Clinical drug investigation
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Randomized Controlled Trial Multicenter Study
Diclofenac epolamine plus heparin plaster versus diclofenac epolamine plaster in mild to moderate ankle sprain: a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase III trial.
In general sports, ankle sprain is the most frequently reported ankle injury and can cause chronic lateral ankle pain and tenderness. Treatment with NSAIDs is preferred, and several topical NSAID formulations are now available, helping to avoid the systemic adverse events typically associated with oral preparations. ⋯ The fixed-dose DHEP/heparin plaster is effective and has advantages over the DHEP plaster in relieving pain, and possibly also swelling, associated with mild to moderate acute ankle sprains with oedema in adults.
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Randomized Controlled Trial
Safety, tolerability and pharmacokinetics of dalcetrapib following single and multiple ascending doses in healthy subjects: a randomized, double-blind, placebo-controlled, phase I study.
Dalcetrapib is a modulator of cholesteryl ester transfer protein (CETP) activity developed to raise levels of high-density lipoprotein cholesterol (HDL-C) with the goal of further reduction of cardiovascular events additive to standard of care alone. In clinical studies, dalcetrapib has been shown to effectively increase levels of HDL-C with no significant safety concerns. ⋯ Single-dose dalcetrapib up to 4500 mg and multiple doses up to 3900 mg were generally safe and well tolerated.
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Opioids are the most powerful analgesic drugs currently available and consequently form an essential part of the treatment options for malignant and non-malignant chronic pain. However, the benefits of these medications can be offset by gastrointestinal adverse events such as nausea, vomiting and constipation, as well as adverse events affecting the CNS. These occur relatively frequently in patients receiving long-term opioids for pain relief and are a cause of additional patient suffering and reduced work and social functioning, measured as reductions in quality-of-life outcomes. ⋯ Estimated preference ratings, providing an insight into the trade-off between effective pain control and adverse events, have shown that utility decrements associated with an increase in adverse-event severity were similar in size to those caused by a shift from well controlled to poorly controlled pain. Given the rising prevalence of chronic pain conditions (affecting one in five adult Europeans), the direct and indirect costs incurred from the management of adverse events with long-term opioids are likely to be multiplied, contributing to the socioeconomic burden of chronic pain. For this reason, the adverse-event profile of opioid-based analgesics should be improved to achieve more efficient long-term pain control.
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Numerous controlled clinical trials have demonstrated the safety and efficacy of pregabalin in the treatment of neuropathic pain. The objectives of the present study were to assess the impact of pregabalin under real-world conditions on pain, pain-related sleep interference and general well-being, and to assess the tolerability and safety of pregabalin in patients diagnosed with neuropathic pain of central or peripheral origin. ⋯ Significant reductions in pain and pain-related sleep interference, combined with reductions in feelings of anxiety and depression, suggest that pregabalin under real-world conditions improves the overall health and well-being of patients with neuropathic pain.
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Comparative Study
Intra- and interindividual variabilities in the pharmacokinetics of fentanyl buccal soluble film in healthy subjects: a cross-study analysis.
Breakthrough pain describes transient exacerbations of pain that occur in cancer patients with adequately controlled background pain. Transmucosal fentanyl administration produces rapid-onset and short-duration analgesia that is effective for treating patients with breakthrough pain. Although a significant amount of research has been devoted to the study of speed of analgesia onset of transmucosal fentanyl products, few data exist on their variability in absorption, particularly within the same individual, despite the importance of this characteristic to the dose-to-dose reliability of their analgesic effect. This cross-study analysis aimed to evaluate the intra- and interindividual pharmacokinetic differences of fentanyl administered via fentanyl buccal soluble film in healthy subjects. ⋯ The minimal intraindividual variability in fentanyl absorption from the buccal soluble film demonstrates a predictable dose-to-dose exposure, which is a very desirable attribute for a medicine that is intended to treat breakthrough cancer pain, suggesting that this product would be expected to produce consistent effects in clinical practice. The greater interindividual variability highlights the need for individual titration of this product (as occurs with similar transmucosal fentanyl products), and for the availability of an adequately wide dose range.