Clinical trial NCT04710407: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: pharmacokinetics
TBPM-PI-HBr
tebipenem
alveolar macrophages (AM)
epithelial lining fluid (ELF)
intrapulmonary
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Clinartis
First posted: 2021-01-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Plasma PK and lung penetration of SPR859 following multiple doses
timeFrame: Day 1 to Day 3
measure: Plasma PK and lung penetration of SPR859 following multiple doses
timeFrame: Day 1 to Day 3
Secondary outcomes:
measure: Safety and tolerability, including adverse events (AEs)
timeFrame: Day 1 to Day 10
measure: Safety and tolerability, including clinically significant changes from baseline in clinical laboratory values
timeFrame: Day 1 to Day 10
measure: Safety and tolerability, including physical examination
timeFrame: Day 1 to Day 10
measure: Safety and tolerability, including ECG
timeFrame: Day 1 to Day 10
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates
state: Arizona
Study officials:
affiliation: Pulmonary Associates
name: David Baratz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.