Phase 1 Study of Oral QPX2015 in Healthy Adult Subjects

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single and Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics of Oral QPX2015 in Healthy Adult Subjects

QPX2015 (beta-lactam antibiotic) is being studied at higher than approved doses to combine with a new beta-lactamase inhibitor to treat bacterial infections, including those due to multi-drug resistant bacteria.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: QPX2015

Detailed Description

The worldwide spread of resistance to antibiotics among gram-negative bacteria, particularly members of the ESKAPE group of pathogens, has resulted in a crisis in the treatment of both hospital acquired and community acquired infections. In particular, the increase in Enterobacteriaceae expressing extended spectrum beta-lactamases (ESBLs) and carbapenemases that are resistant to all oral beta-lactams and fluoroquinolones in the community have resulted in many patients requiring admission just for IV antibiotics to treat their infections.

Qpex Biopharma is developing a fixed combination antibiotic of QPX2015 (beta-lactam antibiotic) plus a new beta-lactamase inhibitor.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia
      • CMAX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adult males and/or females of non-child bearing potential, 18 to 55 years of age (inclusive).
2. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
3. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms [ECGs], physical examination) as assessed by the PI.
4. Voluntarily consent to participate in the study.
5. If male, agree to be sexually abstinent or agree to use two approved methods of contraception when engaging in sexual activity from study check-in through completion of the end-of-study. Subjects must agree to use two approved methods of contraception for 30 days following the last administration of the study drug, and to not donate sperm during this same period of time. In the event that the sexual partner is surgically sterile, contraception is not necessary.
6. Females of non-childbearing potential with serum FSH levels ≥ 40 mIU/mL are either postmenopausal (defined as 12 months spontaneous amenorrhea) or have undergone sterilization procedures at least 6 months prior to dosing.

Exclusion Criteria:

1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
2. Positive urine drug/alcohol testing at screening or check-in (Day -1).
3. Positive testing for HIV, hepatitis B or C
4. History or presence of alcoholism or drug abuse within last 2 years
5. Use of more than 5 packs/week of tobacco/nicotine-containing product within last 6 months prior dosing.
6. Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to dosing.
7. Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within the 7 days prior to dosing.
8. Use of antacids, H2 receptor blockers or proton pump inhibitors 3 days prior to dosing.
9. History of any hypersensitivity or allergic reaction to cephalosporins, penicillins, carbapenems, or monobactams).
10. Participation in another investigational clinical trial within 30 days prior to Dosing or within 5 half-lives of the previous investigational drug, whichever is longer.
11. Females who are pregnant or lactating.
12. QTcF interval >450 msec, or history of prolonged QT syndrome at screening or check-in
13. Calculated creatinine clearance less than 80 mL/min (Cockcroft-Gault method) at screening or check-in.
14. Subjects who have any clinically significant abnormalities on laboratory values: White blood cell count < 3,000/mm3, hemoglobin < 11g/dL or Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3.
15. Liver function abnormalities defined by an elevation in bilirubin, AST or ALT 1.5 x ULN of the normal range for subjects based on age and sex.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matched placebo	Drug: Placebo oral capsule; Placebo comparator; Other Names: oral dose
Experimental: QPX2015; QPX2015, antibiotic	Drug: QPX2015; antibiotic; Other Names: oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment -Emergent Adverse events by subject and by cohort	Number of patients with Treatment-Emergent AEs by treatment arm, severity and relationship to treatment	Study Day 1 to 13
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 treatment arm	Study Day 1 to 13
Peak plasma Concentration measurements by subject and by cohort (Cmax)	Comparison will be performed between the cohorts for Cmax. Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.	Study Day 1 to 13
Time concentration data measurements by subject and by cohort (Tmax)	Comparison will be performed between the cohorts for Tmax.	Study Day 1 to 13
Area under the plasma concentration versus time curve (AUC) between cohorts	Comparison will be performed between the cohorts for AUC. Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.	Study Day 1 to 13
Urine PK amount excreted by subject and by cohort	Urine PK parameters such as amount excreted will be calculated from urinary excretion data	Study Day 1 to 13
Urine PK % dose excreted by subject and by cohort	Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data	Study Day 1 to 13

Collaborators and Investigators

• Sponsor: Qpex Biopharma, Inc.
• Collaborators: Biomedical Advanced Research and Development Authority

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2019
• Primary Completion (Actual): October 6, 2019
• Study Completion (Actual): October 6, 2019

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 3, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: beta-lactam antibiotic
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: Qpex-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No