Pharmacokinetic and Safety Study of HYR-PB21 vs Bupivacaine Hydrochloric Acid in Healthy Participants

Inclusion Criteria:

1. Healthy male or female adult participants
2. Age 18 to 50 years old (inclusive)
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 and weight ≥50 kg.

4. Participant is generally healthy, as determined by the Investigator based on medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG) at screening.

   Additional Detailed Inclusion Criteria Include:

5. Female participants who engage in heterosexual intercourse must be non-pregnant or non-lactating. Female participants of childbearing potential must agree to use 2 acceptable methods of contraception with their male partner from screening until 6 months after the last dose of the study drug and refrain from donating ovum for this same period. (Refer to contraception section).Females of non-childbearing potential must either be :

   1. Post menopausal as defined by at least 12 months of consecutive Amenorrhea and Follicle-Stimulating Hormone(FSH) and estradiol confirming Post menopausal status at screening. See Appendix Section 13 for additional details.
   2. Surgically sterile at least 6 months prior to screening with documentation.
   1. Bilateral tubal ligation
   2. Hysterectomy (partial or total)
   3. Bilateral salpingectomy
   4. Bilateral oophorectomy
6. Male participants, if sexually active with a female partner of child-bearing potential, must be vasectomized or agree to take appropriate precautions to prevent conception, including practicing an effective method of contraception, and must not donate sperm from screening through 12 weeks following administration of the last dose of study medication.
7. Only non-smokers are eligible. For a period of at least six months prior to Screening, all participants must have been free from excessive alcohol intake or regular use of illegal recreational drugs. Participants with any past or current history of marijuana use are not eligible for the study.
8. Ability to understand and willingness to sign a written informed consent form (The consent form must be signed by the participant prior to any study-specific procedures.)
9. Willingness and able to comply with catheter placement and blood draws throughout the course of study and comply with study procedures and follow-up examination.

Exclusion Criteria:

Participants will be excluded if they have

1. A history of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics;
2. Have a personal or family history of clotting disorder or hematologic abnormality, such as excessive bleeding, joint hematoma, thrombovascular disease, thrombocytopenia, or any chronic condition requiring treatment with transfusions; have a history of recurrent bleeding episodes (eg, epistaxis, bruising or gingival bleeding) within 1 month prior to Screening, or a longstanding history of such bleeding.

3. Participants who were detected to have Glucose-6-phosphate dehydrogenase(G6PD) deficiency during the screening period.

   Additional detailed exclusion criteria include:

4. Females who are pregnant, lactating, or have plans to become pregnant during the study
5. History and/or recent evidence within six months prior to Screening of alcohol or drug/substance abuse disorder
6. History of clinically significant allergies, including drug allergies, or allergic bronchial asthma, or related bronchospastic conditions
7. Participants who have a history of unexplained syncope or fainting or a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration.
8. Participants who have used P-gp and/or Cytochrome P450 hepatic microsomal enzyme-inducing or inhibiting drugs (e.g., propafenone, voriconazole, fluconazole, cimetidine) within 30 days of first dosing, refer to Appendix 15-16 for detailed list

9. Participants with a history or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease, or active sexually transmitted disease to include:

   1. Current or history of thrombosis or thromboembolic disorders
   2. Any history of malignancy, especially breast cancer or other hormone-sensitive cancers
   3. Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
   4. Cholestatic jaundice of pregnancy
   5. Liver tumors, benign or malignant, or active liver disease
   6. Uncontrolled hypertension
10. History or evidence of acute or chronic respiratory disorders, including but not limited to chronic obstructive pulmonary disease (COPD) or asthma
11. History or presence of significant cardiovascular abnormalities, including, without limitation, severe bradycardia, sick sinus syndrome, second- or third-degree atrial ventricular block, long QT syndrome, cardiogenic shock, and decompensated heart failure
12. Participant family history of sudden cardiac death or long QT syndrome and baseline QT prolongation >450 for males and >470 for females at screening
13. Participants with estimated glomerular filtration rate (eGFR - utilizing Chronic Kidney Disease Epidemiology Collaboration formula) < 80 mL/min/1.73 m2; participants with slightly lower values may be included upon agreement between the sponsor medical representative and the Principal Investigator at screening

14. Participants meeting any of the following laboratory criteria will be excluded:

    1. Screening total bilirubin > 1.3 mg/dL; participants with a documented history of Gilbert's syndrome can be enrolled if the direct bilirubin is < 0.4 mg/dL
    2. Screening alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) > upper limits of normal (ULN)
    3. Screening platelets < 140,000/microliter
    4. Screening international normalized ratio > 1.2
15. Participants who test positive at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody
16. Participants who test positive at Screening and/or admission (Day 0) for alcohol and/or drugs of abuse
17. Participants who donated ≥ 500 mL of blood within 56 days prior to the study period or ≥ 50 mL and ≤ 499 mL of blood within 30 days prior to the study period
18. Participants who are unable to refrain from or anticipatethe use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [Hypericum perforatum]) approximately 2 weeks prior to study drug administration.
19. Participant who is unable to refrain from excessive alcohol consumption within one week prior to the study start throughout the study, until the final study visit. Moderate alcohol consumption is defined as one standard drink per day for women and two drinks per day for men; whereby one standard drink is equivalent to 12 oz beer (5% alcohol), 5 ounces of wine (12% alcohol), and 1.5 ounces of 80 proof (40% alcohol). Excessive consumption would be considered consistently in excess of twice the moderate recommendation.
20. Participant who consumes excessive amounts of caffeine for one month prior to the study drug administration, defined as greater than six servings (one serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
21. Participants who donated plasma (e.g., plasmapheresis) within 14 days prior to the study period; participants will be advised not to donate plasma for 14 days after completing the study
22. Participant with tattoos to the abdominal area, which in the opinion of the investigator, could interfere with study drug administration.
23. Participant has poor venous access or has a history of difficulty tolerating venipuncture such as vasovagal syncope.
24. Participants who have participated in another clinical trial which required blood draws within 30 days prior to the first study drug dosing
25. Have any other condition that, in the opinion of the Investigator, would interfere with a participant's ability to adhere to the protocol, interfere with assessment of the investigational product, or compromise the safety of the participant or the quality of the data.