Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain.

Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6-hour, randomized, single-dose, double-blind, parallel-group analgesic trial. All active treatments were statistically superior (p less than 0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model.     

Establishing the dosage equivalency of oxymorphone extended release and oxycodone controlled release in patients with cancer pain: a randomized controlled study

OBJECTIVE: To compare the analgesic efficacy and safety of oxymorphone extended release (ER) and oxycodone controlled release (CR) in patients with moderate to severe cancer pain. Research design and methods: This randomized, multicenter, double-blind, 2-period crossover study included adult outpatients (>or= 18 years of age) with moderate or severe cancer pain who were first titrated for 3-10 days with open-label oxymorphone or oxycodone to achieve a stable dose that provided and other efficacy parameters were comparable for adequate analgesia with tolerable adverse events and no requirement for more than 2 doses of rescue medication per day. The subsequent double-blind treatment phase was a 7- to 10-day period of oxycodone CR or oxymorphone ER treatment followed by crossing over to the alternate medication for another 7-10 days. During the treatment phase, up to 2 doses per day of morphine sulfate 15-mg tablets were allowed as rescue. MAIN OUTCOMES AND MEASURES: Assessments included the Brief Pain Inventory, global evaluations, Karnofsky performance status, and clinical laboratory evaluations (serum chemistry profile, complete blood count, urinalysis). Efficacy variables were analyzed using a mixed-effects model with treatment, sequence, and period as fixed effects and subject as a random effect. RESULTS: Forty-seven patients entered the titration/stabilization phase, 44 received at least 1 dose of study drug, 42 completed the first double-blind phase, and 40 completed the second double-blind phase. Mean pain intensity scores the 2 groups. The mean daily dosage of oxycodone CR (91.9 mg) was twice that of oxymorphone ER (45.9 mg), an equianalgesic dose ratio of 2:1. Rescue medication use was low in both groups (approximately 1 tablet of morphine sulfate 15 mg/day). No significant differences in opioid adverse events were observed between the groups. CONCLUSIONS: Adult patients with cancer who were taking oxycodone CR were readily converted to oxymorphone ER and required half the milligram dose to stabilize their pain. Within 72 h, most patients achieved a stable dose that provided adequate relief with similar opioid adverse events.     

口服氨酚羟考酮和盐酸曲马多治疗妇科腹腔镜手术后早期疼痛的研究

目的 :观察妇科腹腔镜手术病人术后早期单次口服氨酚羟考酮 (泰勒宁 )和盐酸曲马多 (奇曼丁 )进行镇痛的有效性和安全性。方法 :12 0例VAS评分 >3分的妇科腹腔镜手术病人 ,随机分 3组 ,分别口服泰勒宁、奇曼丁或安慰剂 1片 ,3组病人均给予吗啡静脉自控止痛泵作为补救镇痛用药。观察并记录服药即刻、服药后 0 .2 5、0 .5、0 .75、1、2、4、6、8、12、2 4h的VAS评分、PCA用量以及不良反应 ,根据VAS评分计算疼痛缓解度 ,2 4h进行总体镇痛满意度评估。结果 :泰勒宁组和奇曼丁组VAS评分低于安慰剂组 (P <0 .0 5 ) ,泰勒宁组和奇曼丁组之间VAS评分相近 (P >0 .0 5 )。泰勒宁组和奇曼丁组补救PCA吗啡用量明显低于安慰剂组 (P <0 .0 5 ) ,泰勒宁组和奇曼丁组补救PCA吗啡用量相当 (P >0 .0 5 )。泰勒宁组和奇曼丁组总体镇痛满意度评估优于安慰剂组 (P <0 .0 5 )。 2 4h恶心呕吐率方面 ,奇曼丁组明显高于其他两组 (P <0 .0 5 )。结论 :口服泰勒宁和奇曼丁能有效地缓解妇科腹腔镜病人手术后的中至重度疼痛 ,早期口服给药镇痛的方式安全、有效。与奇曼丁组相比 ,泰勒宁组的不良反应发生率更低。     

Establishing the dosage equivalency of oxymorphone extended release and oxycodone controlled release in patients with cancer pain: a randomized controlled study

SUMMARY

Objective: To compare the analgesic efficacy and safety of oxymorphone extended release (ER) and oxycodone controlled release (CR) in patients with moderate to severe cancer pain.

Research design and methods: This randomized, multicenter, double-blind, 2-period crossover study included adult outpatients (≥ 18?years of age) with moderate or severe cancer pain who were first titrated for 3–10?days with open-label oxymorphone or oxycodone to achieve a stable dose that provided adequate analgesia with tolerable adverse events and no requirement for more than 2 doses of rescue medication per day. The subsequent double-blind treatment phase was a 7- to 10-day period of oxycodone CR or oxymorphone ER treatment followed by crossing over to the alternate medication for another 7–10?days. During the treatment phase, up to 2 doses per day of morphine sulfate 15-mg tablets were allowed as rescue.

Main outcomes and measures: Assessments included the Brief Pain Inventory, global evaluations, Karnofsky performance status, and clinical laboratory evaluations (serum chemistry profile, complete blood count, urinalysis). Efficacy variables were analyzed using a mixed-effects model with treatment, sequence, and period as fixed effects and subject as a random effect.

Results: Forty-seven patients entered the titration/stabilization phase, 44 received at least 1 dose of study drug, 42 completed the first double-blind phase, and 40 completed the second double-blind phase. Mean pain intensity scores and other efficacy parameters were comparable for the 2 groups. The mean daily dosage of oxycodone CR (91.9?mg) was twice that of oxymorphone ER (45.9?mg), an equianalgesic dose ratio of 2:1. Rescue medication use was low in both groups (approximately 1 tablet of morphine sulfate 15?mg/day). No significant differences in opioid adverse events were observed between the groups.

Conclusions: Adult patients with cancer who were taking oxycodone CR were readily converted to oxymorphone ER and required half the milligram dose to stabilize their pain. Within 72?h, most patients achieved a stable dose that provided adequate relief with similar opioid adverse events.     

Comparison of rofecoxib and a multidose oxycodone/ acetaminophen regimen for the treatment of acute pain following oral surgery: a randomized controlled trial

OBJECTIVE: To compare the efficacy of a single dose of rofecoxib 50 mg with a single dose of oxycodone/acetaminophen 10/650 mg over 6 h as well as with a multidose regimen of oxycodone/acetaminophen 10/650 mg followed by oxycodone/acetaminophen 5/325 mg over 24 h. Research design and methods: In this double-blind, randomized, two-phase study, patients with moderate to severe pain after surgical extraction of >or= 2 third molars, including one mandibular impaction, were treated with rofecoxib 50 mg, oxycodone/acetaminophen 10/650 mg (singledose phase) followed by 5/325 mg every 6h as needed (multidose phase), or placebo. Patients rated their pain relief and intensity at 18 time points over 24 h. Efficacy was measured over 6 and 24 h by total pain relief (TOPAR), sum of pain intensity difference (SPID), and patient global assessment of response to therapy (PGART). Primary endpoint for the single dose comparison was TOPAR over 6 h; SPID was the key 24-h endpoint. Onset of analgesic effect, peak analgesic single dose of oxycodone/acetaminophen. effect, and duration of analgesic effect were also evaluated. Adverse experiences were recorded. RESULTS: 271 patients were randomized to treatment with rofecoxib (n = 121), oxycodone/acetaminophen (n = 120), or placebo (n = 30). For the single dose comparison, rofecoxib-treated patients achieved pain relief at least as effective as oxycodone/acetaminophentreated patients as assessed by TOPAR6 (12.9 vs 11.3, 95% CI on difference = [-0.1, 3.2], p = 0.059). Patients also rated a single dose of rofecoxib as at least as effective as multidose oxycodone/acetaminophen over 24 h on SPID24 (21.9 vs 18.1, 95% CI on difference = [-1.0, 8.8], p = 0.122). Patients treated with oxycodone/ acetaminophen had a shorter time to onset of analgesia than patients treated with rofecoxib (24 vs 35 min, p < 0.05). Patients in the active treatment groups achieved similar peak effects during the single-dose phase. Individuals treated with rofecoxib demonstrated a longer duration of analgesic effect than those treated with a Patients on active treatment demonstrated better efficacy than patients on placebo on these prespecified endpoints (p < 0.001 for both comparisons). Fewer rofecoxib than oxycodone/acetaminophen patients experienced adverse events (47.9 vs 75.8%, p < 0.001), including nausea (19.0 vs 42.5%, p < 0.001), vomiting (9.9 vs 24.2%, p < 0.01), and dizziness (7.4 vs 31.7%, p < 0.001). CONCLUSION: Patients treated with a single dose of rofecoxib 50 mg achieved an overall analgesic effect at least as effective as patients treated with a single-dose of oxycodone/acetaminophen 10/650 mg over 6 h and multidose oxycodone/acetaminophen over 24 h, with fewer adverse experiences of nausea (p < 0.001), vomiting (p < 0.01), and dizziness (p < 0.001).     

Analgesic efficacy of amfenac, aspirin and placebo after extraction of impacted teeth

Amfenac, an arylacetic acid derivative, is a new investigational, nonsteroidal antiinflammatory agent that has exhibited analgesic properties superior to those of phenylbutazone in animals. This double-blind, randomized, parallel study was an early clinical trial to evaluate the analgesic efficacy of one oral dose of amfenac 100 mg compared to aspirin 600 mg and placebo in 120 subjects with moderate to severe pain after extraction of impacted molar teeth. Self-evaluated subjective pain intensity and relief reports for 4 hours were used as indexes of response. Analgesic effects of amfenac were significantly superior to those of placebo (p less than 0.001) and aspirin (p less than 0.05) by most measurements. Aspirin 600 mg was superior to placebo based on total pain relief and global scores (p less than 0.05). Compared with aspirin 600 mg, amfenac 100 mg provided greater and faster analgesia, lasting at least for 4 hours. Ordinal pain intensity scores correlated well with the visual pain analog scale. Seven (17.5%) patients taking amfenac compared to 5 (12.5%) taking placebo reported minor adverse effects).     

Analysis of the analgesic efficacy of acetaminophen 1000 mg, codeine phosphate 60 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg in the relief of postoperative pain

Patients who experienced pain after surgery were administered a single dose of 1 of 3 treatments: acetaminophen 1000 mg, codeine phosphate 60 mg, or a combination of these. Patients rated their pain intensity on ordinal and visual analog scales just prior to medication and at intervals thereafter for up to 5 hours. They also rated pain relief, pain half gone, and any adverse effects. Sum of pain intensity difference and total pain relief scores were analyzed using Dunnett's procedure. The drug combination was statistically superior to codeine as measured by SPID, TOTPAR, pain half gone, and time to remedication. The combination achieved better mean scores than acetaminophen on all efficacy measures, but was (marginally) statistically superior only in pain half gone. No appreciable differences in adverse effects were noted among the treatments. The difficulty of showing the analgesic efficacy of codeine in a single dose trial is discussed.     

Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain

ABSTRACT

Objective: Opioid therapy is frequently associated with treatment-limiting constipation. Naloxone is an opioid antagonist with low oral systemic bioavailability. This Phase III clinical trial assessed the safety and efficacy of an oral fixed-ratio combination of oxycodone prolonged-release (PR) and naloxone PR compared with oxycodone PR in relieving opioid-induced constipation.

Study design: This double-blind, multicenter trial was conducted in specialist and primary care centers in four European countries in an out-patients setting. The study included 322 adult patients with moderate-to-severe, noncancer pain requiring opioid therapy in a range of ≥20 mg/day and ≤50 mg/day oxycodone. Following a run-in phase patients were randomized to receive oxycodone PR/naloxone PR or oxycodone PR for 12 weeks. The primary outcome was improvement in constipation as measured using the Bowel Function Index (BFI). Secondary/exploratory assessments focused on pain intensity and additional bowel parameters.

Trial registration: NCT00412152.

Results: A significant improvement in BFI scores occurred with oxycodone PR/naloxone PR compared with oxycodone PR after 4 weeks of double-blind treatment (?26.9 vs. ?9.4, respectively; p < 0.0001), observed after only 1 week of treatment and continued until study end. A significant increase in the number of complete spontaneous bowel movements and decrease in laxative use were also reported. This improvement in bowel function was achieved without compromising the analgesic efficacy of the oxycodone component; pain intensity remained constant throughout the study. The incidence of adverse events was comparable in both groups and consistent with those expected of opioid analgesics. As the study was limited to a dose range of up to 50 mg oxycodone equivalent per day, further research on higher doses would be recommended.

Conclusion: The fixed-ratio combination of oxycodone PR/naloxone PR is superior to oxycodone PR alone, offering patients effective analgesia while significantly improving opioid-induced constipation.     

Evaluation of Two Opioid-Acetaminophen Combinations and Placebo in Postoperative Oral Surgery Pain

Study Objective. To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery. Design . Randomized, double-blind, single-dose, placebo-controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6. Setting . Private, oral surgery practice sites. Patients . Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data. Interventions . Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports. Measurements and Main Results . This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment. Conclusions . A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.     

A randomized,double-blind,placebo-controlled phase 3 study of the relative efficacy and tolerability of tapentadol IR and oxycodone IR for acute pain

ABSTRACT

Objective: To evaluate the relative efficacy and tolerability of tapentadol immediate release (IR) and oxycodone IR for management of moderate to severe pain following orthopedic surgery (bunionectomy).

Methods: Randomized patients (N?=?901) received oral tapentadol IR 50 or 75?mg, oxycodone HCl IR 10?mg, or placebo every 4–6?h over a 72-h period following surgery. Acetaminophen (≤2?g) was allowed in the first 12?h after the first dose of study drug. In the primary analysis, tapentadol IR (50 and 75?mg) was evaluated for efficacy superior to placebo and non-inferior to oxycodone HCl IR 10?mg (using sum of pain intensity difference [SPID] over 48?h), and tolerability superior to oxycodone IR (using incidence of treatment-emergent adverse events [TEAEs] of nausea and/or vomiting).

Results: Statistically significantly higher mean SPID₄₈ values were observed with tapentadol IR (50 and 75?mg) and oxycodone HCl IR 10?mg than placebo (all p?<?0.001). The efficacy of tapentadol IR 50?mg and 75?mg was non-inferior to oxycodone HCl IR 10?mg. The incidence of TEAEs of nausea and/or vomiting was statistically significantly lower with tapentadol IR 50?mg versus oxycodone IR 10?mg (35 vs. 59%; p?<?0.001). No statistically significant difference in the incidence of nausea and/or vomiting was observed between tapentadol IR 75?mg and oxycodone IR 10?mg (51 vs. 59%; p?=?0.057). A possible limitation of this study was that the intense dose and patient monitoring may not represent real-world situations and may result in higher incidences of TEAEs than expected in a practice setting; this bias would be similar for all treatment groups.

Conclusions: Clinically meaningful and statistically significant improvements were observed with tapentadol IR 50?mg and 75?mg compared with placebo for the relief of moderate-to-severe acute pain after orthopedic surgery. Tapentadol IR 50?mg and 75?mg were non-inferior to oxycodone HCl IR 10?mg for the treatment of acute pain based on the primary efficacy endpoint of SPID₄₈ and the pre-specified margin of 48 points. The incidence of nausea and/or vomiting was statistically significantly lower for tapentadol IR 50?mg and numerically lower for tapentadol IR 75?mg than for oxycodone HCl IR 10?mg.     

Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain.

Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia, antipyresis, and various arthritic conditions. A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension, with both a higher Cmax and an earlier tmax than any solid tablet. The objective of this single-dose, double-blind, triple-dummy, parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg, ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo in 239 patients with moderate or severe pain following third molar extractions. Treatments were compared over 6 hours using standard scales for pain intensity and relief and stopwatch onset of meaningful relief. All active treatments provided meaningful relief significantly faster compared with placebo. Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. In addition, both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference. Consistent results were seen with respect to the 6-hour summary efficacy variables: the three active treatments were significantly better than placebo, and ibuprofen was significantly better than both acetaminophen and ketoprofen. Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg, acetaminophen 1000 mg, and placebo. No serious adverse effects were reported in this single-dose study.     

Preoperative flurbiprofen in oral surgery: a method of choice in controlling postoperative pain

The analgesic efficacy of a single 50-mg preoperative dose of flurbiprofen was compared with ACC-30 (aspirin 375 mg, codeine 30 mg, caffeine 30 mg) and a placebo. Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double-blind, randomized study. Using a within-subject design we compared the analgesic efficacy of (1) preoperative flurbiprofen 50 mg with placebo in 20 patients, and (2) preoperative ACC-30 with placebo in 20 other patients. Using a between-group design, we then compared the analgesic efficacy of (3) each drug given preoperatively and postoperatively, and (4) each drug given postoperatively only. Patients rated 2 pain dimensions, intensity and unpleasantness, hourly for 8 hours after the presurgical dose. The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery. Conversely, preoperative administration of ACC-30 did not demonstrate any significant influence on postsurgical analgesia. When comparing the 2 drugs, flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery. There was no difference between them when given only after surgery. Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC-30.     

Comparison of the analgesic efficacy and safety oral ciramadol, codeine, and placebo in patients with chronic cancer pain

Ciramadol is a new opioid agonist-antagonist analgesic with low potential for dependency. Forty-three patients with moderate to severe chronic pain from primary or metastatic malignancy of the bone or major organs were enrolled in a randomized double-blind study that compared orally administered ciramadol (30 mg or 90 mg) to codeine (60 mg) and placebo. A single-dose, four-way crossover design, with a randomized Latin-square treatment sequence, was used. Data for 40 patients who received the above four study medications were included in the final statistical analysis of efficacy. Analgesic efficacy was measured at 0, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, and 6.0 hours, using standard visual and verbal pain relief and pain intensity scales. All active therapies provided greater pain relief than placebo (P less than .05). Ciramadol 30 mg and codeine 60 mg demonstrated equal analgesic activity, whereas ciramadol 90 mg was superior to both therapies. The predominant adverse experiences associated with ciramadol were nausea and drowsiness, which were apparently not dose related. Ciramadol appears to be an effective analgesic at the doses tested, with tolerable gastrointestinal central nervous system side effects at both the 30-and 90-mg dose levels.     

Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain

Eighty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single, oral dose of flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.     

Double-blind comparison of the analgesic potency of ciramadol,codeine and placebo against postsurgical pain in ambulant patients

Summary The efficacy and safety of ciramadol (Cir) as an analgesic in relieving moderate to severe pain after oral surgery has been studied in 79 patients randomly assigned to receive single oral doses of Cir 15, 30 or 60 mg, codeine 60 mg or placebo. During the 6-hour observation period, the three ciramadol-treated groups indicated greater pain relief than the codeine 60 mg or placebo groups. In general, Cir 60 mg was significantly more effective than codeine 60 mg, and all doses of Cir were superior to placebo. The proportion of patients in each Cir group reporting adverse experiences was significantly higher than in either the placebo or codeine groups. The experimental system proved very effective in demonstrating analgesic potency of Cir. The very high incidence of side-effects in the three ciramadol-treated groups makes it unfit for further clinical use in ambulant patients.     

Efficacy and safety of tapentadol prolonged release for moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind,randomized, placebo- and oxycodone controlled release-controlled studies

Objective: To compare efficacy and safety of tapentadol prolonged-release (PR) and oxycodone-controlled release (CR) in moderate-to-severe chronic osteoarthritis knee pain.

Methods: Data from two double-blind, randomized, placebo- and oxycodone CR-controlled phase 3 studies with a 3-week titration period and 12-week controlled dose adjustment maintenance period were pooled. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).

Results: A total of 2,010 patients were assessed. For both primary end-points, tapentadol PR was significantly more effective than oxycodone CR (LS mean difference of –0.41 [95% CI?=?–0.65, –0.16; p?=?0.001] at week 12 and –0.35 [95% CI?=?–0.58, –0.12; p?=?0.003] over 12 weeks of maintenance [last observation carried forward]). Significantly better outcomes than for oxycodone CR were also observed for patient global impression of change, both Short Form-36 component scores, and EuroQoL-5Dimensions health status index (all p?p?Conclusions: The analyses suggest that tapentadol PR provided superior pain relief and a more improved overall health status than oxycodone CR in a large patient population with moderate-to-severe chronic osteoarthritis pain. Compared to oxycodone CR, tapentadol PR showed a more favorable tolerability profile with better gastrointestinal tolerability.     

Oral ciramadol: a new analgesic for postoperative pain

Ciramadol, a new synthetic narcotic agonist-antagonist analgesic, was compared in 30 and 60 mg doses with pentazocine 50 mg, aspirin 650 mg, and placebo in the treatment of 153 patients with postoperative pain. All drugs were administered between six and 72 hours after surgery. Analgesic efficacy was assessed for six hours after study drug administration using verbal pain intensity, analog pain intensity, and verbal pain relief scales. Significantly (P less than .05) higher analgesic efficacy scores were seen with ciramadol 30 mg than with pentazocine 50 mg and placebo at most of the evaluation points. Doses of ciramadol 30 mg were significantly (P less than .05) more effective than aspirin 650 mg at several time periods, and ciramadol 60 mg was better than pentazocine and placebo at several evaluation times. The 30-mg dose of ciramadol was generally more effective than the 60-mg dose. The mean six-hour cumulative sum of pain intensity difference scores, total pain relief scores, and sum of pain analog intensity difference scores showed that the best analgesic response occurred in the ciramadol 30 mg group, followed by the ciramadol 60 mg, aspirin 650 mg, pentazocine 50 mg, and placebo groups. Side effects were rare and mild. There were no medically important changes in vital signs in any treatment group.     

Comparison of rofecoxib and a multidose oxycodone/acetaminophen regimen for the treatment of acute pain following oral surgery: a randomized controlled trial

SUMMARY

Objective: To compare the efficacy of a single dose of rofecoxib 50?mg with a single dose of oxycodone/acetaminophen 10/650?mg over 6?h as well as with a multidose regimen of oxycodone/acetaminophen 10/650?mg followed by oxycodone/acetaminophen 5/325?mg over 24?h.

Research design and methods: In this double-blind, randomized, two-phase study, patients with moderate to severe pain after surgical extraction of ≥ 2 third molars, including one mandibular impaction, were treated with rofecoxib 50?mg, oxycodone/acetaminophen 10/650?mg (single-dose phase) followed by 5/325?mg every 6?h as needed (multidose phase), or placebo. Patients rated their pain relief and intensity at 18 time points over 24?h. Efficacy was measured over 6 and 24?h by total pain relief (TOPAR), sum of pain intensity difference (SPID), and patient global assessment of response to therapy (PGART). Primary endpoint for the single dose comparison was TOPAR over 6?h; SPID was the key 24-h endpoint. Onset of analgesic effect, peak analgesic effect, and duration of analgesic effect were also evaluated. Adverse experiences were recorded.

Results: 271 patients were randomized to treatment with rofecoxib (n = 121), oxycodone/acetaminophen (n = 120), or placebo (n = 30). For the single dose comparison, rofecoxib-treated patients achieved pain relief at least as effective as oxycodone/acetaminophen-treated patients as assessed by TOPAR6 (12.9 vs 11.3, 95% CI on difference = [–0.1, 3.2], p = 0.059). Patients also rated a single dose of rofecoxib as at least as effective as multidose oxycodone/acetaminophen over 24?h on SPID24 (21.9 vs 18.1, 95% CI on difference = [–1.0, 8.8], p = 0.122). Patients treated with oxycodone/acetaminophen had a shorter time to onset of analgesia than patients treated with rofecoxib (24 vs 35?min, p < 0.05). Patients in the active treatment groups achieved similar peak effects during the single-dose phase. Individuals treated with rofecoxib demonstrated a longer duration of analgesic effect than those treated with a single dose of oxycodone/acetaminophen. Patients on active treatment demonstrated better efficacy than patients on placebo on these prespecified endpoints (?p < 0.001 for both comparisons). Fewer rofecoxib than oxycodone/acetaminophen patients experienced adverse events (47.9 vs 75.8%, p < 0.001), including nausea (19.0 vs 42.5%, p < 0.001), vomiting (9.9 vs 24.2%, p < 0.01), and dizziness (7.4 vs 31.7%, p < 0.001).

Conclusion: Patients treated with a single dose of rofecoxib 50?mg achieved an overall analgesic effect at least as effective as patients treated with a single-dose of oxycodone/acetaminophen 10/650?mg over 6?h and multidose oxycodone/acetaminophen over 24?h, with fewer adverse experiences of nausea (?p < 0.001), vomiting (?p < 0.01), and dizziness (?p < 0.001).     

Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain

The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy.     

Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation

Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.