P1 Single and Multiple Ascending Dose (SAD/MAD) Study of IV QPX7728 Alone and Combined With QPX2014 in NHV

NCT04380207 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Qpex-200
• Study Type: interventional
• Target: 82
• Locations: 2 countries
• Sites: 2

Brief Summary

QPX7728 is an ultra-broad-spectrum beta-lactamase inhibitor, with activity against numerous beta-lactamases, including class A extended spectrum beta-lactamases (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-beta-lactamase (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.

Conditions

Bacterial Infections

Keywords

beta-lactam antibiotic

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment -Emergent Adverse events (AEs) by subject and by cohort (single, multiple and combination dose)

  Number of patients with Treatment-Emergent AEs by treatment arm, severity and relationship to treatment

  up to 21 days

• Number of patients with changes from baseline in safety parameters (single, multiple and combination dose)

  Number of patients with changes in safety parameters before and after dosing by subject and treatment arm

  up to 21 days

• Peak plasma Concentration measurements by subject and by cohort (Cmax) (single, multiple and combination dose)

  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.

  up to 21 days

• Area under the plasma concentration versus time curve (AUC) between cohorts (single, multiple and combination dose)

  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.

  up to 21 days

• Urine Pharmacokinetic (PK) amount excreted by subject and by cohort (single, multiple and combination dose)

  Urine PK parameters such as amount excreted will be calculated from urinary excretion data

  up to 21 days

• Urine PK % dose excreted by subject and by cohort (single, multiple and combination dose)

  Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data

  up to 21 days

Study Arms (3)

QPX7728

EXPERIMENTAL

antibiotic

Drug: QPX7728

Placebo

PLACEBO COMPARATOR

Matched placebo

Drug: Placebo

QPX2014

EXPERIMENTAL

antibiotic

Drug: QPX2014

Interventions

QPX7728 DRUG

antibiotic

Also known as: IV

QPX7728

Placebo DRUG

Placebo comparator

Also known as: IV saline

Placebo

QPX2014 DRUG

antibiotic

Also known as: IV

QPX2014

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult males and/or females of non-child bearing potential, 18 to 55 years of age (inclusive).
• Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
• Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms \[ECGs\], physical examination) as assessed by the PI.
• Voluntarily consent to participate in the study.
• 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.
• Females of non-childbearing potential with serum follicle stimulating hormone (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.

You may not qualify if:

• History or presence of significant (based on the PI assessment) cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• 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.
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
• History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
• 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 for the duration of the study.
• 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).
• Use of any prescription medication (with the exception of hormone replacement therapy for females) within 14 days prior to Day 1.
• 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 paracetamol is allowed for acute events at the discretion of the PI.
• Use of antacids, H2 receptor blockers or proton pump inhibitors 3 days prior to Day 1.
• Documented hypersensitivity reaction or anaphylaxis to any medication, including beta-lactam antibiotics.
• Blood donation or significant blood loss (i.e., \> 500 mL) within 56 days prior to Day 1.
• Plasma donation within 7 days prior to Day 1.
• 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.
• Surgery within the past three months prior to Day 1 determined by the PI to be clinically relevant.
• Any significant (based on the PI assessment) acute illness within 30 days prior to Day 1.

Sponsors & Collaborators

• Qpex Biopharma, Inc.: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (2)

Altasciences

Cypress, California, 90630, United States

Location

CMAX

Adelaide, South Australia, Australia

Location

MeSH Terms

Conditions

Bacterial Infections

Interventions

QPX7728; Sodium Chloride

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jeffery S Loutit, MBChB

  Qpex Biopharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blind, placebo controlled ascending single- and multiple-dose
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: double-blind, placebo controlled ascending single, multiple and combination dose

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: May 8, 2020
• Study Start: November 24, 2020
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: October 10, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); AU (1)