Safety and Tolerability Study of 2 Dose Level of Arikayce™ in Patients With Bronchiectasis and Chronic Infection Due to Pseudomonas Aeruginosa.

NCT00775138 | Completed Phase 2 Results DMC

• 1 other identifier: TR02-107
• Study Type: interventional
• Target: 64
• Locations: 9 countries
• Sites: 18

Brief Summary

This is a study to determine the safety and tolerability of 28 days of daily dosing of two doses (280 mg and 560 mg) of Arikayce™ versus placebo in patients who have bronchiectasis and chronic infection due to Pseudomonas infection.

Conditions

Bronchiectasis

Keywords

Bronchiectasis; Respiratory Infections; Amikacin; Respiratory Tract Diseases; Respiratory Tract Infections; Lung Diseases; Pseudomonas aeruginosa; Amikacin liposome inhalation suspension (ALIS)

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment

  Number of Subjects reporting TEAE in the Arikayce™ groups and the placebo groups during the study. The table shows the events incidents, not the number of participants.

  Day 1 through 56.

• Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation

  Number of subjects reporting Incidence of clinically significant abnormalities in clinical values (Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 3) in Arikayce™ and placebo groups.

  Day 1 through 56.

• Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment

  Changes in PFT from pre-dose during the study were measured on Days 1, 14, and 28. Acute tolerability of the study treatment was assessed by examining the relative (rel.) changes in FEV1 from pre-dose assessments to 0-1 hour post-dose and 2-4 hours post-dose for each time point at which post-dose spirometry was conducted.

  Pre-dose, 0-1 hour post-dose and 2-4 hours post-dose on day 1, 0-1 hour post-dose and 2-4 hours post-dose on day 14, and 0-1 hour post-dose and 2-4 hours post-dose on day 28

• Treatment-emergent PFT Abnormalities up to the End of Study

  Number of Subjects with Decrease of \>= 15% in FEV1 (L) from Pre- to Post-dose by Study Day

  Day 1, Day 14 and Day 28

• Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication

  Screening to Day 56

• Serious Adverse Events up to 28 Days After Study Medication Discontinuation

  Number of subjects with a SAE in the Arikace™ groups and the placebo group up to 28 days after study medication discontinuation. See SAE table in the safety section for details.

  Screening to Day 56

Secondary Outcomes (4)

• Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum.

  Baseline to Day 14, Day 28 and Day 42.

• Total Pulmonary Symptom Severity Score (PSSS)

  Baseline to Day 14, Day 28, Day 42 and Day 56.

• To Evaluate Change in St. George's Respiratory Questionnaire Measurements

  Day 1 to Day 14, Day 28, Day 42 and Day 56.

• To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy

  Screening to Day 56.

Study Arms (4)

Cohort 1 - 280 mg Arikayce™

EXPERIMENTAL

Subjects in this arm of the cohort 1 will receive 280 mg of Arikayce™

Drug: 280 mg Arikayce™

Cohort 1 - Placebo

PLACEBO COMPARATOR

Subjects in this arm of the cohort 1 will receive matching placebo.

Drug: Matching Placebo for Cohort 1

Cohort 2 - 560 mg Arikayce™

EXPERIMENTAL

Subjects in this arm of the cohort 2 will receive 560 mg of Arikayce™

Drug: 560 mg Arikayce™

Cohort 2 - Placebo

PLACEBO COMPARATOR

Subjects in this arm of the cohort 2 will receive matching placebo

Drug: Matching Placebo for Cohort 2

Interventions

280 mg Arikayce™ DRUG

Study subjects will receive Arikace™ 280 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Also known as: liposomal amikacin for inhalation

Cohort 1 - 280 mg Arikayce™

Matching Placebo for Cohort 1 DRUG

Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Cohort 1 - Placebo

560 mg Arikayce™ DRUG

Study subjects will receive Arikace™ 560 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Also known as: liposomal amikacin for inhalation

Cohort 2 - 560 mg Arikayce™

Matching Placebo for Cohort 2 DRUG

Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Cohort 2 - Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female study subjects≥ 18 years of age
• Confirmed diagnosis of multi-focal bronchiectasis in two or more lung segments by HRCT of the chest
• History of chronic infection with P. aeruginosa
• Confirmation of infection with P. aeruginosa 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 at least 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation

You may not qualify if:

• Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted at Screening
• Patients with hemoptysis of ≥60 mL within 4 weeks prior to screening
• Bronchiectasis due to cystic fibrosis (CF), bronchopulmonary Aspergillus, aspiration of foreign body, or secondary to lung compression from tumors
• History of non-tuberculous mycobacterial and/or Aspergillus infection requiring treatment or treated within 2 years prior to screening
• Pulmonary tuberculosis requiring treatment or treated within two years prior to screening
• History of Lung transplantation
• Use of any inhalation or systemic antibiotics (IV antibiotics, or oral antibiotics) within 4 weeks prior to Study Day 1
• Evidence of biliary cirrhosis with portal hypertension
• Smoking tobacco or any substance within 6 months prior to screening, and throughout the study
• History of alcohol, medication, or illicit drug abuse within the 1 year prior to screening

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (18)

Unknown Facility

Washington D.C., District of Columbia, United States

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Philadelphia, Pennsylvania, United States

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Sofia, Bulgaria

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Athens, Greece

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Mosdós, Hungary

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Bangalore, India

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Hyderabad, India

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Manipal, India

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Mumbai, India

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Nagpur, India

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New Delhi, India

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Rabka-Zdrój, Poland

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Belgrade, Serbia

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Kragujevac, Serbia

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Niš, Serbia

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Kiev, Ukraine

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Cambridge, United Kingdom

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London, United Kingdom

Location

MeSH Terms

Conditions

Bronchiectasis; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pseudomonas Infections

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Bronchial Diseases; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

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

Kevin.Mange@Insmed.com

908-947-2651

Study Officials

• Gina Eagle, MD

  Insmed Incorporated

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 17, 2008
• Study Start: June 24, 2008
• Primary Completion: May 11, 2009
• Study Completion: May 11, 2009
• Last Updated: July 10, 2019
• Results First Posted: July 10, 2019

Record last verified: 2019-06

Locations

UA (1); GR (1); BU (1); GB (2); HU (1); SE (3); US (2); IN (6); PL (1)