Single Dose Escalation Study of TR02 (Sustained Lipid Inhalation Technology [SLIT™] Amikacin) in Participants With Cystic Fibrosis (CF) Having Chronic Infections of Pseudomonas Aeruginosa

Safety and Tolerability Study of Single Dose Escalations of TR02 (SLIT™ Amikacin) by Inhalation in Cystic Fibrosis Study Patients With Chronic Infections of Pseudomonas Aeruginosa

The primary purpose of this study is to evaluate the safety and tolerability of three active doses of nebulized amikacin in a SLIT™ formulation.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: SLIT™ Amikacin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Study participants must produce sputum that is positive for Pseudomonas aeruginosa.
• Confirmed diagnosis of CF (positive sweat chloride >60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF phenotype.
• Forced expiratory volume (FEV1) ≥40% predicted at Screening as calculated by the Knudsen reference equations.
• Clinically stable with no evidence of current pulmonary exacerbation.

Exclusion Criteria:

• History of lung transplantation.
• Use of intravenous antibiotics or oral quinolones within 14 days of Screening.
• Use of low dose oral antibiotics (e.g. tetracycline, sulfa) for acne or other conditions within 30 days of Screening.
• Use of systemic corticosteroids (≥20 milligrams [mg] of prednisone per day) within 30 days of Screening.
• Initiation of TOBI® (tobramycin), high dose ibuprofen, recombinant human DNase (rhDNase), or macrolide antibiotics within 60 days of Screening.
• History of sputum or throat swab culture yielding Burkholderia cepacia complex within 2 years of Screening or growth of Burkholderia cepacia complex from the sputum or throat swab culture obtained at Screening.
• History of biliary cirrhosis, portal hypertension, or splenomegaly or splenomegaly on physical exam at Screening or enrollment.
• History of daily continuous oxygen supplementation or requirement for more than 2 liter per minute (L/min) at night.

Note: Other inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Amikacin Dose 1 + Placebo; Participants will receive a single dose of SLIT™ amikacin at Dose 1 or matching placebo by inhalation on Day 0.	Drug: SLIT™ Amikacin; Amikacin administered via the Pari LC STAR™ nebulizer.; Other Names: TR02; Drug: Placebo; Nebulized saline.
Experimental: Cohort 2: Amikacin Dose 2 + Placebo; Participants will receive a single dose of SLIT™ amikacin at Dose 2 or matching placebo by inhalation on Day 0 upon initiation of Cohort 2.	Drug: SLIT™ Amikacin; Amikacin administered via the Pari LC STAR™ nebulizer.; Other Names: TR02; Drug: Placebo; Nebulized saline.
Experimental: Cohort 3: Amikacin Dose 3 + Placebo; Participants will receive a single dose of SLIT™ amikacin at Dose 3 or matching placebo by inhalation on Day 0 upon initiation of Cohort 3.	Drug: SLIT™ Amikacin; Amikacin administered via the Pari LC STAR™ nebulizer.; Other Names: TR02; Drug: Placebo; Nebulized saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who Experience a Treatment Emergent Adverse Event (TEAE)	Safety and tolerability of three active doses of nebulized amikacin in a SLIT™ formulation.	Up to Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration-time Curve (AUC) of SLIT™ Amikacin in Serum	Pre-dose and at multiple time points post-dose up to Day 3
Percent Dose of SLIT™ Amikacin in Urine	At multiple time points post-dose up to Day 3
AUC of SLIT™ Amikacin in Sputum	Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 14, and 28
Change From Baseline in Sputum Density of Pseudomonas Aeruginosa	Baseline up to Day 28

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2004
• Primary Completion (Actual): February 8, 2005
• Study Completion (Actual): February 8, 2005

Study Registration Dates

• First Submitted: January 25, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Estimated): February 2, 2024

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Persistent Infection; Anti-Infective Agents; Anti-Bacterial Agents; Amikacin
• Other Study ID Numbers: TR02-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No