Study to Assess the Intrapulmonary Pharmacokinetics of SPR206 in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: SPR206


Participation Criteria
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Eligibility Criteria
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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): 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 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: White blood cell count < 3,000/mm3, hemoglobin < 11g/dL Absolute neutrophil count ≤ 2,000/mm3, platelet count <120,000/mm3 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPR206<br>Healthy subjects meeting eligibility criteria will receive a total of three 100 mg SPR206 intravenous doses administered every 8 hours. | Drug: SPR206<br>* Three 100 mg SPR206 intravenous doses administered every 8 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve from time 0 to 8 hours (AUC0-8) for ELF, AM, and plasma |  | 8 hours after the start of the third study drug IV infusion | 
| Maximum observed concentration (Cmax) for ELF, AM, and plasma |  | 8 hours after the start of the third study drug IV infusion | 
| Minimum concentration (Cmin) for ELF, AM, and plasma |  | 8 hours after the start of the third study drug IV infusion | 
| Time to the maximum observed concentration (Tmax) for ELF, AM, and plasma |  | 8 hours after the start of the third study drug IV infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | To assess the incidents of treatment-emergent adverse events following three 100mg SPR206 intravenous doses administered every 8 hours. AEs will be classified by System Organ Class (SOC) and Preferred Term (PT). Incidence, frequency, severity and duration will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal vital sign assessments - blood pressure | To assess the incidents of abnormal systolic and diastolic blood pressure assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal vital sign assessments - body temperature | To assess the incidents of abnormal body temperature assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal vital sign assessments - heart rate | To assess the incidents of abnormal heart rate assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal vital sign assessments - respiratory rate | To assess the incidents of abnormal respiratory rate assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency count of significant changes from baseline will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal physical exam assessments | To assess the incidents of abnormal body system assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Changes from baseline in physical examination findings will be classified as Normal, Abnormal NCS, and Abnormal CS. Frequency counts will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal ECG assessments - heart rate | To assess the incidents of abnormal heart rate assessment following three 100mg SPR206 intravenous doses administered every 8 hours. Cardiac (12-Lead ECG) for heart rate will be classified as normal, abnormality that is NCS, and CS abnormality. Frequency counts by dose group and timepoint of collection will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval | To assess the incidents of abnormal PR interval, RR interval, QRS interval, QT interval and QTcF interval assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Cardiac (12-Lead ECG) results will be classified as normal, abnormality that is NCS, and CS abnormality. Frequency counts by dose group and timepoint of collection will be presented. | Day -1 to Day 7 | 
| Incidence of abnormal safety laboratory assessments | To assess the incidents of abnormal hematology, serum chemistry, coagulation and urinalysis assessments following three 100mg SPR206 intravenous doses administered every 8 hours. Frequency counts of significant changes from baseline will be presented. | Day -1 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, alveolar macrophages (AM), epithelial lining fluid (ELF), intrapulmonary, bronchoalveolar lavage