Trial Outcomes & Findings for A Study of Ataluren in Pediatric Participants With Cystic Fibrosis (NCT NCT00458341)
NCT ID: NCT00458341
Last Updated: 2020-03-06
Results Overview
Nasal transepithelial potential difference (TEPD) was assessed in each participant using standardized techniques. Warmed solutions of Ringer's solution, amiloride, chloride-free gluconate, isoproterenol, and adenosine triphosphate (ATP) were perfused for ≥3-minute sequentially through a nasal catheter while a voltage tracing was recorded. Total chloride transport was computed for each nostril. The total chloride transport values were calculated by subtracting the voltages at the end of a perfusion from the voltage at the end of an earlier perfusion (isoproterenol - amiloride). The average of the values for each nostril was computed. If the assessment was available in only 1 nostril, this value was used as if it were the average of both nostrils. Baseline data for Cycle 1 and Cycle 2 and change from Baseline data at Day 14 of Cycles 1 and 2 are presented.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Baseline of Cycle 1 and Cycle 2, Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days)
Results posted on
2020-03-06
Participant Flow
Participants were randomized so that half received the lower-dose level in Cycle 1 and then the higher-dose level in Cycle 2 (low-to-high dose sequence) and half received the higher-dose level in Cycle 1 and then the lower-dose level in Cycle 2 (high-to-low dose sequence).
Participant milestones
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
During Cycle 1, participants received ataluren at 4 milligrams (mg/kg) in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Cycle 1
STARTED
|
15
|
15
|
|
Cycle 1
Received at Least 1 Dose of Study Drug
|
15
|
15
|
|
Cycle 1
COMPLETED
|
14
|
15
|
|
Cycle 1
NOT COMPLETED
|
1
|
0
|
|
Cycle 2
STARTED
|
15
|
15
|
|
Cycle 2
Received at Least 1 Dose of Study Drug
|
15
|
15
|
|
Cycle 2
COMPLETED
|
15
|
15
|
|
Cycle 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
During Cycle 1, participants received ataluren at 4 milligrams (mg/kg) in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Cycle 1
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Study of Ataluren in Pediatric Participants With Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
12 years
STANDARD_DEVIATION 3.53 • n=93 Participants
|
13 years
STANDARD_DEVIATION 3.38 • n=4 Participants
|
12.5 years
STANDARD_DEVIATION 3.43 • n=27 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline of Cycle 1 and Cycle 2, Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days)Population: All randomized participants who received at least 1 dose of study drug and had evaluable chloride transport data.
Nasal transepithelial potential difference (TEPD) was assessed in each participant using standardized techniques. Warmed solutions of Ringer's solution, amiloride, chloride-free gluconate, isoproterenol, and adenosine triphosphate (ATP) were perfused for ≥3-minute sequentially through a nasal catheter while a voltage tracing was recorded. Total chloride transport was computed for each nostril. The total chloride transport values were calculated by subtracting the voltages at the end of a perfusion from the voltage at the end of an earlier perfusion (isoproterenol - amiloride). The average of the values for each nostril was computed. If the assessment was available in only 1 nostril, this value was used as if it were the average of both nostrils. Baseline data for Cycle 1 and Cycle 2 and change from Baseline data at Day 14 of Cycles 1 and 2 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Total Chloride Transport at Day 14 of Cycles 1 and 2
Baseline of Cycle 1
|
1.45 millivolts (mV)
Standard Deviation 5.671
|
0.66 millivolts (mV)
Standard Deviation 4.563
|
|
Change From Baseline in Total Chloride Transport at Day 14 of Cycles 1 and 2
Change at Day 14 of Cycle 1
|
-2.81 millivolts (mV)
Standard Deviation 6.543
|
-2.69 millivolts (mV)
Standard Deviation 7.289
|
|
Change From Baseline in Total Chloride Transport at Day 14 of Cycles 1 and 2
Baseline of Cycle 2
|
-0.92 millivolts (mV)
Standard Deviation 4.474
|
-3.76 millivolts (mV)
Standard Deviation 6.729
|
|
Change From Baseline in Total Chloride Transport at Day 14 of Cycles 1 and 2
Change at Day 14 of Cycle 2
|
-2.39 millivolts (mV)
Standard Deviation 5.426
|
1.10 millivolts (mV)
Standard Deviation 7.179
|
PRIMARY outcome
Timeframe: Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days)Population: All randomized participants who received at least 1 dose of study drug and had evaluable chloride transport response data.
