A Phase 2, Double-Blind, Placebo-Controlled Trial to Investigate Potential Drug-Drug Interactions Between Cannabidiol and Clobazam.


. 2020 Jul 11.

doi: 10.1002/jcph.1634. Online ahead of print.

Affiliations

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Kevan E VanLandingham et al. J Clin Pharmacol. .

Abstract

We investigated the effects of cannabidiol (CBD; 21-day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20 patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evaluated by liquid chromatography tandem mass spectrometry. PK parameters of CLB and major metabolite N-desmethylclobazam (N-CLB), valproic acid, stiripentol, levetiracetam, topiramate, plant-derived highly purified CBD (Epidiolex in the United States; 100 mg/mL oral solution) and its major metabolites were derived using noncompartmental analysis. There was no evidence of a drug-drug interaction (DDI) between CBD and CLB: geometric mean ratio (GMR) of day 33:day 1 CLB was 1.0 (90%CI, 0.8-1.2) for Cmax and 1.1 (90%CI, 0.9-1.2) for AUCtau . There was a significant DDI between CBD and N-CLB: the GMR of day 33:day 1 N-CLB was 2.2 (90%CI, 1.4-3.5) for Cmax and 2.6 (90%CI, 2.0-3.6) for AUCtau . Placebo had no effect on CLB or N-CLB; CBD had no effect on levetiracetam. Data were insufficient regarding DDIs with other antiepileptic drugs. The safety profile of CBD (20 mg/kg/day) with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate. One serious AE (seizure cluster) led to CBD discontinuation. One patient withdrew after intolerable AEs. Although there was no evidence of a CBD and CLB DDI, there was a significant DDI between CBD and N-CLB. The safety profile of GW Pharmaceuticals’ CBD formulation with CLB was consistent with other GW-sponsored trials.

Keywords: cannabidiol; cannabinoid; clobazam; drug; epilepsy; interaction.

References

    1. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011-2020.
    1. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378(20):1888-1897.
    1. Devinsky O, Patel AD, Thiele EA, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90(14):e1204-e1211.
    1. Greenwich Biosciences. EPIDIOLEX® (cannabidiol) oral solution prescribing information. Carlsbad, CA: Greenwich Biosciences; 2018.
    1. GW Research. EPIDYOLEX® (cannabidiol oral solution) summary of product characteristics. B.V. Amersfoort, Nederlands: GW Research; 2019.

Grant support

L’article A Phase 2, Double-Blind, Placebo-Controlled Trial to Investigate Potential Drug-Drug Interactions Between Cannabidiol and Clobazam. est apparu en premier sur Cannabis Belgique.

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