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Limburg an der Lahn, Germany

Arendt-Nielsen L.,University of Aalborg | Andresen T.,University of Aalborg | Andresen T.,University of Aarhus | Malver L.P.,University of Aarhus | And 4 more authors.
Clinical Journal of Pain | Year: 2012

Objectives: The descending pain inhibitory system is impaired in chronic pain and it is important to know how analgesics interact with this system. The aim of this human experimental pain, double-blind, randomized, placebo-controlled, 3 way cross-over study was to investigate the effect of 2 different opioids on descending pain inhibition using conditioning pain modulation (CPM) as a screening tool. Methods: Twenty-two healthy male volunteers were randomized to 72 hours of treatment with transdermal patches of fentanyl (25 μg/h), buprenorphine (20 μg/h), or placebo. The CPM was induced by immersing the hand into cold (3.0±0.3°C) water and the evoked pain was continuously rated on a visual analogue scale (VAS). The test stimulus [pressure pain tolerance threshold (PPTol)] was applied to the contra-lateral arm. The CPM test was performed at baseline, 24, 48, and 72 hours after application of the patches. Results: The opioid treatments did not significantly (F=2.249; P=0.07) modulate the PPTol over the treatment period compared with placebo. The CPM-evoked PPTol increases (percentage increase from what was obtained at the baseline before patch application) were significantly enhanced by buprenorphine (P=0.004) and fentanyl (P=0.005) compared with placebo, with no differences between the 2 active drugs. Fentanyl significantly attenuated the time to cold water-evoked VAS peak compared with placebo (P=0.005), and the same trend was observed for buprenorphine (P=0.06). The VAS pain intensity was not affected. Discussion: The opioids buprenorphine and fentanyl significantly potentiate the effect of descending pain inhibition in healthy volunteers. © 2012 by Lippincott Williams & Wilkins. Source

Smith K.,Mundipharma Research Ltd | Hopp M.,Mundipharma Research GmbH and Co. KG | Mundin G.,Mundipharma Research Ltd | Bond S.,University of Cambridge | And 6 more authors.
Expert Opinion on Investigational Drugs | Year: 2011

Objectives: This exploratory study in healthy volunteers investigated the effect of single doses of oxycodone on gastrointestinal (GI) transit time and the degree to which a single dose of naloxone reverses the oxycodone-induced effect. Methods: Fifteen healthy male volunteers received: oxycodone 10 and 20 mg, oxycodone/naloxone 10/5 and 20/10 mg (all as prolonged release tablets) and placebo. Each dose was radiolabelled and administered with a capsule containing radiolabelled resin (surrogate for GI contents). Results: Scintigraphic analysis showed that 20 mg oxycodone significantly increased colon arrival time (mean 7.19 vs 5.15 h for placebo, p = 0.0159). Mean colon arrival time for oxycodone/naloxone 20/10 mg (5.16 h) was similar to placebo, although the difference between oxycodone/naloxone 20/10 mg versus oxycodone 20 mg was not significant (p = 0.0653). Colonic geometric centre analysis showed a significant increase in mean time for the resin to reach the colon following oxycodone 10 and 20 mg compared with placebo (increases of 5.3 and 8.8 h). There was no significant effect of naloxone at the lower dose; however, oxycodone/naloxone 20/10 mg significantly reduced mean colonic transit time by 2.1 h (p = 0.0376). Conclusion: A single dose of oxycodone 20 mg significantly prolonged GI transit time but this effect was reduced by co-administration of naloxone. © 2011 Informa UK, Ltd. Source

Schilder A.,University of Heidelberg | Hoheisel U.,University of Heidelberg | Magerl W.,University of Heidelberg | Benrath J.,University of Heidelberg | And 3 more authors.
Pain | Year: 2014

Injection of hypertonic saline into deep tissues of the back (subcutis, muscle, or the surrounding fascia) can induce acute low back pain (LBP). So far, no study has analyzed differences in temporal, qualitative, and spatial pain characteristics originating from these tissues. The current study aimed to investigate the role of the thoracolumbar fascia as a potential source of LBP. In separate sessions, 12 healthy subjects received ultrasound-guided bolus injections of isotonic saline (0.9%) or hypertonic saline (5.8%) into the erector spinae muscle, the thoracolumbar fascia (posterior layer), and the overlying subcutis. Subjects were asked to rate pain intensity, duration, quality, and spatial extent. Pressure pain thresholds were determined pre and post injection. Injections of hypertonic saline into the fascia resulted in significantly larger area under the curve of pain intensity over time than injections into subcutis (P < 0.01) or muscle (P < 0.001), primarily based on longer pain durations and, to a lesser extent, on higher peak pain ratings. Pressure hyperalgesia was only induced by injection of hypertonic saline into muscle, but not fascia or subcutis. Pain radiation and pain affect evoked by fascia injection exceeded those of the muscle (P < 0.01) and the subcutis significantly (P < 0.05). Pain descriptors after fascia injection (burning, throbbing, and stinging) suggested innervation by both A- and C-fiber nociceptors. These findings show that the thoracolumbar fascia is the deep tissue of the back that is most sensitive to chemical stimulation, making it a prime candidate to contribute to nonspecific LBP but not to localized pressure hyperalgesia. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Source

Dunlop W.,Mundipharma International Ltd | Uhl R.,Mundipharma Research GmbH and Co. KG | Khan I.,Mundipharma Research Ltd | Taylor A.,Napp Pharmaceuticals Ltd | Barton G.,University of East Anglia
Journal of Medical Economics | Year: 2012

Objective: To compare the cost effectiveness of prolonged release oxycodone/naloxone (OXN) tablets (Targinact*) and prolonged release oxycodone (OXY) tablets (OxyContin†) in patients with moderate-to-severe non-malignant pain and opioid-induced constipation (OIC) from the perspective of the UK healthcare system. Methods: A cohort model used data from a phase III randomised, controlled trial (RCT). It calculated the cost difference between treatments by combining the cost of pain therapy with costs of laxatives and other resources used to manage constipated patients. SF-36 scores were converted into EQ-5D utility values to calculate the quality-adjusted life-year (QALY) gains. Deterministic and probabilistic sensitivity analyses were performed. Results: The incremental cost of OXN versus OXY was £159.68 for the average treatment duration of 301 days. OXN gave an incremental QALY gain of 0.0273. The estimated incremental cost-effectiveness ratio (ICER) was £5841.56 per QALY. Sensitivity analyses gave a maximum ICER of £10,347.03. In some scenarios, OXN dominated with a cost saving of up to £4254.70. Probabilistic sensitivity analysis showed that OXN had approximately 96.6% probability of cost effectiveness at the £20,000 threshold. Limitations: The model was conservative in predicting the probability of constipation beyond the 12-week RCT period. UK cost of constipation data were limited and based on primary care physician opinion. Conclusions: In the base case, direct treatment costs were slightly higher for patients treated with OXN than for those treated with OXY. However, patients treated with OXN experienced a quality of life gain, and had an ICER considerably below thresholds commonly applied in the UK. The model was most sensitive to the estimated cost of constipation with a number of realistic scenarios in the sensitivity analysis demonstrating a cost saving with OXN (OXN dominant). OXN is therefore estimated to be a cost-effective option for treating patients with severe non-malignant pain and OIC. © 2012 Informa UK Ltd All rights reserved. Source

Blagden M.,Avondale Surgery | Hafer J.,Praxis fur Schmerztherapie | Duerr H.,Mundipharma Research GmbH and Co. KG | Hopp M.,Mundipharma Research GmbH and Co. KG | Bosse B.,Mundipharma Research GmbH and Co. KG
Neurogastroenterology and Motility | Year: 2014

Background: While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. Methods: Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using 'Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. Key Results: Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (≥12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. Conclusions & Inferences: Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR. Pooled data from the 12-month extension phases of two Phase III trials demonstrate combined oxycodone/naloxone prolonged-release tablets (OXN PR) are an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of opioid-induced constipation. Comparable pain control but with improved bowel function was observed with OXN PR vs oxycodone PR and was maintained during the open-label, long-term treatment. No new safety issues were observed which were attributable to the long-term administration of OXN PR. aScreening and double-blind phases: patients who required laxatives (patients provided with bisacodyl by the study investigator, according to the study protocol). bExtension phases: patients who used laxatives regularly (according to specific dosing and treatment instructions provided by the investigator). cNo study treatment was received during Screening. At Run-in, patients had prestudy opioid converted to open-label Oxy PR, titrated to an effective analgesic dose. © 2014 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd. Source

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