Study of the Absorption, Metabolism, and Excretion of [14C]-Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) Following a Single Oral Dose in Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine the absorption, metabolism, and excretion of [14C]-TBPM-PI-HBr and to characterize and determine the metabolites present in plasma, urine, and where possible, feces in healthy male subjects following a single oral administration.

Official Title
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A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) Following a Single Oral Dose in Healthy Male Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TBPM-PI-HBr


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Healthy adult males, of any race, between 18 and 55 years of age, inclusive. Body mass index between 18.0 and 32.0 kg/m2, inclusive, and a total body weight between 50 and 100 kg, inclusive at Screening. Willing and able to provide written informed consent and comply with all study assessments, restrictions, and adhere to the protocol schedule. Medically healthy with no clinically significant medical history, or abnormalities in physical examination, laboratory variables, vital signs or ECG at the time of screening and Check-in, as deemed by the Investigator (or designee). Have suitable venous access for repeated blood sampling. History of a minimum of 1 bowel movement per day. Exclusion Criteria History or suspicion of routine or chronic drug or alcohol abuse or dependence within 2 years prior to Check-in. Use of tobacco, nicotine, or nicotine-replacement products within 30 days prior to Check-in or planned use during the study. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee). Use/receipt of any prescription or nonprescription medication, herbal products, vitamins or vaccines within 14 days (or 5 half-lives whichever is longer) prior to Check-in, without prior approval from the Medical Monitor. Donation of more than 500 mL of blood or plasma within 56 days prior to Check-in, or receipt of a blood transfusion within 1 year prior to Check-in. Receipt of any other investigational product or participation in another investigational clinical study that included drug treatment within 30 days, or 5 times the t1/2 of the investigational drug, whichever is longer. Have previously completed or withdrawn from this study or any other study investigating TBPM-PI-HBr, and have previously received TBPM-PI-HBr. Subjects with exposure to significant diagnostic or therapeutic radiation (e.g., serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in. Subjects who have participated in a radiolabeled drug study where exposures are known to the Investigator within the previous 3 months prior to admission to the clinic for this study or participated in a radiolabeled drug study where exposures are not known to the Investigator within the previous 6 months prior to admission to the clinic for this study. The total 12-month exposure from this study and a maximum of 3 other previous radiolabeled studies within 3 to 12 months prior to this study will be within the CFR recommended levels considered safe, per United States (US) Title 21 CFR 361.1. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single-Center, Open-Label, Non-Randomized, Phase 1 Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TBPM-PI-HBr<br>Healthy subjects meeting eligibility criteria will receive a single dose of 600mg of TBPM-PI-HBr | Drug: TBPM-PI-HBr<br>* TBPM-PI-HBr (3 x 200 mg tablets) once<br>* Other names: TBPM-PI-HBr oral capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Tebipenem (TBPM) will be determined following administration of [14C]-TBPM-PI-HBr to healthy male subjects | The primary PK outcome endpoints following oral administration of [14C]-TBPM-PI-HBr will be derived for TBPM in plasma (calculated from whole blood concentrations) based on the concentration-time profile | Day 1 to Day 5 | 
| Total radioactivity will be determined following administration of [14C]-TBPM-PI-HBr to healthy male subjects | The primary PK outcome endpoints following oral administration of [14C]-TBPM-PI-HBr will be derived for total radioactivity in whole blood and plasma based on the total radioactivity concentration-time profile | Day 1 to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolite profiling and chemical structuring of metabolites in plasma, urine, and, where possible, feces will be determined after a single oral dose of [14C]-TBPM-PI-HBr | The secondary metabolite outcome endpoints will be derived: metabolic profile of TBPM-PI-HBr metabolic profile of TBPM-PI-HBr | Day 1 to Day 5 | 
| Metabolite profiling and chemical structuring of metabolites in plasma, urine, and, where possible, feces will be determined after a single oral dose of [14C]-TBPM-PI-HBr | The secondary metabolite outcome endpoints will be derived: • identification of the structure of TBPM-PI-HBr metabolites | Day 1 to Day 5 | 
| The safety and tolerability of a single oral dose of [14C]-TBPM-PI-HBr when administered to healthy male subjects. | The secondary safety outcome measures for this study are as follows: • incidence and severity of AEs | Day 1 to Day 5 | 
| The safety and tolerability of a single oral dose of [14C]-TBPM-PI-HBr when administered to healthy male subjects. | The secondary safety outcome measures for this study are as follows: •incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation, and urinalysis test results | Day 1 to Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, TBPM-PI-HBr, tebipenem, absorption, metabolism, excretion