Clinical trial NCT05554237: A Study to Learn About the Study Medicine Called CTB+AVP in Healthy Adult People.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-09-26
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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)
2. Known allergy to the cephalosporin group of antibiotics
3. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
4. 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
5. A positive urine drug test
6. Positive test result for SARS-CoV-2 infection at the time of screening or Day -1

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Time for Cmax (Tmax) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Terminal Half-Life (t1/2) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Apparent Volume of Distribution (Vz/F) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Apparent Clearance (CL/F) of CTB: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: 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
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1
timeFrame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
measure: Number of Participants With Withdrawals Due to TEAEs: Part 1
timeFrame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
measure: Number of Participants With Laboratory Test Abnormalities: Part 1
timeFrame: Up to 24 hours post-dose
measure: Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1
timeFrame: Up to 24 hours post-dose
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1
timeFrame: Up to 24 hours post-dose
measure: Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2
timeFrame: 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
measure: Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2
timeFrame: 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
measure: 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
timeFrame: 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
measure: Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2
timeFrame: 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
measure: Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2
timeFrame: 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
measure: Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
measure: Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2
timeFrame: 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
measure: Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2
timeFrame: 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
measure: Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2
timeFrame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on day 7
measure: Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2
timeFrame: 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
measure: Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2
timeFrame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
measure: Number of Participants With Withdrawals Due to TEAEs: Part 2
timeFrame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
measure: Number of Participants With Laboratory Test Abnormalities: Part 2
timeFrame: From start of treatment up to Day 7
measure: Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2
timeFrame: From start of treatment up to Day 7
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2
timeFrame: From start of treatment up to Day 7
Secondary outcomes:
measure: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2
timeFrame: anytime between 0 to 8 hours post dose on Day 6
measure: 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
timeFrame: anytime between 0 to 8 hours post dose on Day 6
measure: Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2
timeFrame: anytime between 0 to 8 hours post dose on Day 6
measure: Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
measure: Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
measure: 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
timeFrame: 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
measure: Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
measure: Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
measure: Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
measure: Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
timeFrame: 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
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: