Phase I Trial of Pyragrel, a Novel Thromboxane Synthetase Inhibitor, to Evaluate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers

Figures

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  Figure 1. Flow chart of the pyragrel phase I trial study. Flow chart illustrated the study design, clinical screening procedure, information about the number of subjects enrolled, drug administration methods, predetermined time points for blood and urine samples collection in Part I–V.

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  Figure 2. Mean (±SD) concentration-time profiles of pyragrel following a 3 h intravenous infusion of single ascending doses of pyragrel (30, 60, 120, 180, 240, 300 mg) in healthy volunteers (Part I). Fifty-two participants randomized to receive i.v. 3 h infusion of single dose of pyragrel ascendingly (30, 60, 120, 180, 240, 300 mg), ozagrel 80 mg, or placebo diluted in 500 ml saline; pyragrel concentrations of blood samples were determined over 48 h after the initiation of the infusion.

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  Figure 3. Mean (± SD) concentration-time profiles of pyragrel after i.v. 3 h infusion of multiple doses versus single dose of pyragrel 180 mg in 12 healthy volunteers (Part III). Twelve participants received multiple dose of pyragrel 180 mg for 6 days, pyragrel diluted in 250 ml saline and administrated as 3 h i.v. infusion; pyragrel concentrations of blood samples after the first dose (Day 1) and the last dose (Day 6) were determined over 24 h after the initiation of the infusion. The comparison of mean concentration-time profiles is presented in the figure.

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  Figure 4. Mean (± SD) concentration-time profiles of pyragrel in a 3×3 crossover study (60, 120, or 240 mg) in 12 healthy volunteers (Part IV). Twelve participants received three doses (60, 120, or 240 mg), three period pyragrel administrations with a 7-day washout period during doses. Pyragrel diluted in 250 ml saline and infused i.v. for 3 h; pyragrel concentrations of blood samples were determined over 24 h after the initiation of the infusion at each period.

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  Figure 5. Mean (± SD) concentration-time profiles of pyragrel, BBS, and BJS after continuous intravenous infusion of 360 mg of pyragrel within 24 h in healthy volunteers (Part V). A single dose of pyragrel 360 mg was given to four participants. Pyragrel diluted in 600 ml saline and infused i.v. for 24 h; pyragrel, BBS, and BJS concentrations of blood samples were determined over 48 h after the initiation of the infusion.