Bacterial InfectionPhase 1/2NCT03978091
A Trial to Evaluate the Pharmacokinetics and Safety of AVYCAZ(R) in Combination With Aztreonam
A Phase 1/2 study testing AZACTAM and Ceftazidime-Avibactam in people with Bacterial Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Bacterial Infection
- What is being tested?
- AZACTAM and Ceftazidime-Avibactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2019to 23 Nov 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provide a signed and dated written informed consent.
- Be able to understand and willing to comply with study procedures, restrictions, and requirements, as determined by the Principal Investigator (PI).
- Male and female volunteers aged 18 to 45 years inclusive.
- Suitable veins for cannulation or repeated venipuncture.
- Subject must be in good general health as judged by the investigator as determined by medical history, vital signs*, body mass index (BMI) and body weight, clinical laboratory values*, and physical examination (PE).
- Oral temp <38.0 degrees Celsius/100.4 degrees Fahrenheit; pulse 50 to 100 bpm; systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mmHg.
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- BMI between 19-33 kg/m^2 and body weight > / = 50 kg
- Clinical chemistry, hematology, coagulation and urinalysis results within the clinical laboratory reference ranges; clinical laboratory values outside these ranges, if considered by the site investigator to be clinically insignificant, are also acceptable
- Sexually active female subjects must be of non-childbearing potential** or must use a highly effective method of birth control***.
- Non-childbearing potential is defined as being post-menopausal for at least 18 months or surgically sterile via hysterectomy, bilateral oophorectomy, or tubal sterilization.
- Sexually active female subjects of childbearing potential must avoid becoming pregnant by using one of the following acceptable methods of birth control for 30 days prior to study product dosing and must be maintained for 30 days after last dose of study product: Intrauterine contraceptive device; OR Approved hormonal contraceptives (such as birth control pills, skin patches, Implanon(R), Nexplanon(R), DepoProvera(R) or NuvaRing(R)); OR Birth control must be captured on the appropriate data collection form.
- Sexually active male subjects must be vasectomized or agree to use barrier contraception (condom with spermicide) from first dose of study product until 30 days following the last dose of study product.
- Nonsmokers defined as abstinence from cigarette smoking or use of nicotine-containing products for 6 months prior to enrollment into the study.
Who cannot join
- History of any clinically significant (CS) disease or disorder, medical/surgical procedure, or trauma within 4 weeks prior to the first administration of study product(s)*.
- In the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
- History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Known history of a clinically important allergy/hypersensitivity to AVI, any monobactam, any beta-lactam and/or L-arginine.
- Receipt of probenecid or furosemide within 14 days prior to study enrollment.
- Receipt of any antibiotics within 14 days prior to study enrollment.
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- Receipt of prescription medications (except birth control pills or hormone replacement in females) within 14 days prior to study enrollment, unless in the opinion of site investigator the medication will not interfere with the study procedures or impact subject safety.
- Receipt of non-antibiotic medications that interacts with OAT3** within 14 days prior to study enrollment.
- Adefovir, Anagliptin, Baricitinib, Cefaclor, Cimetidine, Ciprofloxacin (Systemic), Clofarabine, Eluxadoline, Empagliflozin, Furosemide, Ketoprofen, Methotrexate, Mycophenolate, PEMEtrexed, Penicillin G (Parenteral/Aqueous), Penicillin G Benzathine, Penicillin G Procaine, Penicillin V Benzathine, Penicillin V Potassium, Zidovudine
- Receipt of herbal and dietary supplements (including St. John's Wort) within 14 days prior to study enrollment.
- ALT or AST laboratory value above the ULN as defined in the toxicity table.
- Prolonged QTcF (> 450 msec) or shortened QTcF (< 340 msec) or family history of long QT syndrome. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG***.
- Abnormalities that may interfere with interpretation of QTc interval changes per the medical judgment of the PI.
- Any positive result on screening for human immunodeficiency virus (HIV) serum hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody.
- Creatinine clearance equal or less than 80 mL/minute (measured by Cockcroft-Gault method).
- History of Clostridium difficile infection in past 90 days.
