A Study to Assess the Effect of Cefiderocol on the Pharmacokinetics (PK) of Midazolam in Healthy Participants

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Open-label, 1-sequence Crossover, Drug-drug Interaction Study to Assess the Effect of Repeated Doses of Cefiderocol on the Pharmacokinetics of Midazolam in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05395104
• Other study ID #: 2136R2118
• Status: Completed
• Phase: Phase 1
• Start date: May 24, 2022
• Est. completion date: July 13, 2022

Study information

• Verified date: March 2023
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effect of repeated doses of cefiderocol on the PK of midazolam.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 13, 2022
• Est. primary completion date: July 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Midazolam
Syrup for oral administration
• Cefiderocol
Liquid for intravenous infusion

Locations

Country	Name	City	State
United States	Worldwide Clinical Trials	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Primary	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
Primary	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
Primary	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/?z], where Clast is the last measured concentration and ?z 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
Primary	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)/?z 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
Primary	Terminal Elimination Rate Constant (?z) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. ?z is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase on Days -1 and 15 and is reported as 1/hours (1/h). Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Primary	Mean Residence Time (MRT) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. MRT was calculated as: AUMC0-inf/AUC0-inf, and AUMC0-inf is the area under the first moment curve extrapolated to infinity 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
Primary	Apparent Total Clearance (CL/F) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. CL/F was calculated as: Dose/AUC0-inf on Days -1 and 15 and is reported as liters/hr. Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Primary	Apparent Volume of Distribution (Vz/F) of Midazolam	This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Vz/F was calculated as: Dose/AUC0-inf/?z on Days -1 and 15 and is reported as liters. Day -1 is defined as Baseline.	0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Secondary	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
Secondary	Tmax of Cefiderocol	This outcome measure presents the pharmacokinetics of cefiderocol when coadministered with midazolam.	Day 15
Secondary	Area Under the Plasma Concentration-time Curve Over the Dosing Interval t (8 Hours) (AUC0-t) of Cefiderocol	This outcome measure presents the pharmacokinetics of cefiderocol when coadministered with midazolam. AUC0-t was calculated by the linear up/log down trapezoidal method and is reported as micrograms times hours/milliliter (µg*hrs/mL).	Day 15
Secondary	CL of Cefiderocol	This outcome measure presents the PK of cefiderocol when coadministered with midazolam. CL was calculated as: Dose/AUC0-t on Day 15.	Day 15