A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Doses of SP-8008 in Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- SP-8008 Prototype Capsule A
- Conditions
- Acute Coronary Syndrome
- Sponsor
- Shin Poong Pharmaceutical Co. Ltd.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with serious adverse drug reactions (SADRs)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Detailed Description
Investigational medicinal product (IMP) will be administered at only 1 dose level at a time. Following each of Periods 1, 2, 3, 4, and 5, there will be a period of interim analysis and review of safety, PK and available PD data from the previous period(s) in order to determine which SP 8008 formulation and dose to administer further regimens. Administration at the next dose level will not begin until the safety and tolerability of the preceding dose level have been evaluated and deemed acceptable by the investigator and sponsor, and the exposure of SP-8008 remains within the pre specified limits following interim review. There will be an interval of no less than 14 days between the dosing of successive cohorts, unless a subject cohort returns to a dose that is lower than that already given in a previous cohort eg to obtain dose linearity information. Dose escalation will be guided by emerging safety, PK and available PD data and confirmed after each interim data review meeting. There is the option to assess the safety, PK and PD of an alternative formulation. This formulation will be invoked if, following review of data from the preceding periods, it is decided that the exposure from the current formulation may not be ideal for future development.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Cohort 1: 200mg SP-8008 Prototype Capsule A
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.
Intervention: SP-8008 Prototype Capsule A
Cohort 1: 200mg SP-8008 Prototype Capsule A
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.
Intervention: Placebo
Cohort 2: 400mg SP-8008 Prototype Capsule A
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.
Intervention: SP-8008 Prototype Capsule A
Cohort 2: 400mg SP-8008 Prototype Capsule A
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.
Intervention: Placebo
Cohort 3: 800mg SP-8008 Prototype Capsule A
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.
Intervention: SP-8008 Prototype Capsule A
Cohort 3: 800mg SP-8008 Prototype Capsule A
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.
Intervention: Placebo
Cohort 4: 800 mg SP-8008 Prototype Capsule B
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.
Intervention: SP-8008 Prototype Capsule B
Cohort 4: 800 mg SP-8008 Prototype Capsule B
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.
Intervention: Placebo
Cohort 5: 1200 mg SP-8008 Prototype Capsule B
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.
Intervention: SP-8008 Prototype Capsule B
Cohort 5: 1200 mg SP-8008 Prototype Capsule B
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.
Intervention: Placebo
Cohort 6: 1800 mg SP-8008 Prototype Capsule B
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.
Intervention: SP-8008 Prototype Capsule B
Cohort 6: 1800 mg SP-8008 Prototype Capsule B
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with serious adverse drug reactions (SADRs)
Time Frame: Follows up to 7 days
The number of subject who experienced a serious adverse drug reaction
Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with severe adverse drug reactions (ADRs)
Time Frame: Follows up to 7 days
The number of subject who experienced a severe adverse drug reaction
Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with clinically significant non-serious adverse events (AEs)
Time Frame: Follows up to 7 days
The number of subject who experienced a clinically significant non serious adverse event
Secondary Outcomes
- 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)
- 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)