Journal of clinical pharmacology
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Randomized Controlled Trial Multicenter Study
Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo-Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients.
Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end-stage renal disease with anemia on hemodialysis. Seventeen patients, on epoetin-alfa maintenance therapy with stable hemoglobin levels ≥10 g/dL, had epoetin-alfa discontinued on day 3 and were enrolled in this double-blind placebo-controlled study. Two cohorts were randomized 3:1 (roxadustat: placebo). ⋯ Roxadustat induced transient elevations of endogenous erythropoietin that peaked between 7 and 14 hours after dosing and returned to baseline by 48 hours after dosing. Peak median endogenous erythropoietin levels were 96 mIU/mL and 268 mIU/mL for the 1- and 2-mg/kg doses, respectively, within physiologic range of endogenous erythropoietin responses to hypoxia at high altitude or after blood loss. No serious adverse events were reported, and there were no treatment- or dose-related trends in adverse event incidence.
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Randomized Controlled Trial
Randomized Crossover Trial to Compare Abuse Liability of Intravenous Remimazolam Versus Intravenous Midazolam and Placebo in Recreational Central Nervous System Depressant Users.
Remimazolam (RMZ) is a new and ultra-fast-acting, short-duration intravenous benzodiazepine, a drug class associated with abuse potential. This trial was designed to compare the abuse potential of remimazolam with placebo and midazolam (MDZ), a well-characterized member of the same pharmacological class in healthy, recreational drug users 18-55 years-of-age, who demonstrated good drug tolerance and were able to discriminate between midazolam and placebo. ⋯ Scores for willingness to take drug again were also lower for RMZ versus MDZ, but not significantly so. We concluded that the abuse potential of RMZ is comparable to or lower than that of MDZ, a drug known to have a low potential for intravenous abuse.
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Randomized Controlled Trial
Ascending-Dose Study of Controlled-Release Ketamine Tablets in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability.
Parenteral ketamine has fast-onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled-release ketamine tablets would improve safety and tolerability compared with injected ketamine by reducing peak ketamine exposures compared with dosing by injection. ⋯ There were no clinically significant changes in ECGs or safety laboratory tests at any time. Compared with injected ketamine, oral controlled-release ketamine tablets did not increase blood pressure or heart rate, and only at doses of 240 mg was dissociation of mild intensity reported. Reducing and delaying ketamine peak concentration by oral dosing with controlled-release ketamine tablets improve this drug's tolerability for patients with depression/anxiety.
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Randomized Controlled Trial Comparative Study
Abuse Potential of Lasmiditan: A Phase 1 Randomized, Placebo- and Alprazolam-Controlled Crossover Study.
Lasmiditan is a centrally penetrant, highly selective 5-hydroxytryptamine (serotonin) receptor 1F (5HT1F ) agonist under development as a novel therapy for acute treatment of migraine. A phase 1 randomized, placebo- and positive-controlled crossover study assessed the abuse potential of lasmiditan in adult recreational polydrug users. Following a qualification phase, subjects were randomized into treatment sequences, each consisting of 5 study treatments: placebo, alprazolam 2 mg, lasmiditan 100, 200 (lasmiditan 100 and 200 mg are proposed therapeutic doses), and 400 mg (supratherapeutic). ⋯ Drug-liking scores for lasmiditan 400 mg were not significantly different from alprazolam (lower 90% confidence limit on difference in LS means < 5), but drug-liking scores at lower doses (100 and 200 mg) were significantly different from alprazolam. During the treatment phase, the incidence of treatment-emergent adverse events (TEAEs) increased with increasing dose of lasmiditan; all TEAEs reported with lasmiditan treatment were mild. Subjective drug-liking effects for lasmiditan versus placebo and versus alprazolam, and the safety and tolerability profile of lasmiditan suggest that lasmiditan has a low potential for abuse.
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Randomized Controlled Trial
Effect of Intravenous Oxycodone Versus Sufentanil on the Incidence of Postoperative Nausea and Vomiting in Patients Undergoing Gynecological Laparoscopic Surgery.
More than 30% of patients who undergo surgery will experience postoperative nausea and vomiting (PONV) if no prophylactic treatments are used. Although numerous studies have been performed to investigate the factors related to PONV, the effect of perioperative intravenous oxycodone on the incidence of PONV has not been well investigated. In this study, gynecological patients (grade I-II, aged 18-65 years, scheduled to undergo elective gynecological laparoscopic surgery under general anesthesia) were randomized to the oxycodone group or the sufentanil group. ⋯ Postoperative pain scores at different time points and hemodynamics were comparable between the oxycodone and sufentanil groups. We concluded that the incidence of PONV in gynecological patients who underwent laparoscopic surgery was lower when using intravenous oxycodone for anesthesia induction, anesthesia maintenance, and postoperative analgesia than when using intravenous sufentanil. However, oxycodone and sufentanil provided the same stable hemodynamics during surgery and satisfactory postoperative analgesia.