Trial Outcomes & Findings for A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation (NCT NCT02725567)
NCT ID: NCT02725567
Last Updated: 2023-09-07
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
57 participants
Primary outcome timeframe
Day 1 through Day 70
Results posted on
2023-09-07
Participant Flow
This study was conducted in participants with cystic fibrosis (CF) who were less than (\<) 24 months of age at Day 1 and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) mutation.
Participant milestones
| Measure |
Part A: 3 to < 24 Months
Participants weighing 5 to less than (\<) 7 kilogram (kg) received 25 milligram (mg) IVA (ivacaftor), 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4.
|
Part B + A/B: 1 to < 24 Months
Participants 4 to \<6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B.
For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
|
|---|---|---|
|
Part A (Up to 5 Days)
STARTED
|
19
|
0
|
|
Part A (Up to 5 Days)
COMPLETED
|
19
|
0
|
|
Part A (Up to 5 Days)
NOT COMPLETED
|
0
|
0
|
|
Part B + A/B ( Up to 24 Weeks)
STARTED
|
0
|
43
|
|
Part B + A/B ( Up to 24 Weeks)
COMPLETED
|
0
|
40
|
|
Part B + A/B ( Up to 24 Weeks)
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Part A: 3 to < 24 Months
Participants weighing 5 to less than (\<) 7 kilogram (kg) received 25 milligram (mg) IVA (ivacaftor), 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4.
|
Part B + A/B: 1 to < 24 Months
Participants 4 to \<6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B.
For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
|
|---|---|---|
|
Part B + A/B ( Up to 24 Weeks)
Lost to Follow-up
|
0
|
1
|
|
Part B + A/B ( Up to 24 Weeks)
Physician Decision
|
0
|
1
|
|
Part B + A/B ( Up to 24 Weeks)
Withdrawal of Consent (not due to adverse event)
|
0
|
1
|
Baseline Characteristics
The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
Baseline characteristics by cohort
| Measure |
Ivacaftor (IVA)
n=57 Participants
Part A: Participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA administered q12h on Days 1 through 3 and 1 morning dose on Day 4.
Participants 4 to \<6 months of age and ≥5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B.
For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
|
|---|---|
|
Age, Customized
Part A · 12 to <24 months
|
7 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part A · 6 to <12 months
|
6 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part A · 4 to <6 months
|
4 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part A · 1 to <4 months
|
2 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part B+ A/B · 12 to <24 months
|
19 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part B+ A/B · 6 to <12 months
|
11 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part B+ A/B · 4 to <6 months
|
6 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Age, Customized
Part B+ A/B · 1 to <4 months
|
7 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Sex: Female, Male
Part A · Female
|
10 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Sex: Female, Male
Part A · Male
|
9 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Sex: Female, Male
Part B + A/B · Female
|
22 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Sex: Female, Male
Part B + A/B · Male
|
21 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Hispanic or Latino
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Not Hispanic or Latino
|
19 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Not collected per local regulations
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Hispanic or Latino
|
1 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Not Hispanic or Latino
|
42 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Not collected per local regulations
|
0 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · White
|
19 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Black or African American
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Asian
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · American Indian or Alaska Native
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part A · Not collected per local Regulations
|
0 Participants
n=19 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · White
|
43 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Black or African American
|
0 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Asian
|
0 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · American Indian or Alaska Native
|
0 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
|
Race/Ethnicity, Customized
Part B + A/B · Not collected per local Regulations
|
0 Participants
n=43 Participants • The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study.
|
PRIMARY outcome
Timeframe: Day 1 through Day 70Population: Safety set included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A: 3 to \<24 months arm.
Outcome measures
| Measure |
Part A: 3 to < 24 Months
n=19 Participants
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h on Days 1 through Day 3 and 1 morning dose on Day 4.
|
|---|---|
|
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Participants with TEAEs
|
10 Participants
|
|
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Participants with Serious TEAEs
|
1 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dosePopulation: Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug in Part A. Here the "Number Analyzed" signifies those participants who were evaluable for the specified time point.
Outcome measures
| Measure |
Part A: 3 to < 24 Months
n=19 Participants
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h on Days 1 through Day 3 and 1 morning dose on Day 4.
