HealthyPhase 1NCT05554237

A Study to Learn About the Study Medicine Called CTB+AVP in Healthy Adult People.

A Phase 1 study testing PF-07612577 and PF-06264006 in people with Healthy, run by Pfizer at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this clinical trial is to learn about the pharmacokinetics, safety and tolerability of various single- and multiple-doses of CTB+AVP in healthy adult participants. CTB+AVP is a study medicine that is being developed to treat people with complicated urinary tract infections. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: PF-07612577 and PF-06264006
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 42 participants
Where: 1 siteBelgium
Study dates: 7 Oct 2022to 23 Jun 2023
Phase: Phase 1
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 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
For optional Japanese cohort only: Japanese participants who have 4 Japanese biologic grandparents who were born in Japan
For optional Chinese cohort only: Chinese participants who were born in mainland China, and both parents are of Chinese descent.

Who cannot join

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing)
Known allergy to the cephalosporin group of antibiotics
History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality [or other conditions or situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence)] that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
A positive urine drug test
Positive test result for SARS-CoV-2 infection at the time of screening or Day -1

Trial locations and contacts

1 site in 1 country.

Belgium1 site

Pfizer Clinical Research Unit - Brussels
Brussels, Bruxelles-capitale, Région de, B-1070

Other trials in Belgium

About this study

Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE AND MULTIPLE-DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07612577 (PF-06264006 [CTB] + PF-07338233 [AVP]) IN HEALTHY ADULT PARTICIPANTS

This study is seeking healthy adult male and female participants, 18-60 years of age, with a body weight > 50 kg and a BMI of 17.5 to 30.5 kg/m2.

Participants in Part-1 of the study will receive increasing single doses of CTB and/or AVP. Participants in Part-2 will receive increasing multiple doses of CTB+AVP three times a day for 7 days. The study team will monitor how each participant is doing with the study treatments via close monitoring in an in-patient setting. Experiences of people receiving CTB+AVP will be compared to those of people who do not. This will help determine if CTB+AVP is safe and well-tolerated at each dose of the study medicine.

Participants will take part in this study for a maximum of 12 weeks for Part-1 (up to 4 weeks for screening, up to 3 weeks of taking study medicine and up to 5 weeks for safety follow-up visit) and for a maximum of 10 weeks for Part-2 (up to 4 weeks for screening, up to 1 week of taking study medicine and up to 5 weeks for safety follow-up visit). During the duration of the study, blood samples for study medicine levels, and various measures for monitoring safety such as blood samples for clinical laboratory measurements, electrocardiograms and vital sign measurements will be taken.

Read the detailed description

This is a 2-part study in healthy male and female adult participants.

Part-1 is to evaluate safety, tolerability and pharmacokinetics (PK) of 3 planned and 2 optional doses in 8 participants, in a 5-period sequential single dose design.

Part-2 is to evaluate safety, tolerability and PK of 1 planned and 2 optional cohorts in 8 participants each, in a multiple dose sequential design, with 7 days of repeated every 8 hours (q8h) dosing in each cohort. In addition, 2 optional cohorts in 6 participants each of Japanese descent and Chinese descent will also receive multiple doses of CTB+AVP repeated every 8 hours (q8h) for 7 days.

Conditions: Healthy
Being tested: Placebo, PF-07612577, PF-06264006

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Also called Placebo comparator
Placebo
PF-07612577Drug
Also called CTB+AVP
PF-07612577
PF-06264006Drug
Also called ceftibuten (CTB)
PF-06264006

Study groups in NCT05554237
Study group	Role	What they receive
PF-07612577	Experimental	Part-1: Dose 1, Dose 2, Dose 4, Dose 5 Part-2: Cohort 2-5 Receives: Drug: PF-07612577
Placebo	Placebo comparator	Part-1: Dose 1-5 Part-2: Cohort 2-4 Receives: Drug: Placebo
PF-06264006	Experimental	Part-1: Dose 3, Dose 5 Receives: Drug: PF-06264006

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Time for Cmax (Tmax) of CTB: Part 1
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1
AUClast was determined using the linear/log trapezoidal method.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1
Dose-normalized Cmax was determined as Cmax/Dose.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1
AUClast(dn) was determined as AUClast/Dose.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1
AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1
AUCinf(dn) was calculated as AUCinf/Dose.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Terminal Half-Life (t1/2) of CTB: Part 1
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Apparent Volume of Distribution (Vz/F) of CTB: Part 1
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Apparent Clearance (CL/F) of CTB: Part 1
CL/F was calculated as Dose/AUCinf.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1
The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1
AUClast(dn) was determined as AUClast/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1
The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of AVP, AVI and HPA: Part 1
AUClast was determined using the linear/log trapezoidal method. The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1
AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1
AUCinf(dn) was calculated as AUCinf/Dose.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1
CL/F was calculated as Dose/AUCinf.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. Severe TEAEs were defined as type of AE that interrupted usual activities of daily life (ADL), or significantly affects clinical status, or may require intensive therapeutic intervention. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study intervention.
Measured: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
Number of Participants With Withdrawals Due to TEAEs: Part 1
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention.
Measured: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
Number of Participants With Laboratory Test Abnormalities: Part 1
The laboratory abnormalities with non-zero participants were reported and it included: monocytes or leukocytes (greater than [>] 1.2* upper limit of normal [ULN]), urine hemoglobin scalar (greater than or equal to [>=1]) and leukocyte esterase scalar (>=1).
Measured: Up to 24 hours post-dose
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1
Vital signs included blood pressure and pulse rate and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinically significant changes in vital signs were determined by the investigator.
Measured: Up to 24 hours post-dose
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QRS duration, QT interval, QT interval correct by Bazzette's formula (QTcB) and QT interval correct by Frederica formula QTcF. ECG abnormalities included: PR interval aggregate (millisecond [msec], maximum [max.] >=300; baseline > 200 and max. increase >= 25 percent (%); baseline > 200 and max. increase >= 25%), QRS duration aggregate (msec, max >=140; max. increase >= 50%), QT interval aggregate (msec, value > 500), QTCB interval aggregate and QTCF interval aggregate (msec, 450 < max <= 480; 480 < max. <= 500; max. > 500; 30 < max. increase <= 60; max. increase > 60).
Measured: Up to 24 hours post-dose
Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of Cis-CTB and Trans-CTB: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2
Dose-normalized Cmax was determined as Cmax/Dose.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2
CL/F was calculated as Dose/AUCinf.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2
The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2
The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on day 7
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2
CL/F was calculated as Dose/AUCinf.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. Severe TEAEs were defined as type of AE that interrupted usual ADL, or significantly affects clinical status, or may require intensive therapeutic intervention. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study intervention.
Measured: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
Number of Participants With Withdrawals Due to TEAEs: Part 2
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention.
Measured: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
Number of Participants With Laboratory Test Abnormalities: Part 2
The laboratory abnormalities with non-zero participants were reported and it included: neutrophils/ leukocytes (less than [<] 0.8x lower limit of normal [LLN]), eosinophils/leukocytes (>1.2x ULN), monocytes/leukocytes (>1.2x ULN), bicarbonate (>1.1x ULN), urine glucose (>=1), ketones scalar (>=1), urine hemoglobin scalar (>=1), leukocyte esterase scalar (>=1).
Measured: From start of treatment up to Day 7
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2
Vital signs included blood pressure and pulse rate and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinically significant changes in vital signs were determined by the investigator.
Measured: From start of treatment up to Day 7
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QRS duration, QT interval, QT interval correct by Bazzette's formula (QTcB) and QT interval correct by Frederica formula QTcF. ECG abnormalities included: PR interval aggregate (millisecond [msec], maximum [max.] >=300; baseline > 200 and max. increase >= 25 percent (%); baseline > 200 and max. increase >= 25%), QRS duration aggregate (msec, max >=140; max. increase >= 50%), QT interval aggregate (msec, value > 500), QTCB interval aggregate and QTCF interval aggregate (msec, 450 < max <= 480; 480 < max. <= 500; max. > 500; 30 < max. increase <= 60; max. increase > 60).
Measured: From start of treatment up to Day 7

Secondary outcomes (11)

Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2
Measured: anytime between 0 to 8 hours post dose on Day 6
Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2
Aetau% was calculated as 100*Aetau/Dose.
Measured: anytime between 0 to 8 hours post dose on Day 6
Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2
Aetau% was calculated as 100*Aetau/Dose.
Measured: anytime between 0 to 8 hours post dose on Day 6
Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for TID dosing. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for TID dosing. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
CL/F was calculated as Dose/AUCinf. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Measured: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Oct 202223 Jun 2023

First posted26 Sep 2022
Study start7 Oct 2022
Primary completion23 Jun 2023
Study completion23 Jun 2023

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 (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies 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 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05554237
Sponsor's protocol ID: C4691001
Other IDs: 2021-005428-39
Status last verified: Jun 2024
First submitted: 21 Sep 2022
Last updated: 10 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: 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

Sahasrabudhe SA, Shoji S, Jakate AS, Abraham BK, Toussi SS, Maligalig BJ, Darekar AS, Tripathy S, Kantaridis C, Mfopou JK, Selivanova O, Bergman A, Alami NN, Singh RSP. Dose Selection for Ceftibuten Combined with Avibactam Tomilopil, a Potential Oral Alternative to Carbapenems for Patients with Complicated Urinary Tract Infections. J Clin Pharmacol. 2026 Sep;66(9):e70263. doi: 10.1002/jcph.70263.
PubMed 42678337

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE AND MULTIPLE-DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07612577 (PF-06264006 [CTB] + PF-07338233 [AVP]) IN HEALTHY ADULT PARTICIPANTS
ClinicalTrials.gov ID: NCT05554237
Acronym / sponsor ID: C4691001
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 7 Oct 2022 (actual)
Primary completion: 23 Jun 2023 (actual)
Study completion: 23 Jun 2023 (actual)
First posted: 26 Sep 2022 (actual)
Results: Posted 10 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is seeking healthy adult male and female participants, 18-60 years of age, with a body weight > 50 kg and a BMI of 17.5 to 30.5 kg/m2.

Detailed description

This is a 2-part study in healthy male and female adult participants.

Part-1 is to evaluate safety, tolerability and pharmacokinetics (PK) of 3 planned and 2 optional doses in 8 participants, in a 5-period sequential single dose design.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
PF-07612577	Experimental	Drug: PF-07612577Part-1: Dose 1, Dose 2, Dose 4, Dose 5 Part-2: Cohort 2-5
Placebo	Placebo comparator	Drug: PlaceboPart-1: Dose 1-5 Part-2: Cohort 2-4
PF-06264006	Experimental	Drug: PF-06264006Part-1: Dose 3, Dose 5

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
For optional Japanese cohort only: Japanese participants who have 4 Japanese biologic grandparents who were born in Japan
For optional Chinese cohort only: Chinese participants who were born in mainland China, and both parents are of Chinese descent.

Key exclusion criteria (6 listed)

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing)
Known allergy to the cephalosporin group of antibiotics
History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality [or other conditions or situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence)] that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
A positive urine drug test

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
PlaceboAlso: Placebo comparatorPlacebo	Drug	Placebo
PF-07612577Also: CTB+AVPPF-07612577	Drug	PF-07612577
PF-06264006Also: ceftibuten (CTB)PF-06264006	Drug	PF-06264006

Primary outcome

Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Time for Cmax (Tmax) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast was determined using the linear/log trapezoidal method.
Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-normalized Cmax was determined as Cmax/Dose.
Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast(dn) was determined as AUClast/Dose.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf(dn) was calculated as AUCinf/Dose.
Terminal Half-Life (t1/2) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Volume of Distribution (Vz/F) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Clearance (CL/F) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
CL/F was calculated as Dose/AUCinf.
Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast(dn) was determined as AUClast/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast was determined using the linear/log trapezoidal method. The lower limit of quantification for AVP was 1.0 ng/mL.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf(dn) was calculated as AUCinf/Dose.
Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
CL/F was calculated as Dose/AUCinf.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. Severe TEAEs were defined as type of AE that interrupted usual activities of daily life (ADL), or significantly affects clinical status, or may require intensive therapeutic intervention. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study intervention.
Number of Participants With Withdrawals Due to TEAEs: Part 1
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention.
Number of Participants With Laboratory Test Abnormalities: Part 1
Time frame: Up to 24 hours post-dose
The laboratory abnormalities with non-zero participants were reported and it included: monocytes or leukocytes (greater than [>] 1.2* upper limit of normal [ULN]), urine hemoglobin scalar (greater than or equal to [>=1]) and leukocyte esterase scalar (>=1).
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1
Time frame: Up to 24 hours post-dose
Vital signs included blood pressure and pulse rate and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinically significant changes in vital signs were determined by the investigator.
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1
Time frame: Up to 24 hours post-dose
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QRS duration, QT interval, QT interval correct by Bazzette's formula (QTcB) and QT interval correct by Frederica formula QTcF. ECG abnormalities included: PR interval aggregate (millisecond [msec], maximum [max.] >=300; baseline > 200 and max. increase >= 25 percent (%); baseline > 200 and max. increase >= 25%), QRS duration aggregate (msec, max >=140; max. increase >= 50%), QT interval aggregate (msec, value > 500), QTCB interval aggregate and QTCF interval aggregate (msec, 450 < max <= 480; 480 < max. <= 500; max. > 500; 30 < max. increase <= 60; max. increase > 60).
Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of Cis-CTB and Trans-CTB: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-normalized Cmax was determined as Cmax/Dose.
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
CL/F was calculated as Dose/AUCinf.
Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
The lower limit of quantification for AVP was 1.0 ng/mL.
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on day 7
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for HPA was 10.0 ng/mL.
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for AVI and HPA was 10.0 ng/mL.
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
CL/F was calculated as Dose/AUCinf.
Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. Severe TEAEs were defined as type of AE that interrupted usual ADL, or significantly affects clinical status, or may require intensive therapeutic intervention. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study intervention.
Number of Participants With Withdrawals Due to TEAEs: Part 2
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention.
Number of Participants With Laboratory Test Abnormalities: Part 2
Time frame: From start of treatment up to Day 7
The laboratory abnormalities with non-zero participants were reported and it included: neutrophils/ leukocytes (less than [<] 0.8x lower limit of normal [LLN]), eosinophils/leukocytes (>1.2x ULN), monocytes/leukocytes (>1.2x ULN), bicarbonate (>1.1x ULN), urine glucose (>=1), ketones scalar (>=1), urine hemoglobin scalar (>=1), leukocyte esterase scalar (>=1).
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2
Time frame: From start of treatment up to Day 7
Vital signs included blood pressure and pulse rate and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinically significant changes in vital signs were determined by the investigator.
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2
Time frame: From start of treatment up to Day 7
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QRS duration, QT interval, QT interval correct by Bazzette's formula (QTcB) and QT interval correct by Frederica formula QTcF. ECG abnormalities included: PR interval aggregate (millisecond [msec], maximum [max.] >=300; baseline > 200 and max. increase >= 25 percent (%); baseline > 200 and max. increase >= 25%), QRS duration aggregate (msec, max >=140; max. increase >= 50%), QT interval aggregate (msec, value > 500), QTCB interval aggregate and QTCF interval aggregate (msec, 450 < max <= 480; 480 < max. <= 500; max. > 500; 30 < max. increase <= 60; max. increase > 60).

11 secondary outcomes

Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2
Time frame: anytime between 0 to 8 hours post dose on Day 6
Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2
Time frame: anytime between 0 to 8 hours post dose on Day 6
Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2
Time frame: anytime between 0 to 8 hours post dose on Day 6
Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7

Results and safety

Results posted to the registry on 10 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CTB400+AVP900mg/CTB 800+AVP1350 mg /CTB800mg/ CTB1200+AVP1350 mg/Placebo for CTB 1600mg(Part1)	2	2
CTB400+AVP900mg /CTB800+AVP1350mg /CTB 800mg/Placebo for CTB1200+AVP1350 mg /CTB1600 mg(Part1)	2	2
CTB400+AVP900mg/ Placebo for CTB800+AVP1350mg/ Placebo CTB800mg/ CTB1200+AVP1350mg/ CTB1600mg(Part1)	2	2
Placebo for CTB400+AVP900mg/ CTB 800+AVP1350mg/ CTB800mg/ CTB1200mg+AVP1350mg/ CTB1600mg(Part1)	2	2
CTB 400 mg + AVP 1350 mg q8h (Part-2)	0	0
Placebo for CTB 400 mg + AVP 1350 mg q8h (Part-2)	0	0
CTB 800 mg + AVP 1350 mg q8h (Part-2)	0	0
Placebo for CTB 800 mg + AVP 1350 mg q8h (Part-2)	0	0
CTB 400 mg + AVP 900 mg q8h (Part-2)	0	0
Placebo for CTB 400 mg + AVP 900 mg q8h (Part-2)	0	0
CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2)	0	0
Placebo for CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2)	0	0
CTB 400 mg + AVP 1350 mg q8h (Chinese) (Part-2)	0	0
Placebo for CTB 400 mg + AVP 1350 mg q8h (Chinese) (Part-2)	0	0

Primary outcome: Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1

Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose. Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram per milliliter (ng/mL)

Measure	CTB 400 mg + AVP 900 mg (Part-1) n = 6	CTB 800 mg + AVP 1350 mg (Part-1) n = 6	CTB 800 mg (Part-1) n = 6	CTB 1200 mg + AVP 1350 mg (Part-1) n = 6	CTB 1600 mg (Part-1) n = 6
Value	18170 (24)	25470 (18)	30510 (16)	27120 (12)	44990 (25)

CTB 800 mg + AVP 1350 mg (Part-1) vs CTB 800 mg (Part-1): Ratio of adjusted geometric means: 83.46 (90% CI 74.67 to 93.29)

Population analysed: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.

Primary outcome: Time for Cmax (Tmax) of CTB: Part 1

Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose. Median (Full Range). Unit: Hours

Measure	CTB 400 mg + AVP 900 mg (Part-1) n = 6	CTB 800 mg + AVP 1350 mg (Part-1) n = 6	CTB 800 mg (Part-1) n = 6	CTB 1200 mg + AVP 1350 mg (Part-1) n = 6	CTB 1600 mg (Part-1) n = 6
Value	3.21 (2.12 to 4.05)	4.03 (3.03 to 4.15)	3.50 (1.50 to 4.02)	5.05 (4.03 to 6.05)	4.01 (2.02 to 4.10)

Primary outcome: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1

Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose. Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram*hours per milliliter

Measure	CTB 400 mg + AVP 900 mg (Part-1) n = 6	CTB 800 mg + AVP 1350 mg (Part-1) n = 6	CTB 800 mg (Part-1) n = 6	CTB 1200 mg + AVP 1350 mg (Part-1) n = 6	CTB 1600 mg (Part-1) n = 6
Value	94050 (18)	154100 (14)	171800 (15)	183600 (15)	319200 (24)

CTB 800 mg + AVP 1350 mg (Part-1) vs CTB 800 mg (Part-1): Ratio of adjusted geometric means: 89.70 (90% CI 87.24 to 92.23)

Primary outcome: Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1

Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose. Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram per milliliter per milligram

Measure	CTB 400 mg + AVP 900 mg (Part-1) n = 6	CTB 800 mg + AVP 1350 mg (Part-1) n = 6	CTB 800 mg (Part-1) n = 6	CTB 1200 mg + AVP 1350 mg (Part-1) n = 6	CTB 1600 mg (Part-1) n = 6
Value	45.45 (24)	31.83 (18)	38.16 (16)	22.61 (12)	28.12 (25)

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days for part 1 and 42 days for part 2). Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CTB 400 mg + AVP 900 mg (Part-1)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Placebo for CTB 400 mg + AVP 900 mg (Part-1)	0 of 2 (0%)	0 of 2 (0%)	0 of 2
CTB 800 mg + AVP 1350 mg (Part-1)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Placebo for CTB 800 mg + AVP 1350 mg (Part-1)	0 of 2 (0%)	1 of 2 (50%)	0 of 2
CTB 800 mg (Part-1)	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Placebo for CTB 800 mg (Part-1)	0 of 2 (0%)	0 of 2 (0%)	0 of 2
CTB 1200 mg + AVP 1350 mg (Part-1)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Placebo for CTB 1200 mg + AVP 1350 mg (Part-1)	0 of 2 (0%)	1 of 2 (50%)	0 of 2
CTB 1600 mg (Part-1)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Placebo for CTB 1600 mg (Part-1)	0 of 2 (0%)	0 of 2 (0%)	0 of 2
CTB 400 mg + AVP 1350 mg q8h (Part-2)	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Placebo for CTB 400 mg + AVP 1350 mg q8h (Part-2)	0 of 2 (0%)	2 of 2 (100%)	0 of 2
CTB 800 mg + AVP 1350 mg q8h (Part-2)	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Placebo for CTB 800 mg + AVP 1350 mg q8h (Part-2)	0 of 2 (0%)	1 of 2 (50%)	0 of 2
CTB 400 mg + AVP 900 mg q8h (Part-2)	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Placebo for CTB 400 mg + AVP 900 mg q8h (Part-2)	0 of 2 (0%)	2 of 2 (100%)	0 of 2
CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2)	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Placebo for CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42678337Sahasrabudhe SA, Shoji S, Jakate AS, Abraham BK, Toussi SS, Maligalig BJ, Darekar AS, Tripathy S, Kantaridis C, Mfopou JK, Selivanova O, Bergman A, Alami NN, Singh RSP. Dose Selection for Ceftibuten Combined with Avibactam Tomilopil, a Potential Oral Alternative to Carbapenems for Patients with Complicated Urinary Tract Infections. J Clin Pharmacol. 2026 Sep;66(9):e70263. doi: 10.1002/jcph.70263.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

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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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07612577 and PF-06264006 in people with Healthy, run by Pfizer at 1 site in Belgium.

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 3 inclusion and 6 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 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 10 Oct 2024). 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?

Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 (time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose). The study lists 46 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 NCT05554237, which also lists 1 linked publication.

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 10 Oct 2024.