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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: TBPM-PI-HBr

• Registration Number: NCT04710407
• Lead Sponsor: Spero Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-07
• Study First Submitted: 2021-01-04
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-14
• Status Verified: 2021-03
• Primary Completion: 2021-03-10
• Study Completion: 2021-03-10
• Last Update Submitted: 2021-03-15
• Last Update Posted: 2021-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TBPM-PI-HBr	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.

Primary Outcome Measures

Name	Time	Method
Plasma PK and lung penetration of SPR859 following multiple doses	Day 1 to Day 3	Plasma PK parameters will include the maximum concentration (Cmax), minimum concentration (Cmin), time to Cmax (tmax), and the terminal-phase half-life (t1/2).

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability, including clinically significant changes from baseline in clinical laboratory values	Day 1 to Day 10	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
Safety and tolerability, including ECG	Day 1 to Day 10	Cardiac (12-Lead ECG) will be summarized at each scheduled time point using descriptive statistics
Safety and tolerability, including adverse events (AEs)	Day 1 to Day 10	Frequency of adverse events by severity, seriouness, system organ class, preferred term and treatment group
Safety and tolerability, including physical examination	Day 1 to Day 10	Change from baseline in vital signs

Trial Locations

Locations (1)

Pulmonary Associates; 🇺🇸 Phoenix, Arizona, United States