|
|---|---|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Pre dose: IVA
|
654 nanogram per milliliter (ng/ml)
Standard Deviation 531
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Pre dose: M1-IVA
|
1880 nanogram per milliliter (ng/ml)
Standard Deviation 1160
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Pre dose: M6-IVA
|
2680 nanogram per milliliter (ng/ml)
Standard Deviation 1990
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
2-4 hrs post dose: IVA
|
956 nanogram per milliliter (ng/ml)
Standard Deviation 497
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
2-4 hrs post dose: M1-IVA
|
1990 nanogram per milliliter (ng/ml)
Standard Deviation 1160
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
2-4 hrs post dose: M6-IVA
|
2460 nanogram per milliliter (ng/ml)
Standard Deviation 2110
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
6-8 hrs post dose: IVA
|
1040 nanogram per milliliter (ng/ml)
Standard Deviation 623
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
6-8 hrs post dose: M1-IVA
|
2440 nanogram per milliliter (ng/ml)
Standard Deviation 1260
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
6-8 hrs post dose: M6-IVA
|
2880 nanogram per milliliter (ng/ml)
Standard Deviation 2180
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
24-60 hrs post dose: IVA
|
129 nanogram per milliliter (ng/ml)
Standard Deviation 68.8
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
24-60 hrs post dose: M1-IVA
|
508 nanogram per milliliter (ng/ml)
Standard Deviation 228
|
|
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
24-60 hrs post dose: M6-IVA
|
1100 nanogram per milliliter (ng/ml)
Standard Deviation 982
|
PRIMARY outcome
Timeframe: Day 1 through Week 38Population: Safety Set included all participants who received at least 1 dose of study drug. The safety and tolerability analyses were assessed for the overall treatment arm. Therefore, the analysis is reported in a overall Part B+ A/B: 1 to \<24 months arm.
Outcome measures
| Measure |
Part A: 3 to < 24 Months
n=43 Participants
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h on Days 1 through Day 3 and 1 morning dose on Day 4.
|
|---|---|
|
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Participants with TEAEs
|
38 Participants
|
|
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Participants with Serious (TEAEs)
|
6 Participants
|
PRIMARY outcome
Timeframe: Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)Population: PK set included participants who received at least 1 dose of study drug in Part A/B. Here the "Number Analyzed" signifies those participants who were evaluable for the specified time point.
Outcome measures
| Measure |
Part A: 3 to < 24 Months
n=7 Participants
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h on Days 1 through Day 3 and 1 morning dose on Day 4.
|
|---|---|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (pre dose): IVA
|
348 ng/ml
Standard Deviation 151
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (pre dose): M1-IVA
|
867 ng/ml
Standard Deviation 412
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (pre dose): M6-IVA
|
1570 ng/ml
Standard Deviation 570
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (2-4 hrs post dose): IVA
|
381 ng/ml
Standard Deviation 135
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (2-4 hrs post dose): M1-IVA
|
851 ng/ml
Standard Deviation 333
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (2-4 hrs post dose): M6-IVA
|
1370 ng/ml
Standard Deviation 450
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (6-8 hrs post dose): IVA
|
501 ng/ml
Standard Deviation 196
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (6-8 hrs post dose): M1-IVA
|
1190 ng/ml
Standard Deviation 420
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (6-8 hrs post dose): M6-IVA
|
1670 ng/ml
Standard Deviation 551
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 15 (pre dose): IVA
|
191 ng/ml
Standard Deviation 134
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 15 (pre dose): M1-IVA
|
614 ng/ml
Standard Deviation 378
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 15 (pre dose): M6-IVA
|
1510 ng/ml
Standard Deviation 1110
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 4 (pre dose): IVA
|
316 ng/ml
Standard Deviation 130
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 4 (pre dose): M1-IVA
|
1170 ng/ml
Standard Deviation 577
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 4 (pre dose): M6-IVA
|
3370 ng/ml
Standard Deviation 2330
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (pre dose): IVA
|
449 ng/ml
Standard Deviation 352
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (pre dose): M1-IVA
|
1030 ng/ml
Standard Deviation 476
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (pre dose): M6-IVA
|
2380 ng/ml
Standard Deviation 1500
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (2-4 hrs post dose): IVA
|
523 ng/ml
Standard Deviation 262
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (2-4 hrs post dose): M1-IVA
|
1360 ng/ml
Standard Deviation 982
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (2-4 hrs post dose): M6-IVA
|
2100 ng/ml
Standard Deviation 1540
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (6-8 hrs post dose): IVA
|
438 ng/ml
Standard Deviation 79.8
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (6-8 hrs post dose): M1-IVA
|
1420 ng/ml
Standard Deviation 606
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (6-8 hrs post dose): M6-IVA
|
2320 ng/ml
Standard Deviation 1330
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 12 (pre dose): IVA
|
213 ng/ml
Standard Deviation 173
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 12 (pre dose): M1-IVA
|
906 ng/ml
Standard Deviation 660
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 12 (pre dose): M6-IVA
|
2500 ng/ml
Standard Deviation 1760
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 18 (pre dose): IVA
|
226 ng/ml
Standard Deviation 153
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 18 (pre dose): M1-IVA
|
815 ng/ml
Standard Deviation 470
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 18 (pre dose): M6-IVA
|
2060 ng/ml
Standard Deviation 1190
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (pre dose): IVA
|
276 ng/ml
Standard Deviation 137
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (pre dose): M1-IVA
|
1120 ng/ml
Standard Deviation 496
|
|
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (pre dose): M6-IVA
|
2380 ng/ml
Standard Deviation 799
|
SECONDARY outcome
Timeframe: Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)Population: PK set included participants who received at least 1 dose of study drug in Part B. Here the "Number Analyzed" signifies those participants who were evaluable for the specified time point.
Outcome measures
| Measure |
Part A: 3 to < 24 Months
n=35 Participants
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h on Days 1 through Day 3 and 1 morning dose on Day 4.
|
|---|---|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (pre dose): IVA
|
457 ng/ml
Standard Deviation 441
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (pre dose): M1-IVA
|
1340 ng/ml
Standard Deviation 934
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (pre dose): M6-IVA
|
1980 ng/ml
Standard Deviation 1790
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (2-4 hrs post dose): IVA
|
812 ng/ml
Standard Deviation 726
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (2-4 hrs post dose): M1-IVA
|
1560 ng/ml
Standard Deviation 1190
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (2-4 hrs post dose): M6-IVA
|
1770 ng/ml
Standard Deviation 1970
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (6-8 hrs post dose): IVA
|
969 ng/ml
Standard Deviation 705
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (6-8 hrs post dose): M1-IVA
|
2210 ng/ml
Standard Deviation 1360
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (6-8 hrs post dose): M6-IVA
|
2140 ng/ml
Standard Deviation 1880
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (pre dose): IVA
|
404 ng/ml
Standard Deviation 376
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (pre dose): M1-IVA
|
1220 ng/ml
Standard Deviation 782
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (pre dose): M6-IVA
|
1720 ng/ml
Standard Deviation 1110
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (1 hrs post dose): IVA
|
466 ng/ml
Standard Deviation 384
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (1 hrs post dose): M1-IVA
|
1100 ng/ml
Standard Deviation 670
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (1 hrs post dose): M6-IVA
|
1500 ng/ml
Standard Deviation 881
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (4 hrs post dose): IVA
|
996 ng/ml
Standard Deviation 520
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (4 hrs post dose): M1-IVA
|
2130 ng/ml
Standard Deviation 950
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 8 (4 hrs post dose): M6-IVA
|
1750 ng/ml
Standard Deviation 1010
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (pre dose): IVA
|
301 ng/ml
Standard Deviation 204
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (pre dose): M1-IVA
|
1050 ng/ml
Standard Deviation 492
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (pre dose): M6-IVA
|
1600 ng/ml
Standard Deviation 783
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (2-4 hrs post dose): IVA
|
794 ng/ml
Standard Deviation 480
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (2-4 hrs post dose): M1-IVA
|
1540 ng/ml
Standard Deviation 783
|
|
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 24 (2-4 hrs post dose): M6-IVA
|
1320 ng/ml
Standard Deviation 592
|
SECONDARY outcome
Timeframe: From Baseline at Week 24Population: The Full Analysis Set (FAS) included all enrolled participants who were exposed to any amount of study drug in Part B + A/B. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
Part A: 3 to < 24 Months
n=23 Participants
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h on Days 1 through Day 3 and 1 morning dose on Day 4.
|
|---|---|
|
Part B + A/B: Absolute Change From Baseline in Sweat Chloride
|
-62.0 millimole per liter (mmol/L)
Standard Deviation 22.2
|
Adverse Events
Part A: 3 to < 24 Months
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Part B + A/B: 1 to <24 Months
Serious events: 6 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A: 3 to < 24 Months
n=19 participants at risk
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and participants weighing 14 to \< 25 kg received 75 mg IVA q12h on days 1 through day 3 and 1 morning dose on day 4.
|
Part B + A/B: 1 to <24 Months
n=43 participants at risk
Participants 4 to \<6 months of age and ≥5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B.
For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Bronchiolitis
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Eczema Coxsackium
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Eczema herpeticum
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
4.7%
2/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
Other adverse events
| Measure |
Part A: 3 to < 24 Months
n=19 participants at risk
Participants weighing 5 to \<7 kg received 25 mg IVA, weighing 7 to \<14 kg received 50 mg IVA, and participants weighing 14 to \< 25 kg received 75 mg IVA q12h on days 1 through day 3 and 1 morning dose on day 4.
|
Part B + A/B: 1 to <24 Months
n=43 participants at risk
Participants 4 to \<6 months of age and ≥5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B.
For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Constipation
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
14.0%
6/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Infantile spitting up
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Teething
|
10.5%
2/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
4.7%
2/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
18.6%
8/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
General disorders
Fatigue
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
General disorders
Pyrexia
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
27.9%
12/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Ear infection
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Hand-foot-and-mouth disease
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
4.7%
2/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Nasopharyngitis
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Otitis media
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
14.0%
6/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Upper respiratory tract infection
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
16.3%
7/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Injury, poisoning and procedural complications
Fall
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Injury, poisoning and procedural complications
Head injury
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
18.6%
8/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
16.3%
7/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Investigations
Blood pressure increased
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Investigations
Pseudomonas test positive
|
0.00%
0/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
7.0%
3/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Psychiatric disorders
Sleep disorder
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.1%
4/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
55.8%
24/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
14.0%
6/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
27.9%
12/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
2.3%
1/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
4.7%
2/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
|
Vascular disorders
Flushing
|
5.3%
1/19 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
0.00%
0/43 • From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place