Nasal TEPD was assessed in each participant using standardized techniques. Warmed solutions of Ringer's solution, amiloride, chloride-free gluconate, isoproterenol, and ATP were perfused for ≥3-minute sequentially through a nasal catheter while a voltage tracing was recorded. Total chloride transport was computed for each nostril. The total chloride transport values were calculated by subtracting the voltages at the end of a perfusion from the voltage at the end of an earlier perfusion (isoproterenol - amiloride). The average of the values for each nostril was computed. If the assessment was available in only 1 nostril, this value was used as if it were the average of both nostrils. Response to study treatment defined as an increase in total chloride transport as indicated by a change of at least -5 mV in nasal TEPD.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Number of Participants With a Chloride Transport Response at Day 14 of Cycles 1 and 2
Day 14 of Cycle 1
|
4 Participants
|
4 Participants
|
|
Number of Participants With a Chloride Transport Response at Day 14 of Cycles 1 and 2
Day 14 of Cycle 2
|
4 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Overall Baseline and Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days)Population: All randomized participants who received at least 1 dose of study drug and had evaluable normalization of chloride transport data.
Nasal TEPD was assessed in each participant using standardized techniques. Warmed solutions of Ringer's solution, amiloride, chloride-free gluconate, isoproterenol, and ATP were perfused for ≥3-minute sequentially through a nasal catheter while a voltage tracing was recorded. Total chloride transport was computed for each nostril. The total chloride transport values were calculated by subtracting the voltages at the end of a perfusion from the voltage at the end of an earlier perfusion (isoproterenol - amiloride). The average of the values for each nostril was computed. If the assessment was available in only 1 nostril, this value was used as if it were the average of both nostrils. Normalization of chloride transport (normal range \[NR\]) was defined as nasal TEPD that was at least as electrically negative as -5 mV. Normalization in chloride transport can also be referred to as hyperpolarization.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=14 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=14 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Number of Participants With Normalization of Chloride Transport Between Baseline and Day 14 of Cycles 1 and 2
Within NR at Baseline of Cycle 1
|
0 Participants
|
0 Participants
|
|
Number of Participants With Normalization of Chloride Transport Between Baseline and Day 14 of Cycles 1 and 2
Within NR at Day 14 of Cycle 1
|
1 Participants
|
5 Participants
|
|
Number of Participants With Normalization of Chloride Transport Between Baseline and Day 14 of Cycles 1 and 2
Outside NR at Baseline/in NR at Day 14 of Cycle 1
|
1 Participants
|
5 Participants
|
|
Number of Participants With Normalization of Chloride Transport Between Baseline and Day 14 of Cycles 1 and 2
Within NR at Baseline of Cycle 2
|
2 Participants
|
4 Participants
|
|
Number of Participants With Normalization of Chloride Transport Between Baseline and Day 14 of Cycles 1 and 2
Within NR at Day 14 of Cycle 2
|
6 Participants
|
3 Participants
|
|
Number of Participants With Normalization of Chloride Transport Between Baseline and Day 14 of Cycles 1 and 2
Outside NR at Baseline/in NR at Day 14 of Cycle 2
|
6 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline of Cycle 1 and Cycle 2, Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days)Population: All randomized participants who received at least 1 dose of study drug and had evaluable transepithelial difference data.
To assess TEPD, warmed solutions of Ringer's solution, amiloride, chloride-free gluconate, isoproterenol and ATP were perfused for ≥3-minutes sequentially through a nasal catheter while a voltage tracing was recorded. Total chloride transport was computed per nostril. Totals were calculated by subtracting voltages at end of perfusion from voltage at end of earlier perfusion for: sodium transport (amiloride-Ringer's solution), intrinsic chloride transport (chloride-free gluconate-amiloride), stimulated chloride transport (isoproterenol-chloride-free gluconate), total potential difference (isoproterenol-Ringer's solution), and ATP-mediated chloride transport (ATP-isoproterenol). Basal potential difference voltage was obtained at end of Ringer's solution perfusion. Average values per nostril were computed. If assessment was available in only 1 nostril, the value was used as if it's the average of both nostrils. Baseline data for Cycles 1 and 2 and change from Baseline data are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Sodium transport, Baseline of C2
|
28.85 mV
Standard Deviation 14.31
|
32.15 mV
Standard Deviation 17.72
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Sodium transport, Change at D14 of C2
|
6.38 mV
Standard Deviation 19.81
|
5.50 mV
Standard Deviation 20.69
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Intrinsic chloride transport, Baseline of C1
|
2.38 mV
Standard Deviation 4.19
|
1.11 mV
Standard Deviation 4.01
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Intrinsic chloride transport, Change at D14 of C1
|
-2.54 mV
Standard Deviation 4.70
|
-2.69 mV
Standard Deviation 4.96
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Intrinsic chloride transport, Baseline of C2
|
-1.32 mV
Standard Deviation 5.61
|
-0.90 mV
Standard Deviation 3.44
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Intrinsic chloride transport, Change at D14 of C2
|
-1.20 mV
Standard Deviation 6.23
|
-1.12 mV
Standard Deviation 5.34
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Stimulated chloride transport, Baseline of C1
|
-0.93 mV
Standard Deviation 2.22
|
-0.45 mV
Standard Deviation 1.63
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Stimulated chloride transport, Change at D14 of C1
|
-0.27 mV
Standard Deviation 3.44
|
0 mV
Standard Deviation 4.26
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Stimulated chloride transport, Baseline of C2
|
0.40 mV
Standard Deviation 4.83
|
-2.86 mV
Standard Deviation 6.98
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Stimulated chloride transport, Change at D14 of C2
|
-1.19 mV
Standard Deviation 5.89
|
2.21 mV
Standard Deviation 8.77
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Total potential difference, Baseline of C1
|
35.83 mV
Standard Deviation 17.25
|
37.06 mV
Standard Deviation 17.25
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Total potential difference, Change at D14 of C1
|
-7.77 mV
Standard Deviation 12.16
|
-1.14 mV
Standard Deviation 13.89
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Total potential difference, Baseline of C2
|
27.93 mV
Standard Deviation 15.37
|
28.39 mV
Standard Deviation 17.18
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Total potential difference, Change at D14 of C2
|
3.99 mV
Standard Deviation 19.48
|
6.59 mV
Standard Deviation 20.20
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
ATP-mediated chloride transport, Baseline C1
|
-19.84 mV
Standard Deviation 10.22
|
-17.65 mV
Standard Deviation 10.62
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
ATP-mediated chloride transport, Change at D14, C1
|
4.93 mV
Standard Deviation 11.56
|
-2.95 mV
Standard Deviation 15.59
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
ATP-mediated chloride transport, Baseline C2
|
-16.87 mV
Standard Deviation 13.24
|
-16.34 mV
Standard Deviation 12.35
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
ATP-mediated chloride transport, Change at D14, C2
|
-0.38 mV
Standard Deviation 17.47
|
-4.58 mV
Standard Deviation 27.93
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Basal nasal TEPD, Baseline of Cycle (C)1
|
-53.91 mV
Standard Deviation 18.81
|
-56.51 mV
Standard Deviation 20.68
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Basal nasal TEPD, Change at Day (D)14 of C1
|
9.31 mV
Standard Deviation 17.72
|
-3.70 mV
Standard Deviation 13.33
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Basal nasal TEPD, Baseline of C2
|
-46.28 mV
Standard Deviation 14.46
|
-50.02 mV
Standard Deviation 17.09
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Basal nasal TEPD, Change at D14 of C2
|
-6.31 mV
Standard Deviation 19.33
|
-5.22 mV
Standard Deviation 24.48
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Sodium transport, Baseline of C1
|
34.38 mV
Standard Deviation 17.72
|
36.40 mV
Standard Deviation 18.44
|
|
Change From Baseline in Parameters of Transepithelial Difference at Day 14 of Cycles 1 and 2
Sodium transport, Change at D14 of C1
|
-4.97 mV
Standard Deviation 15.30
|
1.55 mV
Standard Deviation 18.39
|
SECONDARY outcome
Timeframe: Overall Baseline, Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable apical cell data.
The immunofluorescence staining of normal epithelial cells (for example, from nasal mucosal curettage) reveals the presence of cystic fibrosis transmembrane regulator (CFTR) protein at the apical surface. Cells were stained with antibodies that recognized an epitope in the C-terminal portion of the CFTR protein, and the cells were imaged microscopically. The percentage of epithelial cells that showed apical CFTR staining was determined by 2 expert readers who were blinded to the timepoint at which the samples were obtained. The scores of the reviewers were averaged to determine the final percentage of cells with apical CFTR. Overall Baseline data for the study and change from overall Baseline data at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in CFTR Protein in Nasal Mucosa as Determined by Immunofluorescence at Overall Day 56
Overall Baseline
|
15.95 percentage of apical cells
Standard Deviation 16.797
|
10.47 percentage of apical cells
Standard Deviation 9.270
|
|
Change From Baseline in CFTR Protein in Nasal Mucosa as Determined by Immunofluorescence at Overall Day 56
Change at Overall Day 56
|
10.45 percentage of apical cells
Standard Deviation 24.337
|
22.89 percentage of apical cells
Standard Deviation 29.389
|
SECONDARY outcome
Timeframe: Overall Baseline, Overall Day 42Population: All randomized participants who received at least 1 dose of study drug and had evaluable CFTR mRNA data.
