A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment

Transdermal fentanyl for the treatment of pain caused by osteoarthritis of the knee or hip: an open, multicentre study

BACKGROUND: This study was designed to evaluate the utility of transdermal fentanyl (TDF, Durogesic(®)) for the treatment of pain due to osteoarthritis (OA) of the knee or hip, which was not adequately controlled by non-opioid analgesics or weak opioids. The second part of the trial, investigating TDF in patients with rheumatoid arthritis (RA) is reported separately. METHODS: Current analgesia was optimised during a 1-week run-in. Patients then received 28 days treatment with TDF starting at 25 μg/hr, with the option to increase the dose until adequate pain control was achieved. Metoclopramide was taken during the first week and then as needed. RESULTS: Of the 159 patients recruited, 75 with OA knee and 44 with OA hip completed the treatment phase, 30 knee and 18 hip patients entered the one-week taper-off phase. The most frequently used maximum dose of TDF was 25 μg/hr. The number of patients with adequate pain control increased during the run-in period from 4% to 27%, and further increased during TDF treatment to 88% on day 28. From baseline to endpoint, there were significant reductions in pain (p < 0.001) and improvements in functioning (p < 0.001) and physical (p < 0.001) and mental (p < 0.05) health. Scores for 'pain right now' decreased significantly within 24 hours of starting TDF treatment. TDF was assessed favourably and 84% of patients would recommend it for OA-related pain. Nausea and vomiting were the most common adverse events (reported by 32% and 26% of patients respectively), despite prophylaxis with metoclopramide, which showed limited efficacy in this setting. CONCLUSION: TDF significantly increased pain control, and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting; more effective anti-emetic treatment may enable more people to benefit from strong opioids such as TDF. This study suggests that four weeks is a reasonable period to test the benefit of adding TDF to improve pain control in OA patients and that discontinuing therapy in cases of limited benefit creates no major obstacles

Itraconazole: What clinicians should know?

Our purpose in assembling this paper is 2-fold. First, we hope to review in-depth the properties on itraconazole pellet-capsules and what clinicians should know when considering oral itraconazole and discuss the potential value of treating superficial dermatophyte infections with oral antifungal therapy. Second, we hope to address some of the concerns of the recent epidemic of chronic recalcitrant widespread dermatophytosis in India, with emphasis on better treatment but also considering some of the necessary prophylaxis hygiene measures. An in-depth review of itraconazole (as pellet-capsules), a triazole antifungal will be presented with focus on the pharmacokinetic properties which lead to the development of the 1-week pulse dosing for skin and nail infections. Finally, recommendations for best usage of itraconazole pellet-capsules for management of dermatophytosis will be summarized in this paper

Predicting long-term response to strong opioids in patients with low back pain: findings from a randomized, controlled trial of transdermal fentanyl and morphine

Abstract Background Some patients with long-standing low back pain will benefit from treatment with strong opioids. However, it would be helpful to predict which patients will have a good response. A fixed-term opioid trial has been recommended, but there is little evidence to suggest how long this trial should be. We assessed data from a large-scale randomized comparison of transdermal fentanyl (TDF) and sustained-release oral morphine (slow-release morphine; SRM) to determine characteristics of treatment responders. Methods This was a secondary analysis of a previously published 13-month randomized trial involving 680 patients with long-standing low back pain (median age 52 years, 61% women, median duration of back pain 87 months). Pain relief was recorded using visual analogue scales (VAS). Treatment response was defined as pain relief of at least 30% from baseline to any point during the trial. We used a step-wise logistic regression to identify variables that might predict response to treatment. Covariates included treatment group, sex, age, duration of pain, presence of neuropathic pain, baseline pain scores, educational/employment status, use of high doses of opioids, and social functioning (SF)-36 scores. Results Over half the patients in both groups (n = 370; 54% TDF, 55% SRM) were treatment responders. There were no differences between the TDF and SRM responders in terms of age, sex, type or duration of pain between responders and non-responders. The difference in response to treatment between responders and non-responders could be detected at 3 weeks. Lack of response after 1 month had a stronger negative predictive value (i.e., ability to detect non-responders) than the presence of response after 1 month. The most influential factors for predicting a response were employment status (χ2 = 11.06, p = 0.0259) and use of high doses of opioids (χ2 = 3.04, p = 0.0811). Conclusion No clear pattern of baseline pain (type or severity) or patient characteristics emerged that could be used to predict responders before the start of opioid treatment. However, a 1-month trial period appears sufficient to determine response and tolerability in most cases.</p

Efficacy and safety of paliperidone palmitate 6-Month versus paliperidone palmitate 3-month long-acting injectable in European patients with schizophrenia. A post hoc analysis of a global phase-3 double-blind randomized non-inferiority study

Purpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M).Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan-Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as -10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated.Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of -4.9% (95% CI: -9.2%, -0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs.Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified