Study to Evaluate Arikayce™ in CF Patients With Chronic P... | NCT01315678

NCT01315678

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

CF is a genetic disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CF manifest pathological changes in a variety of organs that express CFTR. The lungs are frequently affected often resulting in chronic infections by bacteria such as Pseudomonas aeruginosa and airway inflammation. Treatment of chronic lung infections is one of the principal goals of CF therapy. Arikayce™ LAI (liposomal amikacin for inhalation) is a sustained-release formulation of amikacin encapsulated inside nanoscale liposomal carriers designed for administration via inhalation. It is hypothesized that the sustained-release pulmonary targeting and biofilm penetration properties of this formulation will have several advantages over current therapies in treating CF patients with chronic lung infection caused by Pseudomonas aeruginosa.

This Phase 3 study has been designed to evaluate the efficacy, safety and tolerability of Arikayce™ in treating CF patients with chronic bronchopulmonary infection compared to a currently available antibiotic, TOBI® Inhalation Solution. Eligible participants will be randomized 1:1 to receive 590 mg of Arikayce™ once daily via a PARI Investigational eFlow® Nebulizer or 300 mg TOBI® BID via a PARI LC® PLUS nebulizer. Participants will receive 3 cycles of treatment with each cycle being comprised of 28 days on treatment followed by 28 days off-treatment. Total study duration is up to 186 days (~6 months) including an up to 18 day Screening period. Participants will be evaluated for safety, tolerability and efficacy bi-weekly during the first 4 weeks of treatment, and thereafter every 4 weeks for the duration of the study. Pharmacokinetics (PK) of Arikayce™ in blood, sputum and 24-hour urine will be determined in a subgroup of study participants who consent to PK evaluation.

At the completion of the TR02-108 protocol, participants who have consented and meet study safety criteria may enroll in the long-term, open-label, multi-cycle extension study of 590 mg of Arikayce™ (under a separate protocol TR02-110). Arikace™, Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and other studies evaluating amikacin liposome inhalation suspension.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arikayce™	Experimental	Arikayce™ is liposomal amikacin for inhalation	Drug: Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer.
TOBI®	Active Comparator	TOBI® is tobramycin inhalation solution	Drug: Tobramycin inhalation solution using a PARI LC® Plus nebulizer.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer.	Drug	Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pulmonary Function Test: Forced Expiratory Volume in 1 Second (FEV1)	Relative Change (%) from baseline to end of study (Day 168) in FEV1 (1 second)	Baseline to168 days

Secondary Outcomes

Measure	Description	Time Frame
Pumonary Function Test: Forced Expiratory Volume in 1 Second (FEV1)	Relative changes (%) from baseline to Study Days 14, 28, 57, 84, 113, 140, 168 in FEV1	Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168.
Number of Participants Experiencing a Pulmonary Exacerbation

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Gina Eagle, MD	Insmed Incorporated	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31451351	Derived	Bilton D, Pressler T, Fajac I, Clancy JP, Sands D, Minic P, Cipolli M, Galeva I, Sole A, Quittner AL, Liu K, McGinnis JP 2nd, Eagle G, Gupta R, Konstan MW; CLEAR-108 Study Group. Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis. J Cyst Fibros. 2020 Mar;19(2):284-291. doi: 10.1016/j.jcf.2019.08.001. Epub 2019 Aug 23.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
BG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG0000.47± 13.930 OG0011.67± 16.050

Secondary

Pumonary Function Test: Forced Expiratory Volume in 1 Second (FEV1)

Relative changes (%) from baseline to Study Days 14, 28, 57, 84, 113, 140, 168 in FEV1

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Posted

Mean

Standard Deviation

percentage (%) change

Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168.

ID	Title	Description
OG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
OG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment

Secondary

Number of Participants Experiencing a Pulmonary Exacerbation

Number of participants experiencing a pulmonary exacerbation measured by number with event and number censored

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Posted

Number

participants

168 days

ID	Title	Description
OG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
OG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment

Secondary

Number of Participants to First Antipseudomonal Antibiotic Treatment for Pulmonary Exacerbation

Number of participants to first antipseudomonal antibiotic treatment for pulmonary exacerbation measured by number with event and number censored

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Posted

Count of Participants

Participants

168 days

ID	Title	Description
OG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
OG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment

Secondary

Number of Participants to First All Cause Hospitalization

Number of participants to first all cause hospitalization measured by number with event and number censored

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Posted

Number

participants

168 days

ID	Title	Description
OG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
OG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment

Secondary

Change in Density (Log CFU) in Pseudomonas Aeruginosa in Sputum

Change in density (Log CFU) from baseline in Pseudomonas aeruginosa in sputum

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Posted

Mean

Standard Deviation

Log 10 CFU

Baseline, Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168

ID	Title	Description
OG000	Arikayce™
OG001	TOBI®

Units	Counts
Participants	OG000

Secondary

Relative Percent (%) Change in Respiratory Symptoms as Measured by the CFQ-R

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.

Modified intent-to-treat (mITT; received at least 1 dose of study drug)

Posted

Least Squares Mean

Standard Error

Percent (%) change

Day 14, Day 28, Day 57, Day 84, Day 113, Day 140 and Day 168

ID	Title	Description
OG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.
OG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arikayce™	Arikayce™ is liposomal amikacin for inhalation Liposomal amikacin for inhalation (Arikayce™) using the PARI Investigational eFlow® Nebulizer: Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization. 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer. Administration time is approximately 13 minutes. Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.	0	148	26	148	114	148
EG001	TOBI®	TOBI® is tobramycin inhalation solution Tobramycin inhalation solution using a PARI LC® Plus nebulizer: 300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer. Nebulization time is approximately 20 minutes for each administration. Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment	0	146	29	146	91	146

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Distal intestinal obstruction syndrome	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected148 at risk EG0011 events1 affected146 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected148 at risk EG0011 events1 affected146 at risk
Haematochezia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected148 at risk EG0011 events1 affected146 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	Systematic Assessment	EG00028 events24 affected148 at risk EG00128 events23 affected146 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected148 at risk EG0012 events2 affected146 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected148 at risk EG0011 events1 affected146 at risk
Bronchopulmonary aspergillosis allergic	Infections and infestations	Systematic Assessment	EG0001 events1 affected148 at risk EG0010 events0 affected146 at risk
Chronic sinusitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected148 at risk EG0010 events0 affected146 at risk
Forced expiratory volume decreased	Investigations	Systematic Assessment	EG0001 events1 affected148 at risk EG0010 events0 affected146 at risk
Pulmonary function test decreased	Investigations	Systematic Assessment	EG0000 events0 affected148 at risk EG0011 events1 affected146 at risk
Bronchial secretion retention	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected148 at risk EG0010 events0 affected146 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected148 at risk EG0010 events0 affected146 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected148 at risk EG0012 events1 affected146 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected148 at risk EG0011 events1 affected146 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00012 events10 affected148 at risk EG0015 events5 affected146 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	Systematic Assessment	EG000138 events82 affected148 at risk EG001117 events72 affected146 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG00029 events24 affected148 at risk EG00143 events33 affected146 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG00021 events15 affected148 at risk EG00114 events9 affected146 at risk
Rhinitis	Infections and infestations	Systematic Assessment	EG00010 events9 affected148 at risk EG0019 events9 affected146 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00022 events12 affected148 at risk EG0018 events5 affected146 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00053 events24 affected148 at risk EG00121 events10 affected146 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00023 events18 affected148 at risk EG00124 events11 affected146 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00028 events18 affected148 at risk EG0019 events8 affected146 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00012 events11 affected148 at risk EG0017 events6 affected146 at risk
General disorders	General disorders	Systematic Assessment	EG00023 events20 affected148 at risk EG00113 events10 affected146 at risk
Investigations	Investigations	Systematic Assessment	EG00015 events12 affected148 at risk EG00111 events10 affected146 at risk
Musculoskeletal and connective	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00014 events12 affected148 at risk EG00112 events10 affected146 at risk
Skin and subcutaneous	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00010 events8 affected148 at risk EG0016 events5 affected146 at risk

ID	Term
D011552	Pseudomonas Infections
D003550	Cystic Fibrosis
D012141	Respiratory Tract Infections

Ancestor Terms

ID	Term
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases

ID	Term
D001239	Inhalation
D009330	Nebulizers and Vaporizers

Units	Counts
Participants	OG000148 OG001146

Units	Counts
Participants	OG000148 OG001146

Facility	Status	City	State	ZIP	Country	Contacts
		Vienna			Austria

ID	Term
D015656	Respiratory Mechanics
D012119	Respiration
D012143	Respiratory Physiological Phenomena
D002943	Circulatory and Respiratory Physiological Phenomena
D004864	Equipment and Supplies