Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ST-2427

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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04475198

Enrollment

Registered

2020-07-17

Start date

2021-03-04

Completion date

2021-08-18

Last updated

2023-08-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute, Post-operative Pain

Keywords

Pain

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.

Interventions

DRUGST-2427

Investigational drug

DRUGPlacebo

5% Dextrose Injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Double-blind

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events Assessed by Blood Pressure	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 Treatment-emergent Events Assessed by Clinical Laboratory Assessments	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	Day 1 through Day 8	Body weight (kg) will be assessed for changes relative to baseline.
Number of Participants With Treatment-emergent Adverse Events	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 ECG	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.

Secondary

Measure	Time frame	Description
Pharmacokinetics of ST-2427 Concentration in Whole Blood: Area Under the Curve	0-9 hours	PK modeling will be performed using compartmental methods. The AUC (area under the curve) of ST-2427 in whole blood after the ST-2427 infusion in the SAD.
Pharmacokinetics of ST-2427 Concentration in Whole Blood: Cmax	0-48 hours	PK modeling will be performed using compartmental methods. The maximum concentration of ST-2427 in whole blood after the ST-2427 infusion in the SAD.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Single Ascending Dose: Cohort 1 5 mg ST-2427 (n=4) administered once over a 60-minute intravenous (IV) infusion. ST-2427: Investigational drug	4
Single Ascending Dose: Cohort 2 10 mg ST-2427 (n=4) administered once over a 60-minute intravenous (IV) infusion. ST-2427: Investigational drug	4
Single Ascending Dose: Cohort 3 15 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion. ST-2427: Investigational drug	4
Single Ascending Dose: Cohort 4 22 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion. ST-2427: Investigational drug	4
Pooled Placebo Pooled placebo (n=8) administered once over a 60-minute intravenous (IV) infusion. Placebo: 5% Dextrose Injection	8
Total	24

Baseline characteristics

Characteristic	Single Ascending Dose: Cohort 1	Single Ascending Dose: Cohort 2	Single Ascending Dose: Cohort 3	Single Ascending Dose: Cohort 4	Pooled Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	4 Participants	4 Participants	4 Participants	4 Participants	8 Participants	24 Participants
Age, Continuous	40.0 years STANDARD_DEVIATION 6.73	49.5 years STANDARD_DEVIATION 3.42	40.0 years STANDARD_DEVIATION 9.93	32.5 years STANDARD_DEVIATION 13.03	43.4 years STANDARD_DEVIATION 11.13	41.5 years STANDARD_DEVIATION 10.36
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	3 Participants	4 Participants	4 Participants	8 Participants	23 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	2 Participants	0 Participants	2 Participants	4 Participants	4 Participants	12 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	1 Participants	4 Participants	2 Participants	0 Participants	3 Participants	10 Participants
Region of Enrollment United States	4 participants	4 participants	4 participants	4 participants	8 participants	24 participants
Sex: Female, Male Female	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	3 Participants
Sex: Female, Male Male	3 Participants	3 Participants	4 Participants	4 Participants	7 Participants	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 4	0 / 4	0 / 4	0 / 8
other Total, other adverse events	3 / 4	1 / 4	2 / 4	1 / 4	2 / 8
serious Total, serious adverse events	0 / 4	0 / 4	0 / 4	0 / 4	0 / 8

Outcome results

Primary

Number of Participants With Adverse Events Assessed by Blood Pressure

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).