Trial Outcomes & Findings for Safety/Tolerability Study of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa (NCT NCT00558844)

NCT ID: NCT00558844

Last Updated: 2019-06-04

Results Overview

To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikayce™, liposomal amikacin for inhalation.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 41 participants
• Primary outcome timeframe: 56 days
• Results posted on: 2019-06-04

Participant Flow

Participant milestones

Measure	Arikayce™ at 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Overall Study STARTED	15	7	7	5	7
Overall Study COMPLETED	12	7	6	5	6
Overall Study NOT COMPLETED	3	0	1	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Baseline characteristics by cohort

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70 mg/140 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Total n=41 Participants Total of all reporting groups
Age, Continuous	31.5 years STANDARD_DEVIATION 14.5 • n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	26.3 years STANDARD_DEVIATION 6.7 • n=7 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	33.1 years STANDARD_DEVIATION 9.7 • n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	35.4 years STANDARD_DEVIATION 6.0 • n=4 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	24.4 years STANDARD_DEVIATION 6.3 • n=21 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	29.9 years STANDARD_DEVIATION 12.6 • n=8 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
Sex: Female, Male Female	5 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	3 Participants n=7 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	6 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	1 Participants n=4 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	5 Participants n=21 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	20 Participants n=8 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
Sex: Female, Male Male	10 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	4 Participants n=7 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	1 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	4 Participants n=4 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	2 Participants n=21 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	21 Participants n=8 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
Race/Ethnicity, Customized White	14 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	6 Participants n=7 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	7 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	5 Participants n=4 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	6 Participants n=21 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	38 Participants n=8 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
Race/Ethnicity, Customized Black	1 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	1 Participants n=7 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	0 Participants n=5 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	0 Participants n=4 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	1 Participants n=21 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug	3 Participants n=8 Participants • Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
Region of Enrollment United States	15 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	5 Participants n=4 Participants	7 Participants n=21 Participants	41 Participants n=8 Participants

PRIMARY outcome

Timeframe: 56 days

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikayce™, liposomal amikacin for inhalation.

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Number of Participants With Treatment-Emergent Adverse Events Patients with AEs	14 Participants	7 Participants	7 Participants	4 Participants	6 Participants
Number of Participants With Treatment-Emergent Adverse Events Patients with Treatment Related AEs	7 Participants	2 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events Deaths	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events Patients with Serious AEs	5 Participants	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events Patients Permanently Discontinuing due to AEs	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1, Day 14 and Day 28

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Measure PK parameter (Cmax) of Arikayce in serum

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Pharmacokinetics of Arikayce™ in Serum Day 1	1.59 mg/L Standard Deviation 0.973	—	0.216 mg/L Standard Deviation 0.054	0.375 mg/L Standard Deviation 0.167	—
Pharmacokinetics of Arikayce™ in Serum Day 14	2.17 mg/L Standard Deviation 1.48	—	0.265 mg/L Standard Deviation 0.060	0.447 mg/L Standard Deviation 0.157	—
Pharmacokinetics of Arikayce™ in Serum Day 28	2.71 mg/L Standard Deviation 1.75	—	0.293 mg/L Standard Deviation 0.026	0.481 mg/L Standard Deviation 0.213	—

SECONDARY outcome

Timeframe: Day 1 post-dose, Day 14 pre- and post-dose, Day 28 pre- and post-dose

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Measure PK parameters (sputum concentration) of Arikayce in sputum, pre- and post-dose

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Pharmacokinetics (PK) of Arikayce™ in Sputum Day 1 1 hour post-dose	4417 mcg/g Standard Deviation 74.5	—	1119 mcg/g Standard Deviation 64.5	1632 mcg/g Standard Deviation 36.9	—
Pharmacokinetics (PK) of Arikayce™ in Sputum Day 14 pre-dose	132 mcg/g Standard Deviation 205	—	150 mcg/g Standard Deviation 221	20.1 mcg/g Standard Deviation 43.8	—
Pharmacokinetics (PK) of Arikayce™ in Sputum Day 14 1 hour post-dose	2643 mcg/g Standard Deviation 101	—	1012 mcg/g Standard Deviation 119	1534 mcg/g Standard Deviation 63.3	—
Pharmacokinetics (PK) of Arikayce™ in Sputum Day 28 pre-dose	124 mcg/g Standard Deviation 114	—	49.7 mcg/g Standard Deviation 189	20.5 mcg/g Standard Deviation 57.0	—
Pharmacokinetics (PK) of Arikayce™ in Sputum Day 28 1 hour post-dose	2670 mcg/g Standard Deviation 66.2	—	753 mcg/g Standard Deviation 82.2	1468 mcg/g Standard Deviation 90.9	—

SECONDARY outcome

Timeframe: Day 1, Day 14 and Day 28

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Measure PK parameter (Ae0-24) of Arikayce in urine

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Pharmacokinetics (PK) of Arikayce™ in Urine Day 1	25.9 mg Standard Deviation 27.1	—	4.80 mg Standard Deviation 1.43	15.2 mg Standard Deviation 8.74	—
Pharmacokinetics (PK) of Arikayce™ in Urine Day 14	63.6 mg Standard Deviation 29.1	—	7.76 mg Standard Deviation 3.19	21.7 mg Standard Deviation 12.4	—
Pharmacokinetics (PK) of Arikayce™ in Urine Day 28	62.9 mg Standard Deviation 38.0	—	7.13 mg Standard Deviation 4.31	17.7 mg Standard Deviation 8.33	—

SECONDARY outcome

Timeframe: Day 1, Day 14 and Day 28

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Measure PK parameter (AUC) of Arikayce in Serum

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Pharmacokinetics (PK) of Arikayce™ in Serum Day 1	11.3 mg*hr/L Standard Deviation 5.81	—	1.06 mg*hr/L Standard Deviation 0.243	2.90 mg*hr/L Standard Deviation 1.08	—
Pharmacokinetics (PK) of Arikayce™ in Serum Day 14	15.0 mg*hr/L Standard Deviation 7.96	—	1.56 mg*hr/L Standard Deviation 0.553	4.32 mg*hr/L Standard Deviation 1.96	—
Pharmacokinetics (PK) of Arikayce™ in Serum Day 28	17.1 mg*hr/L Standard Deviation 7.58	—	1.59 mg*hr/L Standard Deviation 0.531	4.16 mg*hr/L Standard Deviation 1.56	—

SECONDARY outcome

Timeframe: Baseline, Day 28, Day 56, Day 70 and Day 84

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Relative Change (%) from Baseline to Day 28, Day 56, Day 70, and Day 84 in Pulmonary Function

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Pulmonary Function: Pre-Dose FEV1 (%-Predicted) Baseline	68.800 Percent (%) Standard Deviation 17.026	66.143 Percent (%) Standard Deviation 12.020	59.286 Percent (%) Standard Deviation 12.593	70.400 Percent (%) Standard Deviation 10.090	69.286 Percent (%) Standard Deviation 16.550
Pulmonary Function: Pre-Dose FEV1 (%-Predicted) Day 28	-0.003 Percent (%) Standard Deviation 0.124	-0.001 Percent (%) Standard Deviation 0.075	0.029 Percent (%) Standard Deviation 0.124	-0.029 Percent (%) Standard Deviation 0.089	-0.010 Percent (%) Standard Deviation 0.060
Pulmonary Function: Pre-Dose FEV1 (%-Predicted) Day 56	0.029 Percent (%) Standard Deviation 0.092	-0.028 Percent (%) Standard Deviation 0.129	0.024 Percent (%) Standard Deviation 0.076	-0.020 Percent (%) Standard Deviation 0.087	0.011 Percent (%) Standard Deviation 0.067
Pulmonary Function: Pre-Dose FEV1 (%-Predicted) Day 70	0.026 Percent (%) Standard Deviation 0.107	-0.043 Percent (%) Standard Deviation 0.097	—	—	—
Pulmonary Function: Pre-Dose FEV1 (%-Predicted) Day 84	0.000 Percent (%) Standard Deviation 0.078	-0.067 Percent (%) Standard Deviation 0.145	—	—	—

SECONDARY outcome

Timeframe: Day 7, Day 14, Day 21, Day 28 and Day 35

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Change (log10 CFU) from Baseline by Study Day and Treatment Arm

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Density of Pseudomonas Aeruginosa in Sputum Day 28	-1.576 Log 10 CFU/g Standard Deviation 1.979	0.836 Log 10 CFU/g Standard Deviation 1.544	-1.771 Log 10 CFU/g Standard Deviation 1.741	-0.381 Log 10 CFU/g Standard Deviation 0.660	-0.426 Log 10 CFU/g Standard Deviation 0.435
Density of Pseudomonas Aeruginosa in Sputum Day 7	-1.605 Log 10 CFU/g Standard Deviation 1.308	1.118 Log 10 CFU/g Standard Deviation 2.214	-1.093 Log 10 CFU/g Standard Deviation 0.616	-0.637 Log 10 CFU/g Standard Deviation 0.711	-0.254 Log 10 CFU/g Standard Deviation 0.991
Density of Pseudomonas Aeruginosa in Sputum Day 14	-1.082 Log 10 CFU/g Standard Deviation 1.354	1.098 Log 10 CFU/g Standard Deviation 2.477	-1.121 Log 10 CFU/g Standard Deviation 1.404	-0.175 Log 10 CFU/g Standard Deviation 1.014	-0.159 Log 10 CFU/g Standard Deviation 0.499
Density of Pseudomonas Aeruginosa in Sputum Day 21	-0.750 Log 10 CFU/g Standard Deviation 1.466	-0.057 Log 10 CFU/g Standard Deviation 0.600	-1.560 Log 10 CFU/g Standard Deviation 2.845	-0.255 Log 10 CFU/g Standard Deviation 1.977	-0.337 Log 10 CFU/g Standard Deviation 1.384
Density of Pseudomonas Aeruginosa in Sputum Day 35	-1.963 Log 10 CFU/g Standard Deviation 2.456	0.578 Log 10 CFU/g Standard Deviation 0.539	-0.675 Log 10 CFU/g Standard Deviation 0.452	0.256 Log 10 CFU/g Standard Deviation 1.058	0.028 Log 10 CFU/g Standard Deviation 0.243

SECONDARY outcome

Timeframe: Through study duration, approximately 84 days

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Duration of Systemic Anti-Pseudomonal Rescue Therapy	22.800 days Standard Deviation 12.778	30.333 days Standard Deviation 15.044	17.500 days Standard Deviation 4.950	18.000 days Standard Deviation 0	30.500 days Standard Deviation 10.607

SECONDARY outcome

Timeframe: Day 15, Day 28 and Day 42

Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug

Quality of Life was measured by the absolute change from baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory scale. Disease specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms in patients with a diagnosis of cystic fibrosis. Scores range from 0 to 100, with higher scores indicating better health. Scores for each Health Related Quality of Life (HRQoL) domain; after recoding, each item is summed to generate a domain score and standardized.

Outcome measures

Measure	Arikayce™ at 560 mg n=15 Participants Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 Participants Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 Participants Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70mg/140 mg n=7 Participants Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
CFQ-R Respiratory Scale (Relative Change % From Baseline) Day 15	0.385 Percent (%) Standard Deviation 0.638	-0.063 Percent (%) Standard Deviation 0.135	0.075 Percent (%) Standard Deviation 0.273	0.100 Percent (%) Standard Deviation 0.173	0.042 Percent (%) Standard Deviation 0.104
CFQ-R Respiratory Scale (Relative Change % From Baseline) Day 28	0.387 Percent (%) Standard Deviation 0.683	-0.054 Percent (%) Standard Deviation 0.229	0.126 Percent (%) Standard Deviation 0.255	0.228 Percent (%) Standard Deviation 0.304	-0.029 Percent (%) Standard Deviation 0.233
CFQ-R Respiratory Scale (Relative Change % From Baseline) Day 42	0.094 Percent (%) Standard Deviation 0.826	-0.084 Percent (%) Standard Deviation 0.258	-0.012 Percent (%) Standard Deviation 0.305	0.225 Percent (%) Standard Deviation 0.215	0.006 Percent (%) Standard Deviation 0.173

Adverse Events

Arikayce™ at 560 mg

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo at 560 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Arikayce™ at 70 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Arikayce™ at 140 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo at 70 mg/140 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arikayce™ at 560 mg n=15 participants at risk Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 participants at risk Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 participants at risk Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 participants at risk Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70 mg/140 mg n=7 participants at risk Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Infections and infestations LOBE PNEUMONIA	0.00% 0/15	0.00% 0/7	0.00% 0/7	0.00% 0/5	14.3% 1/7 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary exacerbation	13.3% 2/15 • Number of events 2	14.3% 1/7 • Number of events 1	0.00% 0/7	20.0% 1/5 • Number of events 1	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Cystic Fibrosis Exacerbation	26.7% 4/15 • Number of events 4	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Nervous system disorders migraine headaches	0.00% 0/15	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Investigations Elevated LFTs	0.00% 0/15	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7

Other adverse events

Measure	Arikayce™ at 560 mg n=15 participants at risk Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Placebo at 560 mg n=7 participants at risk Matching placebo Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.	Arikayce™ at 70 mg n=7 participants at risk Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Arikayce™ at 140 mg n=5 participants at risk Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.	Placebo at 70 mg/140 mg n=7 participants at risk Matching placebo Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Gastrointestinal disorders Diarrhea	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Gastrointestinal disorders Nausea	13.3% 2/15 • Number of events 2	0.00% 0/7	28.6% 2/7	0.00% 0/5	14.3% 1/7
General disorders Chills	13.3% 2/15 • Number of events 2	0.00% 0/7	0.00% 0/7	20.0% 1/5	14.3% 1/7
General disorders Fatigue	13.3% 2/15 • Number of events 2	0.00% 0/7	28.6% 2/7	20.0% 1/5	14.3% 1/7
General disorders Non cardiac chest pain	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
General disorders Pyrexia	20.0% 3/15 • Number of events 3	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Infections and infestations Laryngitis	13.3% 2/15 • Number of events 2	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Infections and infestations Sinusitis	13.3% 2/15 • Number of events 2	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	28.6% 2/7
Investigations ALT increased	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Investigations AST increased	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Investigations Liver function test abnormal	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 3/15 • Number of events 3	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Musculoskeletal and connective tissue disorders Dizziness	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Musculoskeletal and connective tissue disorders Headache	13.3% 2/15 • Number of events 2	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Musculoskeletal and connective tissue disorders Migraine	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Cough	40.0% 6/15 • Number of events 6	42.9% 3/7 • Number of events 3	14.3% 1/7	0.00% 0/5	14.3% 1/7
Respiratory, thoracic and mediastinal disorders Dysphonia	20.0% 3/15 • Number of events 3	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Dyspnea, exertional	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	20.0% 1/5	14.3% 1/7
Respiratory, thoracic and mediastinal disorders Hemoptysis	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	28.6% 2/7	20.0% 1/5	14.3% 1/7
Respiratory, thoracic and mediastinal disorders Lung disorder	46.7% 7/15 • Number of events 7	14.3% 1/7 • Number of events 1	28.6% 2/7	20.0% 1/5	42.9% 3/7
Respiratory, thoracic and mediastinal disorders Nasal edema	13.3% 2/15 • Number of events 2	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	20.0% 3/15 • Number of events 3	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Productive cough	20.0% 3/15 • Number of events 3	28.6% 2/7 • Number of events 2	28.6% 2/7	20.0% 1/5	14.3% 1/7
Respiratory, thoracic and mediastinal disorders Prolonged expiration	13.3% 2/15 • Number of events 2	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Rales	20.0% 3/15 • Number of events 3	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Rhinorrhea	20.0% 3/15 • Number of events 3	42.9% 3/7 • Number of events 3	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Rhonchi	20.0% 3/15 • Number of events 3	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Sinus Congestion	6.7% 1/15 • Number of events 1	28.6% 2/7 • Number of events 2	0.00% 0/7	20.0% 1/5	14.3% 1/7
Respiratory, thoracic and mediastinal disorders Throat Irritation	6.7% 1/15 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Throat Tightness	20.0% 3/15 • Number of events 3	0.00% 0/7	0.00% 0/7	0.00% 0/5	0.00% 0/7
Respiratory, thoracic and mediastinal disorders Wheezing	20.0% 3/15 • Number of events 3	14.3% 1/7 • Number of events 1	28.6% 2/7	0.00% 0/5	0.00% 0/7
Ear and labyrinth disorders Tinnitus	0.00% 0/15	0.00% 0/7	0.00% 0/7	0.00% 0/5	28.6% 2/7
General disorders Vessel Puncture site hematoma	0.00% 0/15	0.00% 0/7	14.3% 1/7	0.00% 0/5	14.3% 1/7
Investigations Creatinine Renal Clearance INcreased	0.00% 0/15	0.00% 0/7	0.00% 0/7	20.0% 1/5	14.3% 1/7
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/15	0.00% 0/7	0.00% 0/7	20.0% 1/5	14.3% 1/7
Respiratory, thoracic and mediastinal disorders Pulmonary Congestion	0.00% 0/15	0.00% 0/7	0.00% 0/7	20.0% 1/5	14.3% 1/7

Additional Information

Kevin Mange (Senior VP, Clinical Development and Medical Affairs)

Insmed Incorporated

Phone: 908-947-2651

Email: kevin.mange@insmed.com

Results disclosure agreements

• Principal investigator is a sponsor employee Per the signed Investigator Agreement in the study protocol and protocol amendments, the PI agreed "not to originate or use the name of Insmed Incorporated, or study drug code in any publicity, news release, or other public announcement, written or oral, whether to the public, press, or otherwise, relating to this protocol, to any amendment to the protocol, or to the performance of this protocol, without the prior written consent of Insmed Incorporated."
• Publication restrictions are in place

Restriction type: OTHER