Evaluation of gabapentin enacarbil on cardiac repolarization: a randomized, double-blind, placebo- and active-controlled, crossover thorough QT/QTc study in healthy adults.
Clin Ther
; 34(2): 351-362.e3, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22325733
ABSTRACT
BACKGROUND:
Gabapentin enacarbil, a transported prodrug of gabapentin, was recently approved by the US Food and Drug Administration for the treatment of moderate to severe restless legs syndrome.OBJECTIVE:
As part of the overall safety evaluation of gabapentin enacarbil, the present definitive QT/QTc study was conducted to assess the effects of gabapentin enacarbil on cardiac repolarization in accordance with the International Conference on Harmonization E14 guidance.METHODS:
This randomized, double-blind, placebo- and active-controlled, crossover study enrolled 54 healthy adults. Subjects were randomly assigned to receive a single oral dose of gabapentin enacarbil 1200, 6000 mg, moxifloxacin 400 mg (active control), and placebo in a randomized sequence, with treatment periods separated by a 7-day washout. Blood samples were collected for pharmacokinetic analysis, and continuous ECG measurements were recorded using a Holter monitor. The primary end point was the time-matched difference in individualized baseline-adjusted QTc (ddQTcIb) between gabapentin enacarbil and placebo. General tolerability was also monitored.RESULTS:
Of the 54 subjects enrolled in the study (mean [SD] age, 29.2 [10.1]; 42.6% female; mean body mass index, 25.8 [3.0]), 48 (88.9%) completed the study, and 6 were discontinued prematurely after having received ≥ 1 dose of study medication. Thus, the numbers of patients in the safety population were gabapentin enacarbil 1200 mg, 50; gabapentin enacarbil 6000 mg, 50; moxifloxacin, 50; and placebo, 51. The maximum ddQTcIb values were 0.7 msec (upper 95% confidence limit [CL], 3.0) with gabapentin enacarbil 1200 mg; 1.3 msec (upper CL, 3.6) with gabapentin enacarbil 6000 mg; and 7.4 msec (lower CL, 5.1) with moxifloxacin. A QT-concentration relationship was reported with moxifloxacin. Gabapentin exposures were dose-proportional with gabapentin enacarbil doses of 1200 and 6000 mg. The most commonly reported adverse events with gabapentin enacarbil 6000 mg were dizziness and somnolence (60.0% and 54.0%, respectively).CONCLUSION:
In this population of healthy adults, gabapentin enacarbil at doses of 1200 and 6000 mg was not associated with QT prolongation and was generally well-tolerated.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carbamatos
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Eletrocardiografia
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Ácido gama-Aminobutírico
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Coração
Tipo de estudo:
Clinical_trials
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Guideline
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article