Safety and Pharmacokinetic (PK) Study to Assess Bronchopulmonary Disposition of IV Eravacycline (TP-434) in Healthy Men and Women

Study Overview
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Brief Summary
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This is a phase 1, open-label, randomized pharmacokinetic and safety study in healthy adult subjects, who will undergo bronchoscopy and bronchoalveolar lavage (BAL) after receiving seven (7) doses of 1.0 mg/kg IV TP-434.

Detailed Description
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This is a phase 1, open-label, randomized pharmacokinetic and safety study in healthy adult subjects, who will undergo bronchoscopy and bronchoalveolar lavage (BAL) after receiving seven (7) doses of 1.0 mg/kg IV TP-434. Dosing will be twice daily (q12h) for three consecutive days beginning on day one (1) and a morning dose on day four (4). Approximately 20 subjects will be enrolled into the study at one (1) investigational site. The population for this study is healthy male and female subjects 18 to 65 years of age. This study includes a Screening Period of up to 30 days, a 4 day, open-label Treatment Period, and a two week Follow-up Period. There will be one 6 day/5 night inpatient stay (Days -1 to 5) during the Treatment Period and one outpatient visit at the end of the Follow-up Period. Excluding the Screening Period, the total duration of confinement (in the Clinical Research Center) will be approximately six (6) days and the total study duration, not including screening, will be approximately three (3) weeks. Participants will be admitted to the Clinical Research Center on Day -1. Participants will receive four (4) days of intravenous TP-434 1.0 mg/kg of body weight twice daily (q12h) for three consecutive days and a morning dose on day four (4) (for a total of 7 doses) starting on Day 1. Blood and urine samples, ECGs, and vital signs will be collected for safety analysis at specified time points. Pharmacokinetic blood sampling will occur on Day 4before and after the Day 4 dose of TP-434 at specified time points. Participants will be randomized to a single BAL procedure time point. Bronchoscopy and BAL will be performed at the following time points after dosing of TP-434 on Day 4: two (2), four (4), six (6), and 12 hours after start of infusion. Bronchoscopy and BAL will be conducted for up to five (5) different participants at each time point. Each subject will undergo bronchoscopy and BAL only once.

Official Title
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Phase 1, Open-Label, Safety and Pharmacokinetic Study to Assess Bronchopulmonary Disposition of Intravenous TP-434 in Healthy Men and Women

Conditions
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Normal Drug Tolerance

Intervention / Treatment
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* Drug: TP-434 (Eravacycline) reconstituted and administered via an IV infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or non-pregnant, non-lactating healthy females Age >18 to ≤ 65 years of age, inclusive Body mass index of 18 to 33 kg/m2 or, if outside the range, considered not clinically significant by the Investigator Must be willing and able to communicate and participate in the whole study Must provide written informed consent Must agree to use adequate methods of contraception Exclusion Criteria: Participation in a clinical research study within the previous 3 months Subjects who have previously received TP-434 History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) Current smokers and those who have smoked within the last 6 months. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the Investigator Positive tests for drugs of abuse Positive hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV; I and II) results History of chronic respiratory disorders as judged by the Investigator Serious adverse reaction or serious hypersensitivity to tetracyclines, midazolam or like compound, lidocaine or like compounds, or the formulation excipients Donation or loss of greater than 400 mL of blood within the previous 3 months Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (with the exception of anti inflammatory, anti-hypertensive medications, or hormone replacement therapy) in the 14 days before Investigational Medicinal Product administration unless judged to not interfere with the study objectives according to the Investigator and sponsor's medical monitor Failure to satisfy the Investigator of fitness to participate for any other reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TP-434 (Eravacycline) via IV infusion<br>TP-434 (Eravacycline) reconstituted and administered via IV infusion at a dose of 1 mg/kg, every 12 hours, for 7 doses over 4 days. | Drug: TP-434 (Eravacycline) reconstituted and administered via an IV infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the steady-state plasma pharmacokinetics and disposition of TP-434 into the epithelial lining fluid (ELF) and alveolar macrophages (AM) of healthy adult subjects after intravenous (IV) administration. |  | End of Therapy (Day 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and tolerability of TP-434 in healthy adult subjects based primarily on the incidence, intensity and type of adverse events (AEs), clinical laboratory assessments, physical examinations, vital signs, and 12-lead ECGs. |  | Screening Visit through Day 20 |