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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
48
Quotient Sciences
Nottingham, Nottinghamshire, United Kingdom
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
Time frame: 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
Time frame: 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
Time frame: Follows up to 7 days
To evaluate the effect of single dose SP-8008 on platelet function through Shear stress-induced platelet aggregation (SIPA)
Evaluate the pharmacodynamics (PD) effects of SP-8008 to measure platelet functional closure time under SIPA conditions. The effect of SP-8008 on SIPA will be evaluated in anti-coagulated blood with citrate using the Platelet Function Analyser (PFA-100) instrument and optical aggregometry.
Time frame: Follows up to 48 hours
To evaluate the effect of single dose SP-8008 on platelet function through inhibition of platelet aggregation (IPA)
Evaluate the PD effects of SP-8008 to investigate the increment of platelet aggravating physiological factors under IPA conditions. The effect of SP-8008 on IPA will be evaluated in anti-coagulated blood with citrate using the Platelet Function Analyser (PFA-100) instrument and optical aggregometry.
Time frame: Follows up to 48 hours
To characterize the pharmacokinetics of SP-8008 in health male subjects. - Peak Plasma Concentration (Cmax)
Evaluate Maximum Observed Drug Concentration (Cmax) of SP-8008.
Time frame: 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-∞])
Evaluate Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) of SP-8008.
Time frame: Follows up to 48 hours
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