To Learn How Different Forms of Study Medicine Are Taken up Into the Blood and the Effect of Food on Study Medicine in Healthy Adults

An Interventional Open-Label, Single-Dose, 4-Treatment, 4-Period Crossover Study to Evaluate the Relative Bioavailability of CTB and AVI Administered Via Various Tablets or Capsule Formulations of PF-07612577 (PF-06264006 [CTB] - PF-07338233 [AVP]) and the Effect of Food on the Bioavailability of CTB and AVI Administered Via Tablets in Healthy Adult Participants

The purpose of this study is to learn about the study medicine CTB-AVP for the treatment of severe urinary tract infections that require hospitalization.

This study is seeking for:

• adult male and female participants who are healthy and weigh more than 50 kg.
• participants who have normal blood pressure, normal kidney and liver function
• participants willing to stay away from caffeine and other medicines for the duration of the study.

Participants will be required to stay in the study clinic for two weeks. All participants in this study will receive study medicine CTB-AVP by mouth one time each day on four different days. Study medicine will be given in capsules or tablets, on an empty stomach or will be taken with a meal. The study will look at the experiences of people receiving the study medicine. This will help determine if the study medicine is safe and effective.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ceftibuten; Drug: Avibactam prodrug; Drug: CTB-AVP in Tablet

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female participants aged 18 years or older at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and standard 12-lead electrocardiogram (ECGs), and with eGFR ≥75 mL/min (estimated using the 2021 CKD-EPI equation).
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Have a body-mass index (BMI) of 16 to 32 kg/m2; and a total body weight >50 kg (110 lb).
4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease; including any condition affecting oral absorption or known allergy to cephalosporin group of antibiotics
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention or current use of any prohibited concomitant medications.
• Screening supine Blood Pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm Hg for participants ≥60 years old, following at least 5 minutes of supine rest
• Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: alanine aminotransferase (ALT), aspartate aminotransferase (AST), Bilirubin ≥1.5 x Upper Limit of Normal (ULN). Participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTB-AVP Capsules, fasted; Reference formulation of CTB-AVP in capsules, administered under fasted conditions	Drug: Ceftibuten; Ceftibuten dihydrate, formulated in capsules; Drug: Avibactam prodrug; Avibactam prodrug, formulated in capsules
Experimental: CTB-AVP Tablet , fasted; Test formulation of CTB-AVP in tablets, administered under fasted conditions	Drug: CTB-AVP in Tablet; ceftibuten and avibactam prodrug, in Tablet formulation
Experimental: CTB-AVP Tablet , fed; Test formulation of CTB-AVP in tablets, administered under fed conditions	Drug: CTB-AVP in Tablet; ceftibuten and avibactam prodrug, in Tablet formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration [Cmax] of cis-CTB and AVI following test formulation administration in fasted or fed state	Cmax is estimated based on the plasma concentrations for test and reference formulation	Through 48 hours in period 1, 2, 3
Dose-normalized Maximum Observed Plasma Concentration [Cmax(dn)] of cis-CTB and AVI following test/ reference formulation administration	Cmax is estimated based on the plasma concentrations for test and reference formulation and then normalized by dose	Through 48 hours in period 1, 2, 3
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of cis-CTB and AVI following test formulation administration in fasted or fed state	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Through 48 hours in period 1, 2, 3
Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUClast(dn)] of cis-CTB and AVI following test/ reference formulation administration	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) normalized by dose	Through 48 hours in period 1, 2, 3
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of cis-CTB and AVI (if data permit) following test formulation administration in fasted or fed state	AUC (inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUClast plus AUClast to infinity.	Through 48 hours in period 1, 2, 3
Dose-Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf(dn)] of cis-CTB and AVI (if data permit) following test/ reference formulation administration	AUC (inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUClast plus AUClast to infinity normalized by dose	Through 48 hours in period 1, 2, 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment Emergent Adverse Events (TEAE)	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment	Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Severity of treatment-emergent adverse events (TEAEs)		Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Causal relationship of treatment-emergent adverse events (TEAEs)		Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Withdrawals due to treatment-emergent adverse events (TEAEs)		Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Number of Participants With Laboratory Abnormalities	Blood samples collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, alanine aminotransferase [ALT], blood urea nitrogen [BUN], creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.	Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP) and pulse rate. Baseline will be the measurement taken on Day -1 and change from baseline (CFB) will be calculated for all post-baseline timepoints, and would be reported as per Sponsor's reporting standards.	Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings	Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥60 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG	Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention
Time to Cmax (Tmax) of cis-CTB, AVI and hydroxypivalic acid (HPA)	Tmax = time (hours) to maximum plasma concentration (Cmax).	Through 48 hours in period 1, 2, 3
Terminal Elimination Half-Life (t1/2) (if data permit) of cis-CTB, AVI and HPA	Elimination half-life means the time required for the plasma concentration to decline by 50% during the elimination phase- if data permit	Through 48 hours in period 1, 2, 3
Apparent Oral Volume of Distribution (Vz/F) (if data permit) of cis-CTB, AVI and HPA	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-If data permit	Through 48 hours in period 1, 2, 3
Apparent Oral Clearance (CL/F) (if data permit) of cis-CTB, AVI and HPA	Clearance of a drug was measure of the rate at which the drug was metabolized or eliminated by normal biological processes- if data permit	Through 48 hours in period 1, 2, 3
Dose-Normalized Maximum Observed Plasma Concentration [Cmax(dn)] of HPA		Through 48 hours in period 1, 2, 3
Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUClast(dn)] of HPA		Through 48 hours in period 1, 2, 3
Dose-Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf(dn)] (if data permit)of HPA		Through 48 hours in period 1, 2, 3

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Actual): October 11, 2024
• Study Completion (Actual): October 11, 2024

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: September 9, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: relative bioavailability; ceftibuten; avibactam prodrug
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; beta-Lactamase Inhibitors; Ceftibuten; Avibactam
• Other Study ID Numbers: C4691003; 2023-507117-10-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No