Multidose Safety and Tolerability Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKACE™)

NCT00777296 | Completed Phase 1 Results DMC

• 1 other identifier: TR02-105
• Study Type: interventional
• Target: 66
• Locations: 7 countries
• Sites: 11

Brief Summary

A major factor in the respiratory health of cystic fibrosis (CF) subjects is acquisition of chronic Pseudomonas aeruginosa infections. The infection rate with P. aeruginosa increases with age and by age 18 years, 80% of CF subjects in the U.S. are infected. Liposomal Amikacin for Inhalation (Arikace™) is a sterile aqueous liposomal suspension consisting of amikacin sulfate encapsulated in liposomes. This formulation of amikacin maximizes the achievable dose and delivery to the lungs of subjects infected via a nebulizer. Because liposome particles are small enough to penetrate and diffuse through sputum into the bacterial biofilm, they deposit drug in close proximity to the bacterial colonies, thus improving the bioavailability of amikacin at the infection site. The clinically achievable doses of amikacin in the LAI formulation can effectively increase the half-life of the drug in the lungs, and decrease the potential for systemic toxicity. LAI offers several advantages over current therapies in treating CF subjects with chronic infection caused by P. aeruginosa.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Respiratory Infections; Pulmonary Cystic Fibrosis; CFTR

Outcome Measures

Primary Outcomes (1)

• Clinically Significant Laboratory Abnormalities.

  Changes in chemistry and hematology lab tests (clinically significant value of CTCAE grade ≥ 3).

  28 Days

Secondary Outcomes (11)

• Pharmacokinetics (PK) of Arikace™ in Serum.

  Day 1, Day 14 and Day 28

• Pharmacokinetic (PK) of Arikace in Serum (Cmax).

  Day 1, Day 14 and Day 28

• Pharmacokinetics (PK) of Arikace™ in Sputum (AUC).

  28 days

• Pharmacokinetics (PK) of Arikace™ in Urine.

  Day 1, Day 14 and Day 28

• Sputum Amikacin Levels of Arikace™.

  Day 1, Day 14 and Day 28

Study Arms (4)

Cohort 1 - 280 mg ARIKACE™

EXPERIMENTAL

Subjects in this cohort will receive 280 mg of ARIKACE™

Drug: ARIKACE™

Cohort 1 - Placebo

PLACEBO COMPARATOR

Subjects in this arm of cohort 1 will receive matching placebo

Drug: Placebo

Cohort 2 - 560 mg ARIKACE™

EXPERIMENTAL

Subjects in this cohort will receive 560 mg of ARIKACE™

Drug: ARIKACE™

Cohort 2 - Placebo

PLACEBO COMPARATOR

Subjects in this arm of cohort 2 will receive matching placebo

Drug: Placebo

Interventions

ARIKACE™ DRUG

Study start date is before Jan 18, 2017.

Also known as: liposomal amikacin for inhalation, Arikayce

Cohort 1 - 280 mg ARIKACE™; Cohort 2 - 560 mg ARIKACE™

Placebo DRUG

Study start date is before Jan 18, 2017.

Cohort 1 - Placebo; Cohort 2 - Placebo

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from patient or designated legal guardian prior to the performance of any study related procedures.
• Male or female study subjects ≥6 years of age or older
• Confirmed diagnosis of CF
• History of chronic infection with P. aeruginosa
• Study subjects must produce a screening specimen that is positive for growth of P. aeruginosa
• FEV1 ≥ 40% predicted at Screening
• SaO2 ≥ 90% at Screening while breathing room air
• Ability to comply with study medication use, study visits and study procedures as judged by the investigator
• Ability to produce sputum or be willing to undergo an induction to produce sputum for clinical evaluation
• Clinically stable with no evidence of acute upper or lower respiratory tract infection of history of pulmonary exacerbation within 4 weeks prior to screening

You may not qualify if:

• Administration of any investigational drug within 8 weeks prior to Screening
• Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening
• History of alcohol, medication or illicit drug abuse within the 1 year prior to screening
• History of lung transplant
• Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)
• Positive pregnancy test
• Use of any anti-pseudomonal anitbiotics (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones)within the 28 days prior to screening
• Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within 28 days prior to screening
• History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening
• History of mycobacterial or Aspergillus infection
• Requiring treatment within 2 years prior to screening, and/or history of allergic bronchopulmonary aspergillosis.
• History of biliary cirrhosis with portal hypertension, or splenomegaly
• History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night Change in chest x-ray at screening (or within the 3 months prior to screening)

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (11)

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Kaposvár, Hungary

Location

Unknown Facility

Skopje, North Macedonia

Location

Unknown Facility

Rabka-Zdrój, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Belgrade, Serbia

Location

Unknown Facility

Bratislava, Slovakia

Location

Unknown Facility

Košice, Slovakia

Location

Unknown Facility

Kharkiv, Ukraine

Location

Unknown Facility

Kiev, Ukraine

Location

Related Publications (3)

• Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH, Lymp J, Minic P, Quittner AL, Rubenstein RC, Young KR, Saiman L, Burns JL, Govan JR, Ramsey B, Gupta R; Arikace Study Group. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax. 2013 Sep;68(9):818-25. doi: 10.1136/thoraxjnl-2012-202230. Epub 2013 Jun 8.

  PMID: 23749840 BACKGROUND

• Okusanya OO, Bhavnani SM, Hammel JP, Forrest A, Bulik CC, Ambrose PG, Gupta R. Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infections using data from two phase 2 clinical studies. Antimicrob Agents Chemother. 2014 Sep;58(9):5005-15. doi: 10.1128/AAC.02421-13. Epub 2014 Mar 31.

  PMID: 24687506 BACKGROUND

• Meers P, Neville M, Malinin V, Scotto AW, Sardaryan G, Kurumunda R, Mackinson C, James G, Fisher S, Perkins WR. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother. 2008 Apr;61(4):859-68. doi: 10.1093/jac/dkn059. Epub 2008 Feb 27.

  PMID: 18305202 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Respiratory Tract Infections

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Infections

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Dr. Kevin Mange, Sr. Vice President, Clinical Development
• Organization: Insmed Incorporated

Kevin.Mange@Insmed.com

908-947-2651

Study Officials

• Gina Eagle, MD

  Insmed Incorporated

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 22, 2008
• Study Start: February 22, 2007
• Primary Completion: February 27, 2008
• Study Completion: February 27, 2008
• Last Updated: July 30, 2020
• Results First Posted: July 16, 2019

Record last verified: 2020-07

Locations

BE (1); SE (1); PL (2); UA (2); SL (2); NO (1); HU (2)