Clinical therapeutics
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Clinical therapeutics · Dec 2013
Randomized Controlled TrialCardiac repolarization with Gabapentin enacarbil in a randomized, double-blind, placebo- and active-controlled, crossover thorough QT/QTc study in healthy adults.
Gabapentin enacarbil (GEn) is a prodrug of gabapentin and is approved in the United States in adults for the management of postherpetic neuralgia and in the United States and Japan for the treatment of moderate-to-severe primary restless legs syndrome. ⋯ Single doses of GEn, up to 6000 mg, had no effect on cardiac repolarization in this thorough-QT study and are unlikely to cause clinically relevant QT prolongation in clinical use. Assay sensitivity was confirmed with moxifloxacin as an active control. ClinicalTrials.gov identifier: NCT01516372.
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Clinical therapeutics · Dec 2013
ReviewHydromorphone: evolving to meet the challenges of today's health care environment.
Hydromorphone, a potent analogue of morphine, has long had an important role in pain management and is included in several international guidelines for managing pain. Advances in hydromorphone formulations and the ways in which hydromorphone is being used clinically today warrant a review of the drug's pharmacotherapeutic utility. ⋯ Due to the epidemic of prescription opioid overdoses associated with prescription opioid abuse in the United States, development of tamper-resistant opioid formulations that avoid dose-dumping issues has become a significant goal of pharmaceutical manufacturers. The current formulation of hydromorphone extended-release potentially provides the benefits of long-acting hydromorphone (ie, continuous pain control, increased quality of life, freedom to perform daily activities) to appropriate patients, while reducing the risks of abuse and without compromising safety.
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Clinical therapeutics · Dec 2013
Multicenter Study Clinical TrialSingle- and multiple-dose pharmacokinetic, safety, and tolerability profiles of olanzapine long-acting injection: an open-label, multicenter, nonrandomized study in patients with schizophrenia.
This was the first study, to our knowledge, in patients with schizophrenia in which olanzapine long-acting injection (LAI) was used to attempt delivery of depot formulation in multiple therapeutic doses. ⋯ The safety profile and PK data from this study support continued clinical development of olanzapine LAI in controlled efficacy studies at doses ≤300 mg every 2 weeks or 405 mg every 4 weeks. Clinical trial registry ID: 4535 http://www.lillytrials.com/results/ZyprexaLAI.pdf.
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Clinical therapeutics · Dec 2013
Randomized Controlled TrialEvaluation of the effect of Naloxegol on cardiac repolarization: a randomized, placebo- and positive-controlled crossover thorough QT/QTc study in healthy volunteers.
Opioid-induced constipation (OIC) is a common adverse effect associated with opioid use. Naloxegol is a PEGylated derivative of naloxone in clinical development as a once-daily oral treatment of OIC. ⋯ Naloxegol at 25 and 150 mg was not associated with QT/QTc interval prolongation in these healthy men, and at the proposed therapeutic dose of 25 mg/d, naloxegol is not expected to have a clinically relevant effect on cardiac repolarization in patients with OIC. ClinicalTrials.gov identifier: NCT01325415.
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Clinical therapeutics · Dec 2013
Cost-effectiveness of everolimus for second-line treatment of metastatic renal cell carcinoma in Serbia.
New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and/or sorafenib. The only targeted therapy for mRCC currently reimbursed in Serbia is sunitinib. ⋯ Everolimus as a second-line treatment of mRCC is not likely to be a cost-effective option under the present conditions in Serbia, with a relatively limited impact on its budget in oncology. A major constraint on the estimation of the cost-effectiveness of everolimus relates to the uncertainty around the everolimus effect on extending OS. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to construct an economically rational treatment strategy within the mRCC field.