Evidence map›Paper›PMID 29732549›Full record

Trial reportActa neurologica Scandinavica2018

Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.

B E Gidal, M P Jacobson, E Ben-Menachem, M Carreño, D Blum, P Soares-da-Silva, A Falcão, F Rocha, J Moreira, T Grinnell and 4 more

Open access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Acta neurologica Scandinavica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 35% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
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

14 authors at 8 institutions in 4 countries.

B E GidalSchool of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-6681-7134
M P JacobsonDepartment of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
E Ben-MenachemSahlgrenska Academy, Göteborg University, Göteborg, Sweden.
M CarreñoEpilepsy Unit, Hospital Clínic, Barcelona, Spain.
D BlumSunovion Pharmaceuticals Inc., Marlborough, MA, USA.
P Soares-da-SilvaBIAL - Portela & Ca, S.A., S. Mamede do Coronado, Portugal.
A FalcãoFaculty of Pharmacy, Laboratory of Pharmacology, University of Coimbra, Coimbra, Portugal.
F RochaBIAL - Portela & Ca, S.A., S. Mamede do Coronado, Portugal.
J MoreiraBIAL - Portela & Ca, S.A., S. Mamede do Coronado, Portugal.
T GrinnellSunovion Pharmaceuticals Inc., Marlborough, MA, USA.
E LudwigCognigen Corporation, a Simulations Plus company, Buffalo, NY, USA.
J Fiedler-KellyCognigen Corporation, a Simulations Plus company, Buffalo, NY, USA.
J PassarellCognigen Corporation, a Simulations Plus company, Buffalo, NY, USA.
S SunkaraneniSunovion Pharmaceuticals Inc., Marlborough, MA, USA.
Bial (Portugal) · PTSimulations Plus (United States) · USSunovion (United States) · USHospital Clínic de Barcelona · ESTemple University · USUniversity of Coimbra · PTUniversity of Gothenburg · SEUniversity of Wisconsin–Madison · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesEslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL.

methodsEslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses.

resultsEslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline.

conclusionsPharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.

Indexed as

AdultAgedAnticonvulsantsDibenzazepinesDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleHumansMaleMiddle AgedSeizuresAnticonvulsantsDibenzazepineseslicarbazepine acetateantiepilepticepilepsyeslicarbazepinepharmacodynamicspharmacokinetics

Identifiers

PMID29732549
PMCPMC6099471
OpenAlexW2800500531

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.