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

Sponsor

Spero Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT04710407

Collaborator

Clinartis (Industry)

Enrollment

Location

Arm

3.1

Actual Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TBPM-PI-HBr	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 7, 2020

Actual Primary Completion Date :

Mar 10, 2021

Actual Study Completion Date :

Mar 10, 2021

Arms and Interventions

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: TBPM-PI-HBr oral capsule SPR994

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:

TBPM-PI-HBr oral capsule

SPR994

Outcome Measures

Primary Outcome Measures

Plasma PK and lung penetration of SPR859 following multiple doses [Day 1 to Day 3]
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.
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

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 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 physical examination [Day 1 to Day 10]
Change from baseline in vital signs
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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