PMID- 23912473
OWN - NLM
STAT- MEDLINE
DCOM- 20140424
LR  - 20240330
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Print)
IS  - 1173-2563 (Linking)
VI  - 33
IP  - 9
DP  - 2013 Sep
TI  - Effectiveness and tolerability of tapentadol prolonged release compared with 
      prior opioid therapy for the management of severe, chronic osteoarthritis pain.
PG  - 607-19
LID - 10.1007/s40261-013-0102-0 [doi]
AB  - BACKGROUND: Tapentadol prolonged release (PR; 100-250 mg twice daily) has been 
      efficacious and well tolerated for managing moderate-to-severe, chronic 
      osteoarthritis hip or knee pain in phase 3 studies with washout of previous 
      analgesic treatment. OBJECTIVE: The objective of this study was to evaluate the 
      effectiveness and tolerability of tapentadol PR (50-250 mg twice daily) after 
      direct rotation from World Health Organization (WHO) step III opioids in patients 
      with severe osteoarthritis knee pain who previously responded to WHO step III 
      therapy but showed poor tolerability. METHODS: This open-label, phase 3b study 
      (NCT00982280) was conducted from October 2009 through June 2010 (prematurely 
      terminated due to slow recruitment and study drug shortages) in clinical care 
      settings in Europe and Australia. The study population included patients with 
      severe, chronic osteoarthritis knee pain who had taken WHO step III opioids daily 
      for >/=2 weeks before screening, responded to therapy (average pain intensity 
      [11-point numerical rating scale-3 (NRS-3)] </=5 at screening), and reported 
      opioid-related adverse effects as their reason for changing analgesics. Patients 
      switched directly from WHO step III therapy to tapentadol. Patients received oral 
      tapentadol PR (50-250 mg twice daily) during 5-week titration and 7-week 
      maintenance periods. Oral tapentadol immediate release (IR) was permitted 
      (</=twice/day, >/=4 h apart) for acute pain episodes due to index pain or withdrawal 
      symptoms following discontinuation of previous opioids (combined dose of 
      tapentadol [PR and IR] </=500 mg/day). This study was planned to evaluate 
      conversion to tapentadol PR, based on responder rate 1 (percentage of patients 
      with same/less pain [NRS-3] versus Week -1) at Week 6 (primary endpoint), adverse 
      events (AEs), and discontinuation rates. Equianalgesic ratios were calculated for 
      tapentadol prior to WHO step III opioids (PR and PR plus IR formulations). 
      RESULTS: Of 82 patients enrolled, 63 received study medication. In the 
      per-protocol population, responder rate 1 at Week 6 (last observation carried 
      forward) was 94.3 % (50/53; P < 0.0001 vs. the null hypothesis rate [<60 %]). 
      Mean (standard deviation) pain intensity scores were 4.7 (0.66) at baseline, 2.5 
      (1.46) at Week 6, and 1.8 (1.41) at Week 12 in the main analysis population 
      (change from baseline at Weeks 6 and 12, P < 0.0001). Tapentadol to transdermal 
      buprenorphine equianalgesic ratios (PR [n = 48], 262.9:1; PR plus IR [n = 48], 
      281.1:1) and tapentadol to oral oxycodone equianalgesic ratios (PR [n = 4], 
      4.3:1; PR plus IR [n = 6], 4.6:1) were calculated for the main analysis 
      population. In the safety population, prevalence of AEs reported as associated 
      with prior opioids at Week -1 (reasons for rotation) and related to tapentadol 
      treatment at Week 12 decreased over time; the most common were nausea (46.0 vs. 
      24.1 %) and constipation (31.7 vs. 7.4 %). Overall, 14.3 % of patients 
      discontinued the study early; reasons included AEs (9.5 %), lack of efficacy (3.2 
      %), and withdrawal of consent (1.6 %). CONCLUSIONS: Significant improvements in 
      effectiveness were observed for tapentadol PR (50-250 mg twice daily) versus WHO 
      step III opioids in patients with severe, chronic osteoarthritis knee pain who 
      previously responded to WHO step III therapy. Equianalgesic ratios were 
      calculated for tapentadol to transdermal buprenorphine and oral oxycodone and 
      were in line with observations from previous phase 3 studies.
FAU - Steigerwald, Ilona
AU  - Steigerwald I
AD  - Medical Affairs Europe and Australia, Grunenthal GmbH, Zieglerstrasse 6, 52078, 
      Aachen, Germany. ilona.steigerwald@grunenthal.com
FAU - Schenk, Michael
AU  - Schenk M
FAU - Lahne, Uwe
AU  - Lahne U
FAU - Gebuhr, Peter
AU  - Gebuhr P
FAU - Falke, Dietmar
AU  - Falke D
FAU - Hoggart, Barbara
AU  - Hoggart B
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Phenols)
RN  - 0 (Receptors, Opioid, mu)
RN  - H8A007M585 (Tapentadol)
SB  - IM
MH  - Aged
MH  - Analgesics, Opioid/*therapeutic use
MH  - Chronic Pain/*drug therapy
MH  - Delayed-Action Preparations
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/drug therapy
MH  - Phenols/adverse effects/*therapeutic use
MH  - Receptors, Opioid, mu/*agonists
MH  - Tapentadol
PMC - PMC3751342
EDAT- 2013/08/06 06:00
MHDA- 2014/04/25 06:00
PMCR- 2013/08/03
CRDT- 2013/08/06 06:00
PHST- 2013/08/06 06:00 [entrez]
PHST- 2013/08/06 06:00 [pubmed]
PHST- 2014/04/25 06:00 [medline]
PHST- 2013/08/03 00:00 [pmc-release]
AID - 102 [pii]
AID - 10.1007/s40261-013-0102-0 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2013 Sep;33(9):607-19. doi: 10.1007/s40261-013-0102-0.