Clinical trial NCT04868292: Study to Assess the Intrapulmonary Pharmacokinetics of SPR206 in Healthy Volunteers
Official title: A Phase 1, Single-Center, Open-Label Study to Assess the Intrapulmonary Pharmacokinetics of SPR206 by Comparing the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations Following the Intravenous Administration of SPR206 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: pharmacokinetics
alveolar macrophages (AM)
epithelial lining fluid (ELF)
intrapulmonary
bronchoalveolar lavage
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2021-04-30
Enrollment: 34
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: OTHER

Brief summary: To evaluate the intrapulmonary pharmacokinetics (PK), including epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations, of SPR206 as well as plasma concentrations of SPR206 in healthy adult volunteers.


Eligibility criteria: Inclusion Criteria:

* Non-smoker for at least 12 months prior to screening for the study
* BMI ≥ 18.5 and ≤ 32 (kg/m2) and weight between 55.0 and 100.0 kg (both inclusive)
* 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, coagulation, and urinalysis
* Forced expiratory volume in 1 second (FEV1) of at least 80% of predicted value at screening
* Ability and willingness to abstain from alcohol, caffeine, xanthine-containing beverages or food from 48 hours prior to study drug administration until discharge from the clinical unit
* If male, must agree to use a condom and have a non-pregnant female partner of childbearing potential agree to use a highly effective method of contraception
* If female, must be of non-childbearing potential or, if female of childbearing potential, a willingness to abstain from sexual activity or agree to use a high effective method of contraception that could lead to pregnancy
* Other inclusion criteria per protocol

Exclusion Criteria:

* History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, vascular or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant
* Recent history (within 6 months) of known or suspected Clostridium difficile infection
* 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 Ab)
* Positive testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening or prior to first dosing
* Presence of the following symptoms at screening or within 28 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 28 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 Check-In including:

  1. White blood cell count \< 3,000/mm3, hemoglobin \< 11g/dL
  2. Absolute neutrophil count ≤ 2,000/mm3, platelet count \<120,000/mm3
  3. alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) greater than the upper limit of normal (ULN) for the reference laboratory
* History of substance abuse or alcohol abuse
* Use of prescription medicine \& tobacco/nicotine or marijuana-containing products
* A female who is pregnant or breastfeeding
* Other exclusion criteria per protocol

Primary outcomes:
measure: Area under the concentration-time curve from time 0 to 8 hours (AUC0-8) for ELF, AM, and plasma
timeFrame: 8 hours after the start of the third study drug IV infusion
measure: Maximum observed concentration (Cmax) for ELF, AM, and plasma
timeFrame: 8 hours after the start of the third study drug IV infusion
measure: Minimum concentration (Cmin) for ELF, AM, and plasma
timeFrame: 8 hours after the start of the third study drug IV infusion
measure: Time to the maximum observed concentration (Tmax) for ELF, AM, and plasma
timeFrame: 8 hours after the start of the third study drug IV infusion
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal vital sign assessments - blood pressure
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal vital sign assessments - body temperature
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal vital sign assessments - heart rate
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal vital sign assessments - respiratory rate
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal physical exam assessments
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal ECG assessments - heart rate
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval
timeFrame: Day -1 to Day 7
measure: Incidence of abnormal safety laboratory assessments
timeFrame: Day -1 to Day 7
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Medical Facility
Study officials:
affiliation: Spero Therapeutics Inc
name: David Melnick, MD
role: STUDY_DIRECTOR
References: