Trial Outcomes & Findings for MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis (NCT NCT01180634)

Last Updated: 2024-12-18

Results Overview

The start of the exacerbation was determined by the earliest date at which a participant concurrently met at least 4 of the 12 modified Fuchs symptoms/signs; discontinued from the study early; died; or received an antipseudomonal agent for an event that did not meet modified Fuchs criteria but was determined to be an exacerbation by the Blinded Exacerbation. Fuchs symptoms/signs; * Change in sputum * New or increased hemoptysis * Increased cough * Increased dyspnea * Malaise, fatigue or lethargy * Temperature above 38oC * Anorexia or weight loss * Sinus pain or tenderness * Change in sinus discharge * Change in physical examination of the chest * Decrease in pulmonary function by 10 percent or more from a previously recorded value * Radiographic changes indicative of pulmonary infection Median and 95%Ci were estimated using Kaplan Meier estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

330 participants

Primary outcome timeframe

Baseline to end of study (up to 59 days)

Results posted on

2024-12-18

Participant Flow

Participant milestones

Participant milestones
Measure	Aeroquin 240 mg Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Overall Study STARTED	220	110
Overall Study COMPLETED	210	109
Overall Study NOT COMPLETED	10	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Aeroquin 240 mg Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Overall Study Adverse Event	4	1
Overall Study Miscellaneous	2	0
Overall Study Withdrawal by Subject	4	0

Baseline Characteristics

MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aeroquin 240 mg n=219 Participants Participants received 240 mg of Aeroquin by inhalation route, BID for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.	Total n=329 Participants Total of all reporting groups
Age, Continuous	29.4 years STANDARD_DEVIATION 10.34 • n=5 Participants	28.8 years STANDARD_DEVIATION 10.94 • n=7 Participants	29.2 years STANDARD_DEVIATION 10.53 • n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	47 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	114 Participants n=5 Participants	63 Participants n=7 Participants	177 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	209 Participants n=5 Participants	101 Participants n=7 Participants	310 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	212 Participants n=5 Participants	100 Participants n=7 Participants	312 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to end of study (up to 59 days)

Population: Intent-to-treat (IIT) population included all randomized participants.

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=220 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Time to an Exacerbation	58 Days Interval 52.0 to Upper bound of 95% CI was not estimable due to low number of events	51.5 Days Interval 43.0 to Upper bound of 95% CI was not estimable due to low number of events

SECONDARY outcome

Timeframe: Baseline, day 28

Population: ITT Population

FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12-18 years, \>18 years), and baseline FEV1 (\<55%, \>=55%).

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=220 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Absolute Change in Percent Predicted Forced Expiratory Volume in One Second (FEV1)	0.08 Percent Predicted FEV1 Standard Error 0.638	1.49 Percent Predicted FEV1 Standard Error 0.531

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: ITT Population

Pseudomonas aeruginosa density was measured as log10 colony-forming units \[CFU\] per gram sputum. LSMean and standard are determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12-18 years, \>18 years), baseline FEV1 (\<55%, \>=55%), and baseline organism log density.

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=220 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Change From Baseline in Pseudomonas Aeruginosa Sputum Density	0.04 log10 CFU/g Standard Error 0.170	-0.59 log10 CFU/g Standard Error 0.139

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: ITT population with available data at specified time point.

The Cystic Fibrosis Questionnaire (CFQ-R) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. LSMean and standard error were determined from a repeated measures model with terms for treatment, visit, treatment\*visit, region (US, non-US), age (12 to 18 years, \> 18 years), Baseline FEV1 (\<55%, ≥ 55%), and Baseline value.

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=218 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=108 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)	4.66 Score on a scale Standard Error 1.374	4.94 Score on a scale Standard Error 1.118

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: ITT population with available data at specific timepoint.

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=218 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=109 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Relative Change From Baseline in Percent Predicted FEV1	1.24 Percent Predicted FEV1 Standard Error 1.041	3.66 Percent Predicted FEV1 Standard Error 0.866

SECONDARY outcome

Timeframe: Baseline to end of study (up to 59 days)

Population: ITT Population

Participants who had at least one of four worsening respiratory symptoms (increased cough, increased sputum/chest congestion, decreased exercise tolerance, decreased appetite) at the time of administration of the anti-pseudomonal antimicrobial agent were included in the analysis. Median and 95% CI are estimated using Kaplan Meier estimates.

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=220 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Time to Administration of Other Systemic and/or Inhaled Antipseudomonal Antimicrobials	59 Days Interval 53.0 to 60.0	55 Days Interval 43.0 to Upper bound of 95% CI was not estimable due to low number of events

SECONDARY outcome

Timeframe: Baseline to end of study (up to 59 days)

Population: ITT Population

Median and 95%CI was estimated using Kaplan Meier estimates.

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=220 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Time to First Hospitalization	NA Days Interval 60.0 to Median and upper bound of confidence interval were not estimable due to low number of events.	NA Days Median, lower and upper bound of confidence interval were not estimable due to low number of events.

SECONDARY outcome

Timeframe: From start of study until end of study (Up to 59 days)

Population: Safety population included all randomized participants in the study who received at least 1 dose of study drug or placebo.

An AE was defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a Study Drug, whether or not considered related to the Study Drug. An AE could potentially be a new disease, any untoward event, or an exacerbation of a pre-existing condition. AEs included, but were not limited to: * Any symptom not previously reported by the patient (medical history) * An exacerbation of a pre-existing illness * An increase in frequency or intensity of a pre-existing episodic event or condition * A condition first detected or diagnosed after Study Drug administration even though the condition may have been present before the start of the study * Overdose of Study Drug

Outcome measures

Outcome measures
Measure	Aeroquin 240 mg n=219 Participants Participants received 240 milligrams (mg) of Aeroquin by inhalation route twice daily (BID) for a period of 28 days.	Placebo n=110 Participants Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Number of Participants With Treatment Emergent Adverse Events	214 participants	108 participants

Adverse Events

Aeroquin 240 mg

Serious events: 21 serious events

Other events: 207 other events

Deaths: 0 deaths

Placebo

Serious events: 11 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aeroquin 240 mg n=219 participants at risk Participants received 240 mg of Aeroquin by inhalation route, BID for a period of 28 days.	Placebo n=110 participants at risk Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
General disorders Disease progression	6.8% 15/219 • Number of events 15 • From start of study until end of study (Up to 59 days) Safety Population	10.0% 11/110 • Number of events 11 • From start of study until end of study (Up to 59 days) Safety Population
General disorders Pyrexia	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Infections and infestations Bronchopneumonia	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Infections and infestations Influenza	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Infections and infestations Pyelonephritis	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Gastrointestinal disorders Small intestinal obstruction	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Renal and urinary disorders Renal failure acute	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Hypoxia	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Rash	0.46% 1/219 • Number of events 1 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population

Other adverse events

Additional Information

Medical Monitor

Horizon Pharma USA, Inc.

Phone: 1-866-479-6742

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Aeroquin 240 mg n=219 participants at risk Participants received 240 mg of Aeroquin by inhalation route, BID for a period of 28 days.	Placebo n=110 participants at risk Participants placebo matching Aeroquin by inhalation route, BID for a period of 28 days.
Gastrointestinal disorders Nausea	6.4% 14/219 • From start of study until end of study (Up to 59 days) Safety Population	0.91% 1/110 • From start of study until end of study (Up to 59 days) Safety Population
General disorders Nausea	42.0% 92/219 • From start of study until end of study (Up to 59 days) Safety Population	38.2% 42/110 • From start of study until end of study (Up to 59 days) Safety Population
General disorders Exercise tolerance decreased	19.2% 42/219 • From start of study until end of study (Up to 59 days) Safety Population	20.0% 22/110 • From start of study until end of study (Up to 59 days) Safety Population
General disorders Pyrexia	7.3% 16/219 • From start of study until end of study (Up to 59 days) Safety Population	1.8% 2/110 • From start of study until end of study (Up to 59 days) Safety Population
Infections and infestations Pyrexia	4.6% 10/219 • From start of study until end of study (Up to 59 days) Safety Population	5.5% 6/110 • From start of study until end of study (Up to 59 days) Safety Population
Investigations Forced expiratory volume decreased	9.6% 21/219 • From start of study until end of study (Up to 59 days) Safety Population	9.1% 10/110 • From start of study until end of study (Up to 59 days) Safety Population
Investigations Weight decreased	16.4% 36/219 • From start of study until end of study (Up to 59 days) Safety Population	19.1% 21/110 • From start of study until end of study (Up to 59 days) Safety Population
Metabolism and nutrition disorders Decreased appetite	10.0% 22/219 • From start of study until end of study (Up to 59 days) Safety Population	10.9% 12/110 • From start of study until end of study (Up to 59 days) Safety Population
Nervous system disorders Dysgeusia	35.2% 77/219 • From start of study until end of study (Up to 59 days) Safety Population	0.00% 0/110 • From start of study until end of study (Up to 59 days) Safety Population
Nervous system disorders Headache	6.4% 14/219 • From start of study until end of study (Up to 59 days) Safety Population	2.7% 3/110 • From start of study until end of study (Up to 59 days) Safety Population
Nervous system disorders Sinus Headache	11.9% 26/219 • From start of study until end of study (Up to 59 days) Safety Population	15.5% 17/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Cough	56.6% 124/219 • From start of study until end of study (Up to 59 days) Safety Population	46.4% 51/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 11/219 • From start of study until end of study (Up to 59 days) Safety Population	3.6% 4/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	16.0% 35/219 • From start of study until end of study (Up to 59 days) Safety Population	9.1% 10/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Increased viscosity of bronchial secretion	4.6% 10/219 • From start of study until end of study (Up to 59 days) Safety Population	6.4% 7/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	5.5% 12/219 • From start of study until end of study (Up to 59 days) Safety Population	3.6% 4/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	10.5% 23/219 • From start of study until end of study (Up to 59 days) Safety Population	13.6% 15/110 • From start of study until end of study (Up to 59 days) Safety Population
Respiratory, thoracic and mediastinal disorders Sputum increased	41.6% 91/219 • From start of study until end of study (Up to 59 days) Safety Population	38.2% 42/110 • From start of study until end of study (Up to 59 days) Safety Population