title: Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects.
abstract: Spontaneous intracranial hemorrhage (ICH) remains a devastating stroke subtype, affecting as many as 80,000 people annually in the United States and associated with extremely high mortality. In the absence of any pharmacological interventions demonstrated to improve outcome, care for patients with ICH remains largely supportive. Thus, despite advances in the understanding of ICH and brain injury, there remains an unmet need for interventions that improve neurologic recovery and outcomes. Recent research suggesting inflammation and APOE genotype play a role in modifying neurologic outcome after brain injury has led to the development of an APOE-derived peptide agent (CN-105). Preclinical studies have demonstrated that CN-105 effectively downregulates the inflammatory response in acute brain injury, including ICH. Following Investigational New Drug (IND) enabling studies in murine models, this first-in-human single escalating dose and multiple dose placebo-controlled clinical trial was performed to define the safety and pharmacokinetics (PK) of CN-105. A total of 48 subjects (12 control, 36 active) were randomized in this study; all subjects completed the study. No significant safety issues were identified with both dosing regimens, and PK analysis revealed linearity without significant drug accumulation. The median half-life in the terminal elimination phase of CN-105 following a single or repeated dosing regimen did not change (approximately 3.6 hours). With the PK and preliminary safety of CN-105 established, the drug is now poised to begin first-in-disease phase 2 clinical trials in patients with ICH who urgently need new therapeutic options.
authors.affiliation: Department of Neurology, Duke University, Durham, NC, USA.|Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Guptill
authors.affiliation: Department of Neurology, Duke University, Durham, NC, USA.|Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Shruti M
authors.initials: SM
authors.lastname: Raja
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Boakye-Agyeman
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Noveck
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ramey
authors.affiliation: SingHealth, National Neuroscience Institute, Singapore, Republic of Singapore.
authors.forename: Tian Ming
authors.initials: TM
authors.lastname: Tu
authors.affiliation: Department of Neurology, Duke University, Durham, NC, USA.|Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents
keywords: apolipoprotein E; brain injury; intracerebral hemorrhage; neuroinflammation; neuroprotection; pharmacokinetics