Cefiderocol Concentrations in the Lungs of Hospitalized Patients With Bacterial Pneumonia

Bacterial Pneumonia Clinical Trial

Official title:

An Open-label, Multicenter, Single-arm, Phase 1 Study to Assess the Intrapulmonary Concentrations of Cefiderocol at Steady State in Hospitalized Subjects With Known or Suspected Bacterial Pneumonia on Treatment With Standard of Care Antibiotics and Requiring Mechanical Ventilation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03862040
• Other study ID #: 1713R2117
• Status: Terminated
• Phase: Phase 1
• Start date: February 20, 2019
• Est. completion date: October 15, 2019

Study information

• Verified date: October 2020
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to determine the degree of penetration of cefiderocol into infected lung tissue in hospitalized adults with bacterial pneumonia who are being mechanically ventilated.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: October 15, 2019
• Est. primary completion date: October 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject is 18 years or older at the time written informed consent is obtained

2. Subject has provided written informed consent or informed consent has been provided by subject's legally authorized representative

3. Subject has a diagnosis or suspicion of bacterial pneumonia (even if later known that the subject does not have bacterial pneumonia, discontinuation of the study is not necessary)

4. Subject is hospitalized and receiving standard of care antibiotic treatment for pneumonia

5. Subject is mechanically ventilated or expected to be mechanically ventilated at least 48 hours (or 72 hours for subjects with severe renal impairment) after the first dose of cefiderocol

6. Subject has a life expectancy of at least 3 weeks from the Screening visit

7. Subject is male (no contraception required) or female and meets 1 of the following

criteria:

1. Surgically sterile (has had a hysterectomy and/or bilateral oophorectomy, or a bilateral salpingectomy or tubal ligation for the purpose of contraception for at least 6 weeks with appropriate documentation of such surgery)

2. Postmenopausal (defined as older than 45 years of age with cessation of regular menstrual periods for at least 6 months and a follicle-stimulating hormone level of > 40 mIU/mL, or amenorrhea for at least 12 months)

3. Of childbearing potential and using combined (estrogen and progestogen) or progestogen-only hormonal contraception associated with inhibition of ovulation (including oral, intravaginal, injectable, implantable, and transdermal contraceptives), or an intrauterine device (IUD), or intrauterine hormone-releasing system for the entire duration of the study

4. Of childbearing potential and practicing abstinence as a preferred and usual life style and/or agrees to continue practicing abstinence from Screening for the entire duration of the study

5. Of childbearing potential and whose sole heterosexual partner has been successfully vasectomized and agrees to not have other heterosexual partners for the entire duration of the study Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. Subject has a chemical pneumonia that does not require antibiotic treatment (including aspiration of gastric acid, inhalation injury). The term chemical pneumonia refers to the aspiration of substances that are toxic to the lower airways causing chemical burn and injuries in the airway.

2. Subject has a history of any moderate or severe hypersensitivity or allergic reaction to any ß-lactam (Note: for ß-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)

3. Subject has extensive cystic lesion(s) or severe structural abnormality (eg, cystic fibrosis, emphysema, cystic lesions of sarcoidosis or tuberculosis, postobstructive pneumonia due to lung cancer, etc) of the lung that hinders recovery of bronchoalveolar lavage fluid (BALF)

4. Subject is receiving peritoneal dialysis

5. Subject has severe renal impairment requiring hemodialysis (HD) or end-stage renal disease requiring HD

6. Subject is in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at Screening

7. Subject is a female who has a positive pregnancy test at Screening or who is lactating

8. Subject has received another investigational drug within 30 days prior to Screening

9. Subject has previously participated in this clinical study and has received at least 1 dose of cefiderocol within 7 days

10. Subject has any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data

Related Conditions & MeSH terms

• Bacterial Pneumonia
• Pneumonia
• Pneumonia, Bacterial

Intervention

Drug:
• Cefiderocol
Administered intravenously, at a dosage determined based on renal function.
• Standard of Care Antibiotic
Standard of care antibiotic treatment for pneumonia

Locations

Country	Name	City	State
United States	Anschutz Medical Campus	Aurora	Colorado
United States	North Western University	Chicago	Illinois
United States	Hartford Hospital	Hartford	Connecticut
United States	University of Florida	Jacksonville	Florida
United States	U Miami Health Tower	Miami	Florida
United States	Weill Cornell Medical College	New York	New York
United States	Creighton University	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of Cefiderocol in Epithelial Lining Fluid	Samples for determination of cefiderocol concentrations in the epithelial lining fluid (ELF) were collected by bronchoalveolar lavage (BAL) procedure on the inflamed section of the lung (ie, a lobe where pneumonia was expected to be present based on chest radiologic imaging) after multiple doses of cefiderocol sufficient to approximate steady state concentrations in blood. The ELF sample for the determination of cefiderocol concentrations was collected at 3 hours after the start of administration of cefiderocol for the first 4 enrolled participants and at 2 hours after the end of infusion for the following 3 participants.; Cefiderocol concentrations were determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS), with a lower limit of quantification of cefiderocol in ELF of 0.005 µg/mL. Cefiderocol concentrations in ELF were calculated using cefiderocol concentrations in BAL, adjusted by the ratio of urea concentrations in blood and BAL.	At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.
Primary	Ratio of the Concentration of Cefiderocol in Epithelial Lining Fluid Relative to Plasma	The concentration of cefiderocol in ELF to plasma ratio (RC,E/P) represents the penetration of cefiderocol into infected lung tissue.; ELF and plasma cefiderocol concentrations were determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The lower limit of quantification of cefiderocol in plasma and ELF was 0.1 µg/mL and 0.005 µg/mL, respectively.	At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after start of the first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.