Drug-Drug Interaction Study of IV QPX2014 Combined With QPX7728 in Healthy Adult Subjects
Study Details
Study Description
Brief Summary
QPX7728 is an ultra-broad-spectrum beta-lactamase inhibitor, with activity against numerous beta-lactamases, including class A extended spectrum betalactamases (ESBLs), class C cephalosporinases, and extended spectrum class D oxacillinases (OXA) that can hydrolyze cephalosporins and can be found in Enterobacteriaceae and Pseudomonas aeruginosa (P. aeruginosa). QPX7728 is also a potent inhibitor of carbapenemases from all molecular classes, such as class A Klebsiella pheumoniae carbapenemase (KPC), class B New-Dehli Metalo-beta-lactamase (NDM) and Verona integron-encoded metallo-betalactamase (VIM), and class D OXA-48 that are found in carbapenem resistant Enterobacteriaceae, and also class D carbapenemases such as OXA-23 that are found in carbapenem resistant Acinetobacter baumannii.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The Centers for Disease Control (CDC) has listed carbapenem-resistant Enterobacteriaceae and Acinetobacter as urgent threats and multidrug resistant Pseudomonas, and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae as serious threats [CDC, 2019]. Consistent with the global nature of these resistant bacteria, the World Health Organization (WHO) has designated carbapenem-resistant, ESBL-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii, and carbapenem-resistant Pseudomonas aeruginosa as pathogens for which new agents are critically needed [WHO, 2017]. Qpex Biopharma is developing a fixed combination antibiotic of QPX2014 plus an ultra-broad spectrum beta-lactamase inhibitor, QPX7728.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QPX7728 Drug: QPX7728 beta lactamase inhibitor Other names: IV |
Drug: QPX7728
beta lactamase inhibitor
Other Names:
Drug: QPX2014
antibiotic
Other Names:
|
| Experimental: QPX2014 Drug: QPX2014 antibiotic Other names: IV |
Drug: QPX2014
antibiotic
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area under the plasma concentration versus time curve (AUC) between dosing groups [up to 9 days]
Comparison will be performed between the dosing groups for AUC. Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.
- Peak plasma Concentration measurements by subject and by dosing group [up to 9 days]
Comparison will be performed between the dosing groups. 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 dosing group [up to 9 days]
Urine PK parameters such as amount excreted will be calculated from urinary excretion data
- Urine PK % dose excreted by subject and by dosing group [up to 9 days]
Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data
- Incidence of Treatment -Emergent Adverse events (AEs) by subject and by dosing group [up to 9 days]
Number of patients with Treatment-Emergent AEs by treatment arm, severity and relationship to treatment
- Number of patients with changes from baseline in safety parameters [up to 9 days]
Number of patients with changes in safety parameters before and after dosing by subject and treatment arm
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy adult males and/or females of non-childbearing potential, 18 to 55 years of age (inclusive) at the time of screening.
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Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) at the time of screening.
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Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms [ECGs], physical examination) as assessed by the PI.
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Voluntarily consent to participate in the study.
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Male volunteers must agree to be sexually abstinent or agree to use a condom when engaging in any sexual activity from study check-in (on Day -1) through 30 days following the last administration of the study drug, and to not donate sperm during this same period of time. If engaging in sexual activity with a female partner of childbearing potential, an additional method of birth control must be used.
Approved additional methods of birth control include:
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Intrauterine device (IUD) in place for at least 3 months prior to Day 1 through 30 days following the final dosing of the study drug.
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Barrier method (diaphragm) for at least 14 days prior to Day 1 through 30 days following dosing of the study drug.
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Stable hormonal contraceptive for at least 3 months prior to Day 1 through 30 days following dosing of the study drug.
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Surgical sterilization (vasectomy) at least 6 months prior to Day 1.
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Females of non-childbearing potential must be either postmenopausal (defined as 12 months spontaneous amenorrhea) with a serum FSH ≥ 40 mIU/mL or have undergone one of the following sterilization procedures at least 6 months prior to Day 1 (and is documented):
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Bilateral tubal ligation;
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Hysterectomy;
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Hysterectomy with unilateral or bilateral oophorectomy;
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Bilateral oophorectomy.
Exclusion Criteria:
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History or presence of significant (based on the PI assessment) cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
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Positive pregnancy test at screening or check-in (Day 1) for women.
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Positive urine drug/alcohol testing at screening or check-in (Day -1). A repeat test may be performed at the Investigator's discretion in circumstances where a positive result is suspected to be caused by consumption of non-illicit substances.
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Positive pregnancy test at screening or check-in (Day 1) for women.
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Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
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History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
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Use of more than an average of 5 packs/week of tobacco/nicotine-containing product within 6 months prior to Day 1. Subjects must agree to refrain from smoking within 48 hours prior to confinement and for the duration of the study.
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Excessive intake of alcohol, defined as an average daily intake of greater than 2 standard drinks for women and 4 standard drinks for men, (1 bottle of beer (375mL) is equivalent to approximately 1.4 standard drinks, 1 glass of spirits (30mL) is equivalent to approximately 1 standard drink and 1 glass (150mL) of wine is equivalent to approximately 1.5 standard drinks).
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Use of any prescription medication (with the exception of hormone replacement therapy for females) within 14 days prior to Day 1.
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Use of any over-the-counter (OTC) medication, including herbal products, probiotics and vitamins, within the 7 days prior to Day 1. Up to 2 grams per day of acetaminophen is allowed for acute events at the discretion of the PI.
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Use of antacids, H2 receptor blockers or proton pump inhibitors within 3 days prior to Day 1.
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Documented hypersensitivity reaction or anaphylaxis to any medication, including beta-lactam antibiotics.
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Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day
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Plasma donation within 7 days prior to Day 1.
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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.
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Surgery within the past three months prior to Day 1 determined by the PI to be clinically relevant. Minor surgeries allowed include laser vision, minor dental and tooth extraction, mole or basal cell skin removal, endoscopy, and biopsy.
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Any significant acute illness (based on the PI assessment) within 30 days prior to Day
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QTcF interval >450 msec for males and >470 msec for females or history of prolonged QT syndrome at screening or check-in (Day -1).
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Calculated creatinine clearance less than 80 mL/min (Cockcroft- Gault method) at screening or check-in (Day -1).
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Subjects who have any clinically significant laboratory value abnormalities at screening or check-in (Day -1), in particular:
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White blood cell count < 3,000/mm3, hemoglobin < 11g/dL.
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Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3.
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Liver function abnormalities at screening or check-in (Day -1) (defined by an elevation in bilirubin, AST or ALT > ULN for subjects based on age and sex).
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Any other condition or prior therapy, which, in the opinion of the PI, would make the subject unsuitable for this study.
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Participation in a previous QPX7728 or QPX7831 study.
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Participation of research site staff, their close family, or significant others.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Altasciences | Cypress | California | United States | 90630 |
Sponsors and Collaborators
- Qpex Biopharma, Inc.
- Biomedical Advanced Research and Development Authority
Investigators
- Study Director: Jeff S Loutit, MBChB, Qpex Biopharma, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Qpex-201