Phase 1b Study To Evaluate Safety, Tolerability, And Maximum Tolerated Dose Of Pf-05230907 For Intracerebral Hemorrhage

Background and Purpose: This study aimed to determine the maximum tolerated dose and to evaluate the overall safety and tolerability of single doses of PF-05230907 in subjects with acute intracerebral hemorrhage.Methods: Individuals presenting with intracerebral hemorrhage were enrolled in a phase 1, multicenter, open-label clinical trial. A Bayesian modified continual reassessment method design based on treatment-emergent thromboembolic or ischemic events was adopted. Sequential dosing, an external data monitoring committee, and prespecified stopping rules were incorporated as safeguards.Results: Twenty-one subjects received PF-05230907. The mean (+/- SD) age in years and intracerebral hemorrhage volume in mL at baseline were 62 (+/- 9) and 18 (+/- 11), respectively. Two treatment-emergent thromboembolic or ischemic events occurred (deep vein thrombosis and cerebral ischemia), in the 30 mu g/kg dose group. There were no other clear drug-related toxicities at dose levels ranging from 5 to 30 mu g/kg. At the time of study termination, the maximum tolerated dose was estimated to be 24 mu g/kg, with a mean fitted dose-toxicity estimate of 11.9% (95% CI, 1.2%-27.4%).Conclusions: Single doses of PF-05230907 appeared to be tolerated across a range of doses in the intracerebral hemorrhage population, with thrombotic events observed only at the highest dose level tested. Recruitment within the recommended therapeutic window of opportunity remains a challenge.Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02687191.