- Known or suspected history of drug or alcohol abuse within the last 5 years, as judged by the PI.
- Positive screen for drugs of abuse, cotinine (nicotine), or alcohol at screening and at admission to the study site prior to the first administration of the study products(s).
- Received a new chemical entity (compound not approved for marketing) or participated in a study that included drug treatment within 1 month of the first dose of study product(s) for study ****.
- Period of exclusion begins at the time of the last visit of the prior study.
- Note: subjects consented and screened, but not dosed in this study or a previous Phase I study will not be excluded.
- Previous participation in the present study.
- Involvement in the planning and/or conduct of the study.
- Any ongoing/recent (during screening) medical complaints that may interfere with analysis of study data or are considered unlikely to comply with study procedures, restrictions, and requirements *.
- Judgment by the PI that the subject should not participate in the study.
- Known history of past or current epilepsy or seizure disorders, excluding febrile seizures of childhood.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
Durham, North Carolina, 27710-4000
About this study
Official title: A Phase 1, Open-Label Study in Healthy Adults to Evaluate the Safety and Pharmacokinetics of AVYCAZ(R) in Combination With Aztreonam (COMBINE)
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. The study will have 6 arms, arms 1-4 are the single drug administration treatment groups and will include AVYCAZ per label dosing, AVYCAZ as a continuous infusion (CI), ATM per label dosing, and ATM as a CI. Arms 5 and 6 are the two AVYCAZ and ATM combination drug administration treatment groups. The duration of subject participation will be up to 44 days, and the total length of the study will be 15 months. The primary objective of this study is to describe the safety of two dosing regimens of AVYCAZ combined with ATM relative to AVYCAZ alone, and ATM alone in healthy adult subjects.
Read the detailed description
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. The study will have 6 arms, arms 1-4 are the single drug administration treatment groups and will include AVYCAZ per label dosing, AVYCAZ as a continuous infusion (CI), ATM per label dosing, and ATM as a continuous infusion (CI). Arms 5 and 6 are the two AVYCAZ and ATM combination drug administration treatment groups. The duration of subject participation will be up to 44 days, and the total length of the study will be 15 months. The primary objective of this study is to describe the safety of two dosing regimens of AVYCAZ combined with ATM relative to AVYCAZ alone, and ATM alone in healthy adult subjects. The secondary objectives of this study are to; 1) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone at the population level in healthy adult subjects; 2) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone following initiation of dosing on day 1 in healthy adult subjects; and 3) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone following multiple daily dosing in healthy adult subjects.
- Conditions
- Bacterial Infection
- Being tested
- AZACTAM, Ceftazidime-Avibactam
- Keywords
- Aztreonam, Ceftazidime-Avibactam, Efficacy, Healthy, Pharmacokinetics, Population, Safety
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZACTAMDrug
A synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum
Ceftazidime-AvibactamDrug
An antibacterial combination product containing ceftazidime and avibactam
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 2.5g dose of ceftazidime-avibactam (AVYCAZ) administered intravenously as a 2-hour infusion, every 8 hours for 7 days. N=8 Receives: Drug: Ceftazidime-Avibactam |
| Arm 2 | Experimental | 2.5g dose of AVYCAZ administered intravenously as a 2-hour infusion once, then 0.32g dose per hour daily as a continuous infusion (7.5 g/day) for 7 days. N=8 Receives: Drug: Ceftazidime-Avibactam |
| Arm 3 | Experimental | 2g dose of aztreonam (ATM) administered intravenously as a 2-hour infusion, every 6 hours for 7 days. N=8 Receives: Drug: AZACTAM |
| Arm 4 | Experimental | 2g of ATM administered intravenously as a 2-hour infusion once, then 0.33g dose administered intravenously per hour, daily as a continuous infusion (8 g/day) for 7 days. N=8 Receives: Drug: AZACTAM |
| Arm 5 | Experimental | 2.5g dose of AVYCAZ administered intravenously as a 2-hour infusion, every 8 hours for 7 days, and a 1.5g dose of ATM administered intravenously as a 2-hour infusion, every 6 hours for 7 days. N=8 Receives: Drug: AZACTAM; Drug: Ceftazidime-Avibactam |
| Arm 6 | Experimental | 2.5 g dose of AVYCAZ administered intravenously as a 2-hour infusion every 8 hours for 7 days, and a 2g dose of ATM as a 2-hour infusion every 6 hours for 7 days. N=8 Receives: Drug: AZACTAM; Drug: Ceftazidime-Avibactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event
Adverse events include local and systemic reactions. All Grade 2 (moderate) adverse events were reported, regardless of relationship to study product. Number of participants with an AE are summarized by MedDRA system organ class (SOC). Each participant is only counted once per SOC.
Measured: Day 1 through Day 11
Secondary outcomes (15)
Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC]
Mean and standard deviation (SD) of the RAUC PK parameter were estimated for ceftazidime, avibactam, and/or aztreonam by dividing the AUC(0-8) (avibactam and ceftazidime) or AUC(0-6) (aztreonam) on Day 7 by the AUC(0-Tau) on Day 1. AUC(0-8) and AUC(0-6) (µg*hr/mL) on Day 7 and AUC(0-Tau) (µg*hr/mL) on Day 1 were estimated from plasma concentration-time data using Non-compartmental analysis with the linear trapezoidal linear interpolation method for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0.
Measured: Day 1 and Day 7
Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax)
Mean and standard deviation (SD) of the RCmax PK parameter were estimated for ceftazidime, avibactam, and/or aztreonam by dividing the Cmax on Day 7 by the Cmax on Day 1. Cmax (ug/mL) was estimated from plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0.
Measured: Day 1 and Day 7
Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)]
Mean and standard deviation (SD) of the AUC(0-inf) (µg*hr/mL) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 7
Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)]
Mean and standard deviation (SD) of the AUC(0-Tau) (µg*hr/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis using linear trapezoidal linear interpolation method for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. AVYCAZ CI and ATM CI were not reported.
Measured: Day 1
Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level
Number of participants with an AE are summarized by MedDRA system organ class (SOC) and severity. Each participant is only counted once at the highest severity recorded. For clinical laboratory tests, mild abnormal laboratory values that were not, in the investigator's opinion, medically significant were not reported as adverse events.
Measured: Day 1 through Day 14
Maximum Plasma Concentration of Study Drug After the First Dose (Cmax)
Mean and standard deviation (SD) of the Cmax (ug/mL) PK parameter after the first dose were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 1
Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax)
Mean and standard deviation (SD) of the Cmax (ug/mL) PK parameter following multiple daily dosing were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 7
Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin)
Mean and standard deviation (SD) of the Cmin (ug/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0. Cmin was not provided on day 7 because it was the last dosage of the study product administered; Cmin was therefore not calculated for this terminal elimination profile since the minimum concentration after a final dose would only reflect the last time point after Cmax that a blood sample is obtained, or the assay's limit of quantitation. It is therefore not comparable to Cmin calculated on prior days.
Measured: Day 7
Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin)
Mean and standard deviation (SD) of the Cmin (ug/mL) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis for AVYCAZ IV, ATM IV, AVYCAZ + ATM 1.5, and AVYCAZ + ATM 2.0.
Measured: Day 1
Renal Clearance of Study Drug (CLR)
Mean and standard deviation (SD) of the CLR (L/h) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma and urine concentration-time data using Non-compartmental analysis. Renal clearance was calculated as Ae(0-8)/AUC(0-8) for ceftazidime and avibactam and as AE(0-4)/AUC(0-4) for aztreonam where Ae(0-8) and Ae(0-4) are the amounts of study drug excreted into the urine from time of dosing to 8 or 4 h post-dose, respectively, and AUC(0-8) and AUC(0-4) are the areas under the plasma concentration-time curve from time of dosing to 8 or 4 h post-dose, respectively.
Measured: Day 1
Concentration of Study Drug at Steady State After Continuous Infusion (Css)
Mean and standard deviation (SD) of the Css (ug/mL) PK parameter were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data for AVYCAZ CI and ATM CI.
Measured: Day 1
Total Body Plasma Clearance of Study Drug (CL)
Mean and standard deviation (SD) of the CL (L/h) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 7
Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax)
Mean and standard deviation (SD) of the Tmax (h) PK parameter after the first dose were estimated from the Day 1 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 1
Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax)
Mean and standard deviation (SD) of the Tmax (h) PK parameter following multiple daily dosing were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 7
Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss)
Mean and standard deviation (SD) of the Vss (L) PK parameter were estimated from the Day 7 ceftazidime, avibactam, and/or aztreonam plasma concentration-time data using Non-compartmental analysis.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2019
- Study start9 Jul 2019
- Primary completion23 Nov 2020
- Study completion23 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bacterial InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03978091
- Sponsor's protocol ID
- 17-0107
- Other IDs
- 5UM1AI104681-09
- Status last verified
- 7 Feb 2020
- First submitted
- 23 May 2019
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label Study in Healthy Adults to Evaluate the Safety and Pharmacokinetics of AVYCAZ(R) in Combination With Aztreonam (COMBINE)
- ClinicalTrials.gov ID
- NCT03978091
- Acronym / sponsor ID
- 17-0107
- Conditions
- Bacterial Infection
- Keywords
- Aztreonam, Ceftazidime-Avibactam, Efficacy, Healthy, Pharmacokinetics, Population, Safety
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 9 Jul 2019 (actual)
- Primary completion
- 23 Nov 2020 (actual)
- Study completion
- 23 Nov 2020 (actual)
- First posted
- 6 Jun 2019 (actual)
- Results
- Posted 23 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. The study will have 6 arms, arms 1-4 are the single drug administration treatment groups and will include AVYCAZ per label dosing, AVYCAZ as a continuous infusion (CI), ATM per label dosing, and ATM as a CI. Arms 5 and 6 are the two AVYCAZ and ATM combination drug administration treatment groups. The duration of subject participation will be up to 44 days, and the total length of the study will be 15 months. The primary objective of this study is to describe the safety of two dosing regimens of AVYCAZ combined with ATM relative to AVYCAZ alone, and ATM alone in healthy adult subjects.
Detailed description
This is a Phase I, open-label, non-randomized, single center study in 48 healthy adult male and female subjects, aged 18 to 45 years. This study is aimed to investigate the safety and pharmacokinetics of ceftazidime-avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone. The study will have 6 arms, arms 1-4 are the single drug administration treatment groups and will include AVYCAZ per label dosing, AVYCAZ as a continuous infusion (CI), ATM per label dosing, and ATM as a continuous infusion (CI). Arms 5 and 6 are the two AVYCAZ and ATM combination drug administration treatment groups. The duration of subject participation will be up to 44 days, and the total length of the study will be 15 months. The primary objective of this study is to describe the safety of two dosing regimens of AVYCAZ combined with ATM relative to AVYCAZ alone, and ATM alone in healthy adult subjects. The secondary objectives of this study are to; 1) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone at the population level in healthy adult subjects; 2) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone following initiation of dosing on day 1 in healthy adult subjects; and 3) Characterize the PK profiles of two dosing regimens of AVYCAZ combined with ATM, AVYCAZ alone, and ATM alone following multiple daily dosing in healthy adult subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Ceftazidime-Avibactam2.5g dose of ceftazidime-avibactam (AVYCAZ) administered intravenously as a 2-hour infusion, every 8 hours for 7 days. N=8 |
| Arm 2 | Experimental | Drug: Ceftazidime-Avibactam2.5g dose of AVYCAZ administered intravenously as a 2-hour infusion once, then 0.32g dose per hour daily as a continuous infusion (7.5 g/day) for 7 days. N=8 |
| Arm 3 | Experimental | Drug: AZACTAM2g dose of aztreonam (ATM) administered intravenously as a 2-hour infusion, every 6 hours for 7 days. N=8 |
| Arm 4 | Experimental | Drug: AZACTAM2g of ATM administered intravenously as a 2-hour infusion once, then 0.33g dose administered intravenously per hour, daily as a continuous infusion (8 g/day) for 7 days. N=8 |
| Arm 5 | Experimental | Drug: AZACTAM, Drug: Ceftazidime-Avibactam2.5g dose of AVYCAZ administered intravenously as a 2-hour infusion, every 8 hours for 7 days, and a 1.5g dose of ATM administered intravenously as a 2-hour infusion, every 6 hours for 7 days. N=8 |
| Arm 6 | Experimental | Drug: AZACTAM, Drug: Ceftazidime-Avibactam2.5 g dose of AVYCAZ administered intravenously as a 2-hour infusion every 8 hours for 7 days, and a 2g dose of ATM as a 2-hour infusion every 6 hours for 7 days. N=8 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Provide a signed and dated written informed consent.
- Be able to understand and willing to comply with study procedures, restrictions, and requirements, as determined by the Principal Investigator (PI).
- Male and female volunteers aged 18 to 45 years inclusive.
- Suitable veins for cannulation or repeated venipuncture.
- Subject must be in good general health as judged by the investigator as determined by medical history, vital signs*, body mass index (BMI) and body weight, clinical laboratory values*, and physical examination (PE).
Key exclusion criteria (26 listed)
- History of any clinically significant (CS) disease or disorder, medical/surgical procedure, or trauma within 4 weeks prior to the first administration of study product(s)*.
- In the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
- History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Known history of a clinically important allergy/hypersensitivity to AVI, any monobactam, any beta-lactam and/or L-arginine.
- Receipt of probenecid or furosemide within 14 days prior to study enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZACTAMA synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum | Drug | Arm 3, Arm 4, Arm 5, Arm 6 |
| Ceftazidime-AvibactamAn antibacterial combination product containing ceftazidime and avibactam | Drug | Arm 1, Arm 2, Arm 5, Arm 6 |
Primary outcome
Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event
Time frame: Day 1 through Day 11
Adverse events include local and systemic reactions. All Grade 2 (moderate) adverse events were reported, regardless of relationship to study product. Number of participants with an AE are summarized by MedDRA system organ class (SOC). Each participant is only counted once per SOC.
15 secondary outcomes
Accumulation Ratio for AUC (Area Under the Plasma Concentration-time Curve of Study Drug) [RAUC]
Time frame: Day 1 and Day 7
Accumulation Ratio for Cmax (Maximum Plasma Concentration) (RCmax)
Time frame: Day 1 and Day 7
Area Under the Plasma Concentration-time Curve of Study Drug From Time of Dosing Extrapolated to Infinity [AUC(0-Inf)]
Time frame: Day 7
Area Under the Plasma Concentration-time Curve Data of Study Drug During the Dosing Interval on Day 1 [AUC(0-Tau)]
Time frame: Day 1
Incidence of Treatment-emergent Adverse Events, by System Organ Class (SOC) and Maximum Severity Level
Time frame: Day 1 through Day 14
Maximum Plasma Concentration of Study Drug After the First Dose (Cmax)
Time frame: Day 1
Maximum Plasma Concentration of Study Drug Following Multiple Daily Dosing (Cmax)
Time frame: Day 7
Minimum Plasma Concentration of Study Drug at the End of the Dosing Interval on Day 7 (Cmin)
Time frame: Day 7
Minimum Plasma Concentration of Study Drug Following Multiple Daily Dosing on Day 1 (Cmin)
Time frame: Day 1
Renal Clearance of Study Drug (CLR)
Time frame: Day 1
Concentration of Study Drug at Steady State After Continuous Infusion (Css)
Time frame: Day 1
Total Body Plasma Clearance of Study Drug (CL)
Time frame: Day 7
Time of Cmax (Maximum Plasma Concentration) of Study Drug After the First Dose (Tmax)
Time frame: Day 1
Time to Cmax (Maximum Plasma Concentration) of Study Drug Following Multiple Daily Dosing (Tmax)
Time frame: Day 7
Volume of Distribution of Study Drug at Steady-state Based on the Last Observed Concentration (Vss)
Time frame: Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZACTAM and Ceftazidime-Avibactam in people with Bacterial Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With at Least One Grade 2 (Moderate) or Higher Treatment-emergent Adverse Event (time frame: Day 1 through Day 11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2022.