Safety and Efficacy of Trans Sodium Crocetinate (TSC) in Enhancing Tissue Oxygen Levels in Healthy Volunteers

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled, pharmacokinetic, pharmacodynamic study. Subjects will be randomized to TSC or placebo to determine the effect of Trans Sodium Crocetinate (TSC) on Transcutaneous Oximetry Measurements (tcpO2) following a single administration of TSC in subjects breathing oxygen (O2).

Detailed Description
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This is a randomized, double-blind, placebo-controlled, pharmacokinetic, pharmacodynamic study of Trans Sodium Crocetinate (TSC) in healthy volunteers. The primary objective is to determine the effect of TSC on transcutaneous oximetry measurements (tcpO2) following a single administration of TSC in subjects breathing oxygen (O2). 30 healthy volunteers will be randomized to one of 6 treatment groups, to include 5 TSC doses (0.5, 1.0, 1.5, 2.0, and 2.5 mg/kg) and placebo normal saline (7 mL). TcpO2 sensors will be applied to 4 standardized areas on the lower extremity. Subjects will be placed on O2 via simple face mask at 6 L/minute, and will remain on O2 for 70 minutes prior to study drug administration. The first 10 minutes will allow for equilibration of O2 levels, and the subsequent 60 minutes will serve as the baseline period. TcpO2 values and SpO2 will be recorded every 5 minutes during the above periods. At the end of the 70-minute equilibration/baseline period, subjects will receive a single IV bolus injection of TSC at a dose of 0.5, 1.0, 1.5, 2.0 or 2.5 mg/kg, or placebo. Study drug will be administered in a blinded fashion. After study drug is administered, subjects will continue on O2 and be evaluated for an additional 60 minutes, with tcpO2 and SpO2 recorded at 1, 2, and 5 minutes post-dose, and every 5 minutes thereafter. Prior to and following study drug administration, PK samples will be obtained pre-dose, and 1, 10, 30, and 90 minutes post-dose. After the 60 minute post-treatment evaluation period, oxygen will be discontinued and the tcpO2 sensor electrodes removed. Subjects will remain in the procedure room for an additional 30 minutes to allow for collection of the 1.5-hour PK blood draw and repeat vital signs. Subjects will remain in the clinic overnight for observation and discharged the following morning. Subjects will be contacted by telephone at 48 hours (+ 2 days) for a safety follow up to assess adverse events and new medications.

Official Title
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Randomized, Double-blind, Placebo-controlled, Pharmacokinetic, Pharmacodynamic Study of Trans Sodium Crocetinate Utilizing Transcutaneous Oximetry Measurement in Healthy Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Trans-Sodium Crocetinate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female, age 18-50 Able and willing to lie quietly supine or semi-recumbent for up to 2.5 hours Abstinence from exercise, caffeine, alcohol, nicotine, and a heavy meal prior to testing on the day of the Treatment Visit Subject is able to communicate effectively with the Investigator and to comply with all study requirements, restrictions, and directions from the study staff Females of childbearing potential must have a negative blood pregnancy test at screening and agree to use one of the accepted contraceptive regimens, or a double method of birth control (e.g. condom and spermicide), during the study and at least 30 days after the last dose of study drug. Females of non-childbearing potential should be surgically sterile or at least one year post-menopausal. Males who engage in sexual activity that has the risk of pregnancy must agree to use a double barrier method (e.g. condom and spermicide) and agree not to donate sperm during the study and for at least 90 days after the last dose of study drug Exclusion Criteria: Allergy to study medication Pregnant or breastfeeding Current smoker and/or any nicotine use within 4 hours of the start of tcpO2 procedures, to include e-cigarette vaping, snuff, chew, nicotine gum and nicotine patches Body Mass Index (BMI) > 30 Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg), or Hepatitis C Antibody (HCVAb) Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to screening Plasma donation within 7 days prior to screening Treatment with an investigational drug within 30 days or 5 times the half-life (whichever is longer) prior to screening Any skin condition on limbs to be tested that could impair testing (rash, wound, prior radiation therapy, other skin conditions, per Principal Investigator (PI) discretion) Known cardiovascular disease, including treated or untreated hypertension Significant respiratory disease and/or any other significant medical condition Subject has an acute illness (gastrointestinal infection, influenza, or known inflammatory process) at the Treatment Visit Urine screen positive for drugs or positive breathalyzer for alcohol (at screening and enrollment) Concomitant medications used to treat a diagnosed medical condition Subject who, for any reason, is deemed by the Investigator to be unsuitable for the study; or has any condition that would interfere with the evaluation of tissue oxygen measurements or PK of the investigational drug; or is otherwise unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TSC 0.5 mg/kg<br>TSC 0.5 mg/kg given as a one-time IV bolus injection | Drug: Trans-Sodium Crocetinate<br>* TSC given as a one-time IV bolus injection<br>* Other names: TSC;|
| Experimental: TSC 1.0 mg/kg<br>TSC 1.0 mg/kg given as a one-time IV bolus injection | Drug: Trans-Sodium Crocetinate<br>* TSC given as a one-time IV bolus injection<br>* Other names: TSC;|
| Experimental: TSC 1.5 mg/kg<br>TSC 1.5 mg/kg given as a one-time IV bolus injection | Drug: Trans-Sodium Crocetinate<br>* TSC given as a one-time IV bolus injection<br>* Other names: TSC;|
| Experimental: TSC 2.0 mg/kg<br>TSC 2.0 mg/kg given as a one-time IV bolus injection | Drug: Trans-Sodium Crocetinate<br>* TSC given as a one-time IV bolus injection<br>* Other names: TSC;|
| Experimental: TSC 2.5 mg/kg<br>TSC 2.5 mg/kg given as a one-time IV bolus injection | Drug: Trans-Sodium Crocetinate<br>* TSC given as a one-time IV bolus injection<br>* Other names: TSC;|
| Placebo Comparator: Placebo<br>7 mL normal saline given as a one-time IV bolus injection | Drug: Placebo<br>* Placebo normal saline given as a one-time 7 mL one-time IV bolus injection<br>* Other names: 0.9% Sodium Chloride (NaCl);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Dose-Response of TSC on tcpO2 Following a Single Administration of TSC in Subjects Breathing O2. | Summary Statistics of tcpO2 Levels (mmHg) Overall Measurements (Median of 4 Sensors) in Healthy Subjects | 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 minutes post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcutaneous oximetry