Clinical therapeutics
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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 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 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 · Aug 2012
Randomized Controlled Trial Multicenter StudyEffect of once-daily fluticasone furoate/vilanterol on 24-hour pulmonary function in patients with chronic obstructive pulmonary disease: a randomized, three-way, incomplete block, crossover study.
Available inhaled corticosteroid/long-acting β(2)-agonist combinations for chronic obstructive pulmonary disease (COPD) require twice-daily administration. The combination of fluticasone furoate (FF) and vilanterol (VI) FF/VI is being developed in a novel dry powder inhaler for the treatment of COPD and asthma with the potential for once-daily dosing. Results from Phase II studies have shown clinically and statistically significant improvements over placebo in trough (24-hour postdose) forced expiratory volume in 1 second (FEV(1)) after once-daily dosing with FF or VI (VI concurrently with an inhaled corticosteroid) in asthma and VI in COPD. ⋯ FF/VI inhaled once daily in the morning for 28 days produced significant improvements in pulmonary function with a prolonged (>24 hours') duration of action in this population of patients with COPD. The combination was well tolerated. ClinicalTrials.gov identifier: NCT01072149.
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Clinical therapeutics · Aug 2012
Randomized Controlled Trial Multicenter Study Comparative StudyI-ADD study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with irbesartan monotherapy in hypertensive patients uncontrolled with irbesartan 150 mg monotherapy: a multicenter, phase III, prospective, randomized, open-label with blinded-end point evaluation study.
Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. ⋯ These 10-week data from this patient population suggest a greater antihypertensive efficacy of the fixed-dose combination I300/A5 over I300 alone in lowering systolic blood pressure. Both treatments were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00957554.