Clinical trial NCT04808622: Safety and Efficacy of Trans Sodium Crocetinate (TSC) in Enhancing Tissue Oxygen Levels in Healthy Volunteers
Official title: Randomized, Double-blind, Placebo-controlled, Pharmacokinetic, Pharmacodynamic Study of Trans Sodium Crocetinate Utilizing Transcutaneous Oximetry Measurement in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Transcutaneous oximetry
Lead sponsor: Diffusion Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2021-03-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Healthy male or female, age 18-50
2. Able and willing to lie quietly supine or semi-recumbent for up to 2.5 hours
3. Abstinence from exercise, caffeine, alcohol, nicotine, and a heavy meal prior to testing on the day of the Treatment Visit
4. Subject is able to communicate effectively with the Investigator and to comply with all study requirements, restrictions, and directions from the study staff
5. 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.
6. 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:

1. Allergy to study medication
2. Pregnant or breastfeeding
3. 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
4. Body Mass Index (BMI) \> 30
5. Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg), or Hepatitis C Antibody (HCVAb)
6. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to screening
7. Plasma donation within 7 days prior to screening
8. Treatment with an investigational drug within 30 days or 5 times the half-life (whichever is longer) prior to screening
9. 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)
10. Known cardiovascular disease, including treated or untreated hypertension
11. Significant respiratory disease and/or any other significant medical condition
12. Subject has an acute illness (gastrointestinal infection, influenza, or known inflammatory process) at the Treatment Visit
13. Urine screen positive for drugs or positive breathalyzer for alcohol (at screening and enrollment)
14. Concomitant medications used to treat a diagnosed medical condition
15. 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

Primary outcomes:
measure: Determine the Dose-Response of TSC on tcpO2 Following a Single Administration of TSC in Subjects Breathing O2.
timeFrame: 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 minutes post-dose
Secondary outcomes:
Other outcomes:
measure: Summary of ANOVA Results (Difference [95% Confidence Interval]) for tcpO2 Time-Matched Values by TSC Cohort Compared to Placebo.
timeFrame: 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 minutes post-dose
Locations:
city: Overland Park
country: United States
facility: Altasciences Clinical Kansas Inc
state: Kansas
Study officials:
affiliation: Altasciences Clinical Kansas, Inc.
name: Martin K Kankam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: