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

NCT04475198 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: ST-2427-CS-0011UG3DA049599
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute, Post-operative Pain

Keywords

Pain

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events

  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.

  Day 1 through Day 8

• 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).

  Day 1 through Day 8

• Number of Participants With Adverse Events Assessed by ECG

  Cardiodynamic evaluation will be performed to evaluate the treatment effects on heart rate-corrected QT interval using the Fridericia (QTcF) corrections.

  Day 1 through Day 8

• Number of Participants With Treatment-emergent Events Assessed by Clinical Laboratory Assessments

  Descriptive statistics will be used to evaluate the treatment effects on clinical laboratory assessments including clinical chemistry, hematology, and urinalysis.

  Day 1 through Day 8

• Number of Participants With Adverse Events Assessed by Body Weight

  Body weight (kg) will be assessed for changes relative to baseline.

  Day 1 through Day 8

Secondary Outcomes (3)

• Pharmacokinetics of ST-2427 Concentration in Whole Blood: Cmax

  0-48 hours

• Pharmacokinetics of ST-2427 Concentration in Whole Blood: Area Under the Curve

  0-9 hours

• Pharmacokinetics of ST-2427 Concentration in Whole Blood: Area Under the Curve

  0-25 hours

Study Arms (5)

Single Ascending Dose: Cohort 1

EXPERIMENTAL

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.

Drug: ST-2427; Drug: Placebo

Single Ascending Dose: Cohort 2

EXPERIMENTAL

10 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.

Drug: ST-2427; Drug: Placebo

Single Ascending Dose: Cohort 3

EXPERIMENTAL

15 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.

Drug: ST-2427; Drug: Placebo

Single Ascending Dose: Cohort 4

EXPERIMENTAL

22 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.

Drug: ST-2427; Drug: Placebo

Single Ascending Dose: Cohort 5

EXPERIMENTAL

33 mg ST-2427 (n=4) or placebo (n=2) administered once over a 60-minute intravenous (IV) infusion.

Drug: ST-2427; Drug: Placebo

Interventions

ST-2427 DRUG

Investigational drug

Single Ascending Dose: Cohort 1; Single Ascending Dose: Cohort 2; Single Ascending Dose: Cohort 3; Single Ascending Dose: Cohort 4; Single Ascending Dose: Cohort 5

Placebo DRUG

5% Dextrose Injection

Single Ascending Dose: Cohort 1; Single Ascending Dose: Cohort 2; Single Ascending Dose: Cohort 3; Single Ascending Dose: Cohort 4; Single Ascending Dose: Cohort 5

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• Have suitable venous access for blood sampling, as determined by an Investigator at screening;
• 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;
• 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.

You may not qualify if:

• 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;
• 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;
• Documented hypersensitivity reaction or anaphylaxis to any medication;
• 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;
• Dosed in another investigational clinical trial within 30 days prior to Screening;
• Any condition or prior therapy, e.g. seizures, or head trauma, that may lead to CNS effects during the study;

Sponsors & Collaborators

• SiteOne Therapeutics, Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Altasciences

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Pain

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Results Point of Contact

• Title: John Mulcahy
• Organization: SiteOne Therapeutics

john.mulcahy@site1therapeutics.com

+1 (650) 392-0419

Study Officials

• Markus Jerling, MD, PhD

  Unaffliated

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: July 17, 2020
• Study Start: March 4, 2021
• Primary Completion: August 18, 2021
• Study Completion: August 18, 2021
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)