Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a randomised study divided into 2 parts. Part A investigates the effect of prolonged dosing (ten days) with Avibactam and Ceftazidime when given together and how this will effect how much Avibactam and Ceftazidime enters the blood. Part B investigates how much Avibactam (NXL104) and Ceftazidime enter the blood when Avibactam and Ceftazidine are given separately or together intravenously.
A Phase I, 2-Part, Open-Label, Pharmacokinetic and Drug-Drug Interaction Study of CAZ104 (Avibactam and Ceftazidime in Healthy Subjects)
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | CAZ104 (2000mg Ceftazidime/500mg Avibactam) |
|
| 2 | Active Comparator | 500mg Avibactam |
|
| 3 | Active Comparator | 2000mg Ceftazidime |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAZ104 | Drug | IV infusion |
| |
| Avibactam |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including maximum plasma concentration (Cmax) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Cmax (tmax) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including minimum plasma concentration (Cmin) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Cmin (tmin) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including last quantifiable plasma concentration (Clast) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Clast (tlast) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including average plasma concentration during a dosing interval (Cavg) | Up to 24 hours post last dose | |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including fluctuation index |
| Measure | Description | Time Frame |
|---|---|---|
| To assess safety and tolerability of Avibactam by assessment of Adverse events | Up to 24 hours post last dose | |
| To assess safety and tolerability of Avibactam by clinical laboratory assessments | Up to 24 hours post last dose |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mirjana Kujacic, MD | AstraZeneca Research and DevelopmentSE-431 83 Mölndal Sweden | Study Chair |
| Leonard Siew, MBCHB | Quintiles Drug Research Unit at Guy's Hospital 6 Newcomen St London SE1 1YR United Kingdom | Principal Investigator |
| Paul Newell, MD | AstraZeneca R&D Alderly Park, Mereside SK 104 TG Macclesfield, Cheshire United Kingdom | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research site | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26516584 | Background | Das S, Li J, Armstrong J, Learoyd M, Edeki T. Randomized pharmacokinetic and drug-drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects. Pharmacol Res Perspect. 2015 Oct;3(5):e00172. doi: 10.1002/prp2.172. Epub 2015 Aug 25. | |
| 30221827 | Derived | Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28. |
| Label | URL |
|---|---|
| Redaction of D4280C00011 Protocol | View source |
Not provided
Not provided
| ID | Term |
|---|---|
| D014552 | Urinary Tract Infections |
| D059413 | Intraabdominal Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
Not provided
Not provided
| ID | Term |
|---|---|
| C543519 | avibactam |
| D002442 | Ceftazidime |
| ID | Term |
|---|---|
| D002509 | Cephaloridine |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
IV infusion |
|
| Ceftazidime | Drug | IV infusion |
|
| Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including area under the curve of plasma drug concentration (AUC) - time curve from zero to the time of the last quantifiable concentration | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including AUC, Day 1 only | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including AUC during the dosing interval [AUC(0-τ)] | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including terminal half-life (t1/2) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including systemic plasma clearance (CL) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including volume of distribution at steady state (Vss) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including volume of distribution at the terminal phase (Vz) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including accumulation ratio for Cmax and AUC(0-τ) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including linearity index | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Urine pharmacokinetic variables will be measured including amount of drug excreted unchanged into urine from zero to time t [Ae(0-t)] | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Urine pharmacokinetic variables will be measured including fraction of dose excreted unchanged into urine (fe; % dose) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Urine pharmacokinetic variables will be measured including renal clearance (CLR) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Cmax | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including tmax | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Cmin | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including tmin | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Clast | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including tlast | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Cavg | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including fluctuation index | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including AUC(0-t) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including AUC, Day 1 only | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including AUC(0-τ) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including t1/2 | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including CL | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Vss | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Vz | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including accumulation ratio for Cmax and AUC(0-τ) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including linearity index | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Urine pharmacokinetic variables will be measured including Ae(0-t) | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Urine pharmacokinetic variables will be measured including fe; % dose | Up to 24 hours post last dose |
| Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Urine pharmacokinetic variables will be measured including CLR | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Cmax | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including tmax | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Cmin | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including tmin | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Clast | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including tlast | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Cavg | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including fluctuation index | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including AUC(0-t) | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including AUC, Day 1 only | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including AUC(0-τ) | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including t1/2 | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including CL | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Vss | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Vz | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including accumulation ratio for Cmax and AUC(0-τ) | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including linearity index | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Urine pharmacokinetic variables will be measured including Ae(0-t) | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Urine pharmacokinetic variables will be measured including fe; % dose | Up to 24 hours post last dose |
| Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Urine pharmacokinetic variables will be measured including CLR | Up to 24 hours post last dose |
| To assess safety and tolerability of Avibactam by assessment of vital signs | Up to 24 hours post last dose |
| To assess safety and tolerability of Avibactam by assessment of safety electrocardiogram | Up to 24 hours post last dose |
| To assess safety and tolerability of Avibactam by assessment of physical examination | Up to 24 hours post last dose |
| To assess safety and tolerability of Avibactam by assessment of withdrawn | Up to 24 hours post last dose |
| To assess safety and tolerability of Ceftazidime by assessment of Adverse events | Up to 24 hours post last dose |
| To assess safety and tolerability of Ceftazidime by clinical laboratory assessments | Up to 24 hours post last dose |
| To assess safety and tolerability of Ceftazidime by assessment of vital signs | Up to 24 hours post last dose |
| To assess safety and tolerability of Ceftazidime by assessment of safety electrocardiogram | Up to 24 hours post last dose |
| To assess safety and tolerability of Ceftazidime by assessment of physical examination | Up to 24 hours post last dose |
| To assess safety and tolerability of Ceftazidime by assessment of withdrawn | Up to 24 hours post last dose |
| To assess safety and tolerability of CAZ104 by assessment of Adverse events | Up to 24 hours post last dose |
| To assess safety and tolerability of CAZ104 by clinical laboratory assessments | Up to 24 hours post last dose |
| To assess safety and tolerability of CAZ104 by assessment of vital signs | Up to 24 hours post last dose |
| To assess safety and tolerability of CAZ104 by assessment of safety electrocardiogram | Up to 24 hours post last dose |
| To assess safety and tolerability of CAZ104 by assessment of physical examination | Up to 24 hours post last dose |
| To assess safety and tolerability of CAZ104 by assessment of withdrawn | Up to 24 hours post last dose |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000577 |
| Amides |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |