A Study to Assess the Pharmacokinetic Profile, the Safety, and the Tolerability of ME1100 Inhalation Solution in Patients With Mechanically Ventilated Bacterial Pneumonia

A Randomized, Open-Label Phase 1b Study of ME1100 Inhalation Solution Plus Best Available Therapy in the Treatment of Mechanically Ventilated Subjects With Bacterial Pneumonia

This study is a randomized, open-label phase I study. The primary objective of this study is to assess the pharmacokinetic (PK) profile of ME1100 in subjects with mechanically ventilated bacterial pneumonia (MVBP). The secondary objective of this study is to assess the safety and tolerability of ME1100 for the treatment of subjects with MVBP to assess the safety and tolerability of ME1100.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Bacterial
• Intervention / Treatment: Drug: ME1100 inhalation solution; Drug: ME1100 inhalation solution

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Martinez, California, United States
    • Sacramento, California, United States
    • San Diego, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Florida
    • Jacksonville, Florida, United States
  • Kentucky
    • Hazard, Kentucky, United States
  • Massachusetts
    • Worcester, Massachusetts, United States
  • Michigan
    • Kalamazoo, Michigan, United States
  • New York
    • Buffalo, New York, United States
  • North Carolina
    • Greensboro, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Lima, Ohio, United States
    • Toledo, Ohio, United States
  • Texas
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants must meet all of the following inclusion criteria in order to be eligible for the study:

1. Is a hospitalized male or female, ≥ 18 years of age at the Screening Visit;
2. Is on mechanical ventilation;

3. Has a known or suspected mechanically ventilated bacterial pneumonia with at least 1 of the following:

   • Fever (> 38.5ﾟC or > 101.3ﾟF);
   • Hypothermia (≤ 35.0ﾟC or ≤ 95.0ﾟF);
   • Leukopenia (≤ 4500 cells/mm3);
   • Leukocytosis (≤ 10000 cells/mm3);
   • White blood cell count with left shift defined as > 15% immature polymorphonuclear leukocytes (bands) on peripheral blood smear; or
   • Procalcitonin > 0.25 µg/mL;

   Plus at least 2 of the following:

   • Respiratory failure requiring mechanical ventilation;
   • New onset of expectorated or suctioned purulent sputum production or respiratory secretions, or a change in the character of sputum;
   • Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation;
   • Dyspnea, tachypnea, or signs of respiratory distress as evidenced by an increase in respiratory support or oxygen requirement, particularly if any or all of these are progressive in nature; or
   • Hypoxemia by pulse oximetry or arterial blood gas requiring an increase in supplemental oxygen;
4. Has a chest X-ray with a new consolidation consistent with pneumonia or significant worsening of previous findings consistent with pneumonia; and
5. Has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and ≤ 30 at the Screening Visit.

Exclusion Criteria:

Participants who meet any of the following exclusion criteria will not be enrolled in the study:

1. Has a requirement of inhaled non-study antibiotic;
2. Has been treated with any inhaled antibiotic (including inhaled aminoglycosides) within 72 hours of study entry;
3. Has renal insufficiency at Screening as evidenced by an estimated creatinine clearance <50 mL/min based on the Cockcroft-Gault formula;
4. Is at risk of rapidly fatal illness and death within the next 72 hours;
5. Is a pregnant or nursing female. Females of childbearing potential must have a serum pregnancy test prior to enrollment. If results of the serum pregnancy test are not available prior to the Day 1 Treatment Visit, the patients may be enrolled on the basis of a negative urine pregnancy test; however, the results of the serum pregnancy test must still be obtained. If either test is positive, the patients must be excluded;
6. Has myasthenia gravis, parkinsonism, or any other progressive neuromuscular disorder;
7. Has a history of epilepsy or known seizure disorder;
8. Has a history of sensorineural hearing loss resulting from any therapy known as ototoxic (eg, aminoglycosides, cisplatin, loop diuretics, or quinine);
9. Has received any investigational medication in the last 30 days (or 5 half-lives of the investigational medication, whichever is longer) prior to the Screening Visit; or
10. Has known hypersensitivity to ME1100, aminoglycosides, or any of the specified Best Available Therapy agents or their excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose of ME1100	Drug: ME1100 inhalation solution; Low dose of ME1100 inhalation solution twice daily for up to 14 days to be administered via eFlow nebulizer system; Other Names: Arbekacin inhalation solution; Drug: ME1100 inhalation solution; High dose of ME1100 inhalation solution twice daily for up to 14 days to be administered via eFlow nebulizer system; Other Names: Arbekacin inhalation solution
Experimental: High dose of ME1100	Drug: ME1100 inhalation solution; Low dose of ME1100 inhalation solution twice daily for up to 14 days to be administered via eFlow nebulizer system; Other Names: Arbekacin inhalation solution; Drug: ME1100 inhalation solution; High dose of ME1100 inhalation solution twice daily for up to 14 days to be administered via eFlow nebulizer system; Other Names: Arbekacin inhalation solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Arbekacin concentrations in respiratory fluids collected via bronchoalveolar lavage (BAL) for epithelial lining fluid (ELF)	Day 3
Plasma arbekacin concentrations	Day 1 to Day 5
Urinary elimination of arbekacin	Day 2
Arbekacin concentrations in tracheal aspirate	Day 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	Screening through 14 days after the end of treatment

Collaborators and Investigators

• Sponsor: Meiji Seika Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): March 22, 2017
• Study Completion (Actual): March 22, 2017

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: May 29, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2017
• Last Update Submitted That Met QC Criteria: July 3, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents; Pharmaceutical Solutions; Arbekacin; Dibekacin
• Other Study ID Numbers: ME1100-CL-103