Abstract:
PURPOSE:Pulmonary arterial hypertension (PAH) is a life-threatening disease that typically causes shortness of breath and exercise intolerance. Combination therapy with ambrisentan and tadalafil has proven to be more effective at preventing clinical failure events in patients with PAH than either drug alone. The aim of this study was to evaluate the bioequivalence of an ambrisentan/tadalafil fixed-dose combination (FDC) compared with co-administration of the 2 monotherapies. METHODS:This 3-part, randomized, single-dose, open-label crossover study was conducted in healthy volunteers. The first part of the study consisted of a 5-way crossover that compared the relative bioavailability of 4 FDC formulations (10-mg ambrisentan + 40-mg tadalafil) with co-administered reference monotherapies. One formulation was selected and its relative bioavailability was assessed when produced in 3 different granulation sizes during the second part of the study. In the third part of the study, the bioequivalence of the candidate FDC with the reference monotherapies was evaluated for the 10-mg/40-mg dose strength, in addition to 2 other dose strengths (5 mg/20 mg and 5 mg/40 mg). For all parts of the study, blood samples were taken at regular intervals after each dose, ambrisentan and tadalafil concentrations determined, and pharmacokinetic (PK) parameters (Cmax, AUC0-∞, and AUC0-t) obtained. Test/reference ratios of the geometric means of PK parameters were used to evaluate bioequivalence. Safety and tolerability were assessed by recording adverse events and monitoring vital signs, ECGs, and clinical laboratory data. FINDINGS:Of the 174 subjects screened for eligibility, 112 were allocated to a randomized treatment sequence across all study parts, and 100 completed their full assigned treatments. All 4 FDC formulations tested during part 1 of the study yielded PK parameters similar those of the reference treatments. In part 2, granulation size was found to not affect the relative bioavailability of the selected formulation. In part 3, the selected FDC was found to be bioequivalent to co-administration of the monotherapies in both the fasted and fed states. The FDC was also found to be bioequivalent to the reference treatments at the 2 additional dose strengths. All but one of the adverse events was mild to moderate in intensity, and no serious adverse events were reported. IMPLICATIONS:An ambrisentan/tadalafil FDC was bioequivalent to concurrently administered monotherapies and therefore represents a viable alternative treatment to co-administration. Use of an FDC is likely to be associated with reduced costs and improved patient compliance. ClinicalTrials.gov identifier: NCT02688387.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Okour M,Puri A,Chen G,Port K,Berni A,Khindri S,Schneider I,Tenero Ddoi
10.1016/j.clinthera.2019.04.007subject
Has Abstractpub_date
2019-06-01 00:00:00pages
1110-1127issue
6eissn
0149-2918issn
1879-114Xpii
S0149-2918(19)30171-7journal_volume
41pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Exenatide is an antidiabctic agent currently indicated as adjunctive therapy with oral agents for the treatment of type 2 diabetes mellitus (T2DM). Limited published data exist on the off-label use of exenatide in conjunction with insulin in the treatment of T2DM. OBJECTIVE:The aim of this retrospective stu...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.07.021
更新日期:2009-07-01 00:00:00
abstract:PURPOSE:The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime h...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.05.348
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Aspirin is a widely used NSAID that has been extensively studied in numerous conditions. Nonprescription analgesics, such as aspirin, are frequently used for a wide variety of common ailments, including conditions such as dental pain and tension-type headache. OBJECTIVE:We sought to compare the efficacy and...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2011.11.018
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:Each year in France, varicella and zoster affect large numbers of children and adults, resulting in medical visits, hospitalizations for varicella- and zoster-related complications, and societal costs. Disease prevention by varicella vaccination is feasible, wherein a plausible option involves replacing the com...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.01.006
更新日期:2015-04-01 00:00:00
abstract:OBJECTIVES:The aims of this study were to assess how closely cardiologists in Pakistan followed published recommendations for lipid management and to identify the factors associated with such behavior. METHODS:A cross-sectional survey was delivered in person between September and December 2007 to all cardiologists pra...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.07.020
