A Study to Assess the Effect of Cefiderocol on the Pharma... | NCT05395104

NCT05395104

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Cefiderocol Plus Midazolam	Experimental	A total of 2 doses of midazolam and 45 doses of cefiderocol was administered to each participant per specified dosing schedule.	Drug: Midazolam Drug: Cefiderocol

Name	Type	Description	Arm Group Labels	Other Names
Midazolam	Drug	Syrup for oral administration	Cefiderocol Plus Midazolam

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Cmax is reported as nanograms/milliliter (ng/mL). Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Time to Maximum Plasma Concentration (Tmax) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Tmax is reported in hours (hrs). Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. AUC0-last was calculated using the linear up/log down trapezoidal method and is reported as nanograms times hours/milliliter (ng*hrs/mL). Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Area Under the Concentration-time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. AUC0-inf was calculated as: AUC0-last + [Clast/λz], where Clast is the last measured concentration and λz is the plasma terminal elimination rate constant on Days -1 and 15. Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Terminal Elimination Half-life (t1/2,z) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. t1/2,z was calculated as: (ln2)/λz on Days -1 and 15. Day -1 is defined as Baseline.

Secondary Outcomes

Measure	Description	Time Frame
Cmax of Cefiderocol	This outcome measure presents the pharmacokinetics of cefiderocol when coadministered with midazolam. Cmax is reported as micrograms/milliliter (μg/mL).	Day 15
Tmax of Cefiderocol

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead electrocardiography at the Screening Visit and upon admission to the clinical research unit (CRU).
Body weight ≥ 50 kilograms (kg) and body mass index within the range of ≥ 18.5 to ≤ 32.0 kg/meter squared at the Screening Visit.

Exclusion Criteria:

History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
Systolic blood pressure outside the range of 90 to 145 millimeters of mercury (mmHg), diastolic blood pressure outside the range of 50 to 95 mmHg, pulse rate outside the range of 40 to 100 beats per minute, or blood pressure or pulse values considered clinically significant by the investigator at the Screening Visit or upon admission to the CRU. Abnormal values may be retested once.
Lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
Past use of over-the-counter or prescription medication, including herbal medications, traditional Chinese medicines, vitamins, minerals, dietary supplements, and vaccines within 14 days (or 5 terminal half-lives, whichever is longer) prior to admission to the CRU (which will occur on Day -2) or intended use of any of the above throughout the study enrollment.
Significant blood loss of ≥ 500 milliliters or blood or plasma donation within 56 days prior to the Screening Visit until completion of the study, or from the Screening Period until admission to the CRU through completion of the study.
History of coronavirus disease 2019 (COVID-19) infection within 14 days prior to the Screening Visit or admission, or close contact with a COVID-19 patient in the days prior to the Screening Visit or admission as reported by the participant and the participant's medical history.
History of drug or alcohol abuse/addiction.
Regularly consumes excessive amounts of caffeine, defined as > 6 servings of coffee, tea, caffeinated soft drinks, or other caffeinated beverages per day (1 serving is approximately equivalent to 120 milligrams of caffeine).
Used tobacco- or nicotine-containing products (including cigarette, pipe, cigar, chewing tobacco, nicotine patch, or nicotine gum) within 6 months prior to admission to the CRU or refuses to refrain from using tobacco- or nicotine-containing products throughout the study (including Follow-up Period).

Facility	Status	City	State	ZIP	Country	Contacts
Worldwide Clinical Trials		San Antonio	Texas	78217	United States

ID	Title	Description
FG000	Cefiderocol Plus Midazolam	A total of 2 doses (5 milligrams [mg] each) of midazolam and 45 doses (2 grams [g] each) of cefiderocol were administered to each participant per specified dosing schedule.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Cefiderocol Plus Midazolam	A total of 2 doses (5 mg each) of midazolam and 45 doses (2 g each) of cefiderocol were administered to each participant per specified dosing schedule.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Cmax is reported as nanograms/milliliter (ng/mL). Day -1 is defined as Baseline.

Pharmacokinetics Parameter Population: All participants with at least 1 pharmacokinetics parameter estimated appropriately. Participants in the "Midazolam + Cefiderocol" population with available data were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

ID	Title	Description
OG000	Cefiderocol Plus Midazolam	A total of 2 doses (5 mg each) of midazolam and 45 doses (2 g each) of cefiderocol were administered to each participant per specified dosing schedule.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cefiderocol Plus Midazolam	A total of 2 doses of midazolam and 45 doses of cefiderocol were administered to each participant per specified dosing schedule.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 8, 2022	Mar 9, 2023	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Sep 29, 2022	Mar 9, 2023	SAP_001.pdf

ID	Term
D001569	Benzodiazepines
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring