Complicated Intra-Abdominal Infections, cIAIsPhase 2NCT02655419
Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)
A Phase 2 study testing ATM-AVI and Metronidazole in people with Complicated Intra-Abdominal Infections, cIAIs, run by Pfizer at 11 sites in 3 countries.
Trial summary
Determine the PK and safety and tolerability of aztreonam-avibactam (ATM-AVI) in the treatment of hospitalized adults with cIAI Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Complicated Intra-Abdominal Infections, cIAIs
- What is being tested?
- ATM-AVI and Metronidazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 19 May 2016to 26 Oct 2017
- Phase
- Phase 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent
- Male or female from 18 to 90 years
- Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met
- Diagnosis of cIAI
- EITHER:
- Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry
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- Patients who failed prior antibacterial treatment for their current cIAI can be enrolled but must:
- Have a known or suspected pathogen causing cIAI that is resistant to the prior therapy
- Require surgical intervention.
- Patient must have or will have a surgical intervention within 24 hours (before or after) the administration of the first dose of study drug
Who cannot join
- Involvement in the planning and/or conduct of the study
- Patient has been previously enrolled in this study, previously treated with ATM-AVI or previously participated in an investigational study containing AVI
- Patient has participated or intends to participate in any other clinical study that involves the administration of a study drug during the course of the study, or during the 30 days prior to study start.
- History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
- Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery within 24 hours of diagnosis primary etiology is not likely to be infectious
- Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess or ischaemic/necrotic intestine without perforation
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- Staged abdominal repair (STAR), open abdomen technique or where infection source control is not likely to be achieved; unlikely to solely respond to antimicrobial therapy
- Infection due to a pathogen that is unlikely to respond to ATM-AVI plus metronidazole
- Rapidly progressive or terminal illness
- Systemic antibacterial agents received within the 72- hour period prior to study entry, unless:
- A new infection and no more than 24 hours of prior antibiotic treatment received within the 72 hour period prior to study entry or
- Patient is considered to have failed the previous treatment
- Concurrent infection that may interfere with the evaluation of clinical cure for the study therapy
- requirement for effective concomitant systemic antibacterials or antifungals
- Creatinine clearance ≤30 ml/min or requirement for renal replacement therapy
- Acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure
- Hepatic disease as indicated by AST or ALT >3 × ULN. Patients with AST and/or ALT >3 × ULN and < 5 × ULN are eligible if acute, not accompanied by a total bilirubin ≥ 2xULN and documented by the investigator as being directly related to cIAI.
- Patient has a total bilirubin >3 × ULN, unless isolated hyperbilirubinemia is directly related to cIAI or due to known Gilbert's disease
- ALP >3 × ULN. Patients with values >3 × ULN and <5 x ULN are eligible if acute and directly related to the infectious process being treated.
- Immunocompromising illness
- Active Clostridium difficile associated diarrhoea
- Any other condition that may confound the results of the study or pose additional risks
- Do not resuscitate order
- Absolute neutrophil count <1000/μL
- Hematocrit <25% or hemoglobin <8 gm/dL.
- Platelet count <75,000/μL.
- Currently receiving probenecid.
- Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
- Unlikely to comply with protocol,
- Currently receiving anti-convulsant therapy to prevent recurrence of a past history of seizures.
- Prior liver, pancreas or small-bowel transplant.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
Spain7 sites
Hospital Universitario Cruces
Barakaldo, Bizkaia, 48903
Hospital Universitari del Mar
Barcelona, 08003
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Universitario Son Espases
Palma de Mallorca, ISLA Baleares, 07010
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitario Mutua de Tarrasa
Terrassa, 08221
Germany2 sites
Universitaetsklinikum Koeln Innere Medizin I
Cologne, 50937
Universitaetsklinikum Schleswig-Holstein, Klinik fuer Infektiologie und Mikrobiologie, DZIF-CTU
Lübeck, 23538
About this study
Official title: A PHASE IIA PROSPECTIVE, OPEN-LABEL, MULTICENTER STUDY TO DETERMINE THE PHARMACOKINETICS (PK) AND SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) FOR THE TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAIS) IN HOSPITALIZED ADULTS
Determine the PK and safety and tolerability of aztreonam-avibactam (ATM-AVI) in the treatment of hospitalized adults with cIAI
Read the detailed description
A Phase IIa prospective, open-label, multicenter study to determine the pharmacokinetics (PK) and safety and tolerability of aztreonam-avibactam (ATM-AVI) for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults.
- Being tested
- ATM-AVI, Metronidazole
- Keywords
- cIAIs in hospitalized adults
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATM-AVIDrug
Cohort 1:
(Creatinine clearance > 50 mL/min)6500mg ATM/1777mg AVI on day 1 followed by total daily dose of 6000mg ATM/1640mg AVI
Cohorts 2 and 3:
(Creatinine clearance > 50 mL/min) As above, or: 6500 mg ATM/2167 mg on Day 1 followed by a total daily dose of 6000 mg ATM/2000 m AVI
(Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1162 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/820 mg AVI, or:
4250 mg ATM/1417 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/1000 mg AVI
MetronidazoleDrug
Metronidazole 500mg infused over 1 hour every 8 hours
| Study group | Role | What they receive |
|---|---|---|
| ATM-AVI + Metronidazole | Experimental | Aztreonam-avibactam + metronidazole Receives: Drug: ATM-AVI; Drug: Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr
All participants were to have sparse pharmacokinetics (PK) sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above lower limit of quantification (LLOQ). LLOQ for ATM was 0.1 microgram per milliliter (mcg/ml).
Measured: Predose (0 hr) on Day 1
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 0.42 hr Post dose on Day 1
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 3.25 hr Post dose on Day 1
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 5 hr Post dose on Day 1
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 nanogram per milliliter (ng/ml).
Measured: Predose (0 hr) on Day 1
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 0.42 hr Post dose on Day 1
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 3.25 hr Post dose on Day 1
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 5 hr Post dose on Day 1
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: Predose (0 hr) on Day 4
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 2.75 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 5 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: Predose (0 hr) on Day 4
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 2.75 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 5 hr Post dose on Day 4
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: Predose (0 hr) on Day 4
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 0.5 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 1 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 2 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 3 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 3.25 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 3.5 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 3.75 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 4 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 5 hr Post dose on Day 4
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Measured: 6 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: Predose (0 hr) on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 0.5 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 1 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 2 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 3 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 3.25 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 3.5 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 3.75 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 4 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 5 hr Post dose on Day 4
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Measured: 6 hr Post dose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Aztreonam (ATM): Intensive Sampling at Day 4
AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Avibactam (AVI): Intensive Sampling at Day 4
AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Aztreonam (ATM): Intensive Sampling at Day 4
AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Avibactam (AVI): Intensive Sampling at Day 4
AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Plasma elimination half-life was defined as time measured for the plasma concentration of ATM and AVI to decrease by one half of its initial concentration.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Apparent volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Measured: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAEs was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or was an important medical event which may jeopardise the participants or require medical intervention to prevent one of the above outcomes. Treatment-emergent were events between first infusion of study drug and up to late follow-up (LFU) visit (20 to 24 days after last infusion). AEs included both non-serious AEs and SAEs.
Measured: From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Number of Participants With Electrocardiogram (ECG) Abnormalities
Criteria for ECG abnormalities: QT value: greater than or equal to (>=) 450 milliseconds (msec), >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QT: >=30 msec, >=60 msec. Decrease from baseline in QT: >=30 msec, >=60 msec. QTcB value: >=450 msec, >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QT interval using Bazett's correction (QTcB) value: >=30 msec, >=60 msec. Decrease from baseline in QTcB: >=30 msec, >=60 msec. QT interval using Fridericia's correction (QTcF) value: >=450 msec, >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QTcF value: >=30 msec, >=60 msec. Decrease from baseline in QTcF value: >=30 msec, >=60 msec. EOT (end of treatment) visit occurred within 24 hours after last infusion.
Measured: Baseline up to EOT (up to a maximum of 15 days)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters
Criteria for abnormality: Hemoglobin, hematocrit, erythrocytes less than(<) 0.7*lower limit of normal [LLN] and (\&) greater than (>) 30 percent (%) below baseline [BB]; >1.3*upper limit of normal [ULN] \& >30% above baseline [AB], leukocytes <0.65*LLN \& >60% BB; >1.6* ULN \& >100% AB; platelets <0.65*LLN \& >50% BB; >1.5*ULN \& >100% AB; neutrophils <0.65*LLN \& >75% BB; >1.6*ULN \& >100% AB, lymphocytes <0.25*LLN \& >75%BB; >1.5*ULN \& >100% AB, basophils, eosinophils, monocytes>4.0*ULN \& >300% AB. LFU visit occurred within 20 to 24 days after last infusion.
Measured: Baseline up to LFU visit (up to maximum of 38 days)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres
Criteria for abnormality: aspartate aminotransferase, alanine aminotransferase >3.0*ULN \& >100% AB, alkaline phosphatase <0.5 *LLN \& >80% BB\&; >3.0*ULN \& >100% AB; bilirubin >1.5*ULN \& >100% AB; direct bilirubin >2.0*ULN \& >150% AB; protein <0.5*LLN \& >50%BB; >1.5*ULN \& >50% AB, albumin <0.5*LLN \& >50% BB; >1.5*ULN \& >50% AB, urea nitrogen <0.2* LLN \& >100% BB; >3.0*ULN \& >200% AB, creatinine >2.0*ULN \& >100% AB, sodium <0.85*LLN \& >10% BB;>1.1*ULN \&>10% AB; potassium <0.8*LLN \&>20% BB; >1.2*ULN \&>20% AB, chloride <0.8*LLN \&>20% BB;>1.2*ULN \& >20% AB, calcium <0.7*LLN \& >30% BB; >1.3*ULN \& >30% AB, phosphate <0.5*LLN \& >50% BB; >3.0*ULN \& >200% AB, bicarbonate <0.7*LLN \& >40% BB; >1.3*ULN \& >40% AB, glucose <0.6*LLN \& >40% BB, >3.0*ULN \& >200% AB. LFU visit occurred within 20 to 24 days after last infusion.
Measured: Baseline up to LFU visit (up to maximum of 38 days)
Number of Participants With Clinically Significant Vital Signs
Vital sign parameters included: Supine systolic blood pressure (millimeters of mercury [mmHg]), Supine diastolic blood pressure (mmHg), Heart rate (beats per minute), Respiratory rate (breaths per minute) and body temperature (degree celsius). Criteria for clinical significance in vital signs was based on investigator's assessment. LFU visit occurred within 20 to 24 days after last infusion.
Measured: From first dose of study drug up to LFU visit (up to maximum of 38 days)
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population
Physical examinations included an assessment of abdomen, cardiovascular, general appearance, head, eyes, ears, nose, lymph nodes, skin, musculoskeletal, neurological, respiratory systems and other (edemas). Clinically significant abnormality in physical examination was based on investigator's assessment. LFU visit occured within 20 to 24 days after last infusion.
Measured: From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Secondary outcomes (6)
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: MITT Population
Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of the index infection (cIAI) such as no further antimicrobial therapy, drainage, or surgical intervention is necessary and does not meet any of the failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within the abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. TOC visit occurred up to a maximum of 28 days after first dose.
Measured: Test of Cure Visit (up to a maximum of 28 days)
Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population
Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of the index infection (cIAI) such as no further antimicrobial therapy, drainage, or surgical intervention is necessary and does not meet any of the failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within the abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. TOC visit occurred up to a maximum of 28 days after first dose.
Measured: Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population)
AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Measured: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population)
AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Measured: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population)
AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Measured: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population)
AUC(0-6): area under the plasma concentration-time curve from time 0 upto the 6hrs. Clinical cure;complete resolution or significant improvement of signs and symptoms of the index infection(cIAI)such as no further antimicrobial therapy, drainage, or surgical intervention necessary and does not meet any of failure criteria. Failure: death related to intra-abdominal infection; received treatment with additional antibiotics for ongoing symptoms of cIAI; previously met criteria for failure; persisting or recurrent infection within abdomen; post-surgical wound infections included an open wound with signs of local infection such as purulent exudates, erythema, or warmth that requires additional antibiotics and/or non-routine wound care. Data of AUC(0-6) based on intensive sampling at Day4, is reported in this outcome separately and only for those participants who had clinical response of cure and failure at TOC Visit. TOC visit occurred up to a maximum of 28 days after first dose.
Measured: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2016 (estimated)
- Study start19 May 2016
- Primary completion26 Oct 2017
- Study completion26 Oct 2017
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Complicated Intra-Abdominal Infections, cIAIsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Innovative Medicines Initiative
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, PfizerOliver Cornely, Principal investigator, Clinical Trials Centre Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02655419
- Sponsor's protocol ID
- D4910C00009
- Other IDs
- C3601001, 2015-002726-39, 2015
- Status last verified
- Mar 2020
- First submitted
- 1 Dec 2015
- Last updated
- 2 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Das S, Riccobene T, Carrothers TJ, Wright JG, MacPherson M, Cristinacce A, McFadyen L, Xie R, Luckey A, Raber S. Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation. Eur J Clin Pharmacol. 2024 Apr;80(4):529-543. doi: 10.1007/s00228-023-03609-x. Epub 2024 Jan 22.
PubMed 38252170Jimenez-Rodriguez RM, Martin-Gutierrez G, Jimenez-Jorge S, Rosso-Fernandez CM, Tallon-Aguilar L, Roca-Oporto C, Padillo J, Luckey A, Cano A, Lopez-Ruiz J, Gomez-Zorrilla S, Bonnin-Pascual J, Boix-Palop L, Montejo JM, Torre-Cisneros J, Cisneros JM. Factors associated with recruitment success in the phase 2a study of aztreonam-avibactam development programme: a descriptive qualitative analysis among sites in Spain. BMJ Open. 2022 Feb 3;12(2):e051187. doi: 10.1136/bmjopen-2021-051187.
PubMed 35115349Cornely OA, Cisneros JM, Torre-Cisneros J, Rodriguez-Hernandez MJ, Tallon-Aguilar L, Calbo E, Horcajada JP, Queckenberg C, Zettelmeyer U, Arenz D, Rosso-Fernandez CM, Jimenez-Jorge S, Turner G, Raber S, O'Brien S, Luckey A; COMBACTE-CARE consortium/REJUVENATE Study Group. Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study. J Antimicrob Chemother. 2020 Mar 1;75(3):618-627. doi: 10.1093/jac/dkz497.
PubMed 31828337
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE IIA PROSPECTIVE, OPEN-LABEL, MULTICENTER STUDY TO DETERMINE THE PHARMACOKINETICS (PK) AND SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) FOR THE TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAIS) IN HOSPITALIZED ADULTS
- ClinicalTrials.gov ID
- NCT02655419
- Acronym / sponsor ID
- D4910C00009
- Keywords
- cIAIs in hospitalized adults
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Innovative Medicines Initiative
- Study start
- 19 May 2016 (actual)
- Primary completion
- 26 Oct 2017 (actual)
- Study completion
- 26 Oct 2017 (actual)
- First posted
- 14 Jan 2016 (estimated)
- Results
- Posted 4 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determine the PK and safety and tolerability of aztreonam-avibactam (ATM-AVI) in the treatment of hospitalized adults with cIAI
Detailed description
A Phase IIa prospective, open-label, multicenter study to determine the pharmacokinetics (PK) and safety and tolerability of aztreonam-avibactam (ATM-AVI) for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATM-AVI + Metronidazole | Experimental | Drug: ATM-AVI, Drug: MetronidazoleAztreonam-avibactam + metronidazole |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of informed consent
- Male or female from 18 to 90 years
- Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met
- Diagnosis of cIAI
- Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry
Key exclusion criteria (31 listed)
- Involvement in the planning and/or conduct of the study
- Patient has been previously enrolled in this study, previously treated with ATM-AVI or previously participated in an investigational study containing AVI
- Patient has participated or intends to participate in any other clinical study that involves the administration of a study drug during the course of the study, or during the 30 days prior to study start.
- History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
- Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery within 24 hours of diagnosis primary etiology is not likely to be infectious
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 |
|---|---|---|
| ATM-AVICohort 1: (Creatinine clearance > 50 mL/min)6500mg ATM/1777mg AVI on day 1 followed by total daily dose of 6000mg ATM/1640mg AVI Cohorts 2 and 3: (Creatinine clearance > 50 mL/min) As above, or: 6500 mg ATM/2167 mg on Day 1 followed by a total daily dose of 6000 mg ATM/2000 m AVI (Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1162 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/820 mg AVI, or: 4250 mg ATM/1417 mg AVI on Day 1 followed by total daily dose 3000 mg ATM/1000 mg AVI | Drug | ATM-AVI + Metronidazole |
| MetronidazoleMetronidazole 500mg infused over 1 hour every 8 hours | Drug | ATM-AVI + Metronidazole |
Primary outcome
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr
Time frame: Predose (0 hr) on Day 1
All participants were to have sparse pharmacokinetics (PK) sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above lower limit of quantification (LLOQ). LLOQ for ATM was 0.1 microgram per milliliter (mcg/ml).
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr
Time frame: 0.42 hr Post dose on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr
Time frame: 3.25 hr Post dose on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr
Time frame: 5 hr Post dose on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr
Time frame: Predose (0 hr) on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 nanogram per milliliter (ng/ml).
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr
Time frame: 0.42 hr Post dose on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr
Time frame: 3.25 hr Post dose on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr
Time frame: 5 hr Post dose on Day 1
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr
Time frame: Predose (0 hr) on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr
Time frame: 2.75 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr
Time frame: 5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr
Time frame: Predose (0 hr) on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 2.75 hr
Time frame: 2.75 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 5 hr
Time frame: 5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0 hr
Time frame: Predose (0 hr) on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration Aztreonam (ATM): Intensive Sampling at Day 4, 0.5 hr
Time frame: 0.5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 1 hr
Time frame: 1 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 2 hr
Time frame: 2 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3 hr
Time frame: 3 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.25 hr
Time frame: 3.25 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.5 hr
Time frame: 3.5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 3.75 hr
Time frame: 3.75 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 4 hr
Time frame: 4 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 5 hr
Time frame: 5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Aztreonam (ATM): Intensive Sampling at Day 4, 6 hr
Time frame: 6 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0 hr
Time frame: Predose (0 hr) on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 0.5 hr
Time frame: 0.5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 1 hr
Time frame: 1 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 2 hr
Time frame: 2 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3 hr
Time frame: 3 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.25 hr
Time frame: 3.25 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.5 hr
Time frame: 3.5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 3.75 hr
Time frame: 3.75 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 4 hr
Time frame: 4 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 5 hr
Time frame: 5 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Plasma Concentration of Avibactam (AVI): Intensive Sampling at Day 4, 6 hr
Time frame: 6 hr Post dose on Day 4
All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.
Maximum Observed Plasma Concentration (Cmax) of Aztreonam (ATM): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Time of Observed Maximum Concentration (Tmax) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Aztreonam (ATM): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours (AUC[0-6]) for Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
AUC(0-6) was defined as the area under the plasma concentration-time curve from time zero up to the six hours postdose.
Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Aztreonam (ATM): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.
Area Under the Plasma Concentration Time Curve From Time Zero up to the Last Measured Concentration (AUC[0-last]) for Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
AUC(0-last) was defined as the area under the plasma concentration-time curve from time zero up to the time of the last measurable concentration.
Time of Last Measured Concentration (Tlast) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Plasma Elimination Half-life (t1/2) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Plasma elimination half-life was defined as time measured for the plasma concentration of ATM and AVI to decrease by one half of its initial concentration.
Apparent Volume of Distribution at Steady State (Vss) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Apparent volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Volume of Distribution (Vz) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Apparent Clearance (CL) of Aztreonam (ATM) and Avibactam (AVI): Intensive Sampling at Day 4
Time frame: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4
Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug up to the LFU visit (up to maximum of 38 days)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAEs was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or was an important medical event which may jeopardise the participants or require medical intervention to prevent one of the above outcomes. Treatment-emergent were events between first infusion of study drug and up to late follow-up (LFU) visit (20 to 24 days after last infusion). AEs included both non-serious AEs and SAEs.
Number of Participants With Electrocardiogram (ECG) Abnormalities
Time frame: Baseline up to EOT (up to a maximum of 15 days)
Criteria for ECG abnormalities: QT value: greater than or equal to (>=) 450 milliseconds (msec), >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QT: >=30 msec, >=60 msec. Decrease from baseline in QT: >=30 msec, >=60 msec. QTcB value: >=450 msec, >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QT interval using Bazett's correction (QTcB) value: >=30 msec, >=60 msec. Decrease from baseline in QTcB: >=30 msec, >=60 msec. QT interval using Fridericia's correction (QTcF) value: >=450 msec, >=480 msec, >=500 msec, >=500 and increase from baseline >=60 msec. Increase from baseline in QTcF value: >=30 msec, >=60 msec. Decrease from baseline in QTcF value: >=30 msec, >=60 msec. EOT (end of treatment) visit occurred within 24 hours after last infusion.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Hematology Parameters
Time frame: Baseline up to LFU visit (up to maximum of 38 days)
Criteria for abnormality: Hemoglobin, hematocrit, erythrocytes less than(<) 0.7*lower limit of normal [LLN] and (\&) greater than (>) 30 percent (%) below baseline [BB]; >1.3*upper limit of normal [ULN] \& >30% above baseline [AB], leukocytes <0.65*LLN \& >60% BB; >1.6* ULN \& >100% AB; platelets <0.65*LLN \& >50% BB; >1.5*ULN \& >100% AB; neutrophils <0.65*LLN \& >75% BB; >1.6*ULN \& >100% AB, lymphocytes <0.25*LLN \& >75%BB; >1.5*ULN \& >100% AB, basophils, eosinophils, monocytes>4.0*ULN \& >300% AB. LFU visit occurred within 20 to 24 days after last infusion.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities in Clinical Chemistry Paramteres
Time frame: Baseline up to LFU visit (up to maximum of 38 days)
Criteria for abnormality: aspartate aminotransferase, alanine aminotransferase >3.0*ULN \& >100% AB, alkaline phosphatase <0.5 *LLN \& >80% BB\&; >3.0*ULN \& >100% AB; bilirubin >1.5*ULN \& >100% AB; direct bilirubin >2.0*ULN \& >150% AB; protein <0.5*LLN \& >50%BB; >1.5*ULN \& >50% AB, albumin <0.5*LLN \& >50% BB; >1.5*ULN \& >50% AB, urea nitrogen <0.2* LLN \& >100% BB; >3.0*ULN \& >200% AB, creatinine >2.0*ULN \& >100% AB, sodium <0.85*LLN \& >10% BB;>1.1*ULN \&>10% AB; potassium <0.8*LLN \&>20% BB; >1.2*ULN \&>20% AB, chloride <0.8*LLN \&>20% BB;>1.2*ULN \& >20% AB, calcium <0.7*LLN \& >30% BB; >1.3*ULN \& >30% AB, phosphate <0.5*LLN \& >50% BB; >3.0*ULN \& >200% AB, bicarbonate <0.7*LLN \& >40% BB; >1.3*ULN \& >40% AB, glucose <0.6*LLN \& >40% BB, >3.0*ULN \& >200% AB. LFU visit occurred within 20 to 24 days after last infusion.
Number of Participants With Clinically Significant Vital Signs
Time frame: From first dose of study drug up to LFU visit (up to maximum of 38 days)
Vital sign parameters included: Supine systolic blood pressure (millimeters of mercury [mmHg]), Supine diastolic blood pressure (mmHg), Heart rate (beats per minute), Respiratory rate (breaths per minute) and body temperature (degree celsius). Criteria for clinical significance in vital signs was based on investigator's assessment. LFU visit occurred within 20 to 24 days after last infusion.
Number of Participants With Clinical Significant Physical Examination Findings : MITT Population
Time frame: From first dose of study drug up to the LFU visit (up to maximum of 38 days)
Physical examinations included an assessment of abdomen, cardiovascular, general appearance, head, eyes, ears, nose, lymph nodes, skin, musculoskeletal, neurological, respiratory systems and other (edemas). Clinically significant abnormality in physical examination was based on investigator's assessment. LFU visit occured within 20 to 24 days after last infusion.
6 secondary outcomes
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: MITT Population
Time frame: Test of Cure Visit (up to a maximum of 28 days)
Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Modified Intent-to-Treat (mMITT) Population
Time frame: Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population)
Time frame: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (MITT Population)
Time frame: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Aztreonam (ATM) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population)
Time frame: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Area Under the Plasma Concentration Time Curve From Time Zero up to 6 Hours [AUC(0-6)] of Avibactam (AVI) for Participants With Clinical Cure and Failure at TOC Visit: Intensive Sampling at Day 4 (mMITT Population)
Time frame: Plasma samples collection for AUC0-6 at: predose, 0.5 1, 2, 3, 3.25, 3.5, 3.75, 4, 5 and 6 hour postdose on Day 4 assessed for participants with cure and failure at Test of Cure Visit (up to a maximum of 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38252170Das S, Riccobene T, Carrothers TJ, Wright JG, MacPherson M, Cristinacce A, McFadyen L, Xie R, Luckey A, Raber S. Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation. Eur J Clin Pharmacol. 2024 Apr;80(4):529-543. doi: 10.1007/s00228-023-03609-x. Epub 2024 Jan 22.
- Derived from this study: PubMed 35115349Jimenez-Rodriguez RM, Martin-Gutierrez G, Jimenez-Jorge S, Rosso-Fernandez CM, Tallon-Aguilar L, Roca-Oporto C, Padillo J, Luckey A, Cano A, Lopez-Ruiz J, Gomez-Zorrilla S, Bonnin-Pascual J, Boix-Palop L, Montejo JM, Torre-Cisneros J, Cisneros JM. Factors associated with recruitment success in the phase 2a study of aztreonam-avibactam development programme: a descriptive qualitative analysis among sites in Spain. BMJ Open. 2022 Feb 3;12(2):e051187. doi: 10.1136/bmjopen-2021-051187.
- Derived from this study: PubMed 31828337Cornely OA, Cisneros JM, Torre-Cisneros J, Rodriguez-Hernandez MJ, Tallon-Aguilar L, Calbo E, Horcajada JP, Queckenberg C, Zettelmeyer U, Arenz D, Rosso-Fernandez CM, Jimenez-Jorge S, Turner G, Raber S, O'Brien S, Luckey A; COMBACTE-CARE consortium/REJUVENATE Study Group. Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study. J Antimicrob Chemother. 2020 Mar 1;75(3):618-627. doi: 10.1093/jac/dkz497.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Complicated Intra-Abdominal Infections, cIAIs
RecruitingObservational study
Real-World Effectiveness of Aztreonam-Avibactam Against MBL-Producing CRE
Complicated Intra-Abdominal Infections, cIAIs, Hospital-acquired Pneumonia (HAP)
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
Oliver Cornely principal investigator
Clinical Trials Centre Cologne
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATM-AVI and Metronidazole in people with Complicated Intra-Abdominal Infections, cIAIs, run by Pfizer at 11 sites in 3 countries.
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 10 inclusion and 31 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 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Spain, France, Germany. 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 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 4 Mar 2019). 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?
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr (time frame: Predose (0 hr) on Day 1). The study lists 54 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02655419, which also lists 3 linked publications.
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 2 Apr 2020.