Evidence map›Paper›PMID 27683846›Full record

Trial reportNeurology2016

Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

Barry E Gidal, Robert T Wechsler, Raman Sankar, Georgia D Montouris, H Steve White, James C Cloyd, Mary Clare Kane, Guangbin Peng, David M Tworek, Vivienne Shen and 1 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00518713 phase3completednot on this map

Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome

TypeinterventionalSponsorLundbeck LLCRan2007 to 2010Enrolled238ConditionsEpilepsy, Epilepsy, Generalized, SeizuresArmsClobazam Low Dose, Clobazam Medium Dose, Clobazam High Dose, Placebo
NCT01160770 phase3completednot on this map

Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome

TypeinterventionalSponsorLundbeck LLCRan2005 to 2012Enrolled267ConditionsLennox-Gastaut SyndromeArmsClobazam
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Barry E GidalFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL. barry.gidal@wisc.edu.
Robert T WechslerFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
Raman SankarFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
Georgia D MontourisFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
H Steve WhiteFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
James C CloydFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
Mary Clare KaneFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
Guangbin PengFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
David M TworekFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
Vivienne ShenFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.
Jouko IsojarviFrom the School of Pharmacy and Department of Neurology (B.E.G.), University of Wisconsin, Madison; Idaho Comprehensive Epilepsy Center (R.T.W.), Boise; David Geffen School of Medicine at UCLA (R.S.), University of California-Los Angeles; School of Medicine (G.D.M.), Boston University, MA; School of Pharmacy (H.S.W.), University of Washington, Seattle; Center for Orphan Drug Research (J.C.C.), College of Pharmacy, University of Minnesota, Minneapolis; Prescott Medical Communications Group (M.C.K.), Chicago, IL; and Lundbeck LLC (G.P., D.M.T., V.S., J.I.), Deerfield, IL.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome.

methodsEligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg

resultsData from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates.

conclusionsTwo-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. CLINICALTRIALSGOV IDENTIFIER: NCT00518713 and NCT01160770. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment.

Indexed as

Drug ToleranceAdolescentAdultAnticonvulsantsBenzodiazepinesChildChild, PreschoolClobazamDouble-Blind MethodDrug Administration ScheduleFemaleHumansIndividualityLennox Gastaut SyndromeLongitudinal StudiesMaleAnticonvulsantsBenzodiazepinesClobazam

Identifiers

PMID27683846
PMCPMC5089527

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.