The collection and processing of the nasal mucosal curettage from each nostril of each participant for measurement of CFTR protein by immunofluorescence and for quantification of CFTR messenger ribonucleic acid (mRNA) was performed using standardized techniques. The slides were processed and immunostained for detection of CFTR protein. Microscopic images were to be captured photographically for analysis. Because the nasal brushing used to collect nasal mucosal epithelial cells did not result in collection of sufficient cells for RT-PCR to be performed, an insufficient number of paired baseline and follow-up samples were available for analysis. As a result, no data were available to evaluate the effects of ataluren on CFTR mRNA.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable pulmonary function data.
Pulmonary function tests, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow25-75 (FEF25-75), were measured using standard spirometry techniques. Overall Baseline data for the study and change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEV1, Overall Baseline
|
92.68 percent of predicted
Standard Deviation 22.645
|
85.14 percent of predicted
Standard Deviation 27.850
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEV1, Change at Day 14 or 15 of Cycle 1
|
2.73 percent of predicted
Standard Deviation 5.848
|
-4.60 percent of predicted
Standard Deviation 7.579
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEV1, Change at Day 14 or 15 of Cycle 2
|
-0.46 percent of predicted
Standard Deviation 11.031
|
0.02 percent of predicted
Standard Deviation 8.801
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEV1, Change at Overall Day 56
|
-0.36 percent of predicted
Standard Deviation 12.936
|
-0.39 percent of predicted
Standard Deviation 8.191
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FVC, Overall Baseline
|
101.83 percent of predicted
Standard Deviation 13.294
|
95.34 percent of predicted
Standard Deviation 22.515
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FVC, Change at Day 14 or 15 of Cycle 1
|
2.52 percent of predicted
Standard Deviation 7.216
|
-2.33 percent of predicted
Standard Deviation 6.643
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FVC, Change at Day 14 or 15 of Cycle 2
|
-0.44 percent of predicted
Standard Deviation 7.433
|
-0.44 percent of predicted
Standard Deviation 7.433
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FVC, Change at Overall Day 56
|
-0.65 percent of predicted
Standard Deviation 9.117
|
1.02 percent of predicted
Standard Deviation 6.796
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEF 25-75%, Overall Baseline
|
88.32 percent of predicted
Standard Deviation 49.740
|
71.20 percent of predicted
Standard Deviation 41.194
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEF 25-75%, Change at Day 14 or 15 of Cycle 1
|
2.98 percent of predicted
Standard Deviation 19.679
|
-3.63 percent of predicted
Standard Deviation 12.300
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEF 25-75%, Change at Day 14 or 15 of Cycle 2
|
3.19 percent of predicted
Standard Deviation 22.712
|
-0.39 percent of predicted
Standard Deviation 19.192
|
|
Change From Baseline in Pulmonary Function as Measured by Spirometry at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
FEF 25-75%, Change at Overall Day 56
|
-2.76 percent of predicted
Standard Deviation 27.406
|
-4.29 percent of predicted
Standard Deviation 23.379
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable sputum markers of inflammation data.
The inflammatory marker free elastase was measured in induced sputum from each participant. Hypertonic saline (3%) inhalation was used to induce the sputum (with efforts made to avoid oropharyngeal contamination). The sputum sample was divided into 4 aliquots (1 aliquot each for determination of cell count, IL-8 level, and elastase activity and 1 aliquot for potential future viscosity measurements). Change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Sputum Markers of Inflammation (Free Elastase) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Free Elastase, Baseline
|
108.85 micrograms/milliliters (μg/mL)
Standard Deviation 107.617
|
60.92 micrograms/milliliters (μg/mL)
Standard Deviation 56.170
|
|
Change From Baseline in Sputum Markers of Inflammation (Free Elastase) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Free Elastase, Change at Day 14 or 15 of Cycle 1
|
-37.78 micrograms/milliliters (μg/mL)
Standard Deviation 95.154
|
74.66 micrograms/milliliters (μg/mL)
Standard Deviation 83.258
|
|
Change From Baseline in Sputum Markers of Inflammation (Free Elastase) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Free Elastase, Change at Day 14 or 15 of Cycle 2
|
-24.40 micrograms/milliliters (μg/mL)
Standard Deviation 93.804
|
37.33 micrograms/milliliters (μg/mL)
Standard Deviation 65.240
|
|
Change From Baseline in Sputum Markers of Inflammation (Free Elastase) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Free Elastase, Change at Overall Day 56
|
12.47 micrograms/milliliters (μg/mL)
Standard Deviation 84.427
|
57.18 micrograms/milliliters (μg/mL)
Standard Deviation 139.211
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable sputum markers of inflammation data.
The inflammatory marker MMP-9 active was measured in induced sputum from each participant. Hypertonic saline (3%) inhalation was used to induce the sputum (with efforts made to avoid oropharyngeal contamination). The sputum sample was divided into 4 aliquots (1 aliquot each for determination of cell count, IL-8 level, and elastase activity and 1 aliquot for potential future viscosity measurements). Change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Sputum Markers of Inflammation (Matrix Metalloproteinase 9 [MMP-9] Active) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
MMP-9 Active, Baseline
|
69431.28 nanograms/milliliter (ng/mL)
Standard Deviation 109894.966
|
20908.56 nanograms/milliliter (ng/mL)
Standard Deviation 28441.612
|
|
Change From Baseline in Sputum Markers of Inflammation (Matrix Metalloproteinase 9 [MMP-9] Active) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
MMP-9 Active, Change at Day 14 or 15 of Cycle 1
|
-44527.45 nanograms/milliliter (ng/mL)
Standard Deviation 92493.455
|
71639.89 nanograms/milliliter (ng/mL)
Standard Deviation 150716.037
|
|
Change From Baseline in Sputum Markers of Inflammation (Matrix Metalloproteinase 9 [MMP-9] Active) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
MMP-9 Active, Change at Day 14 or 15 of Cycle 2
|
-51330.37 nanograms/milliliter (ng/mL)
Standard Deviation 108057.265
|
14947.54 nanograms/milliliter (ng/mL)
Standard Deviation 69337.080
|
|
Change From Baseline in Sputum Markers of Inflammation (Matrix Metalloproteinase 9 [MMP-9] Active) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
MMP-9 Active, Change at Overall Day 56
|
-49644.49 nanograms/milliliter (ng/mL)
Standard Deviation 86334.812
|
56884.39 nanograms/milliliter (ng/mL)
Standard Deviation 158498.793
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable sputum markers of inflammation data.
The inflammatory markers TNF-α, IL-8, and TGF-β1 were measured in induced sputum from each participant. Hypertonic saline (3%) inhalation was used to induce the sputum (with efforts made to avoid oropharyngeal contamination). The sputum sample was divided into 4 aliquots (1 aliquot each for determination of cell count, IL-8 level, and elastase activity and 1 aliquot for potential future viscosity measurements). Change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
IL-8, Baseline
|
352539.57 picograms/milliliter (pg/mL)
Standard Deviation 331865.227
|
121879.75 picograms/milliliter (pg/mL)
Standard Deviation 83684.594
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
IL-8, Change at Day 14 or 15 of Cycle 1
|
-171764.67 picograms/milliliter (pg/mL)
Standard Deviation 296343.195
|
98483.55 picograms/milliliter (pg/mL)
Standard Deviation 154432.714
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
IL-8, Change at Day 14 or 15 of Cycle 2
|
-71206.95 picograms/milliliter (pg/mL)
Standard Deviation 289379.557
|
-4087.25 picograms/milliliter (pg/mL)
Standard Deviation 127038.632
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
IL-8, Change at Overall Day 56
|
-121626.94 picograms/milliliter (pg/mL)
Standard Deviation 263731.747
|
52880.35 picograms/milliliter (pg/mL)
Standard Deviation 176223.116
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TGF-b1, Baseline
|
80.84 picograms/milliliter (pg/mL)
Standard Deviation 280.044
|
322.56 picograms/milliliter (pg/mL)
Standard Deviation 612.153
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TGF-b1, Change at Day 14 or 15 of Cycle 1
|
0 picograms/milliliter (pg/mL)
Standard Deviation 0
|
-322.56 picograms/milliliter (pg/mL)
Standard Deviation 612.15
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TGF-b1, Change at Day 14 or 15 of Cycle 2
|
-97.01 picograms/milliliter (pg/mL)
Standard Deviation 306.773
|
-168.91 picograms/milliliter (pg/mL)
Standard Deviation 774.276
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TGF-b1, Change at Overall Day 56
|
-61.32 picograms/milliliter (pg/mL)
Standard Deviation 367.788
|
-392.21 picograms/milliliter (pg/mL)
Standard Deviation 771.006
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TNF-alpha, Baseline
|
203.15 picograms/milliliter (pg/mL)
Standard Deviation 185.530
|
95.69 picograms/milliliter (pg/mL)
Standard Deviation 139.550
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TNF-alpha, Change at Day 14 or 15 of Cycle 1
|
-58.94 picograms/milliliter (pg/mL)
Standard Deviation 183.812
|
46.38 picograms/milliliter (pg/mL)
Standard Deviation 67.679
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TNF-alpha, Change at Day 14 or 15 of Cycle 2
|
-85.28 picograms/milliliter (pg/mL)
Standard Deviation 123.341
|
-58.45 picograms/milliliter (pg/mL)
Standard Deviation 144.728
|
|
Change From Baseline in Sputum Markers of Inflammation (Tumor Necrosis Factor-Alpha [TNF-α], Interleukin-8 [IL-8], Transforming Growth Factor Beta 1 [TGF-β1]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
TNF-alpha, Change at Overall Day 56
|
1.50 picograms/milliliter (pg/mL)
Standard Deviation 267.702
|
0.25 picograms/milliliter (pg/mL)
Standard Deviation 122.285
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable sputum markers of inflammation data.
The inflammatory marker UTP was measured in induced sputum from each participant. Hypertonic saline (3%) inhalation was used to induce the sputum (with efforts made to avoid oropharyngeal contamination). The sputum sample was divided into 4 aliquots (1 aliquot each for determination of cell count, IL-8 level, and elastase activity and 1 aliquot for potential future viscosity measurements). Change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Sputum Markers of Inflammation (Uridine-5'-Triphosphate [UTP]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
UTP, Baseline
|
800.27 milligrams/deciliter (mg/dL)
Standard Deviation 509.794
|
483.31 milligrams/deciliter (mg/dL)
Standard Deviation 222.102
|
|
Change From Baseline in Sputum Markers of Inflammation (Uridine-5'-Triphosphate [UTP]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
UTP, Change at Day 14 or 15 of Cycle 1
|
-202.85 milligrams/deciliter (mg/dL)
Standard Deviation 427.324
|
411.50 milligrams/deciliter (mg/dL)
Standard Deviation 359.669
|
|
Change From Baseline in Sputum Markers of Inflammation (Uridine-5'-Triphosphate [UTP]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
UTP, Change at Day 14 or 15 of Cycle 2
|
-200.94 milligrams/deciliter (mg/dL)
Standard Deviation 549.730
|
198.03 milligrams/deciliter (mg/dL)
Standard Deviation 436.888
|
|
Change From Baseline in Sputum Markers of Inflammation (Uridine-5'-Triphosphate [UTP]) at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
UTP, Change at Overall Day 56
|
-220.16 milligrams/deciliter (mg/dL)
Standard Deviation 414.258
|
-15.86 milligrams/deciliter (mg/dL)
Standard Deviation 242.686
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable data of neutrophil levels in blood.
To assess inflammatory markers in the blood, neutrophil levels in the blood were measured. Higher levels of neutrophils are indicative of more inflammation. Change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Clinically Significant Neutrophil Levels in Blood at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Neutrophils - Absolute, Baseline
|
3.555 10^9/liters
Standard Deviation 1.2328
|
4.709 10^9/liters
Standard Deviation 3.0884
|
|
Change From Baseline in Clinically Significant Neutrophil Levels in Blood at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Neutrophils - Absolute, Day 14 or 15 of Cycle 1
|
-0.332 10^9/liters
Standard Deviation 1.3416
|
-0.330 10^9/liters
Standard Deviation 2.7710
|
|
Change From Baseline in Clinically Significant Neutrophil Levels in Blood at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Neutrophils - Absolute, Day 14 or 15 of Cycle 2
|
-0.290 10^9/liters
Standard Deviation 1.4881
|
-0.748 10^9/liters
Standard Deviation 2.2473
|
|
Change From Baseline in Clinically Significant Neutrophil Levels in Blood at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Neutrophils - Absolute, Overall Day 56
|
-0.114 10^9/liters
Standard Deviation 1.4724
|
-0.931 10^9/liters
Standard Deviation 2.7452
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 or 15 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable serum levels of C-reactive data.
To assess inflammatory markers in the blood, serum levels of C-reactive protein were measured. Higher levels of C-reactive protein are indicative of more inflammation. Change from overall Baseline data at Day 14 or 15 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Clinically Significant Serum Levels of C-Reactive Protein at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
C-Reactive Protein, Baseline
|
6.432 milligrams/liter (mg/L)
Standard Deviation 4.9133
|
8.273 milligrams/liter (mg/L)
Standard Deviation 7.8838
|
|
Change From Baseline in Clinically Significant Serum Levels of C-Reactive Protein at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
C-Reactive Protein, Day 14 or 15 of Cycle 1
|
-0.150 milligrams/liter (mg/L)
Standard Deviation 1.6337
|
7.059 milligrams/liter (mg/L)
Standard Deviation 16.9563
|
|
Change From Baseline in Clinically Significant Serum Levels of C-Reactive Protein at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
C-Reactive Protein, Day 14 or 15 of Cycle 2
|
-0.233 milligrams/liter (mg/L)
Standard Deviation 0.7761
|
2.933 milligrams/liter (mg/L)
Standard Deviation 12.0167
|
|
Change From Baseline in Clinically Significant Serum Levels of C-Reactive Protein at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
C-Reactive Protein, Overall Day 56
|
2.361 milligrams/liter (mg/L)
Standard Deviation 7.4765
|
1.240 milligrams/liter (mg/L)
Standard Deviation 7.7170
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable body weight data.
Body weight were measured for each participant in kilograms (kg). Overall Baseline data for the study and change from overall Baseline data at Day 14 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in Body Weight at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Overall Baseline
|
40.35 kg
Standard Deviation 12.239
|
41.72 kg
Standard Deviation 11.435
|
|
Change From Baseline in Body Weight at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Change at Day 14 of Cycle 1
|
0.12 kg
Standard Deviation 1.064
|
-0.01 kg
Standard Deviation 1.031
|
|
Change From Baseline in Body Weight at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Change at Day 14 of Cycle 2
|
0.37 kg
Standard Deviation 1.293
|
0.03 kg
Standard Deviation 0.980
|
|
Change From Baseline in Body Weight at Day 14 or 15 of Cycles 1 and 2 and Overall Day 56
Change at Overall Day 56
|
0.43 kg
Standard Deviation 1.278
|
0.23 kg
Standard Deviation 1.528
|
SECONDARY outcome
Timeframe: Overall Baseline, Day 14 of Cycle 1 and Cycle 2 (1 cycle=28 days), and Overall Day 56Population: All randomized participants who received at least 1 dose of study drug and had evaluable CF-related symptom scores.
The CF symptom questionnaire includes questions related to daytime cough, nighttime cough, sputum volume, sputum clearance, physical fatigue, and shortness of breath. The participants (or their guardians) completed the CF symptom questionnaire, under the Investigator's supervision, before the TEPD, nasal mucosal curettage, pulmonary function tests, or sputum induction procedures were performed. For each symptom, the participants were asked to choose the response that best matched their experience during the 3 days before the questionnaire was completed. The scale of the 4 possible responses for each question was 0 (best response) to 4 (worse response). The sum of the scores for all of the questions was calculated. The scale for the sum of the scores was 0 (best response) to 24 (worse response). Overall Baseline data for the study and change from overall Baseline data at Day 14 of Cycles 1 and 2 and at overall Day 56 are presented.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=15 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Change From Baseline in the CF-Related Symptom Scores, as Assessed Using a Participant-Reported Questionnaire at Day 14 of Cycles 1 and 2 and Overall Day 56
Overall Baseline
|
14.0 scores on a scale
Interval 7.0 to 19.0
|
11.0 scores on a scale
Interval 7.0 to 17.0
|
|
Change From Baseline in the CF-Related Symptom Scores, as Assessed Using a Participant-Reported Questionnaire at Day 14 of Cycles 1 and 2 and Overall Day 56
Change at Day 14 of Cycle 1
|
-0.5 scores on a scale
Interval -7.0 to 6.0
|
0 scores on a scale
Interval -5.0 to 4.0
|
|
Change From Baseline in the CF-Related Symptom Scores, as Assessed Using a Participant-Reported Questionnaire at Day 14 of Cycles 1 and 2 and Overall Day 56
Change at Day 14 of Cycle 2
|
-1.0 scores on a scale
Interval -5.0 to 7.0
|
1.0 scores on a scale
Interval -5.0 to 8.0
|
|
Change From Baseline in the CF-Related Symptom Scores, as Assessed Using a Participant-Reported Questionnaire at Day 14 of Cycles 1 and 2 and Overall Day 56
Change at Overall Day 56
|
-1.0 scores on a scale
Interval -7.0 to 9.0
|
0 scores on a scale
Interval -6.0 to 8.0
|
SECONDARY outcome
Timeframe: 0 (predose), 2 and 3 hours postdose of the morning dose; 0 (predose), 2 and 3 hours postdose of the midday dose; and 0 hours (predose), 2, 3, and 12 hours postdose of the evening dose on Day 14 of Cycle 1 and Cycle 2Population: All randomized participants who received at least 1 dose of study drug and had evaluable AUC0-24 data. The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
