Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open‐label, Phase 3b/4 Trial

Abstract

& AbstractObjective: To evaluate tolerability, safety, and quality-oflife outcomes in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. oxycodone/naloxone PR. Methods: Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. Results: For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus oxycodone/naloxone PR for the PAC-SYM total score was [À0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than oxycodone/naloxone PR (P ≤ 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were

Validation of Pain Severity Assessment using the PainDETECT Questionnaire

“…This might be possibly supported by a previous finding that the PD-Q score was less sensitive to reflect pain severity and the analgesic effect of an experimental drug in patients with a PD-Q score between 13 and 18 than in those with a much higher PD-Q score (≥ 19) [10]. Moreover, supporting evidence comes from another previous finding that patients with a much higher PD-Q score (≥ 19) showed a larger effect size of clinically meaningful improvements in all SF-12 subscale scores used for assessing an experimental drug, but patients with a PD-Q score between 13 and 18 showed improvements in limited SF-12 subscale scores [8]. We previously reported that a higher PD-Q score reflects stronger impairments of patients' mental and physical states in both patients with neuropathic and nociceptive pain [7].…”

“…However, a small fraction of patients who had a low PD-Q score (<13) did not demonstrate such validity. Previous longitudinal studies on drug treatment used the PD-Q score as one of the inclusion criteria (i.e., score ≥ 13) to identify patients with NeP components [8][9][10][11], and these studies successfully revealed that the experimental drug showed significant improvements in the NRS as well as the PD-Q scores. Different from these studies, a small prospective open-label study [13] used the PD-Q in addition to the NRS to evaluate cancer pain severity.…”

“…These correlations were also observed in the subset of 35 patients with a high PD-Q score (≥ 13) (current pain, r=0.38, p=0.03; average pain in the past 4 weeks, r=0.53, p=0.001; worst pain in the past 4 weeks, r=0.28, p=0.098). However, the and secondary endpoints [8][9][10][11][12][13]15]. The patients were asked to complete them twice.…”

“…Many drug studies have reported the change of the PD-Q symptom intensity and its scores over time. Some studies have reported the PD-Q score and used it to identify patients with NeP components at baseline [8][9][10][11]. Other studies have used the PD-Q to assess the response of NeP components to therapy [12,13].…”

Is There a Role for Opioids in the Treatment of Fibromyalgia?

“…The analgesic effects of tapentadol are significantly contributed to by the NRI action of the molecule, which means that less opioid is required to achieve equivalent analgesia to higher doses of other opioids. For instance, in a comparative study with oxycodone in patients with low back pain there were less of the opioid-related side effects of nausea and vomiting, although not neurological side effects [51]. There is a trade off somewhat with NE-type side effects, including palpitations and sweating [52].…”