Clinical trial NCT05395104: A Study to Assess the Effect of Cefiderocol on the Pharmacokinetics (PK) of Midazolam in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


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).

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Time to Maximum Plasma Concentration (Tmax) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Area Under the Concentration-time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Terminal Elimination Half-life (t1/2,z) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Terminal Elimination Rate Constant (λz) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Mean Residence Time (MRT) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Apparent Total Clearance (CL/F) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
measure: Apparent Volume of Distribution (Vz/F) of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15
Secondary outcomes:
measure: Cmax of Cefiderocol
timeFrame: Day 15
measure: Tmax of Cefiderocol
timeFrame: Day 15
measure: Area Under the Plasma Concentration-time Curve Over the Dosing Interval τ (8 Hours) (AUC0-τ) of Cefiderocol
timeFrame: Day 15
measure: CL of Cefiderocol
timeFrame: Day 15
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
References: