Phase 1 Evaluation of (2R,6R)-Hydroxynorketamine
Phase I randomised, double-blind IV infusion study in healthy volunteers (n=74): SAD (6 cohorts, 0.1–4.0 mg/kg single 40-min infusions), MAD (2 cohorts, 1.0–2.0 mg/kg on Days 1,4,7,10), plus CSF cohort; PK, qEEG and safety-focused assessments.
Details
This Phase I study evaluates (2R,6R)-hydroxynorketamine hydrochloride in healthy adult volunteers using a slow 40-minute intravenous infusion across single ascending dose (SAD) cohorts, multiple ascending dose (MAD) cohorts, and a CSF capture cohort. Primary objectives are safety, tolerability, and pharmacokinetics including plasma and CSF sampling.
Safety assessments include AEs/SAEs, vitals, ECGs, clinical labs, ophthalmologic exams, C-SSRS, POMS, CADSS and MOAA/S. Pharmacodynamic measures include qEEG and serial PK sampling at multiple timepoints.
Study design incorporates sentinel dosing, placebo controls in each cohort, and predefined halting rules for dose escalation; MAD dosing occurs over four administrations with intensive safety monitoring.