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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

  1. Fever, chills or sweats (temperature of 38 °C / 100.4 °F or higher)
  2. Difficulty breathing
  3. Cough
  4. Sore throat
  5. New or recent loss of taste or smell
  6. 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:

  1. White blood cell count < 3,000/mm3, hemoglobin < 11g/dL;
  2. Absolute neutrophil count <1,200/mm3, platelet count <120,000/mm3;
  3. 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

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 total of five doses of TBPM-PI-HBr 600 mg orally every 8 hours.	Drug: TBPM-PI-HBr; TBPM-PI-HBr (2 x 300mg tablets) a total of five doses; Other Names: SPR994; TBPM-PI-HBr oral capsule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Collaborators: Clinartis
• Investigators: Principal Investigator: David Baratz, MD, Pulmonary Associates

Publications and helpful links

General Publications

• Rodvold KA, Gotfried MH, Gupta V, Ek A, Srivastava P, Talley A, Bruss J. Plasma and Intrapulmonary Concentrations of Tebipenem following Oral Administration of Tebipenem Pivoxil Hydrobromide to Healthy Adult Subjects. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0059022. doi: 10.1128/aac.00590-22. Epub 2022 Jun 28.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 10, 2021

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: pharmacokinetics; TBPM-PI-HBr; tebipenem; alveolar macrophages (AM); epithelial lining fluid (ELF); intrapulmonary
• Other Study ID Numbers: SPR994-108

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