A Phase I Study to Evaluate Safety and Pharmacokinetics of Escalating Single Doses and Multiple Doses of SP-8356

Study Overview
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Brief Summary
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This is a 2-part, single-centre, randomised study in healthy males. Part 1 is a double-blind, randomised, placebo-controlled, single ascending dose (SAD) study in healthy males. Part 2 is a double-blind, randomised, placebo-controlled, multiple ascending dose (MAD) study in healthy males.

Detailed Description
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2-part, single-centre, randomised study in healthy males. Part 1 is a double-blind, randomised, placebo-controlled, single ascending dose (SAD) study in healthy males. Part 2 is a double-blind, randomised, placebo-controlled, multiple ascending dose (MAD) study in healthy males.

Official Title
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A Phase I Single-Centre, Randomised, Double-Blind, Placebo-Controlled Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses and Multiple Doses of SP-8356

Conditions
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Atherosclerosis, Ischemic Stroke

Intervention / Treatment
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* Drug: SP-8356
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Aged 18 to 55 years, inclusive, at the time of signing informed consent Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening Must be willing and able to communicate and participate in the whole study Must provide written informed consent Must agree to adhere to the contraception requirements Exclusion Criteria: Females Subjects who have received any IMP in a clinical research study within the 90 days prior to the planned first dosing date Subjects who are, or are immediate family members of a study site or sponsor employee Evidence of recent or current SARS-CoV-2 infection. A minimum period of 3 months from resolution of COVID-19 symptoms to dosing must have passed Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2 History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption in males > 21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type) A confirmed positive alcohol breath test at screening or admission Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening Clinically significant abnormal biochemistry, haematology, or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are not allowed Subjects that have either a known of family history of QT prolongation or chronic QT prolongation syndrome (i.e. QTc > 450 msec) in repeated ECG Subjects with any clinically significant medical disorders increasing tendency to bleed easily, or having history of recent trauma or surgery, or having history of gout or renal stones Subjects with a clinically significant history of skin disorder such as photosensitivity, eczema or psoriasis. Subjects with a clinically significant history of eye disorders that may affect the interpretation of the ophthalmology assessments as per the judgement of the investigator (only for subjects where ophthalmology assessments will be performed). Confirmed positive drugs of abuse test result Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results Evidence of renal impairment at screening, as indicated by an estimated glomerular filtration rate (eGFR) of <80 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator Subjects with a history of cholecystectomy or gall stones (Part 1 Cohort 3 only) Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active Donation or loss of greater than 400 mL of blood within the previous 3 months Has a history of photosensitivity or photoallergy Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day) in the 14 days before IMP administration Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the investigator Is taking medication known to cause phototoxic reactions (e.g., tetracyclines, thiazides, nonsteroidal anti-inflammatory drugs) within 4 weeks of enrolling into the study Failure to satisfy the investigator of fitness to participate for any other reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Interventional Model Description: Dose escalation
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SP-8356 powder<br>Part1 will consist of escalating single doses in five sequential cohorts. Each dose level cohort will consist of 8 subjects: 6 subjects will receive SP-8356 and 2 subjects will receive placebo in fasted state according to the randomization schedule. Subjects in Cohort 3 will receive a single dose of SP-8356 or placebo in the fasted then fed state on separate dosing occasions. | Drug: SP-8356<br>* SP-8356 demonstrates anti-atherosclerotic and anti-ischaemic activity as a novel CD147 inhibitor.<br>|
| Placebo Comparator: Placebo<br>Part1 will consist of escalating single doses in five sequential cohorts. Each dose level cohort will consist of 8 subjects: 6 subjects will receive SP-8356 and 2 subjects will receive placebo in fasted state according to the randomization schedule. Subjects in Cohort 3 will receive a single dose of SP-8356 or placebo in the fasted then fed state on separate dosing occasions. | Drug: Placebo<br>* Placebo for SP-8356 powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part 1)To investigate the safety and tolerability of single oral doses of SP-8356 in healthy male subjects | Incidence of adverse events (AEs), and assessment of physical examinations, safety laboratory tests, vital signs, electrocardiograms (ECGs) and ophthalmologic examinations | up to 3days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part 1)To characterise the pharmacokinetic (PK) profile of single oral doses of SP-8356 Maximum Observed Drug Concentration (Cmax) | Evaluate Maximum Observed Drug Concentration (Cmax) of SP-8356. | up to 3days | 
| (Part 1)]To characterise the pharmacokinetic (PK) profile of single oral doses of SP-8356- Area under the plasma concentration versus time curve from time zero to infinity (AUC[0-∞]) | Evaluate Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-∞]) of SP-8356. | up to 3days | 
| (Part 1)To characterise the effect of food on the PK profile of SP-8356 following single oral doses of SP-8356 Maximum Observed Drug Concentration (Cmax) | Evaluate the effect of food on Maximum Observed Drug Concentration (Cmax) of SP-8356. | up to 3days | 
| (Part 1)To characterise the effect of food on the PK profile of SP-8356 following single oral doses of SP-8356 - Area under the plasma concentration versus time curve from time zero to infinity (AUC[0-∞]) | Evaluate the effect of food on Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-∞]) of SP-8356. | up to 3days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SP-8356, Shinpoong, atherosclerosis, ischaemic stroke