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Abstract Details

Phase 1, Open-label, Fixed-sequence, Bidirectional, Pharmacokinetic (PK) Drug-drug Interaction (DDI) Study Between Cannabidiol (CBD) and Cenobamate (CNB) in Healthy Adult Participants
Epilepsy/Clinical Neurophysiology (EEG)
P11 - Poster Session 11 (11:45 AM-12:45 PM)
10-002
Evaluate PK DDIs between CBD and CNB.

Plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) is approved for treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. CBD and CNB are antiseizure medications with limited data on their concomitant use. PK mediated DDIs were speculated between CBD and CNB but had not been assessed.

Healthy adults received CBD 7.5 mg/kg BID on Day (D) 1–D4 and a morning dose D5. After washout (D6–D12), CNB was titrated up to 200 mg QD by D93. Participants then received CBD 7.5 mg/kg BID and CNB 200 mg QD D94–D98. Samples were collected on D5 (CBD reference; n=20), D93 (CNB reference; n=17), and D98 (CBD+CNB test; n=17). PK parameters, including AUC0-12h for CBD, 7-OH-CBD (active metabolite), and 7-COOH-CBD; AUC0-24h for CNB and CNB glucuronide; and Cmax were assessed using geometric least-squares mean (GLSM) ratios and 90% CIs comparing coadministration to single agents. Safety was monitored throughout.
GLSM ratios and 90% CIs were within 80–125% range for CBD (AUC0-12h: 94.3 [82.1–108.3]; Cmax: 98.1 [80.5–119.5]) and CNB (AUC0-24h: 107.6 [104.9–110.4]; Cmax: 102.0 [98.2–106.0]). Ratios were outside this range for metabolites: 7-OH-CBD (AUC0-12h: 46.4 [38.4–55.9]; Cmax: 43.6 [34.5–55.0]), 7-COOH-CBD (AUC0-12h: 34.8 [30.1–40.2]; Cmax: 35.4 [30.1–41.6]), and CNB glucuronide (AUC0-24h: 141.1 [136.2–146.0]; Cmax: 139.1 [133.1–145.4]). Treatment-emergent adverse events (TEAEs) occurred in 4 participants receiving CBD+CNB, 10 receiving CBD alone, and 12 receiving CNB alone; diarrhea (40%) and headache (25%) were most common. Two participants discontinued due to TEAEs. No serious AEs, severe TEAEs, or deaths occurred.
No PK interactions were observed for CBD or CNB parent molecules. Clinical significance of reduced CBD metabolite exposures is unknown. These findings do not support CBD dose reduction when coadministered with CNB.
Authors/Disclosures
Arjun Vijan, PhD
PRESENTER 		Dr. Vijan has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Vijan has or had stock in Jazz Pharmaceuticals.
Hongwei Xue Mr. Xue has nothing to disclose.
Patricia Chandler Patricia Chandler has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Patricia Chandler has stock in Jazz Pharmaceuticals.
Sujith Madhavan Dr. Madhavan has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Madhavan has or had stock in Jazz Pharmaceuticals.
Cuiping Chen Cuiping Chen has stock in Jazz Pharmacenticals.