Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SP-8008

NCT04770194 | Completed Phase 1 DMC

• 2 other identifiers: SP-8008-10012019-000098-21
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-centre, double-blind, randomised, placebo-controlled single oral-dose escalation study in healthy male subjects. It is planned to enrol approximately 48 subjects into up to 6 planned dose level cohorts. Subjects will be randomly assigned to receive a single oral dose of active Investigational medicinal product (IMP) or matching placebo in a sequential escalating manner with at least 14 days planned between dose cohorts. Dose review of the preceding dose will take place during the 14 day interval. The study will consist of escalating single doses in sequential cohorts. Each dose level cohort will consist of 8 subjects; 6 subjects will receive SP-8008 and 2 subjects will receive placebo according to the randomisation schedule. For all dose levels the first 2 sentinel subjects will be randomised 1:1 to placebo or SP-8008, and the remaining 6 subjects will be randomised 1:5 to placebo or SP-8008, respectively.

Conditions

Acute Coronary Syndrome; Stroke

Keywords

antiplatelet drug; shear stress; SP-8008

Outcome Measures

Primary Outcomes (3)

• Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with serious adverse drug reactions (SADRs)

  The number of subject who experienced a serious adverse drug reaction

  Follows up to 7 days

• Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with severe adverse drug reactions (ADRs)

  The number of subject who experienced a severe adverse drug reaction

  Follows up to 7 days

• Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with clinically significant non-serious adverse events (AEs)

  The number of subject who experienced a clinically significant non serious adverse event

  Follows up to 7 days

Secondary Outcomes (4)

• To evaluate the effect of single dose SP-8008 on platelet function through Shear stress-induced platelet aggregation (SIPA)

  Follows up to 48 hours

• To evaluate the effect of single dose SP-8008 on platelet function through inhibition of platelet aggregation (IPA)

  Follows up to 48 hours

• To characterize the pharmacokinetics of SP-8008 in health male subjects. - Peak Plasma Concentration (Cmax)

  Follows up to 48 hours

• To characterize the pharmacokinetics of SP-8008 in health male subjects. - Area under the plasma concentration versus time curve from time zero to infinity (AUC[0-∞])

  Follows up to 48 hours

Other Outcomes (3)

• Laboratory measures of von Willebrand Factor (VWF) activity through Shear stress-induced platelet aggregation (SIPA)

  Follows up to 48 hours

• To characterize the pharmacokinetics of SP-8008 metabolites- Peak Plasma Concentration (Cmax)

  Follows up to 48 hours

• To characterize the pharmacokinetics of SP-8008 metabolites- Area under the plasma concentration versus time curve from time zero to infinity (AUC[0-∞])

  Follows up to 48 hours

Study Arms (6)

Cohort 1: 200mg SP-8008 Prototype Capsule A

EXPERIMENTAL

Treat 200 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.

Drug: SP-8008 Prototype Capsule A; Drug: Placebo

Cohort 2: 400mg SP-8008 Prototype Capsule A

EXPERIMENTAL

Treat 400 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.

Drug: SP-8008 Prototype Capsule A; Drug: Placebo

Cohort 3: 800mg SP-8008 Prototype Capsule A

EXPERIMENTAL

Treat 800 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.

Drug: SP-8008 Prototype Capsule A; Drug: Placebo

Cohort 4: 800 mg SP-8008 Prototype Capsule B

EXPERIMENTAL

Treat 800 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.

Drug: SP-8008 Prototype Capsule B; Drug: Placebo

Cohort 5: 1200 mg SP-8008 Prototype Capsule B

EXPERIMENTAL

Treat 1200 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.

Drug: SP-8008 Prototype Capsule B; Drug: Placebo

Cohort 6: 1800 mg SP-8008 Prototype Capsule B

EXPERIMENTAL

Treat 1600 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.

Drug: SP-8008 Prototype Capsule B; Drug: Placebo

Interventions

SP-8008 Prototype Capsule A DRUG

Oral

Also known as: SP-8008

Cohort 1: 200mg SP-8008 Prototype Capsule A; Cohort 2: 400mg SP-8008 Prototype Capsule A; Cohort 3: 800mg SP-8008 Prototype Capsule A

SP-8008 Prototype Capsule B DRUG

Oral

Also known as: SP-8008

Cohort 4: 800 mg SP-8008 Prototype Capsule B; Cohort 5: 1200 mg SP-8008 Prototype Capsule B; Cohort 6: 1800 mg SP-8008 Prototype Capsule B

Placebo DRUG

Oral

Cohort 1: 200mg SP-8008 Prototype Capsule A; Cohort 2: 400mg SP-8008 Prototype Capsule A; Cohort 3: 800mg SP-8008 Prototype Capsule A; Cohort 4: 800 mg SP-8008 Prototype Capsule B; Cohort 5: 1200 mg SP-8008 Prototype Capsule B; Cohort 6: 1800 mg SP-8008 Prototype Capsule B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males
• Age 18 to 55 years of age at the time of signing informed consent
• Body mass index of 18.0 to 32.0 kg/m2 as measured at screening
• Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), electrocardiogram (ECG) and laboratory investigations (haematology, coagulation, clinical chemistry and urinalysis) and bleeding time (bleeding time may be measured on Day 1)
• 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

You may not qualify if:

• Female subjects
• Subjects who had received any investigator medicinal product (IMP) in a clinical research study within the 3 months or 90 days prior to Day 1
• Subjects who were study site employees, or immediate family members of a study site or sponsor employee
• Subjects who had previously been enrolled in this study
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption \>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)
• Current smokers and those who had smoked within the last 12 months. A confirmed breath carbon monoxide (CO) reading of greater than 10 ppm at screening or admission Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
• Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
• Subjects without suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
• Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator including investigator medicinal product (PT) \>14 s, investigator medicinal product (aPTT) \> reference laboratory values, platelet count ≤100,000 mm3, alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) \>2× upper limit of normal, white blood cells ≤3000 × 109/L, haemoglobin \<11 g/dL, total bilirubin \>20 µmol/L, bleeding time \>15 min
• Any clinically significant medical disorders increasing the tendency to bleed easily, or a history of recent trauma or surgery, or a history of gout and renal stones
• Confirmed positive drugs of abuse test result
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
• Evidence of renal impairment at screening, as indicated by an estimated Creatinine Clearance (CrCl) of \<80 mL/min using the Cockcroft-Gault equation
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator

Sponsors & Collaborators

• Shin Poong Pharmaceutical Co. Ltd.: lead

Study Sites (1)

Quotient Sciences

Nottingham, Nottinghamshire, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Acute Coronary Syndrome; Stroke

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Stuart Mair, MD

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Subjects will be screened for inclusion in the study up to 28 days prior to dosing. Subjects will be admitted to the clinical unit on the morning of Day -1, and will be dosed in a randomised, double-blind manner on the morning of Day 1 following an overnight fast (approximately 10 h). Drug administration will be performed with an appropriate interval (approximately 10 min) between subjects based on logistical requirements. Subjects will remain resident in the clinical unit until up to 48 h after dosing (up to Day 3). Subjects with AEs that represent a cause for concern will be asked to remain resident in the clinical unit until the AE resolves or stabilises. The minimum interval between dose administrations will be 14 days to allow for interim review of PK and safety data from the previous regimen. A follow-up visit will take place 5 to 7 days post-dose for assessment of safety and tolerability.

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: February 25, 2021
• Study Start: October 1, 2019
• Primary Completion: January 23, 2020
• Study Completion: January 23, 2020
• Last Updated: February 25, 2021

Record last verified: 2021-02

Locations

GB (1)