A Phase 1, Randomized, Placebo-Controlled Safety and Tolerability Study Of Intravenous SBS-1000 in Healthy Adults

Study Overview
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Brief Summary
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This study will be a single-center, double-blind, randomized placebo-controlled, adaptive, single ascending dose study.

Detailed Description
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This study will be a single-center (clinical research unit), double-blind, placebo-controlled, randomized, adaptive, single-ascending dose study receiving either Investigational Product (IP [SBS-1000]) or placebo IV infusion. Up to 56 subjects will be randomized. A total of 6 ascending dose cohorts will be used to assess the MTD of SBS-1000. Each cohort will be comprised of up to 8 subjects randomized 6:2 (IP:placebo). A sentinel group of 2 subjects randomized 1:1 (IP:placebo) will be used for each cohort with the sentinel group being dosed at least 48 hours prior to dosing the remaining subjects of the cohort, and contingent on the results of ongoing safety evaluation. Blood samples will be collected over 72 hours postdose and urine samples over 48 hours postdose for pharmacokinetic (PK) assessments in all cohorts. Pharmacodynamic assessments will be performed throughout the study in cohorts 1 through 6. The sampling parameters may be adjusted based on the interim safety review. Once the maximum tolerated dose (MTD) is established, dosing with the MTD or a lower dose, as determined by an interim safety review, an additional cohort (7) will occur to investigate the cardiodynamic effects of SBS-1000 using Holter monitoring. Cohort 7 will be comprised of 8 subjects randomized 6:2 (IP:placebo). No sentinel dosing administration will occur in this cohort.

Official Title
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A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of SBS-1000 Administered by Intravenous Infusion to Healthy Adult Subjects

Conditions
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Pain, Acute Pain

Intervention / Treatment
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* Drug: SBS-1000
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form (ICF) Healthy adult male or female, aged 18 to 59 years, inclusive, at Screening Body mass index (BMI) within 18.0 kg/m^2 to 33.0 kg/m^2, inclusively Minimum body weight of at least 50.0 kg at Screening Willingness to comply with all study procedures If female, agrees to use an acceptable contraceptive method. If male, agrees to use an acceptable contraceptive method. Healthy as determined by no clinically significant findings at screening and clinic admission. Non- or ex-smoker Exclusion Criteria: Has a current medical condition that would affect sensitivity to cold or pain Personal or family history of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, dermatologic, or other clinically significant disease that may interfere with the study Any clinically significant illness in the 28 days prior to the first study drug administration Use of any prescription drugs in the 28 days prior to the first study drug administration, that in the opinion of an investigator would put into question the status of the participant as healthy Routine or chronic use of acetaminophen and/or nonsteroidal anti-inflammatory drugs (NSAIDs) Any clinically significant laboratory results at screening or prior to the first drug administration intake of an investigational product within 28 days prior to study drug administration. Positive test for alcohol and/or drugs of abuse Positive for HIV or hepatitis Donation of plasma 7 days prior to study drug administration and/or donation of blood within 56 days prior to study drug administration. Significant ECG abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SBS-1000<br>Investigational Product | Drug: SBS-1000<br>* SBS-1000 administered as a single continuous IV infusion over 60 minutes<br>* Other names: arylepoxamide agonist;|
| Placebo Comparator: Placebo<br>Normal saline (0.9% sodium chloride [NaCl]) | Drug: Placebo<br>* Normal saline (0.9% sodium chloride [NaCl]) administered as a single dose IV infusion over 60 minutes<br>* Other names: sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AEs) | Adverse events as assessed by electrocardiogram, vital signs, end-tidal carbon dioxide, oxygen saturation, physical examination, clinical laboratory tests, OAAS, C-SSRS, slit-lamp examination, gastrointestinal/esophageal assessment and concomitant medications | From start of infusion to 4 (±2) days after the last blood draw in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration (AUC) and Cmax versus time curve of SBS-1000 | Assessment of systemic pharmacokinetics (PK) and urinary excretion of SBS-1000 by evaluation of AUC, Cmax, tmax, Ke t 1/2, Cl, V and Urine PK | From start of infusion to 72 hours post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arylepoxamide, Safety, Tolerability, SBS-1000, SBS1000, 6TM, AEAr Agonist