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出境医 / 临床实验 / Phase 1 Study of Oral QPX2015 in Healthy Adult Subjects

Phase 1 Study of Oral QPX2015 in Healthy Adult Subjects

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Bacterial Infections Drug: QPX2015 Drug: Placebo oral capsule Phase 1

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: double-blind, placebo controlled ascending single- and multiple-dose
Masking: Double (Participant, Investigator)
Masking Description: double-blind, placebo controlled ascending single- and multiple-dose
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 20, 2019
Actual Primary Completion Date : October 6, 2019
Actual Study Completion Date : October 6, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: QPX2015
QPX2015, antibiotic
Drug: QPX2015
antibiotic
Other Name: oral dose

Placebo Comparator: Placebo
Matched placebo
Drug: Placebo oral capsule
Placebo comparator
Other Name: oral dose

Outcome Measures
Primary Outcome Measures :
  1. Incidence of Treatment -Emergent Adverse events by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Number of patients with Treatment-Emergent AEs by treatment arm, severity and relationship to treatment

  2. Number of patients with changes from baseline in safety parameters [ Time Frame: Study Day 1 to 13 ]
    Number of patients with changes in safety parameters before and after dosing by subject and treatment arm

  3. Peak plasma Concentration measurements by subject and by cohort (Cmax) [ Time Frame: Study Day 1 to 13 ]
    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.

  4. Time concentration data measurements by subject and by cohort (Tmax) [ Time Frame: Study Day 1 to 13 ]
    Comparison will be performed between the cohorts for Tmax.

  5. Area under the plasma concentration versus time curve (AUC) between cohorts [ Time Frame: Study Day 1 to 13 ]
    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.

  6. Urine PK amount excreted by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Urine PK parameters such as amount excreted will be calculated from urinary excretion data

  7. Urine PK % dose excreted by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations

Locations
Layout table for location information
Australia, South Australia
CMAX
Adelaide, South Australia, Australia
Sponsors and Collaborators
Qpex Biopharma, Inc.
Biomedical Advanced Research and Development Authority
Investigators
Layout table for investigator information
Study Director: Jeffery S Loutit, MBChB Qpex Biopharma, Inc.
Tracking Information
First Submitted Date  ICMJE May 1, 2019
First Posted Date  ICMJE May 6, 2019
Last Update Posted Date October 23, 2019
Actual Study Start Date  ICMJE May 20, 2019
Actual Primary Completion Date October 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Incidence of Treatment -Emergent Adverse events by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    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 [ Time Frame: Study Day 1 to 13 ]
    Number of patients with changes in safety parameters before and after dosing by subject and treatment arm
  • Peak plasma Concentration measurements by subject and by cohort (Cmax) [ Time Frame: Study Day 1 to 13 ]
    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.
  • Time concentration data measurements by subject and by cohort (Tmax) [ Time Frame: Study Day 1 to 13 ]
    Comparison will be performed between the cohorts for Tmax.
  • Area under the plasma concentration versus time curve (AUC) between cohorts [ Time Frame: Study Day 1 to 13 ]
    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.
  • Urine PK amount excreted by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Urine PK parameters such as amount excreted will be calculated from urinary excretion data
  • Urine PK % dose excreted by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • Incidence of Treatment -Emergent Adverse events by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Number of patients with Treatment-Emergent AEs by treatment arm, severity and relationship to treatment
  • Number of patients with changes from baseline in vitals, ECGs and laboratory parameters [ Time Frame: Study Day 1 to 13 ]
    Number of patients with changes in vital signs, normal to abnormal shifts in ECGs and laboratory values by subject and treatment arm
  • Peak plasma Concentration measurements by subject and by cohort (Cmax) [ Time Frame: Study Day 1 to 13 ]
    Comparison will be performed between the cohorts for Cmax. Mean graphical presentation of the data will be reported. Statistical analysis of dose proportionality of exposure parameters will be performed.
  • Time concentration data measurements by subject and by cohort (Tmax) [ Time Frame: Study Day 1 to 13 ]
    Comparison will be performed between the cohorts for Tmax. Mean graphical presentation of the data will be reported. Statistical analysis of dose proportionality of exposure parameters will be performed.
  • Area under the plasma concentration versus time curve (AUC) between cohorts [ Time Frame: Study Day 1 to 13 ]
    Comparison will be performed between the cohorts for AUC. Mean graphical presentation of the data will be reported. Statistical analysis of dose proportionality of exposure parameters will be performed
  • Urine PK concentrations by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Urine PK parameters such as amount excreted will be calculated from urinary excretion data
  • Urine PK concentrations by subject and by cohort [ Time Frame: Study Day 1 to 13 ]
    Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of Oral QPX2015 in Healthy Adult Subjects
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
double-blind, placebo controlled ascending single- and multiple-dose
Masking: Double (Participant, Investigator)
Masking Description:
double-blind, placebo controlled ascending single- and multiple-dose
Primary Purpose: Treatment
Condition  ICMJE Bacterial Infections
Intervention  ICMJE
  • Drug: QPX2015
    antibiotic
    Other Name: oral dose
  • Drug: Placebo oral capsule
    Placebo comparator
    Other Name: oral dose
Study Arms  ICMJE
  • Experimental: QPX2015
    QPX2015, antibiotic
    Intervention: Drug: QPX2015
  • Placebo Comparator: Placebo
    Matched placebo
    Intervention: Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2019)
40
Original Estimated Enrollment  ICMJE
 (submitted: May 3, 2019)
50
Actual Study Completion Date  ICMJE October 6, 2019
Actual Primary Completion Date October 6, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03939429
Other Study ID Numbers  ICMJE Qpex-100
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Qpex Biopharma, Inc.
Study Sponsor  ICMJE Qpex Biopharma, Inc.
Collaborators  ICMJE Biomedical Advanced Research and Development Authority
Investigators  ICMJE
Study Director: Jeffery S Loutit, MBChB Qpex Biopharma, Inc.
PRS Account Qpex Biopharma, Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP