A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ST-2427 IV Infusion in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- ST-2427
- Conditions
- Acute, Post-operative Pain
- Sponsor
- SiteOne Therapeutics, Inc.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-emergent Adverse Events
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief 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.
Detailed Description
This is a Phase 1, randomized, double-blind, placebo-controlled study in healthy adult males and females of non-child-bearing potential to evaluate the safety, tolerability, and pharmacokinetics (PK) of ST-2427. This trial will include careful assessments of treatment effects on vital signs including cardiac and respiratory function and body temperature over a range of doses of ST-2427, administered as single doses. SiteOne Therapeutics, Inc. plans to use the safety, tolerability, and PK findings from this study to inform the doses and study design for Phase 2 clinical studies in subjects with acute post-operative pain. Approximately 30 subjects, 6 subjects into each of 5 cohorts, will be enrolled in this study at a single clinical site. Subjects will be randomized 4:2 to receive a single dose of ST-2427 or placebo in a Single Ascending Dose (SAD) design. The Study will evaluate 5 dose strengths of ST-2427, one dose level in each of 5 cohorts of subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Only subjects who meet the following criteria will be eligible for inclusion:
- •Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of age (inclusive) at the time of screening;
- •Body mass index (BMI) within 18.0 to 35.0 kg/m2, inclusive (minimum weight of at least 50.0 kg at Screening);
- •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;
- •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
- •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);
- •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;
- •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;
- •Willing and able to provide written informed consent;
- •Willing and able to comply with all study assessments and adhere to the protocol schedule;
Exclusion Criteria
- •Subjects will be excluded from the study if they meet any of the following criteria:
- •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;
- •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);
- •History of orthostatic reactions
- •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.
- •History of seizure disorders, except for non-complex febrile seizures in childhood with absence of non-febrile seizures in parents and siblings.;
- •Positive urine drug/alcohol testing at Screening or Day -2;
- •Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb);
- •Positive test results for COVID-19 (PCR or Antibodies)
- •History of substance abuse or alcohol abuse (defined as greater than 2 standard drinks per day) within the previous 2 years;
Arms & Interventions
Single Ascending Dose: Cohort 1
5 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (ST-2427 n=1, placebo n=1) before remainder of cohort.
Intervention: ST-2427
Single Ascending Dose: Cohort 1
5 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (ST-2427 n=1, placebo n=1) before remainder of cohort.
Intervention: Placebo
Single Ascending Dose: Cohort 2
10 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: ST-2427
Single Ascending Dose: Cohort 2
10 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: Placebo
Single Ascending Dose: Cohort 3
15 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: ST-2427
Single Ascending Dose: Cohort 3
15 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: Placebo
Single Ascending Dose: Cohort 4
22 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: ST-2427
Single Ascending Dose: Cohort 4
22 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: Placebo
Single Ascending Dose: Cohort 5
33 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: ST-2427
Single Ascending Dose: Cohort 5
33 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Treatment-emergent Adverse Events
Time Frame: Day 1 through Day 8
For purposes of monitoring safety, treatment-emergent adverse events (AEs) will be graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers (FDA 2007) which is appropriate for healthy subjects.
Number of Participants With Adverse Events Assessed by Blood Pressure
Time Frame: Day 1 through Day 8
Blood pressure, including orthostatic blood pressure (BP; diastolic blood pressure \[DBP\], systolic blood pressure \[SBP\]), will be used to analyze for change from baseline. Adverse events assessed by blood pressure include hypertension and hypotension (MedDRA Preferred Term).
Number of Participants With Adverse Events Assessed by ECG
Time Frame: Day 1 through Day 8
Cardiodynamic evaluation will be performed to evaluate the treatment effects on heart rate-corrected QT interval using the Fridericia (QTcF) corrections.
Number of Participants With Treatment-emergent Events Assessed by Clinical Laboratory Assessments
Time Frame: Day 1 through Day 8
Descriptive statistics will be used to evaluate the treatment effects on clinical laboratory assessments including clinical chemistry, hematology, and urinalysis.
Number of Participants With Adverse Events Assessed by Body Weight
Time Frame: Day 1 through Day 8
Body weight (kg) will be assessed for changes relative to baseline.
Secondary Outcomes
- Pharmacokinetics of ST-2427 Concentration in Whole Blood: Cmax(0-48 hours)
- Pharmacokinetics of ST-2427 Concentration in Whole Blood: Area Under the Curve(0-25 hours)