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P1, DDI & MAD PK and Safety Study of Xeruborbactam Oral Prodrug in Combo With Ceftibuten in Healthy Participants

Primary Purpose

Bacterial Infections

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Xeruborbactam Oral Prodrug
Ceftibuten
Xeruborbactam Oral Prodrug Placebo
Ceftibuten Placebo
Sponsored by
Qpex Biopharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bacterial Infections focused on measuring beta-lactamase inhibitor

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Participants will be eligible to be included in the study only if all of the following criteria apply: Age 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 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 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 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. 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: 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 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 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 Surgical sterilization (vasectomy) of partner at least 6 months prior to Day 1 Informed Consent 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 History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease. 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. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). Females who are pregnant or lactating. Surgery within the past 3 months prior to Day 1 determined by the investigator, sub-investigator, or medical officer to be clinically relevant. Any acute illness within 30 days prior to Day 1. 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 Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day 1. 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. 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 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 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). Calculated creatinine clearance < 80 mL/min (Cockcroft-Gault method) at screening or check-in (Day -1). Any clinically significant abnormalities in laboratory values at screening or check-in (Day -1), in particular: White blood cell count < 3,000/mm3, hemoglobin < 11g/dL Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3 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 Exclusion Criteria Blood donation or significant blood loss (ie, > 500 mL) within 56 days prior to Day 1. Plasma donation within 7 days prior to Day 1. Positive urine drug/alcohol testing at screening or check-in (Day -1). History or presence of alcoholism or drug abuse within the 2 years prior to Day 1. Use of more than 5 packs/week of cigarettes (or equivalent amount of nicotine-containing product) within 6 months prior to Day 1. Use of all nicotine containing products 48 hours prior to admission to clinical research unit. Participants must agree to refrain from smoking for the duration of the study. Excessive intake of alcohol, defined as an average daily intake of > 2 standard drinks for women and > 4 standard drinks for men, (standard drink is the equivalent to 4 oz of wine (approximately 12% abv), 12 oz of regular beer (approximately 5% abv), or 1.5 oz of spirits (80 proof).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Single Dose Drug-Drug-Interaction Crossover & Multiple Dose Cohorts

    Placebo Comparator to maintain the blind

    Arm Description

    During the DDI crossover part of the study, 24 subjects will be enrolled into 3 cohorts of 8 subjects each, Cohorts 1, 2, & 3 respectively. All subjects in Cohorts 1, 2, and 3 will receive a single dose of xeruborbactam oral prodrug on Day 1. On Day 6, they will receive a single dose of ceftibuten. On Day 9 they will receive a single combined dose of xeruborbactam oral prodrug and ceftibuten. During the MAD part of the study, 48 subjects will be enrolled into 3 cohorts of 16 subjects each, Cohorts 4, 5, & 6 respectively. All subjects in Cohorts 4, 5, and 6 will receive either a combined dose of xeruborbactam oral prodrug and ceftibuten, active ceftibuten, or active xeruborbactam oral prodrug. Cohort 4 & 5 will be dosed BID on Days 1 through 9, with last and final dose on the morning of Day 10. Cohort 6 will be dosed BID on Day 1, and then QD on Days 2 through 10 with last dose on the morning of Day 10. All subjects will be followed for safety and PK data collection.

    During the multiple-dose portion of the study, Xeruborbactam Oral Prodrug Placebo and Ceftibuten placebo will be used to maintain the blind. In Cohorts 4, 5, and 6, ten (10) subjects in each cohort will receive a combined dose of xeruborbactam oral prodrug and ceftibuten. Three (3) subjects in each cohort will receive active ceftibuten capsules with xeruborbactam oral prodrug placebo capsules. Three (3) subjects in each cohort will receive active xeruborbactam oral prodrug capsules with ceftibuten placebo capsules.

    Outcomes

    Primary Outcome Measures

    Incidence of Treatment -Emergent Adverse events by subject and by cohort (single dose, multiple doses)
    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
    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)
    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)
    Comparison will be performed between the cohorts for time concentration data measurements (Tmax)
    Area under the plasma concentration versus time curve (AUC) between cohorts
    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
    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
    Urine Pharmacokinetic (PK) parameters such as amount of % dose excreted will be calculated from urinary excretion data

    Secondary Outcome Measures

    Full Information

    First Posted
    October 6, 2023
    Last Updated
    October 18, 2023
    Sponsor
    Qpex Biopharma, Inc.
    Collaborators
    Shionogi Inc., Biomedical Advanced Research and Development Authority
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06079775
    Brief Title
    P1, DDI & MAD PK and Safety Study of Xeruborbactam Oral Prodrug in Combo With Ceftibuten in Healthy Participants
    Official Title
    A Phase 1, Randomized, Double-blind, Controlled, Drug-drug Interaction and Multiple-dose Pharmacokinetics and Safety Study of Xeruborbactam Oral Prodrug (QPX7831) in Combination With Ceftibuten in Healthy Adult Participants
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 11, 2024 (Anticipated)
    Primary Completion Date
    September 30, 2024 (Anticipated)
    Study Completion Date
    December 30, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Qpex Biopharma, Inc.
    Collaborators
    Shionogi Inc., Biomedical Advanced Research and Development Authority

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    A Phase 1, Randomized, Double-blind, Controlled, Drug-drug Interaction and 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: 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. To assess whether there is any PK interaction between xeruborbactam oral prodrug and ceftibuten when administered in combination to healthy adult participants.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Bacterial Infections
    Keywords
    beta-lactamase inhibitor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Model Description
    Randomized, Double-Blind, Controlled, Crossover, ascending single-and multipledose design
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    matched oral placebo capsules
    Allocation
    Randomized
    Enrollment
    72 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Single Dose Drug-Drug-Interaction Crossover & Multiple Dose Cohorts
    Arm Type
    Experimental
    Arm Description
    During the DDI crossover part of the study, 24 subjects will be enrolled into 3 cohorts of 8 subjects each, Cohorts 1, 2, & 3 respectively. All subjects in Cohorts 1, 2, and 3 will receive a single dose of xeruborbactam oral prodrug on Day 1. On Day 6, they will receive a single dose of ceftibuten. On Day 9 they will receive a single combined dose of xeruborbactam oral prodrug and ceftibuten. During the MAD part of the study, 48 subjects will be enrolled into 3 cohorts of 16 subjects each, Cohorts 4, 5, & 6 respectively. All subjects in Cohorts 4, 5, and 6 will receive either a combined dose of xeruborbactam oral prodrug and ceftibuten, active ceftibuten, or active xeruborbactam oral prodrug. Cohort 4 & 5 will be dosed BID on Days 1 through 9, with last and final dose on the morning of Day 10. Cohort 6 will be dosed BID on Day 1, and then QD on Days 2 through 10 with last dose on the morning of Day 10. All subjects will be followed for safety and PK data collection.
    Arm Title
    Placebo Comparator to maintain the blind
    Arm Type
    Placebo Comparator
    Arm Description
    During the multiple-dose portion of the study, Xeruborbactam Oral Prodrug Placebo and Ceftibuten placebo will be used to maintain the blind. In Cohorts 4, 5, and 6, ten (10) subjects in each cohort will receive a combined dose of xeruborbactam oral prodrug and ceftibuten. Three (3) subjects in each cohort will receive active ceftibuten capsules with xeruborbactam oral prodrug placebo capsules. Three (3) subjects in each cohort will receive active xeruborbactam oral prodrug capsules with ceftibuten placebo capsules.
    Intervention Type
    Drug
    Intervention Name(s)
    Xeruborbactam Oral Prodrug
    Other Intervention Name(s)
    QPX7831
    Intervention Description
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Ceftibuten
    Intervention Description
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Xeruborbactam Oral Prodrug Placebo
    Other Intervention Name(s)
    QPX7831 Placebo
    Intervention Description
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Ceftibuten Placebo
    Intervention Description
    Placebo Comparator
    Primary Outcome Measure Information:
    Title
    Incidence of Treatment -Emergent Adverse events by subject and by cohort (single dose, multiple doses)
    Description
    Number of patients with Treatment-Emergent Adverse Events by subject, by cohort, severity and relationship to treatment
    Time Frame
    16 days
    Title
    Number of patients with changes from baseline in safety parameters
    Description
    Number of patients with changes in safety parameters before and after dosing by subject and cohort
    Time Frame
    16 days
    Title
    Peak plasma Concentration measurements by subject and by cohort (Cmax)
    Description
    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 Frame
    16 days
    Title
    Time concentration data measurements by subject and by cohort (Tmax)
    Description
    Comparison will be performed between the cohorts for time concentration data measurements (Tmax)
    Time Frame
    16 days
    Title
    Area under the plasma concentration versus time curve (AUC) between cohorts
    Description
    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.
    Time Frame
    16 days
    Title
    Urine Pharmacokinetic (PK) amount excreted by subject and by cohort
    Description
    Urine Pharmacokinetic (PK) parameters such as amount excreted will be calculated from urinary excretion data
    Time Frame
    16 days
    Title
    Urine Pharmacokinetic (PK) % dose excreted by subject and by cohort
    Description
    Urine Pharmacokinetic (PK) parameters such as amount of % dose excreted will be calculated from urinary excretion data
    Time Frame
    16 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Participants will be eligible to be included in the study only if all of the following criteria apply: Age 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 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 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 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. 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: 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 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 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 Surgical sterilization (vasectomy) of partner at least 6 months prior to Day 1 Informed Consent 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 History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease. 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. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). Females who are pregnant or lactating. Surgery within the past 3 months prior to Day 1 determined by the investigator, sub-investigator, or medical officer to be clinically relevant. Any acute illness within 30 days prior to Day 1. 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 Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day 1. 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. 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 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 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). Calculated creatinine clearance < 80 mL/min (Cockcroft-Gault method) at screening or check-in (Day -1). Any clinically significant abnormalities in laboratory values at screening or check-in (Day -1), in particular: White blood cell count < 3,000/mm3, hemoglobin < 11g/dL Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3 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 Exclusion Criteria Blood donation or significant blood loss (ie, > 500 mL) within 56 days prior to Day 1. Plasma donation within 7 days prior to Day 1. Positive urine drug/alcohol testing at screening or check-in (Day -1). History or presence of alcoholism or drug abuse within the 2 years prior to Day 1. Use of more than 5 packs/week of cigarettes (or equivalent amount of nicotine-containing product) within 6 months prior to Day 1. Use of all nicotine containing products 48 hours prior to admission to clinical research unit. Participants must agree to refrain from smoking for the duration of the study. Excessive intake of alcohol, defined as an average daily intake of > 2 standard drinks for women and > 4 standard drinks for men, (standard drink is the equivalent to 4 oz of wine (approximately 12% abv), 12 oz of regular beer (approximately 5% abv), or 1.5 oz of spirits (80 proof).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Shawnee Gehrke, MPH
    Phone
    (760) 419-7428
    Email
    sgehrke@qpexbio.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jeff Loutit, MBChB
    Organizational Affiliation
    Qpex Biopharma, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    P1, DDI & MAD PK and Safety Study of Xeruborbactam Oral Prodrug in Combo With Ceftibuten in Healthy Participants

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