Abstract
Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone
assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent.
This trial evaluated dose equivalence using a measure of assay sensitivity. Patients
were converted to open-label IR hydromorphone, underwent dose titration, and those
on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of:
1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone
ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy
was measured using breakthrough medication use, pain, sleep, and global assessments.
Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable
effects on all measures. Although the prespecified primary analysis of the difference
in total daily dose of breakthrough medication between the full-dose ER and half-dose
ER groups was not significant, more patients in the half-dose ER group required an
increase in breakthrough medication (P = .026) and the half-dose ER group both increased the number of breakthrough doses
(P = .026) and had greater percent change in the total daily dose of breakthrough medication
(P = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone
at the same daily dose provides equivalent analgesia.
Perspective
In a randomized, double-blind trial, the same total daily dose of immediate-release
hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had
comparable effects. Detection of different effects between blinded dose levels was
used as a measure of assay sensitivity. The measure of assay sensitivity can enhance
the interpretation of dose equivalence or noninferiority trials.
Key words
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Article info
Publication history
Published online: March 19, 2012
Accepted:
January 4,
2012
Received in revised form:
November 4,
2011
Received:
August 3,
2011
Footnotes
Funded by Knoll Phamaceuticals and Covidien.
Dr. Cruciani is a member of the Speaker Bureau for Covidien. Dr. Nathaniel Katz was a consultant for Knoll Pharmaceuticals, Alza, Neuromed, and is a consultant for Covidien. During the past 3 years, Dr. Portenoy participated in single advisory meetings sponsored by Neuromed and Covidien, respectively, to discuss the drug evaluated in the study.
Identification
Copyright
© 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.
