Comparative Pharmacokinetics and Safety of Cannabidiol in a Powder Formulation, CBtru(®), vs an Oil-Based Formulation, Epidyolex(®), Under Fasted and Fed Conditions in Healthy Participants: A Randomized Open-Label Cross-Over Phase I Study.

内容摘要

Emerging evidence indicates that cannabidiol (CBD) may offer meaningful therapeutic benefits across neurological, pain, and psychiatric disorders. Cannabidiol is already approved for the treatment of pediatric epilepsy. Owing to its high lipophilicity, it is typically delivered in oil-based formulations to overcome the low oral bioavailability of pure CBD. However, pharmacokinetic (PK) and safety data remain limited across different CBD formulations. This study evaluated the PK profile, tolerability, and safety of an encapsulated powdered emulsion formulation (CBtru®) compared with a marketed oil-based formulation (Epidyolex®/Epidiolex®) under fasted and fed conditions in healthy adults. This Phase I, single-center, open-label, randomized, 4-way crossover PK trial was conducted in healthy adults. All participants received a single 400-mg dose of CBtru® and Epidyolex® under both fasted and fed conditions, with a minimum 14-day washout between administrations. Pharmacokinetic parameters and safety were assessed throughout. Under fasted conditions, CBtru® trended to higher CBD exposure (AUC0-24) and maximum concentration in plasma (Cmax) relative to Epidyolex®. CBtru® demonstrated significantly greater metabolite exposure (7-OH-CBD, 7-COOH-CBD), along with higher active drug exposure (ADE = CBD + 7-OH-CBD) and higher total drug exposure (TDE=CBD + 7-OH-CBD + 7-COOH-CBD). Median tmax was shorter with CBtru® (3 h vs 3.5 h), indicating faster absorption. In line with previous studies, CBD exposure and concentrations were significantly higher in fed rather than in fasted conditions. Under fed conditions, median tmax was shorter with CBtru® (5 h vs 8 h), while CBD and metabolite exposure were comparable. CBtru® also showed lower interindividual variability in plasma CBD profiles, suggesting more predictable PK across both conditions. Both formulations were well tolerated, with no safety concerns reported. Both formulations demonstrated distinct PK profiles under fasted and fed conditions. CBtru® showed comparable bioavailability to Epidyolex®, with faster absorption in fasted and fed conditions, higher metabolite exposure in fasted conditions, and more consistent systemic levels in the fasted condition. These findings support further development of CBtru® as a novel oral CBD formulation for clinical use in relevant indications. gov ID number: NCT06578455.