Bacterial PneumoniaPhase 1NCT03862040
Cefiderocol Concentrations in the Lungs of Hospitalized Patients With Bacterial Pneumonia
A Phase 1 study testing Cefiderocol in people with Bacterial Pneumonia, run by Shionogi at 7 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Pneumonia
- What is being tested?
- Cefiderocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 7 sitesUnited States
- Study dates
- 20 Feb 2019to 15 Oct 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is 18 years or older at the time written informed consent is obtained
- Subject has provided written informed consent or informed consent has been provided by subject's legally authorized representative
- 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)
- Subject is hospitalized and receiving standard of care antibiotic treatment for pneumonia
- 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
- Subject has a life expectancy of at least 3 weeks from the Screening visit
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- Subject is male (no contraception required) or female and meets 1 of the following criteria:
- 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)
- 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)
- 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
- 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
- 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
Who cannot join
- Subjects who meet any of the following criteria will be excluded from the study:
- 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.
- Subject has a history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)
- 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)
- Subject is receiving peritoneal dialysis
- Subject has severe renal impairment requiring hemodialysis (HD) or end-stage renal disease requiring HD
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- Subject is in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at Screening
- Subject is a female who has a positive pregnancy test at Screening or who is lactating
- Subject has received another investigational drug within 30 days prior to Screening
- Subject has previously participated in this clinical study and has received at least 1 dose of cefiderocol within 7 days
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Anschutz Medical Campus
Aurora, Colorado, 80045
North Western University
Chicago, Illinois, 60611
Hartford Hospital
Hartford, Connecticut, 06102
University of Florida
Jacksonville, Florida, 32209
U Miami Health Tower
Miami, Florida, 33136
Weill Cornell Medical College
New York, New York, 10065
Creighton University
Omaha, Nebraska, 68124
About this study
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
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.
- Conditions
- Bacterial Pneumonia
- Being tested
- Cefiderocol, Standard of Care Antibiotic
- Medical subject headings
- Pneumonia, Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefiderocolDrug
Also called S-649266)
Administered intravenously, at a dosage determined based on renal function.
Standard of Care AntibioticDrug
Standard of care antibiotic treatment for pneumonia
| Study group | Role | What they receive |
|---|---|---|
| Cefiderocol | Experimental | All participants were receiving standard of care (SOC) antibiotic treatment for pneumonia. Forty hours after the start of SOC treatment, participants will be administered 2 g doses of cefiderocol (or renally adjusted doses) infused intravenously over 3 hours, every 8 hours (or every 6 hours for participants with augmented renal function), for an expected minimum of 3 doses and up to a total of 6 doses in participants with normal renal function and participants with mild or moderate renal impairment, and for an expected minimum of 6 doses and up to a total of 9 doses in participants with severe renal impairment. Receives: Drug: Cefiderocol; Drug: Standard of Care Antibiotic |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start20 Feb 2019
- Primary completion8 Oct 2019
- Study completion15 Oct 2019
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bacterial PneumoniaStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03862040
- Sponsor's protocol ID
- 1713R2117
- Status last verified
- Oct 2020
- First submitted
- 28 Feb 2019
- Last updated
- 5 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03862040
- Acronym / sponsor ID
- 1713R2117
- Conditions
- Bacterial Pneumonia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- ShionogiIndustry (pharma, biotech, devices)
- Study start
- 20 Feb 2019 (actual)
- Primary completion
- 8 Oct 2019 (actual)
- Study completion
- 15 Oct 2019 (actual)
- First posted
- 5 Mar 2019 (actual)
- Results
- Posted 5 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cefiderocol | Experimental | Drug: Cefiderocol, Drug: Standard of Care AntibioticAll participants were receiving standard of care (SOC) antibiotic treatment for pneumonia. Forty hours after the start of SOC treatment, participants will be administered 2 g doses of cefiderocol (or renally adjusted doses) infused intravenously over 3 hours, every 8 hours (or every 6 hours for participants with augmented renal function), for an expected minimum of 3 doses and up to a total of 6 doses in participants with normal renal function and participants with mild or moderate renal impairment, and for an expected minimum of 6 doses and up to a total of 9 doses in participants with severe renal impairment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subject is 18 years or older at the time written informed consent is obtained
- Subject has provided written informed consent or informed consent has been provided by subject's legally authorized representative
- 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)
- Subject is hospitalized and receiving standard of care antibiotic treatment for pneumonia
- 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
Key exclusion criteria (11 listed)
- 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.
- Subject has a history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)
- 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)
- Subject is receiving peritoneal dialysis
- Subject has severe renal impairment requiring hemodialysis (HD) or end-stage renal disease requiring HD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CefiderocolAlso: S-649266)Administered intravenously, at a dosage determined based on renal function. | Drug | Cefiderocol |
| Standard of Care AntibioticStandard of care antibiotic treatment for pneumonia | Drug | Cefiderocol |
Primary outcome
Concentration of Cefiderocol in Epithelial Lining Fluid
Time frame: 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.
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.
Ratio of the Concentration of Cefiderocol in Epithelial Lining Fluid Relative to Plasma
Time frame: 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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shionogi Clinical Trials Administrator Clinical Support Help Line study director
Shionogi
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cefiderocol in people with Bacterial Pneumonia, run by Shionogi at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of Cefiderocol in Epithelial Lining Fluid (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2020.