ADME
Conditions
Brief summary
This is a single-dose, phase 1 open-label study to determine the mass balance recovery and metabolic profiling and identification for intravenous (IV) administered \[14C\]xeruborbactam. This study will investigate the primary route of excretion, profile \[14C\]xeruborbactam metabolites in plasma, urine and faeces, and assess the safety, tolerability, and pharmacokinetics (PK) of a single IV dose of \[14C\]xeruborbactam in healthy adult male participants.
Interventions
DRUG[14C]Xeruborbactam
Carbon Radiolabeled Xeruborbactam
Sponsors
Shionogi Inc.
Qpex Biopharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and cardiac (12-lead electrocardiogram (ECG)) monitoring. * Body weight within 55.0 and 100.0 kg (inclusive) and body mass index (BMI) within the range of 18.0 and 32.0 kg/m2 (inclusive). * Participants who have regular bowel movements (ie, average stool production of ≥ 1 and ≤ 3 stools per day) * Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Capable of giving signed informed consent
Exclusion criteria
* History or presence of significant cardiovascular, respiratory/pulmonary, hepatic, renal, hematological, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurological, or psychiatric disease capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the investigational intervention; or interfering with the interpretation of data * Surgery within the past 3 months prior to Day 1 determined by the investigator to be clinically relevant * History of GI surgery including but not limited to, gastric resection and/or intestinal resection that may result in a clinically significant abnormality in GI function (expect for an appendectomy for noncomplicated appendicitis unless it was performed in the previous 12 months) * Acute diarrhea, loose stools, or constipation within 14 days prior to the screening visit or upon admission to the clinical research unit (CRU) (Day -1). Diarrhea will be defined as the passage of liquid faeces and/or a stool frequency of ≥ 3 times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ratio of whole blood to plasma total radioactivity | Day 1 to Day 15 |
| Amount of total radioactivity excreted expressed as a percentage of the radioactive dose administered (Fe) | Day 1 to Day 15 |
| Cumulative amount of total radioactivity excreted expressed as percentage of the radioactive dose administered (CumFe) | Day 1 to Day 15 |
| Ratio of plasma xeruborbactam concentrations relative to total radioactivity based on Cmax | Day 1 to Day 15 |
| Ratio of plasma xeruborbactam concentrations relative to total radioactivity based on AUC0-last | Day 1 to Day 15 |
| Ratio of plasma xeruborbactam concentrations relative to total radioactivity based on AUC0-inf | Day 1 to Day 15 |
| Whole blood to plasma total radioactivity ratio based on Cmax | Day 1 to Day 15 |
| Whole blood to plasma total radioactivity ratio based on AUC0-last | Day 1 to Day 15 |
| Whole blood to plasma total radioactivity ratio based on AUC0-inf | Day 1 to Day 15 |
| Maximum plasma concentration (Cmax) for xeruborbactam | Day 1 to Day 15 |
| Time to maximum plasma concentration (Tmax) for xeruborbactam | Day 1 to Day 15 |
| Area under the concentration time curve from zero to infinity (AUC0-inf) for xeruborbactam | Day 1 to Day 15 |
| Maximum plasma and whole blood concentration (Cmax) of total radioactivity | Day 1 to Day 15 |
| Time to maximum plasma and whole blood concentration (Tmax) of total radioactivity | Day 1 to Day 15 |
| Area under the concentration time curve from zero to infinity (AUC0-inf) of total radioactivity in plasma and whole blood | Day 1 to Day 15 |
| Amount of total radioactivity excreted in urine (Aeu) | Day 1 to Day 15 |
| Amount of total radioactivity excreted in in urine expressed as a percentage of the radioactive dose administered (Feu) | Day 1 to Day 15 |
| Identification of the chemical structure of each metabolite accounting for 5% or more in plasma by area under the time concentration curve (AUC) | Day 1 to Day 15 |
| Identification of the chemical structure of each metabolite in urine and faeces that account for 5% or more of the administered radioactive dose | Day 1 to Day 15 |
| Total amount of radioactivity excreted (Ae) | Day 1 to Day 15 |
| Cumulative amount of total radioactivity excreted (CumAe) | Day 1 to Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of participants with Treatment-Emergent Adverse Events | Day 1 to Day 15 |
Countries
United Kingdom
Outcome results
None listed