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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TBPM-PI-HBr

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Collaborators: Covance
• Investigators: Principal Investigator: Irene Mirkin, MD, Covance Clinical Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): October 16, 2020
• Study Completion (Actual): October 16, 2020

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; metabolism; absorption; excretion; TBPM-PI-HBr; tebipenem
• Other Study ID Numbers: SPR994-106

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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