Baseline In Pain Score Research Articles

O-135 Long term secondary efficacy of linzagolix for heavy menstrual bleeding (HMB) due to uterine fibroids (UF): 52-week results from two placebo-controlled, randomized, phase 3 trials

Abstract Study question Are symptomatic improvements in women with UF observed after 24 weeks of linzagolix treatment with or without add-back therapy (ABT) maintained over 52 weeks? Summary answer Improvements in anemia, pain and quality of life previously reported at 24 weeks were maintained at 52 weeks. What is known already We previously reported that partial or full suppression of estradiol (E2) with once daily doses of either 100 or 200 mg linzagolix for 24 weeks, with or without ABT, were effective in reducing heavy menstrual bleeding associated with uterine fibroids, improving other symptoms such as pain and anemia and improving quality of life. Here we report the maintenance of effect on secondary endpoints after 52 weeks of treatment. Study design, size, duration Linzagolix is an investigational, oral GnRH antagonist being developed to treat HMB due to UF. PRIMROSE 1 (P1, USA, NCT03070899) and PRIMROSE 2 (P2, Europe and USA, NCT03070951) are randomized, double-blind, placebo-controlled Phase 3 trials, with essentially identical design, investigating the efficacy and safety of linzagolix with and without hormonal add-back therapy (ABT: 1 mg estradiol/0.5 mg norethindrone acetate) once daily for 52 weeks. Participants/materials, setting, methods Participants had HMB due to UF (>80mL menstrual blood loss (MBL)/cycle) and were equally randomized to: placebo, linzagolix 100mg, linzagolix 100mg+ABT, linzagolix 200mg, or linzagolix 200mg+ABT. After 24 weeks, subjects originally randomized to placebo or linzagolix 200mg were switched to linzagolix 200mg+ABT except in P1 where 50% placebo subjects continued placebo until 52 weeks. Secondary efficacy assessments included hemoglobin, pain (0–10 numeric rating scale) and health related quality of life (HRQL) on the UF-QoL questionnaire. Main results and the role of chance P1 trial subjects (n = 526) had a mean age of 42 years, pain score of 6.6 and HRQL total score (0–100) of 36.4 and 63% were Black. P2 trial subjects (n = 511) had a mean age of 43 years, pain score 4.8 and HRQL total score of 46.1 and 5% were Black. Mean baseline MBL was about 200 mL per cycle in both studies. In both trials, significant improvements compared to placebo observed at week 24 for secondary endpoints, including pain, anemia and QoL in all linzagolix treatment groups were maintained at 52 weeks. Mean±SD hemoglobin levels in anemic patients (<12 g/dL) increased from baseline by 1.7±1.9, 1.9±1.7, 2.2±2.4, 2.7±1.9 in P1 and 1.2±1.9, 2.9±1.8, 2.4±2.1, 3.0±1.4 in P2 in the 100mg, 100mg+ABT, 200mg/200mg+ABT, 200mg+ABT groups, respectively, compared to 0.6±1.8 with placebo (P1). Mean±SD change from baseline in pain scores were -3.3±3.1, -2.7±3.2, -2.6±3.0, -3.9±3.2 in P1 and -2.6±3.1, -2.6±2.8, -3.0±2.6, -2.8±3.0 in P2 in the 100mg, 100mg+ABT, 200mg/200mg+ABT, 200mg+ABT groups, respectively, compared to -0.4±2.5 with placebo (P1). Mean±SD change in HRQL total scores were 25.0±26.2, 34.2±30.1, 29.7±29.2, 38.3±29.2 in P1 and 16.8±24.0, 29.6±23.2, 31.9±26.8, 30.7±26.0 in P2 in the 100mg, 100mg+ABT, 200mg/200mg+ABT, 200mg+ABT groups, respectively, compared to 14.6±23.9 with placebo (P1). Limitations, reasons for caution Here we report data in both trials up to 52 weeks of treatment. No statistical comparisons were done at 52 weeks (the primary analysis was done after 24 weeks treatment). Post-treatment follow-up will provide more information in symptom recurrence after stopping treatment. Wider implications of the findings All linzagolix treatments provided sustained benefit. Two regimens previously identified for potential long-term treatment, 200mg with ABT and 100mg without ABT, provided sustained improvements of anemia, pain and associated quality of life. These different treatment regimens could be important to address the diverse needs of women suffering from uterine fibroids. Trial registration number ClinicalTrials.gov: NCT03070899, NCT03070951

Does Inhaled Methoxyflurane Implement Fast and Efficient Pain Management in Trauma Patients? A Systematic Review and Meta-Analysis.

IntroductionEvidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs).MethodsRCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs).ResultsA total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from − 0.44 to − 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference − 5.29 min; 95% CI − 6.97 to − 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17–1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72–5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes.ConclusionsIn emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT.Clinical Trial NumberPROSPERO registration number CRD42020223000.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00258-9.

The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

PurposePeripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC.MethodsThis post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms.ResultsAmong 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal.ConclusionFocal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

The Use of Paravertebral Analgesia in the Management of Pain in the Elderly Patient With Rib Fractures.

Elderly patients with rib fractures carry a high morbidity rate, particularly due to pulmonary complications as decreased respiratory efforts ensue secondary to pain. Risk of bleeds in the elderly on anticoagulant therapy is high. The effort to reduce narcotic use in patients is now a health care priority. We propose that the use of paravertebral analgesia (PVA) pumps is an alternative pain control method with less risk and easy placement. Two hundred and seventy-nine patients were admitted with multiple fractured ribs to the Trauma Center of Community Hospital and treated with the application of continuous PVA via a pump (72 patients). Pain scores were recorded before and after the initiation of the pump. These patients were compared with a group of the remaining 207 patients who received intravenous narcotics only. The mean change from baseline in pain scores for all patients was 1.43 (SD = 2.75). The mean change in pain for the treatment group was 1.93 (SD = 2.60), and the change in pain for the control group was 1.24 (SD = 2.79). Change in pain differed between groups (1.3 vs 1.8; P = .01) although it was a small difference. After adjusting for age, gender, Injury Severity Score, Glasgow Coma Scale, number of fractures, and comorbid conditions, there was no significant difference in pain post-procedure (odds ratio = 0.75; P = 0.39) with an effect size of 30% and total sample size of 279. The PVA pump using bupivacaine is an effective safe and alternative method for managing elderly patients with rib fractures eliminating the serious side effects associated with narcotics.

A phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of vaginal rings containing nomegestrol acetate or etonogestrel and 17β-estradiol in the treatment of women with primary dysmenorrhea

ObjectiveTo evaluate the effect of investigational vaginal rings containing nomegestrol acetate (NOMAC) plus 17β-estradiol (E2) or etonogestrel (ENG) plus E2 in women with moderate to severe primary dysmenorrhea. Study designThis was a Phase 2b randomized, placebo-controlled, multicenter, double-blind study. We randomized participants to one of five treatment groups: four hormonal rings and one placebo ring. The investigational vaginal rings released 300 μg of E2 daily along with 700 μg or 900 μg of NOMAC or 100 μg or 125 μg of ENG. Each participant received 2 identical rings and was to insert each for 21 days followed by a 7-day ring-free period. The primary endpoint, as assessed by a daily electronic diary (e-Diary), was the change in menstrual pain score from baseline to the second in-treatment withdrawal bleeding episode (Cycle 2). The pain score was the mean of the three highest scores for menstrual cramping pain (0–4 point scale) recorded from the day before menses to the third day of bleeding. The primary hypothesis was that at least one investigational vaginal ring would demonstrate a statistically significant larger reduction from baseline in pain score compared to placebo. Secondary endpoints included total mean impact score (which assessed the negative impact on work/school, physical activities, leisure/social activities) and the amount and days of rescue medication (ibuprofen) used. Clinical trial registration number: NCT01670656. ResultsWe randomized 439 participants. The mean pain score decreased from baseline to Cycle 2 in all groups; the decrease in all four treatment groups compared to placebo was statistically significant (p-values ≤0.002). All treatment groups had greater reductions than placebo in ibuprofen intake and greater improvement in impact scores; these differences were statistically significant for both endpoints for the ENG-E2 100/300 μg/day group, while the other groups were not statistically significant for one or both endpoints. ConclusionAll four investigational rings produced a statistically significantly larger reduction from baseline in mean menstrual pain score compared to placebo while pain medication use decreased. ImplicationsThis placebo-controlled study provides evidence that vaginal contraceptive rings containing NOMAC-E2 or ENG-E2 improve moderate to severe dysmenorrhea, across all of doses studied. This adds to the evidence that hormonal contraceptives are effective treatments for dysmenorrhea.

Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib\u2009+\u2009letrozole: results from MONALEESA-2

PurposeEvaluate patient-reported outcomes (PROs) for postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer treated with first-line ribociclib plus letrozole.MethodsIn the phase III MONALEESA-2 study (NCT01958021), 668 patients were randomized 1:1 to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole. PROs were assessed using the European Organisation for Research and Treatment of Cancer core quality-of-life (EORTC QLQ-C30) and breast cancer-specific (EORTC QLQ-BR23) questionnaires. Changes from baseline and time to deterioration in health-related quality of life (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression models, respectively. Exploratory analysis of area-under-the-curve for change from baseline in pain score (AUC-pain) was performed.ResultsOn-treatment HRQoL scores were consistently maintained from baseline and were similar between arms. A clinically meaningful (> 5 points) reduction in pain score was observed as early as Week 8 and was maintained up to Cycle 15 in the ribociclib arm. A statistically significant increase in mean AUC-pain was also observed in the ribociclib arm. Scores for all other EORTC QLQ-C30 and EORTC QLQ-BR23 domains were maintained from baseline and were similar between arms.ConclusionsHRQoL was consistently maintained from baseline in postmenopausal women with HR+, HER2− advanced breast cancer receiving ribociclib plus letrozole and was similar to that observed in the placebo plus letrozole arm. Together with the improved clinical efficacy and manageable safety profile, these PRO results provide additional support for the benefit of ribociclib plus letrozole in this patient population.

Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies.

Opioids are critical for managing cancer pain, but may provide inadequate relief and/or unacceptable side effects in some cases. To assess the analgesic efficacy of adjunctive Sativex (Δ9-tetrahydrocannabinol (27 mg/mL): cannabidiol (25 mg/mL)) in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. This report describes two phase 3, double-blind, randomized, placebo-controlled trials. Eligible patients had advanced cancer and average pain numerical rating scale (NRS) scores ≥4 and ≤8 at baseline, despite optimized opioid therapy. In Study-1, patients were randomized to Sativex or placebo, and then self-titrated study medications over a 2-week period per effect and tolerability, followed by a 3-week treatment period. In Study-2, all patients self-titrated Sativex over a 2-week period. Patients with a ≥15% improvement from baseline in pain score were then randomized 1:1 to Sativex or placebo, followed by 5-week treatment period (randomized withdrawal design). The primary efficacy endpoint (percent improvement (Study-1) and mean change (Study-2) in average daily pain NRS scores) was not met in either study. Post hoc analyses of the primary endpoints identified statistically favourable treatment effect for Sativex in US patients <65 years (median treatment difference: 8.8; 95% confidence interval (CI): 0.00-17.95; p = 0.040) that was not observed in patients <65 years from the rest of the world (median treatment difference: 0.2; 95% CI: -5.00 to 7.74; p = 0.794). Treatment effect in favour of Sativex was observed on quality-of-life questionnaires, despite the fact that similar effects were not observed on NRS score. The safety profile of Sativex was consistent with earlier studies, and no evidence of abuse or misuse was identified. Sativex did not demonstrate superiority to placebo in reducing self-reported pain NRS scores in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy, although further exploration of differences between United States and patients from the rest of the world is warranted.

Development and preliminary validation of an integrated efficacy-tolerability composite measure for the evaluation of analgesics.

The goal of this analysis was to develop and evaluate integrated measures of benefit and tolerability of analgesic drugs in clinical trials. We evaluated an efficacy-tolerability composite (ETC) measure combining different cutoff values for daily pain reduction (≥20%, ≥30%, or ≥50% pain reduction) and adverse events (AEs) (no AE, no or mild AEs, no or mild drug-related AEs). Nine ETC cutoff values (3 × 3) were tested using data from a randomized double-blind trial comparing tapentadol extended release (ER) (n = 310), oxycodone controlled release (CR) (n = 322), and placebo (n = 314) in subjects with chronic low back pain. Efficacy-tolerability composite scores were calculated as the mean number of days a subject met the ETC criterion divided by the number of days the subject was expected to be in study; ETC scores were then averaged in each treatment group. For all 9 ETC measures, validity was demonstrated by significant correlation of ETC scores with patients' Global Impression of change and with change from baseline in pain scores. Tapentadol ER ETC scores were statistically significantly higher than oxycodone CR ETC scores for 4 of the ETC measures. "No/mild drug-related AE and ≥20% pain reduction" demonstrated the best overall validity (correlation with patients' global impression of change) and responsiveness (discrimination between treatment groups), yielding a higher standardized effect size for tapentadol ER compared with placebo (0.19 [95% confidence interval: 0.031-0.346]) and with oxycodone CR (0.23 [95% confidence interval: 0.070-0.383]) than other cutoff values. Thus, we have identified herein a composite measure that seems to be a valid and responsive measure of the overall efficacy and tolerability of analgesics in clinical trials.

Percutaneous Cervical Cordotomy for the Management of Pain from Cancer: A Prospective Review of 45 Cases

Percutaneous cervical cordotomy (PCC) is a well recognized but infrequently performed procedure for the relief of unilateral intractable pain from malignancy. There is a paucity of data regarding efficacy and safety of PCC. The study's objectives were to demonstrate the efficacy and safety of PCC in cancer pain. The study was a prospective review of 45 cases undergoing PCC at a tertiary referral center over a three-year period. All patients were suffering from severe, refractory unilateral pain secondary to malignancy with poor pain relief or intolerable side effects of conventional analgesics including opioids and adjuvants. Variables recorded preprocedure, at 2 days, and at 28 days postprocedure were numerical rating scale for maximum and average pain, oral morphine equivalent dose, and global impression of change. Adverse events and survival postprocedure were recorded. Prospective data was obtained in 45 patients. Survival postprocedure ranged from 7 days to 33 months. There was a significant reduction from baseline in pain scores at 2 days and at 28 days postprocedure. Thirty-two patients experienced significant pain relief--average numerical rating scale (NRS) of zero--on day 2. Improvement in pain scores was sustained at 28 days. There were no serious adverse events observed such as respiratory failure. PCC is a safe and highly effective procedure to treat intractable unilateral cancer pain. It offers significant advantages over other pain control methods. Patient selection and attention to detail is paramount for a successful outcome.

Is Botulinum Toxin A Effective for the Treatment of Plantar Fasciitis?

Botulinum toxin A (BoNT-A) is used as an alternative treatment for chronic orthopedic conditions. This study was conducted to investigate the efficacy and safety of BoNT-A on pain and functional outcome in patients with chronic plantar fasciitis. In this short-term, randomized, multicenter, double-blind, placebo-controlled study, patients (N=40) were randomized to receive 200 units of BoNT-A (Dysport) or saline placebo. The injection was administered in a fan-shaped manner directly at the calcaneal origin of the plantar fascia. The primary outcome measure was the proportion of responders at week 6 [≥50% decrease from baseline in pain score (visual analog scale) while moving during the previous 48 h). Global assessments were performed by the patient and physician at each visit up to week 18. More patients in the BoNT-A group achieved a response at week 6 (25% vs. 5% for placebo; P=0.18). Differences between treatments were in favor of BoNT-A on secondary measures of pain, but did not reach statistical significance. In the BoNT-A group, 52.7% (vs. 40% for placebo) assessed their condition as slightly/significantly improved at week 6. At study endpoint (week 18), 63.1% of the BoNT-A group perceived an improvement versus 55% of the placebo group. There was no difference in global assessment between physician and patient. No adverse events related to treatment were noted. There is a need for larger, prospective, long-term, placebo-controlled studies to fully establish the role of BoNT-A for the treatment of plantar fasciitis.

Cost effectiveness of pregabalin in the treatment of fibromyalgia from a UK perspective

Background:Fibromyalgia is a chronic condition associated with widespread pain, sleep disturbance and disability. Disease related costs are high and effective treatment options few.Objectives:To evaluate the cost effectiveness of pregabalin in the treatment of fibromyalgia.Methods:A decision-analytic model was developed comparing pregabalin 300 mg or 450 mg against placebo, duloxetine 60 mg or 120 mg, gabapentin, tramadol and amitriptyline. After a 12 week treatment phase patients who responded to treatment entered an ongoing treatment phase using a Markov model in which patients maintained response, lost response or dropped out. The base case considered patients with severe fibromyalgia defined as a Fibromyalgia Impact Questionnaire score of ≥59 and a pain score of ≥6.5 at baseline. Response rates for pregabalin and placebo were taken from three randomised trials, and a 1 year open-label extension study was used for long-term parameters. Response was defined as a ≥30% improvement over baseline in pain score and a patient global impression of change rating of much improved or very much improved. Relative rates of response for other comparators over placebo were extracted from a systematic review of published randomised controlled studies. The primary effectiveness endpoint was Quality Adjusted Life Years (QALYs). Utilities gained over baseline were estimated by applying the SF-6D utility algorithm to SF-36 data collected in the pregabalin trials. Resource use associated with fibromyalgia management was estimated from published studies and costs were estimated from the UK NHS perspective at 2008 prices. Costs and QALYs were discounted at 3.5%. Non-parametric bootstrapping analysis was used to generate confidence intervals.Results:In the base case, pregabalin 300 mg and 450 mg increased cost per patient by £601 (95% CI: 532, 669) and £653 (587, 727) and improved QALYs per patient by 0.03 (−0.03, 0.06) and 0.03 (−0.04, 0.08) respectively compared to placebo. The cost per QALY gained (CQG) was £23,166 and £22,533. In the base case population CQG for pregabalin 450 mg against duloxetine 60 mg and 120 mg was £19,224 and £14,096, against gabapentin £35,737, against tramadol £98,072, and was dominated by amitriptyline. Sensitivity analysis found the cost effectiveness of pregabalin to be most sensitive to drug price and response rates. Limitations of the analysis include different definitions of response used and lack of subgroup data reported in the published studies synthesised, and limited data on long-term effect of therapies in fibromyalgia. Although the analysis was based on the best available evidence, the comparisons against amitriptyline and tramadol rely on old studies that were not designed to meet current quality criteria.Conclusion:This model found pregabalin 300 mg and 450 mg to be cost effective compared with placebo and, within the limits of available evidence, against duloxetine using standard UK criteria in patients with fibromyalgia experiencing severe pain.

A Double-Blind, Randomized, Placebo-Controlled Trial of High Dose Vitamin D Therapy on Musculoskeletal Pain and Bone Mineral Density in Anastrozole-Treated Breast Cancer Patients with Marginal Vitamin D Status.

Abstract Rationale: Musculoskeletal (MS)pain is a known adverse class effect of aromatase inhibitors. Previously we reported high prevalence of Vitamin D deficiency in breast cancer patients complaining of MS pain, and anecdotal improvement of MS pain with weekly supplementation of high dose Vitamin D (HDD) (1). Here we report on a randomized double-blind, placebo-controlled trial of weekly HDD (ergocalciferol 50,000 IU) versus placebo (PBO) in breast cancer patient receiving anastrozole, with new or worsening MS pain since initiation of treatment, and with marginal levels of 25-OH Vitamin D (25OHD). The secondary aim was to determine whether HDD supplementation protects from bone loss.Methods: Inclusion criteria: 1) Postmenopausal women with invasive breast cancer (stage I - IIIB) on Anastrozole for at least 8 weeks; 2) new or worsening MS pain; 3) serum 25OHD level between 10 and 29 ng/ml. Design: 2 strata: 1) if 25OHD levels between 20-29 ng/ml, patients received 8 weeks of HDD then monthly HDD until the end of study (6 months) or PBO; 2) if 25OHD levels between 10-19 ng/ml, patients received 16 weeks HDD followed by monthly HDD until the end of the study or PBO. In addition, all patients received calcium (1000 mg/day) and standard Vitamin D supplementation (400 IU/day). Pain was measured by validated questionnaires (BPI, HAQ, FIQ) at baseline, month 2, month 4 and month 6. Bone Mineral Density was measured at baseline and at 6 months using a Hologic densitometer.Results: Sixty patients were enrolled. Mean age was 61.5 years. HDD and PBO groups did not differ at baseline in pain scores and 25OHD levels.At 2 months the HDD group reported lower scores on pain-related questions on BPI (question #3) at 2 mo, p=0.01 and FIQ (question #15), at 2 mo p=0.02. There was also a trend for better scores for walking and climbing steps on the HAQ [Group x Time Chi-square=3.6; at 2 mo p=0.02; p=0.009 at 4 mo]. Preliminary analysis of bone density data show higher femoral neck values in the HDD group at 6 months [% change 0-6 mo: HDD=0.54±0.71, PBO= -1.43±0.66, p=0.05]. There were no significant toxicities.Conclusions: HDD is well tolerated in this study, improves MS pain in patients receiving anastrozole, and may help functional activity. The effect was limited to the 2 month interval when patients on the active arm were receiving weekly treatment. Improvements decreased at 4 and 6 months once patients switched to monthly supplements. HDD may have also a positive effect on bone health. Limits of this pilot randomized study include the small number of patients, and the difficulty of measuring pain using clinical questionnaires.1) Taylor ME, Rastelli A, et.al. Incidence of 25-OH vitamin D deficiency in patients with a history of breast cancer who have musculoskeletal symptomatology. San Antonio Breast Cancer Symposium, Poster # 3072, December 2004Supported by Astra-Zeneca Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 803.

The ACTION study: A randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA®) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin®) for the treatment of chronic, moderate to severe low back pain

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)--AVINZA (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin (O-ER), oxycodone modified-release tablets given twice a day--in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the A-MQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose.

(813): Oral once-a-day AVINZA (morphine sulfate extended-release capsules) vs. twice daily OxyContin (oxycodone hydrochloride controlled-release): A randomized, multicenter study for the treatment of chronic moderate to severe low back pain

We evaluated and compared two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in patients with chronic moderate-to-severe low back pain. This was an open-label, randomized, parallel-group multicenter study open to enrollment of SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe (pain score ’4 on a 0-10 BPI scale) low back pain. A total of 392 subjects were enrolled and underwent opioid dose titration for a period of 3 to 6 weeks. Opioid dose stabilization (pain score< 4 for 3 consecutive days with≤ 2 doses of ibuprofen pain rescue medication per day) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered the 8-week evaluation phase of the study. AVINZA achieved pain control that was significantly better than OxyContin, as demonstrated by a greater decrease from baseline in pain scores evaluated 6, 9, and 12 hours after the morning dose of both opioids (p≤0.02). Subjective sleep parameters assessed by the PSQI were significantly better in the AVINZA group for the entire Evaluation period from Week 1 to 8 (p<0.04). The number of ibuprofen pain rescue medication doses adjusted for the number of patient-days was significantly lower in the AVINZA group (p<0.01). Pain control was achieved with a significantly lower daily opioid dose expressed in morphine-equivalents in the AVINZA group (median of 58 mg and 85 mg, respectively p=0.017). The incidence and severity of elicited opioid side effects was similar in the two treatment groups. This randomized trial showed that AVINZA was significantly better than OxyContin for around-the-clock pain relief and improved sleep, with the added advantage of once-a-day dosing, a lower median morphine-equivalent daily dose, fewer ibuprofen doses for breakthrough pain, and a comparable safety profile. Supported by Ligand Pharmaceuticals Inc, and Organon Pharmaceuticals USA Inc.