Bacterial Infections
Conditions
Keywords
beta-lactamase inhibitor
Brief summary
A Phase 1, Open-Label, Drug-drug Interaction, and Randomized, Double-blind, Controlled, Multiple-dose Pharmacokinetics and Safety Study of Xeruborbactam Oral Prodrug (QPX7831) in Combination with Ceftibuten in Healthy Adult Participants
Detailed description
Qpex Biopharma, Inc. is developing an oral dosage form that delivers Xeruborbactam, a new boron-based beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases, for oral treatment in combination with a beta-lactam antibiotic. Ceftibuten is a cephalosporin antibiotic approved in the US for acute exacerbations of chronic bronchitis, acute bacterial otitis media and pharyngitis/tonsillitis. This Phase 1 study will assess if a PK interaction exists between xeruborbactam oral prodrug and ceftibuten when given in combination at doses of each drug that have previously been shown to be safe. The study will also assess the safety of the combination with dosing over 10 days. Study Objectives: 1. To assess the safety, tolerability, and PK of single and multiple doses of xeruborbactam oral prodrug and ceftibuten both in combination and alone, in healthy adult participants. 2. To assess whether there is any PK interaction between xeruborbactam oral prodrug and ceftibuten when administered in combination to healthy adult participants.
Interventions
Experimental
DRUGCeftibuten
Experimental
DRUGXeruborbactam Oral Prodrug Placebo
Placebo Comparator
DRUGCeftibuten Placebo
Placebo Comparator
Sponsors
Shionogi Inc.
Biomedical Advanced Research and Development Authority
Qpex Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
matched oral placebo capsules
Intervention model description
Randomized, Double-Blind, Controlled, Crossover, ascending single-and multipledose design
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Participants will be eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be a healthy adult male or female, 18 to 55 years of age (inclusive) at the time of screening. Type of Participant and Disease Characteristics 2. Participants who are overtly medically healthy with clinically insignificant screening results (eg, laboratory profiles, medical histories, ECGs, physical examination) as assessed by the investigator, sub-investigator, or medical officer. Weight 3. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive). Note: BMI = kg/m2 where kg is a weight in kilograms and m2 is a height in meters squared. Sex and Contraceptive/Barrier Requirements 4. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: If male, agree to be sexually abstinent or agree to use 2 approved methods of contraception (refer to inclusion criterion #5) when engaging in sexual activity from study check-in through 30 days following the last administration of the study drug, and to not donate sperm during this same period of time. If the sexual partner is surgically sterile, contraception is not necessary. 5. Female participants: Females of childbearing potential must either be sexually abstinent for 14 days prior to Day 1 and agree to remain so through 30 days following the last administration of the study drug, OR have been using (or agree to use) 2 of the following acceptable methods of birth control for the times specified: 1. Intra-uterine device (IUD) in place for at least 3 months prior to Day 1 through 30 days following the final dosing of the study drug 2. Barrier method (condom or diaphragm) for at least 14 days prior to Day 1 through 30 days following the final dosing of the study drug 3. Stable hormonal contraceptive for at least 3 months prior to Day 1 and barrier method (condom or diaphragm) for at least 14 days prior to Day 1 through 30 days following final dosing of the study drug 4. Surgical sterilization (vasectomy) of partner at least 6 months prior to Day 1 Informed Consent 6. Capable of giving signed informed consent as described in Appendix 1 Informed Consent Form (Section 10.1.3) that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
Participants will be excluded from the study if any of the following criteria apply: Medical Conditions 1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease. 2. Documented hypersensitivity reaction or anaphylaxis to any medication, including ceftibuten or other beta-lactam antibiotics (e.g. cephalosporins, penicillins, carbapenems or monobactams) or any excipients used in this formulation. 3. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). 4. Females who are pregnant or lactating. 5. Surgery within the past 3 months prior to Day 1 determined by the investigator, sub-investigator, or medical officer to be clinically relevant. 6. Any acute illness within 30 days prior to Day 1. 7. Any other condition or prior therapy, which, in the opinion of the investigator, sub-investigator, or medical officer would make the participant unsuitable for this study. Prior/Concomitant Therapy 8. Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day 1. 9. Use of any over-the-counter medication, including herbal products, probiotics and vitamins, within the 7 days prior to Day 1. Up to 2 grams per day of paracetamol is allowed for acute events at the discretion of the investigator, sub-investigator, or medical officer. 10. Use of antacids, H2 receptor blockers or proton pump inhibitors 7 days prior to Day 1. This includes calcium carbonate. Prior/Concurrent Clinical Study Experience 11. Participation in another investigational clinical trial within 30 days prior to Day 1 or within 5 half-lives of the previous investigational drug, whichever is longer. Diagnostic Assessments 12. QTc corrected according to Fridericia's formula (QTcF) interval \> 450 msec for males and \> 470 for females or history of prolonged QT syndrome at screening or check-in (Day -1). 13. Calculated creatinine clearance \< 80 mL/min (Cockcroft-Gault method) at screening or check-in (Day -1). 14. Any clinically significant abnormalities in laboratory values at screening or check-in (Day -1), in particular: 1. White blood cell count \< 3,000/mm3, hemoglobin \< 11g/dL 2. Absolute neutrophil count \< 1,200/mm3 or platelet count \< 120,000/mm3 3. Liver function abnormalities at screening or check-in (Day -1) (defined by an elevation in bilirubin, AST, or ALT \> ULN for participants based on age and sex) Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment -Emergent Adverse events by subject and by cohort (single dose, multiple doses) | 16 days | Number of patients with Treatment-Emergent Adverse Events by subject, by cohort, severity and relationship to treatment |
| Number of patients with changes from baseline in safety parameters | 16 days | Number of patients with changes in safety parameters before and after dosing by subject and cohort |
| Peak plasma Concentration measurements by subject and by cohort (Cmax) | 16 days | Comparison will be performed between the cohorts for concentration measurements (Cmax). Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed. |
| Time concentration data measurements by subject and by cohort (Tmax) | 16 days | Comparison will be performed between the cohorts for time concentration data measurements (Tmax) |
| Area under the plasma concentration versus time curve (AUC) between cohorts | 16 days | Comparison will be performed between the cohorts for area under the plasma concentration versus time curve (AUC). Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed. |
| Urine Pharmacokinetic (PK) amount excreted by subject and by cohort | 16 days | Urine Pharmacokinetic (PK) parameters such as amount excreted will be calculated from urinary excretion data |
| Urine Pharmacokinetic (PK) % dose excreted by subject and by cohort | 16 days | Urine Pharmacokinetic (PK) parameters such as amount of % dose excreted will be calculated from urinary excretion data |
Countries
Australia
Outcome results
None listed