An Evaluation of The Absolute Bioavailability of TH104

Inclusion criteria

• Subject age between 18 to 55 years old.
• Subject body weight ≤ 120 kg, with a BMI within of 18-30 kg/m2
• Subject is able to complete the clinical study including the follow-up.
• Subject is capable of providing written informed consent.

Exclusion criteria

• Breastfeeding female.
• Positive pregnancy test (female).
• Systolic blood pressure outside 80-140 mm Hg or diastolic blood pressure outside 50-80 mm Hg.
• Bradycardia defined as symptomatic heart rate < 60 bpm or asymptomatic heart rate < 55 bpm and tachycardia defined as resting heart rate > 100 bpm.
• Clinically significant ECG abnormalities.
• QTc > 450 ms for male and > 460 ms for female.
• A history of allergies, or any significant adverse reactions, to any medications.
• A history of seizures or convulsions.
• Clinically significant medical, familial, or surgical history of eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, genitourinary, neurological, hematopoietic, lymphatic, endocrine, metabolic, dermatological, musculoskeletal, psychological and/or other major disease or malignancy.
• Family history of sudden cardiac death.
• Clinically significant physical examination finding.
• Clinically significant laboratory abnormalities.
• Hemoglobin < 12.0 g/dL for male and < 11.0 g/dL for female at screening.
• Creatinine clearance <90 mL/m2/min
• Total bilirubin , ALT/AST greater than upper limit of normal, or CPK > 2 x upper limit of normal.
• Hepatitis B, Hepatitis C or HIV positive.
• Positive test for drugs of abuse.
• Smoke more than 10 sticks of cigarettes a day, vape more than 20 mg of liquid nicotine a day, or equivalent.
• A history of drug or substance abuse, including alcohol (≥ 7 units per week) within 6 months before dosing (1 unit of alcohol equals approximately ½ pint [240 mL] of beer, 1 glass [125 mL] of wine, or 1 shot [25 mL] of spirit).
• Have taken any medications (including herbal remedies) within 7 days before dosing, with the exception of birth control medications and other medications deemed acceptable by the Investigator.
• Use of any opioid antagonist (e.g., naloxone, naltrexone, nalmefene) in the past.
• Clinically significant illness or injury or hospitalization for any reason within 28 days before dosing.
• Participation in other clinical study involving a marketed or investigational drug within 28 days or 10 half-lives of the drug before dosing, whichever is longer.
• Donation of > 500 mL of plasma within 14 days before dosing; or donation or loss of whole blood (excluding the amount of blood collected during screening) before dosing as follows:

• 50-300 mL within 28 days,
• 301-500 mL within 42 days, or
• 500 mL within 84 days.
• Any other medical condition or reason that, in the opinion of the Investigator or Research Physician, makes the subject unsuitable to participate in the clinical study.
• Female of childbearing potential having unprotected sexual intercourse with any non-sterile male partner within 14 days before dosing and until 60 days after receiving the last dose; acceptable methods of contraception include:

• double barrier (1 by each partner), and at least 1 of these barriers (condom, cervical cap, diaphragm or sponge) must contain spermicide,
• hormonal (oral, injectable, transdermal, intravaginal or implantable),
• intrauterine contraceptive system,
• surgical (vasectomy or tubal ligation), or
• sexual abstinence.