Condition or disease | Intervention/treatment | Phase |
---|---|---|
Bacterial Infection | Drug: AZACTAM Drug: Ceftazidime-Avibactam | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 48 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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) |
Actual Study Start Date : | July 9, 2019 |
Actual Primary Completion Date : | November 23, 2020 |
Actual Study Completion Date : | November 23, 2020 |
Arm | Intervention/treatment |
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Experimental: Arm 1
2.5g dose of ceftazidime-avibactam (AVYCAZ) administered intravenously as a 2-hour infusion, every 8 hours for 7 days. N=8
|
Drug: Ceftazidime-Avibactam
An antibacterial combination product containing ceftazidime and avibactam
|
Experimental: Arm 2
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
|
Drug: Ceftazidime-Avibactam
An antibacterial combination product containing ceftazidime and avibactam
|
Experimental: Arm 3
2g dose of aztreonam (ATM) administered intravenously as a 2-hour infusion, every 6 hours for 7 days. N=8
|
Drug: AZACTAM
A synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum
|
Experimental: Arm 4
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
|
Drug: AZACTAM
A synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum
|
Experimental: Arm 5
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
|
Drug: AZACTAM
A synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum
Drug: Ceftazidime-Avibactam An antibacterial combination product containing ceftazidime and avibactam
|
Experimental: Arm 6
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
|
Drug: AZACTAM
A synthetic monobactam antibiotic originally isolated from Chromobacterium violaceum
Drug: Ceftazidime-Avibactam An antibacterial combination product containing ceftazidime and avibactam
|
Ages Eligible for Study: | 18 Years to 45 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
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.
**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.
Exclusion Criteria:
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
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
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.
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.
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.
United States, North Carolina | |
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit | |
Durham, North Carolina, United States, 27710-4000 |
Tracking Information | |||||||
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First Submitted Date ICMJE | May 23, 2019 | ||||||
First Posted Date ICMJE | June 6, 2019 | ||||||
Last Update Posted Date | June 4, 2021 | ||||||
Actual Study Start Date ICMJE | July 9, 2019 | ||||||
Actual Primary Completion Date | November 23, 2020 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Number of subjects with at least one Grade 2 or higher treatment-emergent adverse event [ Time Frame: Day 1 through Day 11 ] | ||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | A Trial to Evaluate the Pharmacokinetics and Safety of AVYCAZ(R) in Combination With Aztreonam | ||||||
Official Title ICMJE | A Phase 1, Open-Label Study in Healthy Adults to Evaluate the Safety and Pharmacokinetics of AVYCAZ(R) in Combination With Aztreonam (COMBINE) | ||||||
Brief 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. 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 Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Bacterial Infection | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
48 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | November 23, 2020 | ||||||
Actual Primary Completion Date | November 23, 2020 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 45 Years (Adult) | ||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03978091 | ||||||
Other Study ID Numbers ICMJE | 17-0107 5UM1AI104681-09 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Not Provided | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | National Institute of Allergy and Infectious Diseases (NIAID) | ||||||
Study Sponsor ICMJE | National Institute of Allergy and Infectious Diseases (NIAID) | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE | Not Provided | ||||||
PRS Account | National Institute of Allergy and Infectious Diseases (NIAID) | ||||||
Verification Date | February 7, 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |