Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ST-2427
Condition: Acute, Post-operative Pain
MeSH terms: Pain, Postoperative
Intervention: ST-2427; Placebo
Intervention description: Investigational drug; 5% Dextrose Injection
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Double-blind
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pain

Summary:

      This randomized, double-blind, placebo controlled, study will be conducted to evaluate the
      safety, tolerability, and pharmacokinetics of ST-2427. Subjects will be randomized to receive
      a single dose of ST-2427 or placebo in a Single Ascending Dose (SAD) design.

      A total of 30 subjects will be enrolled. Subjects will be randomized in a 4:2 ratio of
      ST-2427 to placebo. Study drug will be blinded to all subjects and investigators.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Only subjects who meet the following criteria will be eligible for inclusion:

               1. Healthy adult males and/or females (of non-childbearing potential), 18 to 55
                  years of age (inclusive) at the time of screening;

               2. Body mass index (BMI) within 18.0 to 35.0 kg/m2, inclusive (minimum weight of at
                  least 50.0 kg at Screening);

               3. Medically healthy without clinically significant abnormalities at the screening
                  visit, including physical examination and vital signs within the following
                  ranges: heart rate 50 to 100 bpm, systolic blood pressure 100 to 149 mmHg;
                  diastolic 70 to 94 mmHg;

               4. The mean QTcF interval duration ≤450 msec for males and ≤470 msec for females
                  measured from the triplicate ECGs taken at least 1 minute apart with QT wave
                  corrected for heart rate (HR) using Fredericia's method

               5. Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count equal to
                  or greater than the lower limit of normal range of the reference laboratory (may
                  be confirmed upon repeat testing without Sponsor approval);

               6. Creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT) and
                  aspartate aminotransferase (AST) equal to or less than the upper limit of normal
                  for the reference laboratory (may be confirmed upon repeat testing); results of
                  all other clinical chemistry and urine analytes without any clinically
                  significant abnormality;

               7. Non-smokers (including tobacco, e-cigarettes or marijuana), and no use of any
                  tobacco product for at least 1 month prior to admission in the study;

               8. Willing and able to provide written informed consent;

               9. Willing and able to comply with all study assessments and adhere to the protocol
                  schedule;

              10. Have suitable venous access for blood sampling, as determined by an Investigator
                  at screening;

              11. If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated
                  by follicle stimulating hormone (>40 mIU/mL), or surgically sterilized by tubal
                  ligation or hysterectomy). Site personnel's review of the subject's medical
                  records, medical examination, or medical history interview is acceptable evidence
                  of female sterilization, verbal confirmation is adequate;

              12. If male, willing not to donate sperm from the time of first study drug
                  administration until 90 days after the final administration of study drug. If
                  male and not intending to engage in sexual intercourse over the duration of the
                  study, willing to agree to abstinence at screening. If male and engaging in
                  sexual intercourse, willing to use a double barrier method of contraception
                  (condom and spermicide). The latter criterion applies to all males (and/or female
                  partners) including males who are surgically sterile and must be followed from
                  the time of first study drug administration until 90 days after the final
                  administration of study drug.

        Exclusion Criteria:

          -  Subjects will be excluded from the study if they meet any of the following criteria:

               1. History or presence of significant cardiovascular (including arrhythmia and
                  ventricular tachyphylaxis), pulmonary, hepatic, renal, hematological,
                  gastrointestinal, endocrine, immunologic, dermatologic or neurological disease,
                  including any acute illness or surgery within the past 3 months determined by an
                  Investigator to be clinically relevant;

               2. Creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT) and
                  aspartate aminotransferase (AST) equal to 1.5 x upper limit of normal for the
                  reference laboratory (may be confirmed upon repeat testing);

               3. History of orthostatic reactions

               4. Orthostatic reaction at screening defined as drop in systolic blood pressure by
                  ≥20 mmHg or drop in systolic blood pressure to <90 mmHg on standing for 3 minutes
                  from the supine position.

               5. History of seizure disorders, except for non-complex febrile seizures in
                  childhood with absence of non-febrile seizures in parents and siblings.;

               6. Positive urine drug/alcohol testing at Screening or Day -2;

               7. Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen
                  (HBsAg) or Hepatitis C Antibody (HCVAb);

               8. Positive test results for COVID-19 (PCR or Antibodies)

               9. History of substance abuse or alcohol abuse (defined as greater than 2 standard
                  drinks per day) within the previous 2 years;

              10. Use of any prescription medication or any over-the-counter medication, including
                  herbal products and vitamins within 14 days or 5 half-lives (whichever is longer)
                  prior to randomization;

              11. Documented hypersensitivity reaction or anaphylaxis to any medication;

              12. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days
                  prior to screening, or receipt of a blood transfusion within 1 year of screening;

              13. Dosed in another investigational clinical trial within 30 days prior to
                  Screening;

              14. Any condition or prior therapy, e.g. seizures, or head trauma, that may lead to
                  CNS effects during the study;

              15. Documented or self-reported history of orthostatic hypotension or symptoms of
                  hypotension such as dizziness, syncope or blurred vision upon standing;

              16. Any condition which is associated with increased brain permeability, e.g.
                  cerebral ischemia, brain trauma, multiple sclerosis, brain tumors, brain
                  infection.