Clinical therapeutics
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Clinical therapeutics · Sep 2012
Randomized Controlled Trial Multicenter StudyEfficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial.
Some patients with type 2 diabetes mellitus (T2DM) receiving monotherapy with a sulfonylurea (SU) are unable to meet recommended glycemic targets over the long term and require additional pharmacologic agents to maintain glycemic control. This study was designed to assess the utility of adjunctive therapy with the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in patients with T2DM inadequately controlled with SU monotherapy. ⋯ The addition of linagliptin to SU therapy for 18 weeks in these patients with T2DM was associated with statistically significant and clinically meaningful reductions in HbA(1c) compared with placebo. The overall tolerability of linagliptin was similar to that of placebo, with a low risk for hypoglycemia and no significant weight gain. These findings support the use of linagliptin as adjunctive therapy in patients with T2DM inadequately controlled on SU monotherapy. ClinicalTrials.gov identifier: NCT00819091.
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Clinical therapeutics · Sep 2012
Randomized Controlled Trial Comparative StudyAscending single-dose study of the safety profile, tolerability, and pharmacokinetics of bosutinib coadministered with ketoconazole to healthy adult subjects.
Bosutinib (SKI-606) is an orally bioavailable, competitive tyrosine kinase inhibitor that selectively targets both Src and Abl tyrosine kinases. Bosutinib is metabolized primarily through the cytochrome P450 3A4 pathway. Inhibition of bosutinib metabolism by coadministration with the potent cytochrome P450 3A4 inhibitor ketoconazole could potentially increase plasma concentrations of bosutinib, allowing for the study of bosutinib tolerability at supratherapeutic concentrations in a healthy subject population. ⋯ Single doses of bosutinib up to 600 mg coadministered with multiple doses of ketoconazole were acceptably well tolerated in this small, selected group of healthy male volunteers. In addition, supratherapeutic exposure was achieved within this range for bosutinib when coadministered with ketoconazole. ClinicalTrials.gov identifier: NCT00777530.
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Clinical therapeutics · Sep 2012
Randomized Controlled Trial Comparative StudyEffects of a supratherapeutic dose of investigational orally inhaled dihydroergotamine (MAP0004) on QT interval: a randomized, double-blind, active- and placebo-controlled crossover study in healthy volunteers.
MAP0004 is an orally inhaled investigational drug containing dihydroergotamine (DHE). Although DHE has been used for 60 years with no reported cardiac arrhythmias, a thorough QT study had not previously been performed with DHE. ⋯ A supratherapeutic dose of MAP0004 was not associated with prolonged QTc intervals. At the proposed clinical dose (1.0 mg), MAP0004 is unlikely to affect the QT interval. MAP0004 and its primary metabolite showed no evidence for prolongation of the QTc interval in healthy subjects according to the criteria required from regulatory agencies. ClinicalTrials.gov identifier: NCT01191723.
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Clinical therapeutics · Sep 2012
Randomized Controlled TrialAssessment of the effect of mirodenafil on the hemodynamics of healthy male Korean volunteers administered tamsulosin: a randomized, double-blind, placebo-controlled, 2-period crossover study.
Both mirodenafil, a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction, and tamsulosin, a selective α(1A)-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia, have mild vasodilational effects. ⋯ The coadministration of mirodenafil 100 mg did not induce a significant decrease in BP when associated with an increase in PR in these healthy male Korean volunteers administered tamsulosin 0.2 mg compared with placebo. (Clinical Trial Registry, http://cris.cdc.go.kr/cris/en/: KCT0000117).
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Clinical therapeutics · Sep 2012
Comparative StudyStatins and new-onset diabetes: a retrospective longitudinal cohort study.
Statins have been linked to new-onset diabetes (NOD); however, the effect of statins on the development of NOD in patients with hypertension and dyslipidemia has not been well studied. ⋯ These outpatients with hypertension and dyslipidemia who took fluvastatin, lovastatin, and rosuvastatin were at lower risk of NOD, whereas patients who took pravastatin were at greater risk. Simvastatin and atorvastatin seemed to have a neutral effect. Our study also demonstrated that atorvastatin has a dose-response effect on NOD risk. Because this was a descriptive study, temporality and subsequent causality of all statins and NOD could not be shown. Further study and independent confirmation of the causality between statin use and NOD in larger clinical trials are warranted.