Phase 1
N=11
Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal Impairment
Renal Insufficiency
Bottom Line
View on ClinicalTrials.gov: NCT04486625 ↗Enrolled (actual)
11
Serious AEs
0.0%
Results posted
Jul 2023
Primary outcome: Primary: Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM) — 922.9; 733.5 Microgram*hour per milliliter (ug*hr/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Aztreonam-Avibactam (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Sep 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM) |
922.9; 733.5 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of ATM |
57.34; 43.34 | — |
| PRIMARY AUC0-24,ss of Avibactam (AVI) |
164.8; 204.6 | — |
| PRIMARY Cmax of AVI |
11.08; 11.35 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM |
230.8; 244.3 | — |
| SECONDARY Time for Cmax (Tmax) of ATM |
2.92; 2.92 | — |
| SECONDARY Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM |
21.43; 18.55 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) of ATM |
2.605; 4.902 | — |
| SECONDARY Clearance (CL) of ATM |
6.499; 2.761 | — |
| SECONDARY Renal Clearance (CLr) of ATM |
4.527; 1.477 | — |
| SECONDARY Apparent Volume of Distribution (Vz) of ATM |
24.25; 18.79 | — |
| SECONDARY Apparent Volume of Distribution at Steady-state (Vss) of ATM |
23.70; 18.46 | — |
| SECONDARY Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM |
1047; 361.2 | — |
| SECONDARY Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM |
69.68; 53.51 | — |
| SECONDARY AUC0-tau of AVI |
41.19; 68.31 | — |
| SECONDARY Tmax of AVI |
2.46; 2.92 | — |
| SECONDARY Ctau of AVI |
3.100; 5.597 | — |
| SECONDARY t1/2 of AVI |
3.188; 6.524 | — |
| SECONDARY CL of AVI |
12.16; 3.295 | — |
| SECONDARY CLr of AVI |
11.30; 3.948 | — |
| SECONDARY Vz of AVI |
55.83; 30.14 | — |
| SECONDARY Vss of AVI |
37.37; 27.78 | — |
| SECONDARY Ae0-tau of AVI |
465.6; 270.0 | — |
| SECONDARY Ae0-tau% of AVI |
93.19; 119.9 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) |
2; 3; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With TEAEs (Treatment-related) |
0; 3; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Categorical Post-Baseline Vital Signs Data |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiogram (ECG) |
0; 0; 0; 2; 0; 0 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) |
0; 3; 0; 3; 0; 4 | — |
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 severe renal impairment which was based on modelling/simulation.
Eligibility Criteria
Inclusion Criteria
- 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 /= 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 - 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
Data sourced from ClinicalTrials.gov (NCT04486625). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.