All PK parameters were calculated using the actual postdose blood sampling times in relationship to the time of the first dose (morning dose) on Day 14 of each treatment cycle. AUC0-24 values were calculated by WinNonlin by extrapolation to 24 hours if the last sampling timepoint was before 24 hours and by interpolation if the last sampling timepoint was after 24 hours. Extrapolation of AUC to 24 hours was performed only if the last sampling timepoint did not deviate from the nominal collection time by more than approximately 10%.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=30 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=30 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
PK: Area Under the Concentration Time Curve From Time 0 (Dosing) to 24 Hours (AUC0-24) of Ataluren
|
121.52 microgram*hours/milliliter (μg*h/mL)
Standard Error 9.79
|
348.75 microgram*hours/milliliter (μg*h/mL)
Standard Error 21.46
|
SECONDARY outcome
Timeframe: Baseline up to Day 14 in Cycle 1 and Cycle 2Population: All randomized participants who received at least 1 dose of study drug and had evaluable compliance data. The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
For each participant, compliance was described in terms of the percentage of drug actually taken relative to the amount that was prescribed (taking into account physician-prescribed reductions and interruptions). The number of doses described as "taken less than planned" includes cases in which the participants took less than the prescribed dose and/or cases in which the Investigator reduced the dose.
Outcome measures
| Measure |
Ataluren 4, 4, and 8 mg/kg, Then Ataluren 10, 10, and 20 mg/kg
n=30 Participants
During Cycle 1, participants received ataluren at 4 mg/kg in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 10, 10, and 20 mg/kg) for Cycle 2.
|
Ataluren 10, 10, and 20 mg/kg, Then Ataluren 4, 4, and 8 mg/kg
n=30 Participants
During Cycle 1, participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment. Then, the participants crossed over to the other ataluren dose regimen (ataluren 4, 4, and 8 mg/kg) for Cycle 2.
|
|---|---|---|
|
Compliance With Study Treatment
Percentage of doses taken as planned
|
97.50 percentage of doses
Interval 81.8 to 100.0
|
100.0 percentage of doses
Interval 65.1 to 100.0
|
|
Compliance With Study Treatment
Percentage of doses missed
|
2.40 percentage of doses
Interval 0.0 to 15.8
|
0 percentage of doses
Interval 0.0 to 16.2
|
|
Compliance With Study Treatment
Percentage of doses taken less than planned
|
0 percentage of doses
Interval 0.0 to 10.5
|
0 percentage of doses
Interval 0.0 to 30.2
|
|
Compliance With Study Treatment
Percentage of doses taken greater than planned
|
0 percentage of doses
Interval 0.0 to 0.0
|
0 percentage of doses
Interval 0.0 to 0.0
|
Adverse Events
Ataluren 4, 4, and 8 mg/kg
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Ataluren 10, 10, and 20 mg/kg
Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ataluren 4, 4, and 8 mg/kg
n=30 participants at risk
Participants received ataluren at 4 milligrams in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment.
|
Ataluren 10, 10, and 20 mg/kg
n=30 participants at risk
Participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cystic fibrosis pulmonary exacerbation
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Haematemesis
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
Other adverse events
| Measure |
Ataluren 4, 4, and 8 mg/kg
n=30 participants at risk
Participants received ataluren at 4 milligrams in the morning, 4 mg/kg at midday, and 8 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment.
|
Ataluren 10, 10, and 20 mg/kg
n=30 participants at risk
Participants received ataluren at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by a 14-day follow-up period without treatment.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
6/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
26.7%
8/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
3/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Nausea
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
General disorders
Chest pain
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
General disorders
Pyrexia
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Infections and infestations
Nasopharyngitis
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Infections and infestations
Rhinitis
|
23.3%
7/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
23.3%
7/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Infections and infestations
Stenotrophomonas infection
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
10.0%
3/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Respiratory, thoracic and mediastinal disorders
Cystic fibrosis pulmonary exacerbation
|
13.3%
4/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
20.0%
6/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
10.0%
3/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
General disorders
Asthenia
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
General disorders
Fatigue
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
General disorders
Thirst
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Infections and infestations
Laryngitis
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Nervous system disorders
Headache
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
6.7%
2/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
3.3%
1/30 • Overall Baseline up to Overall Day 56
The data for each dose level represents pooled data for participants in the low-to-high dose sequence and the high-to-low dose sequence.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the Principal Investigator is that the Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication embargo.
- Publication restrictions are in place
Restriction type: OTHER