Clinical trial NCT06593054: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ceftibuten
avibactam prodrug
relative bioavailability
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration [Cmax] of cis-CTB and AVI following test formulation administration in fasted or fed state
timeFrame: Through 48 hours in period 1, 2, 3
measure: Dose-normalized Maximum Observed Plasma Concentration [Cmax(dn)] of cis-CTB and AVI following test/ reference formulation administration
timeFrame: Through 48 hours in period 1, 2, 3
measure: 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
timeFrame: Through 48 hours in period 1, 2, 3
measure: 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
timeFrame: Through 48 hours in period 1, 2, 3
measure: 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
timeFrame: Through 48 hours in period 1, 2, 3
measure: 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
timeFrame: Through 48 hours in period 1, 2, 3
Secondary outcomes:
measure: Number of participants with Treatment Emergent Adverse Events (TEAE)
timeFrame: 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
measure: Severity of treatment-emergent adverse events (TEAEs)
timeFrame: 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
measure: Causal relationship of treatment-emergent adverse events (TEAEs)
timeFrame: 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
measure: Withdrawals due to treatment-emergent adverse events (TEAEs)
timeFrame: 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
measure: Number of Participants With Laboratory Abnormalities
timeFrame: 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
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: 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
measure: Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings
timeFrame: 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
measure: Time to Cmax (Tmax) of cis-CTB, AVI and hydroxypivalic acid (HPA)
timeFrame: Through 48 hours in period 1, 2, 3
measure: Terminal Elimination Half-Life (t1/2) (if data permit) of cis-CTB, AVI and HPA
timeFrame: Through 48 hours in period 1, 2, 3
measure: Apparent Oral Volume of Distribution (Vz/F) (if data permit) of cis-CTB, AVI and HPA
timeFrame: Through 48 hours in period 1, 2, 3
measure: Apparent Oral Clearance (CL/F) (if data permit) of cis-CTB, AVI and HPA
timeFrame: Through 48 hours in period 1, 2, 3
measure: Dose-Normalized Maximum Observed Plasma Concentration [Cmax(dn)] of HPA
timeFrame: Through 48 hours in period 1, 2, 3
measure: Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUClast(dn)] of HPA
timeFrame: Through 48 hours in period 1, 2, 3
measure: Dose-Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf(dn)] (if data permit)of HPA
timeFrame: Through 48 hours in period 1, 2, 3
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: