Cystic Fibrosis Clinical Trial
Official title:
Phase 2a Multidose Safety and Tolerability Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKACE™) In Cystic Fibrosis Patients With Chronic Infections Due To Pseudomonas Aeruginosa.
Verified date | July 2020 |
Source | Insmed Incorporated |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 66 |
Est. completion date | February 27, 2008 |
Est. primary completion date | February 27, 2008 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 6 Years and older |
Eligibility |
Inclusion Criteria: - 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 Key Exclusion Criteria: - 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) |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Insmed Incorporated |
Belgium, Hungary, North Macedonia, Poland, Serbia, Slovakia, Ukraine,
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Clinically Significant Laboratory Abnormalities. | Changes in chemistry and hematology lab tests (clinically significant value of CTCAE grade = 3). | 28 Days | |
Secondary | Pharmacokinetics (PK) of Arikace™ in Serum. | Measure PK parameters (AUC0-infinity) of Arikace™ in serum. | Day 1, Day 14 and Day 28 | |
Secondary | Pharmacokinetic (PK) of Arikace in Serum (Cmax). | Measure PK parameter (Cmax) of Arikace™ in serum. | Day 1, Day 14 and Day 28 | |
Secondary | Pharmacokinetics (PK) of Arikace™ in Sputum (AUC). | Measure PK parameter (AUC0-24) of Arikace™ in sputum. | 28 days | |
Secondary | Pharmacokinetics (PK) of Arikace™ in Urine. | Measure PK parameter (Ae0-24 (mg) of Arikace™. | Day 1, Day 14 and Day 28 | |
Secondary | Sputum Amikacin Levels of Arikace™. | Measure PK parameter (sputum amicakin concentration) of Arikace™ in sputum. | Day 1, Day 14 and Day 28 | |
Secondary | Pulmonary Function: FEV1 %-Predicted. | Relative Change (%) from Baseline to End of treatment (Day 28) and Day 56 in Pulmonary Function. | Baseline, Day 28, and Day 56 | |
Secondary | Pulmonary Function: FEV1. | Mean Percent Change (%) from Baseline to End of treatment (Day 28) and Day 56 in Pulmonary Function. | Baseline, Day 28, and Day 56 | |
Secondary | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | End-of-treatment (Day 28) from baseline in density of P. aeruginosa (log10 CFU/g) in sputum. | Day 7, Day 14, Day 21, Day 28 and Day 35 | |
Secondary | Duration of Systemic Antipseudomonal Rescue Therapy. | Duration of systemic antipseudomonal rescue therapy during the study in both the ARIKACE™ and placebo groups. | Through study duration, approximately 56 days | |
Secondary | Number of Subjects Requiring Antipseudomonal Rescue Therapy. | Number of Subjects requiring systemic antipseudomonal rescue therapy during the study in both the ARIKACE™ and placebo groups. | Through study duration, approximately 56 days | |
Secondary | CFQ-R Respiratory Scale (Absolute Change From Baseline). | 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. | Baseline/Day 1, Day 15, Day 28 and Day 42 |
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