SAD/MAD Safety and PK Study of QPX9003 (Novel Polymyxin) in Normal Healthy Volunteers

NCT04808414 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Qpex-300
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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 hospital acquired infections. In particular, the presence of multi-drug resistant Acinetobacter baumannii and Pseudomonas aeruginosa in hospitals around the world poses a considerable threat. .

Conditions

Bacterial Infections

Keywords

polymyxin

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 13 days

• Peak plasma Concentration measurements by subject and by cohort (Cmax) (single 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 13 days

• Area under the plasma concentration versus time curve (AUC) between cohorts (single and multiple 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 13 days

• Urine amount excreted by subject and by cohort (single and combination dose)-PK

  Urine amount excreted will be calculated from urinary excretion data

  up to 13 days

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

  Urine amount of % dose excreted will be calculated from urinary excretion data

  up to 13 days

Study Arms (2)

QPX9003 for IV infusion

EXPERIMENTAL

IV novel polymyxin antibiotic Single and Multiple IV doses x 7 days via IV infusion q6hrs

Drug: QPX9003 for IV Infusion

Placebo for Infusion

PLACEBO COMPARATOR

IV saline Single and Multiple IV doses x 7 days via IV infusion q6hrs

Drug: Placebo for IV infusion

Interventions

QPX9003 for IV Infusion DRUG

antibiotic

Also known as: novel IV polymyxin antibiotic

QPX9003 for IV infusion

Placebo for IV infusion DRUG

Placebo comparator

Also known as: IV saline

Placebo for Infusion

Eligibility Criteria

• Age: 18 Years - 60 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 60 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 a condom when engaging in any sexual activity from Day -1 check-in to the clinic 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:
• 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 (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 through 30 days following the final dosing of the study drug.
• Surgical sterilization (vasectomy) at least 6 months prior to Day 1.
• Females of non-childbearing potential must meet at least one of the following criteria:
• postmenopausal (defined as 12 months spontaneous amenorrhea) with a serum FSH leve l≥ 40 mIU/mL.
• have undergone one of the following sterilization procedures documented at least 6 months prior to Day 1:
• Bilateral tubal ligation
• Hysterectomy

You may not qualify if:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• Positive urine drug screen or alcohol breath test at screening or check-in (Day -1).
• Positive testing for HIV, hepatitis B or C
• History or presence of alcoholism or drug abuse within last 2 years
• Use of more than 5 packs/week of tobacco/nicotine-containing product within last 6 months prior dosing.
• Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to dosing.
• Use of any over-the-counter (OTC) medication, including herbal products, probiotics and vitamins, within the 7 days prior to dosing.
• Use of antacids, H2 receptor blockers or proton pump inhibitors 7 days prior to dosing.
• History of any hypersensitivity reaction or anaphylaxis to any medication, including polymyxin antibiotics.
• 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.
• Females who are pregnant or lactating.
• QTcF interval \>450 msec for males and \>470 msec for females, or history of prolonged QT syndrome at screening or check-in.
• Calculated creatinine clearance less than 80 mL/min (Cockcroft-Gault method) at screening or check-in.
• 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.
• Liver function abnormalities defined by an elevation in bilirubin, Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) 1.5 x Upper Limit of Normal (ULN) of the normal range for subjects based on age and sex.

Sponsors & Collaborators

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

Study Sites (1)

Altasciences

Cypress, California, 90630, United States

Location

Related Publications (1)

• Watkins M, Zhu Y, Griffith DC, Loutit JS, Margolis D, Gu P. Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants. Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0128824. doi: 10.1128/aac.01288-24. Epub 2024 Dec 9.

  PMID: 39651882 DERIVED

MeSH Terms

Conditions

Bacterial Infections

Interventions

Infusions, Intravenous; Sodium Chloride

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral; 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 and multiple dose

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 22, 2021
• Study Start: June 3, 2021
• Primary Completion: July 14, 2022
• Study Completion: July 14, 2022
• Last Updated: October 10, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)