Safety and Tolerability of PF-05230907 in Intracerebral Hemorrhage

A PHASE 1B MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND TOLERABILITY AND DETERMINE THE MAXIMUM TOLERATED DOSE OF PF-05230907 IN SUBJECTS WITH INTRACEREBRAL HEMORRHAGE (ICH)

This study employs a modified continual reassessment method (mCRM) design to estimate the maximum tolerated dose (MTD) of PF-05230907, defined as a target toxicity rate of 15% based on treatment emergent thromboembolic and/or ischemic events (TIEs). The mCRM design utilizes Bayesian methodology to continuously learn the dose-toxicity relationship, which is characterized by a parametric model.

Subjects with a diagnosis of ICH (determined by computed tomography) will be enrolled in cohorts of 3. The total length of time planned for study participation is approximately 3 months; 6.0 hours for screening, a single dose administration with a 4-day minimum hospital confinement period and follow-up visits through Day 91.

Severity of adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All subjects who receive PF-05230907 are evaluable for TIEs. The determination of MTD using mCRM modeling will be based on TIEs which occur through 7 days post-dose (Day 8).

Inclusion Criteria:

• ICH as documented by CT scan within 6.0 hours of symptom onset
• Baseline ICH volume > 5mL and < 60 mL

Exclusion Criteria:

• Deep coma (Glasgow Coma Scale < 6)
• Modified Rankin Score > 3 prior to ICH onset
• Known history of schemic, vaso-occlusive or thrombotic events within 6 months prior to screening
• Known prothrombotic disorders
• Known secondary ICH related to aneurysm, arteriovenous malformation, subarachnoid hemorrhage, trauma, or other causes. CT angiography, MR, or other diagnostic studies obtained as part of the standard of care may be used to assess eligibility.
• Known use of oral anticoagulant(s)
• Known use of low-molecular weight heparin or heparin