participants	36 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: Burkholderia · Positive	0 Participants	0 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: MRSA · Negative	16 Participants	33 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: MRSA · Positive	2 Participants	5 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24:MRSA · Negative	17 Participants	35 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24:MRSA · Positive	2 Participants	1 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: MSSA · Negative	12 Participants	26 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: MSSA · Positive	6 Participants	12 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: MSSA · Negative	13 Participants	26 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: MSSA · Positive	6 Participants	10 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: P. Aeruginosa Mucoid · Negative	18 Participants	37 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: P. Aeruginosa Mucoid · Positive	0 Participants	1 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: P. Aeruginosa Mucoid · Negative	19 Participants	35 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: P. Aeruginosa Mucoid · Positive	0 Participants	1 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: P. Aeruginosa Non-Mucoid · Negative	17 Participants	35 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: P. Aeruginosa Non-Mucoid · Positive	1 Participants	3 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: P. Aeruginosa Non-Mucoid · Negative	16 Participants	34 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: P. Aeruginosa Non-Mucoid · Positive	3 Participants	2 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: P. Aeruginosa Small Colony Variant · Negative	18 Participants	38 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: P. Aeruginosa Small Colony Variant · Positive	0 Participants	0 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: P. Aeruginosa Small Colony Variant · Negative	19 Participants	36 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Week 24: P. Aeruginosa Small Colony Variant · Positive	0 Participants	0 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: Stenotrophomonas Maltophilia · Negative	17 Participants	37 Participants
Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 Baseline: Stenotrophomonas Maltophilia · Positive	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: 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.

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

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg 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 Weight): LUM 150 mg/IVA 188 mg n=12 Participants 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: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24	—	0.5 percentage of predicted FEV1 Standard Deviation 11.6

SECONDARY outcome

Timeframe: Week 24, Week 26

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=17 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=31 Participants 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: Absolute Change in Sweat Chloride From Week 24 at Week 26	34.4 mmol/L Standard Deviation 14.9	32.2 mmol/L Standard Deviation 13.8

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=18 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=38 Participants 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: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 2 · Liked it a Little	2 Participants	5 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 2 · Not sure	4 Participants	6 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 1 · Liked it Very Much	9 Participants	30 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 1 · Liked it a Little	4 Participants	6 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 1 · Not sure	3 Participants	1 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 1 · Disliked it a Little	0 Participants	0 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 1 · Disliked it Very Much	2 Participants	1 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 2 · Liked it Very Much	4 Participants	6 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 2 · Disliked it a Little	3 Participants	6 Participants
Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale Evaluation 2 · Disliked it Very Much	5 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=3 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=14 Participants 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: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24	0.27 ratio Standard Deviation 0.48	-0.76 ratio Standard Deviation 1.19

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=3 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=14 Participants 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: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24	0.24 ratio Standard Deviation 0.40	-0.12 ratio Standard Deviation 0.69

SECONDARY outcome

Timeframe: Week 24

Population: 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.

Outcome measures

Outcome measures
Measure	Part A (<14 kg Weight): LUM 100 mg/IVA 125 mg n=19 Participants 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 Weight): LUM 150 mg/IVA 188 mg n=41 Participants 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: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites LUM	9060 ng/mL Standard Deviation 4060	9390 ng/mL Standard Deviation 4830
Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites LUM Metabolite (M28 LUM)	1420 ng/mL Standard Deviation 846	1510 ng/mL Standard Deviation 752
Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites IVA	108 ng/mL Standard Deviation 109	110 ng/mL Standard Deviation 108
Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites IVA Metabolite (M1 IVA)	555 ng/mL Standard Deviation 560	521 ng/mL Standard Deviation 478
Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites IVA Metabolite (M6 IVA)	2050 ng/mL Standard Deviation 1940	1900 ng/mL Standard Deviation 1430

Adverse Events

Part A: LUM 100 mg/IVA 125 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part A: LUM 150 mg/IVA 188 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: LUM 100 mg/IVA 125 mg

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Part B: LUM 150 mg/IVA 188 mg

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: LUM 100 mg/IVA 125 mg n=4 participants at risk 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.	Part A: LUM 150 mg/IVA 188 mg n=8 participants at risk 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: LUM 100 mg/IVA 125 mg n=19 participants at risk 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.	Part B: LUM 150 mg/IVA 188 mg n=41 participants at risk 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.
Gastrointestinal disorders Constipation	0.00% 0/4 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	0.00% 0/8 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	5.3% 1/19 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	0.00% 0/41 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	0.00% 0/4 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	0.00% 0/8 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	0.00% 0/19 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	4.9% 2/41 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26
Infections and infestations Gastroenteritis viral	0.00% 0/4 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	0.00% 0/8 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	5.3% 1/19 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26	0.00% 0/41 • Part A: Day 1 up to Day 25; Part B: Day 1 up to Week 26

Other adverse events

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER