Study to Assess the Intrapulmonary Pharmacokinetics of SPR859 by Comparing the Plasma, Epithelial Lining Fluid (ELF), and Alveolar Macrophages (AM) Concentrations Following the Oral Administration of Five Doses of SPR994 in Healthy, Nonsmoking Volunteers

Study Overview
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Brief Summary
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To evaluate the intrapulmonary pharmacokinetics (PK), including ELF and AM concentrations, of SPR859 (tebipenem) compared to plasma concentrations of SPR859 (tebipenem) (the active moiety in plasma of the prodrug SPR994) in nonsmoking healthy adult volunteers.

Official Title
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A Phase 1, Single-center, Open-label Study to Assess the Intrapulmonary Pharmacokinetics of SPR859 by Comparing the Plasma, Epithelial Lining Fluid (ELF), and Alveolar Macrophages (AM) Concentrations Following the Oral Administration of Five Doses of SPR994 in Healthy, Nonsmoking Volunteers

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: Adult males or female subjects, between 18 and 55 years of age (both inclusive) at the time of screening BMI ≥ 18.5 and ≤ 32 (kg/m2) and weight between 55.0 and 100.0 kg (both inclusive) Willing and able to provide written informed consent; Willing and able to comply with all study assessments and adhere to the protocol schedule Medically healthy without clinically significant abnormalities as assessed by the Investigator based on screening medical history, physical examination, vital signs, 12-lead ECG, hematology, biochemistry and urinalysis Have suitable venous access for blood sampling Exclusion Criteria: History of seizure disorders Positive urine drug, alcohol or cotinine testing at screening or check-in (Day -1) Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HCV); Positive testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening; Presence of the following symptoms at screening or within 14 days prior to screening or Check-in (Day -1) Fever, chills or sweats (temperature of 38 °C / 100.4 °F or higher) Difficulty breathing Cough Sore throat New or recent loss of taste or smell Nausea, vomiting or diarrhea; Close contact with anyone who tested positive for SARS-CoV-2 infection within 14 days prior to screening or Check-in (Day -1); Electrocardiogram (ECG) with QTcF interval duration equal or greater than 450 msec for males and 470 msec for females Subjects who have any of the following abnormalities on laboratory values at screening or prior confinement including: White blood cell count < 3,000/mm3, hemoglobin < 11g/dL; Absolute neutrophil count <1,200/mm3, platelet count <120,000/mm3; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 1.5 x the upper limit of normal (ULN) for the reference laboratory; History of substance abuse or alcohol abuse Use of tobacco/nicotine- or marijuana-containing products (including vaping products) within 12 months prior to screening; Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication

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

Sexes Eligible for Study
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All

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
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 total of five doses of TBPM-PI-HBr 600 mg orally every 8 hours. | Drug: TBPM-PI-HBr<br>* TBPM-PI-HBr (2 x 300mg tablets) a total of five doses<br>* Other names: SPR994;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma PK and lung penetration of SPR859 following multiple doses | Plasma PK parameters will include the area under the curve (AUC) from time zero to the last quantifiable sample (AUC0-t), AUC from time zero to end of dosing interval (AUC0-8). The AUC0-8 values for ELF and AM will be determined. The ratios of the AUC0-8 of ELF to the AUC0-8 of plasma and the AUC0-8 of AM to the AUC0-8 of plasma will be calculated. | Day 1 to Day 3 | 
| Plasma PK and lung penetration of SPR859 following multiple doses | Plasma PK parameters will include the maximum concentration (Cmax), minimum concentration (Cmin), time to Cmax (tmax), and the terminal-phase half-life (t1/2). | Day 1 to Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability, including adverse events (AEs) | Frequency of adverse events by severity, seriouness, system organ class, preferred term and treatment group | Day 1 to Day 10 | 
| Safety and tolerability, including clinically significant changes from baseline in clinical laboratory values | Change from baseline in selected laboratory assays including WBC, hemoglobin, platelet count, liver function tests (AST, ALT, AP), blood urea nitrogen (BUN), serum creatinine (Cr), and estimated Cr clearance (based on Cockcroft-Gault formula), by treatment group | Day 1 to Day 10 | 
| Safety and tolerability, including physical examination | Change from baseline in vital signs | Day 1 to Day 10 | 
| Safety and tolerability, including ECG | Cardiac (12-Lead ECG) will be summarized at each scheduled time point using descriptive statistics | Day 1 to Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TBPM-PI-HBr, pharmacokinetics, tebipenem, alveolar macrophages (AM), epithelial lining fluid (ELF), intrapulmonary