Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SP-8008
Condition: Acute Coronary Syndrome; Stroke
MeSH terms: Acute Coronary Syndrome
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): SP-8008 Prototype Capsule A; SP-8008 Prototype Capsule B; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Oral; Oral; Oral
Other intervention name(s): SP-8008; SP-8008
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: antiplatelet drug; shear stress; SP-8008