PMID- 32652616
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20210730
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 60
IP  - 10
DP  - 2020 Oct
TI  - A Phase 2, Double-Blind, Placebo-Controlled Trial to Investigate Potential 
      Drug-Drug Interactions Between Cannabidiol and Clobazam.
PG  - 1304-1313
LID - 10.1002/jcph.1634 [doi]
AB  - 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 C(max) and 1.1 (90%CI, 0.9-1.2) for AUC(tau) . 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 C(max) and 2.6 (90%CI, 2.0-3.6) for AUC(tau) . 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.
CI  - (c) 2020 The Authors. The Journal of Clinical Pharmacology published by Wiley 
      Periodicals LLC on behalf of American College of Clinical Pharmacology.
FAU - VanLandingham, Kevan E
AU  - VanLandingham KE
AD  - Greenwich Biosciences Inc., Carlsbad, California, USA.
FAU - Crockett, Julie
AU  - Crockett J
AD  - GW Research Ltd., Cambridge, UK.
FAU - Taylor, Lesley
AU  - Taylor L
AD  - GW Research Ltd., Cambridge, UK.
FAU - Morrison, Gilmour
AU  - Morrison G
AD  - GW Research Ltd., Cambridge, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT02565108
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200711
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Anticonvulsants)
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 2MRO291B4U (Clobazam)
SB  - IM
MH  - Adult
MH  - Anticonvulsants/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Cannabidiol/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Clobazam/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Double-Blind Method
MH  - Drug Interactions
MH  - Drug Therapy, Combination/adverse effects
MH  - Epilepsy/blood/drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
PMC - PMC7540496
OTO - NOTNLM
OT  - cannabidiol
OT  - cannabinoid
OT  - clobazam
OT  - drug
OT  - epilepsy
OT  - interaction
COIS- K.V.L. is an employee of Greenwich Biosciences Inc. and owns share options in the 
      company. J.C. and G.M. are employees of GW Research Ltd. and own share options in 
      the company. L.T. was an employee of GW Research Ltd. when the trial was 
      conducted.
EDAT- 2020/07/12 06:00
MHDA- 2021/07/31 06:00
PMCR- 2020/10/07
CRDT- 2020/07/12 06:00
PHST- 2019/11/22 00:00 [received]
PHST- 2020/04/10 00:00 [accepted]
PHST- 2020/07/12 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2020/07/12 06:00 [entrez]
PHST- 2020/10/07 00:00 [pmc-release]
AID - JCPH1634 [pii]
AID - 10.1002/jcph.1634 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2020 Oct;60(10):1304-1313. doi: 10.1002/jcph.1634. Epub 2020 
      Jul 11.