Renal InsufficiencyPhase 1NCT04486625
Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal Impairment
A Phase 1 study testing Aztreonam-Avibactam in people with Renal Insufficiency, run by Pfizer at 1 site in United States.
Trial summary
This Phase 1 study is being conducted to evaluate the effect of severe renal impairment on the PK, safety and tolerability of Aztreonam-Avibactam. Results from this study along with previous renal impairment data from each of the Aztreonam-Avibactam components will be used to confirm the proposed dosing adjustment in… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Insufficiency
- What is being tested?
- Aztreonam-Avibactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2020to 18 Oct 2021
- Phase
- Phase 1
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy female subjects and/or male subjects between the ages of 18 and 75 years, inclusive. Male and female subjects of childbearing potential must agree to use highly effective method(s) of contraception
- Body mass index (BMI) of 17.5 to 40.5 kg/m2; and a total body weight >50 kg (110 lb)
- Stable renal function defined as </=25% difference between 2 measurements of eGFR obtained on 2 separate occasions during the screening period that are at least 72 hours but no more than 14 days apart Specific Requirements for Healthy Subjects with Normal Renal Function
- Normal renal function (eGFR>/= 80 mL/min) at Screening based on the Day -2 value, using the MDRD formula adjusting for BSA
- Demographically comparable to the group of subjects with severe impaired renal function Specific Requirements for Subjects with Severe Renal Impairment
- Good general health commensurate with the population with chronic kidney disease.
- Documented severe renal impairment indicated by eGFR >15 -</=30 mL/min but not requiring hemodialysis, using the MDRD formula adjusting for BSA
Who cannot join
- Positive urine drug test
- History of regular alcohol use (within 6 months) exceeding 7 drinks/week for female or 14 drinks/week for male subjects
- Treatment with an investigational product within 30 days or 5 half-lives preceding the first dose of investigational product (whichever is longer)
- Subjects with abnormalities in clinical laboratory tests (AST, ALT, Total bilirubin, aPTT, PT, INR) at Screening
- Pregnant females; breastfeeding females; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception
- Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product. For subjects with severe renal impairment, concomitant medications may be given if considered necessary for the subject welfare (eg, standard therapy for underlying diseases), are not contraindicated with the study drug, and are unlikely to interfere with the PK/PD response of the study drug. Use of oral anticoagulants and potent inhibitors of OAT1 and/or OAT3 (eg, probenecid) are prohibited in all subjects.
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- Blood donation (excluding plasma donations) of approximately 1 pint or more within 60 days prior to dosing
- History of sensitivity to heparin or heparin-induced thrombocytopenia
- History of serious allergy, hypersensitivity or any serious reaction to aztreonam, carbapenem, monobactam or other beta-lactam antibiotics, avibactam, or any of the excipients of the respective (investigational) medicinal products
- History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- Other acute or chronic medical or psychiatric condition
- Past or current history of epilepsy or seizure disorders excluding febrile seizures of childhood Exclusion criteria: Subjects with Severe Renal Impairment
- Any significant hepatic, cardiac, or pulmonary disease
- Renal allograft recipients or subjects who are clinically nephrotic
- Subjects requiring dialysis
- Screening supine 12-lead ECG demonstrating QT interval corrected by Fridericia's formula (QTcF) >470 msec or a QRS interval >120 msec
- Screening supine BP >/=180 millimeters of mercury (mm Hg) (systolic) or >/=110 mm Hg (diastolic), on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest Exclusion criteria: Subjects with Normal Renal Function
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including clinically relevant and significant drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
- Screening supine 12-lead ECG demonstrating QTcF >450 msec or a QRS interval >120 msec
- Screening supine BP >/=140 mm Hg (systolic) or >/=90 mm Hg (diastolic), following at least 5 minutes of supine rest
Trial locations and contacts
1 site in 1 country.
United States1 site
Prism Research LLC dba Nucleus Network
Saint Paul, Minnesota, 55114
About this study
Official title: AN OPEN-LABEL, PARALLEL-GROUP, PHARMACOKINETIC STUDY OF MULTIPLE INTRAVENOUS DOSES OF AZTREONAM AND AVIBACTAM IN SUBJECTS WITH SEVERE RENAL IMPAIRMENT AND NORMAL RENAL FUNCTION
This Phase 1 study is being conducted to evaluate the effect of severe renal impairment on the PK, safety and tolerability of Aztreonam-Avibactam. Results from this study along with previous renal impairment data from each of the Aztreonam-Avibactam components will be used to confirm the proposed dosing adjustment in severe renal impairment which was based on modelling/simulation.
- Conditions
- Renal Insufficiency
- Being tested
- Aztreonam-Avibactam
- Keywords
- Infection
- Medical subject headings
- Renal Insufficiency, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aztreonam-AvibactamDrug
500/167 mg ATM/AVI loading infusion, followed by 1500/500 mg ATM/AVI extended loading infusion, then 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours
Aztreonam-AvibactamDrug
675/225 mg ATM/AVI loading infusion, followed by 675/225 mg ATM/AVI extended loading infusion, then 675/225 mg ATM/AVI maintenance dose infusion every 8 hours
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Normal renal function Receives: Drug: Aztreonam-Avibactam |
| Cohort 2 | Experimental | Severe renal impairment (not on dialysis) Receives: Drug: Aztreonam-Avibactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)
AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Maximum Plasma Concentration (Cmax) of ATM
The Cmax of ATM was observed directly from data.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
AUC0-24,ss of Avibactam (AVI)
AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Cmax of AVI
The Cmax of AVI was observed directly from data.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Secondary outcomes (25)
Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM
The AUC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Time for Cmax (Tmax) of ATM
The Tmax was observed directly from data as time of first occurrence.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM
The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Terminal Elimination Half-life (t1/2) of ATM
The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Clearance (CL) of ATM
The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Renal Clearance (CLr) of ATM
The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Apparent Volume of Distribution (Vz) of ATM
The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Apparent Volume of Distribution at Steady-state (Vss) of ATM
Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM
The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM
The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
AUC0-tau of AVI
The UC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).A
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Tmax of AVI
The Tmax was observed directly from data as time of first occurrence.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Ctau of AVI
The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
t1/2 of AVI
The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
CL of AVI
The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the plasma concentration-time profile from time 0 to to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
CLr of AVI
The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Vz of AVI
The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Vss of AVI
Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.
Measured: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Ae0-tau of AVI
The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Ae0-tau% of AVI
The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
Measured: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality)
An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.
Measured: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).
Number of Participants With TEAEs (Treatment-related)
An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event attributed to the study medication. A serious AE is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.
Measured: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).
Number of Participants With Categorical Post-Baseline Vital Signs Data
Categorical post-baseline vital signs included: (1) pulse rate: value less than (<) 40 beats per minute (bpm), lager than (>) 120 bpm; (2) supine diastolic blood pressure (DBP): value <50 mmHg, change of more than or equal to (>=) 20 mmHg increase, change of >=20 mmHg decrease; (3) supine systolic blood pressure (SBP): value <90 mmHg, change of >=30 mmHg increase, change of >=30 mmHg decrease.
Measured: Days 1 to 3
Number of Participants With Abnormal Electrocardiogram (ECG)
Criteria for ECG abnormalities: maximum QT interval >500 milliseconds (msec); maximum QTc interval of >=450 msec to less than or equal to (<=) 480 msec, >480 msec, and >500 msec and a maximum change of <30 change<=60 or >60 msec from baseline; maximum QTcF (Fridericia's Correction) interval of >=450 msec to <=480 msec, >480 msec, and >500 msec and a maximum change of <30 change<=60 or >60 msec from baseline.
Measured: Days 1 to 3
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Following laboratory parameters were abnormal (without regard to baseline abnormality): hemoglobin, hematocrit, erythrocytes, lymphocytes, neutrophils, activated partial thromboplastin time, protein, urea nitrogen, creatinine, urate, urine glucose, and urine protein.
Measured: Days 1 to 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start10 Aug 2020
- Primary completion20 Sep 2021
- Study completion18 Oct 2021
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 Renal InsufficiencyStudies of the same condition, open and under way.
- More trials run by PfizerThe 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
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04486625
- Sponsor's protocol ID
- C3601006
- Status last verified
- Sep 2022
- First submitted
- 22 Jul 2020
- Last updated
- 28 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AN OPEN-LABEL, PARALLEL-GROUP, PHARMACOKINETIC STUDY OF MULTIPLE INTRAVENOUS DOSES OF AZTREONAM AND AVIBACTAM IN SUBJECTS WITH SEVERE RENAL IMPAIRMENT AND NORMAL RENAL FUNCTION
- ClinicalTrials.gov ID
- NCT04486625
- Acronym / sponsor ID
- C3601006
- Conditions
- Renal Insufficiency
- Keywords
- Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2020 (actual)
- Primary completion
- 20 Sep 2021 (actual)
- Study completion
- 18 Oct 2021 (actual)
- First posted
- 24 Jul 2020 (actual)
- Results
- Posted 28 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 1 study is being conducted to evaluate the effect of severe renal impairment on the PK, safety and tolerability of Aztreonam-Avibactam. Results from this study along with previous renal impairment data from each of the Aztreonam-Avibactam components will be used to confirm the proposed dosing adjustment in severe renal impairment which was based on modelling/simulation.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Aztreonam-AvibactamNormal renal function |
| Cohort 2 | Experimental | Drug: Aztreonam-AvibactamSevere renal impairment (not on dialysis) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy female subjects and/or male subjects between the ages of 18 and 75 years, inclusive. Male and female subjects of childbearing potential must agree to use highly effective method(s) of contraception
- Body mass index (BMI) of 17.5 to 40.5 kg/m2; and a total body weight >50 kg (110 lb)
- Stable renal function defined as </=25% difference between 2 measurements of eGFR obtained on 2 separate occasions during the screening period that are at least 72 hours but no more than 14 days apart Specific Requirements for Healthy Subjects with Normal Renal Function
- Normal renal function (eGFR>/= 80 mL/min) at Screening based on the Day -2 value, using the MDRD formula adjusting for BSA
- Demographically comparable to the group of subjects with severe impaired renal function Specific Requirements for Subjects with Severe Renal Impairment
Key exclusion criteria (20 listed)
- Positive urine drug test
- History of regular alcohol use (within 6 months) exceeding 7 drinks/week for female or 14 drinks/week for male subjects
- Treatment with an investigational product within 30 days or 5 half-lives preceding the first dose of investigational product (whichever is longer)
- Subjects with abnormalities in clinical laboratory tests (AST, ALT, Total bilirubin, aPTT, PT, INR) at Screening
- Pregnant females; breastfeeding females; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception
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 |
|---|---|---|
| Aztreonam-Avibactam500/167 mg ATM/AVI loading infusion, followed by 1500/500 mg ATM/AVI extended loading infusion, then 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours | Drug | Cohort 1 |
| Aztreonam-Avibactam675/225 mg ATM/AVI loading infusion, followed by 675/225 mg ATM/AVI extended loading infusion, then 675/225 mg ATM/AVI maintenance dose infusion every 8 hours | Drug | Cohort 2 |
Primary outcome
Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).
Maximum Plasma Concentration (Cmax) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
The Cmax of ATM was observed directly from data.
AUC0-24,ss of Avibactam (AVI)
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).
Cmax of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
The Cmax of AVI was observed directly from data.
25 secondary outcomes
Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Time for Cmax (Tmax) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Terminal Elimination Half-life (t1/2) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Clearance (CL) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Renal Clearance (CLr) of ATM
Time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Apparent Volume of Distribution (Vz) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Apparent Volume of Distribution at Steady-state (Vss) of ATM
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM
Time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM
Time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
AUC0-tau of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Tmax of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Ctau of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
t1/2 of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
CL of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
CLr of AVI
Time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Vz of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Vss of AVI
Time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
Ae0-tau of AVI
Time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Ae0-tau% of AVI
Time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality)
Time frame: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).
Number of Participants With TEAEs (Treatment-related)
Time frame: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).
Number of Participants With Categorical Post-Baseline Vital Signs Data
Time frame: Days 1 to 3
Number of Participants With Abnormal Electrocardiogram (ECG)
Time frame: Days 1 to 3
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time frame: Days 1 to 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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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.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aztreonam-Avibactam in people with Renal Insufficiency, run by Pfizer 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 7 inclusion and 20 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 28 Jul 2023. 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 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.
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 28 Jul 2023). 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?
Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM) (time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.). The study lists 4 primary outcomes in all. 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 28 Jul 2023.