The effect of a combination of gabapentin and donepezil in an experimental pain
model in healthy volunteers: Results of a randomized controlled trial.
Author(s): Boyle Y(1), Fernando D(1), Kurz H(2), Miller SR(3), Zucchetto M(4), Storey J(5).
Affiliation(s): Author information:
(1)GlaxoSmithKline Clinical Unit Cambridge, Addenbrooke's Centre for Clinical
Investigation, Addenbrooke's Hospital, Cambridge, UK. (2)GlaxoSmithKline,
Brentford, UK. (3)GlaxoSmithKline, Stevenage, UK. (4)GlaxoSmithKline, Verona,
Italy. (5)GlaxoSmithKline, Stevenage, UK. Electronic address:
james.d.storey@gsk.com.
Publication date & source: 2014, Pain. , 155(12):2510-6
This double-blind, placebo-controlled, 3-period cross-over, 4-treatment option,
incomplete block study (ClinicalTrials.gov number NCT01485185), with an adaptive
design for sample size re-estimation, was designed to evaluate gabapentin plus
donepezil in an established experimental model of electrical hyperalgesia. Thirty
healthy male subjects aged 18-55 years were randomized to receive gabapentin 900
mg or gabapentin 900 mg+donepezil 5mg for 2 of the 3 treatment periods, with 50%
of subjects randomized to receive placebo (negative control) and 50% to
gabapentin 1800 mg (positive control) for the remaining period. Each treatment
period was 14 days. Gabapentin or corresponding placebo was administered on Day
13 and the morning of Day 14. Donepezil or corresponding placebo was administered
nocturnally from Day 1-13 and the morning of Day 14. Co-primary endpoints were
the area of pinprick hyperalgesia (260 mN von Frey filament) and allodynia
(stroking by cotton bud) evoked by electrical hyperalgesia on Day 14. Gabapentin
1800 mg (n=14) significantly reduced the area of allodynia vs placebo (n=14;
-12.83 cm(2); 95% confidence interval [CI] -23.14 to -2.53; P=0.015) with
supportive results for hyperalgesia (-14.04 cm(2); 95% CI -28.49-0.41; P=0.057),
validating the electrical hyperalgesia model. Gabapentin+donepezil (n=30)
significantly reduced the area of hyperalgesia vs gabapentin 900 mg (n=30; -11.73
cm(2); 95% CI -21.04 to -2.42; P=0.014), with supportive results for allodynia
(-6.62 cm(2); 95% CI -13.29-0.04; P=0.052). The adverse event profile for
gabapentin+donepezil was similar to the same dose of gabapentin. Data are
supportive of further clinical investigation of a gabapentin-and-donepezil
combination in patients with an inadequate response to gabapentin.
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