Dose conversion between tapentadol immediate and extended release for low back pain.
BACKGROUND
Tapentadol, a novel, centrally acting analgesic with 2 mechanisms of action (mu-opioid receptor agonism and norepinephrine reuptake inhibition), has been developed in an immediate-release (IR) and an extended-release (ER) formulation. Determination of the safety and equianalgesic ratios for conversion between formulations is important for physicians with patients taking tapentadol IR who may want to switch to tapentadol ER, or vice versa, for any reason.


OBJECTIVE
To test whether the total daily dose (TDD) of tapentadol IR may be directly converted into a comparable TDD of tapentadol ER, and vice versa, with equivalent efficacy and comparable safety.


METHODS
Randomized, double-blind, 2-period (2 weeks each) crossover study.


METHODS
Study centers (N = 13) in the United States.


METHODS
Patients with moderate to severe chronic low back pain received tapentadol IR 50, 75, or 100 mg every 4 or 6 hours (maximum TDD, 500 mg) during the 3-week open-label period to identify an optimal, stable dose of tapentadol IR for each patient. Patients were then randomized in a 1:1 ratio to receive, during the first 2-week double-blind period, either the optimal dose of tapentadol IR identified during the open-label period or a TDD of tapentadol ER (100, 150, 200, or 250 mg bid) that was as close as possible to the TDD of tapentadol IR from the open-label period. During a subsequent, 2-week double-blind period, patients received whichever formulation was not received during the first double-blind period. The primary endpoint was the mean average daily pain intensity (on an 11-point numerical rating scale) during the last 3 days of each double-blind treatment period. If the 95% confidence intervals (CIs) of the least squares mean difference between formulations were within the range of -2 to 2, the formulations were considered equivalent.


RESULTS
Of the 88 patients who were randomized, 72 completed both double-blind treatments, and 60 were included in the per-protocol analysis. The mean (standard deviation [SD]) pain intensity score decreased from 7.3 (1.19) pre-treatment to 4.2 (2.13) after 3 weeks of open-label treatment with tapentadol IR and remained constant throughout double-blind treatment (3.9 or 4.0 each week) for both formulations. The mean (SD) of the average pain intensity scores over the last 3 days of double-blind treatment was 3.9 (2.17) with tapentadol IR and 4.0 (2.29) with tapentadol ER, for an estimated difference of 0.1 (95% CI, -0.09 to 0.28). For both tapentadol IR and tapentadol ER, the median TDD administered was 300.0 mg, and acetaminophen was used by 39.5% and 45.2% of patients, respectively. The incidence of treatment-emergent adverse events during double-blind treatment was similar between the tapentadol IR and tapentadol ER groups.


CONCLUSIONS
Use of rescue medication theoretically could have influenced pain measurements, but in practice, pain measurements did not differ between treatments.


CONCLUSIONS
Approximately equivalent TDDs of tapentadol IR and tapentadol ER provided equivalent analgesic efficacy for the relief of moderate to severe chronic low back pain and were similarly well tolerated, allowing for direct conversion between the 2 formulations.


BACKGROUND
NCT00594516.
Etropolski
Mila S
MS
Johnson & Johnson Pharmaceutical Research & Development, CNS/Pain, Titusville, NJ 08560, USA. metropol@its.jnj.com
Okamoto
Akiko
A
Shapiro
Douglas Y
DY
Rauschkolb
Christine
C
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010636:Phenols / Q000008:administration & dosage*; D000077432:Tapentadol; D016896:Treatment Outcome; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D000701:Analgesics, Opioid; D010636:Phenols; D000077432:Tapentadol