Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Trans Sodium Crocetinate in Healthy Volunteers Exercising at Altitude

Study Overview
=================
Brief Summary
-----------------
This is a randomized, placebo-controlled, crossover study of Trans Sodium Crocetinate (TSC) in healthy volunteers, age 18-40 (inclusive), exercising at altitude. The primary objective is to determine the effect of (TSC) on partial pressure of oxygen (PaO2) and maximal oxygen consumption (VO2 max); the secondary objective is to assess the effect of TSC on oxygen saturation (SpO2).

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Trans Sodium Crocetinate in Healthy Volunteers Exercising at Altitude

Conditions
-----------------
Healthy Volunteers With Induced Hypoxia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males and females ages 18-40 Non-smoking Able to provide informed consent and agree to adhere to all study visits and requirements. 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 during the study and at least 30 days after the last dose of study drug. Males who engage in sexual activity that has the risk of pregnancy must agree to use a double barrier method 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 breast feeding Received investigational medicine (IMP) within past 30 days VO2 max < 35 mL/kg/min (male), < 30 mL/kg/min (female) at screening Abnormal pulmonary function testing at screening Surgery or hospitalization in past 3 months determined by the PI to be clinically relevant History of ongoing alcohol or substance abuse Known cardiovascular disease, including treated or untreated hypertension Respiratory disease and/or any other significant medical condition, including psychiatric disorders Clinically significant abnormality on ECG per PI discretion 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 History of smoking Urine screen positive for drugs or positive breathalyzer for alcohol (at screening and Treatment Visit Day 1) History of seizures Previous pneumothorax or pneumomediastinum Hypo/Hyperglycemia Diabetes Regularly taking medications which may alter heart rate, blood pressure or cardiac output Previous history of middle ear equalization problems at discretion of PI

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 mg/kg Trans Sodium Crocetinate<br>Subjects will receive a single IV bolus dose of 0.5 mg/kg TSC. Subjects will also receive a single IV dose of normal saline as placebo, thereby serving as their own control. | Drug: Trans Sodium Crocetinate<br>* Single IV bolus<br>|
| Experimental: 1.5 mg/kg Trans Sodium Crocetinate<br>Subjects will receive a single IV bolus dose of 1.5 mg/kg TSC. Subjects will also receive a single IV dose of normal saline as placebo, thereby serving as their own control. | Drug: Trans Sodium Crocetinate<br>* Single IV bolus<br>|
| Experimental: 2.5 mg/kg Trans Sodium Crocetinate<br>Subjects will receive a single IV bolus dose of 2.5 mg/kg TSC. Subjects will also receive a single IV dose of normal saline as placebo, thereby serving as their own control. | Drug: Trans Sodium Crocetinate<br>* Single IV bolus<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequence matched median PaO2 per dose cohort comparing TSC vs PBO | Comparison of partial pressure of oxygen (PaO2) at altitude between control and experimental exposures | Up to 10 ± 1 minutes after final VO2 max | 
| Sequence matched median VO2 per dose cohort comparing TSC vs PBO | Comparison of maximal oxygen consumption (VO2 max) at altitude between control and experimental exposures | Up to 33 minutes (achievement of peak wattage) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of TSC on Median Oxygen Saturation | Comparison of oxygen saturation (SpO2) between the control and experimental exposures | Up to 33 minutes (achievement of peak wattage) | 
| Effect of TSC on Median Serum Lactate Concentration | Comparison of lactate between the control and experimental exposures | Up to 33 minutes (achievement of peak wattage) |