更新日期:2009-07-01 00:00:00
abstract::As a result of recent advances in our understanding of the role of nitric oxide and endothelial-derived relaxing factor (EDRF) in vascular control, physicians now have the potential to overcome the loss of EDRF effect by administering nitrates. Nitrates are converted to nitric oxide, resulting in vasodilator effects t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1994-03-01 00:00:00
abstract:PURPOSE:Saliva is a reliable, noninvasive, and cost-effective alternative to biomarkers measured in other biological fluids. Within certain populations, saliva sampling may be difficult because of insufficient saliva flow, which may compromise disease diagnosis or research integrity. Methods to improve flow rates (eg, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.02.015
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Besifloxacin is a topical fluoroquinolone with potent in vitro activity against a broad spectrum of ocular pathogens, including drug-resistant strains. Besifloxacin ophthalmic suspension 0.6% given 3 times daily for 5 days has been reported to be more effective than its vehicle in the treatment of bacterial ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2010.12.004
更新日期:2011-01-01 00:00:00
abstract::Recently published guidelines for the treatment of dyspepsia have emphasized the importance of age, Helicobacter pylori infection, and alarm symptoms such as weight loss, anemia, and dysphagia in patient assessment. However, the currently available guidelines were not designed specifically for regions in which the inc...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)70002-5
更新日期:1998-01-01 00:00:00
abstract::Long-term safety and efficacy of feprazone (4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione), an antirheumatic drug that is well tolerated in the gastrointestinal tract, were assessed in a noncontrolled multicenter trial. Administered at a daily dosage of 600 mg for a mean duration of 114.1 days, feprazone was well tolera...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::The acid-neutralizing capacity and sodium content of nine antacid products available in Belgium were evaluated and compared with typical values for Mylanta-II. Liquid and tablets of Mylanta-II have a higher acid-neutralizing capacity per unit dose than do all the other Belgian antacids tested. On a unit dose basis, th...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:In a previous study, we found that past medication use was associated with medication adherence in patients prescribed atypical antipsychotics. OBJECTIVE:The present study aimed to determine whether past medication experience was associated with adherence in patients prescribed selective serotonin reuptake ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.08.014
更新日期:2008-09-01 00:00:00
abstract::Moxifloxacin (BAY 12-8039) is an investigational 8-methoxy-fluoroquinolone with broad-spectrum gram-positive and gram-negative activity. To determine the absolute bioavailability of moxifloxacin, this open-label, randomized, crossover study compared the pharmacokinetic characteristics of a single 100-mg dose administe...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0149-2918(00)88306-X
更新日期:1999-03-01 00:00:00
abstract::The US population is multiethnic in composition: many languages thrive, and Spanish is the second most frequently spoken language. The Hispanic population is one of the fastest growing ethnic groups in the United States. The majority of Hispanics speak Spanish at home (63%), and a significant proportion speak little o...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/0149-2918(95)80054-9
更新日期:1995-07-01 00:00:00
abstract::A multicenter, double-blind clinical evaluation of three formulations of betamethasone dipropionate was conducted in 258 patients with severe psoriasis. The results obtained after a standard two-week treatment period clearly indicated that a new glycol preparation produced significantly greater improvement than the oi...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract:OBJECTIVE:The goal of this health economic analysis was to asses the cost-effectiveness of a fixed combination of aspirin plus extended-release dipyridamole (ASA/ER-DP) or clopidogrel compared with ASA monotherapy for prevention of recurrent ischemic stroke. BACKGROUND:The second European Stroke Prevention Study (ASA/...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)80041-7
更新日期:2000-03-01 00:00:00
abstract::Biotechnology represents an opportunity for innovative products, new markets, or capital investments, depending on one's perspective. A primary consideration in regulating this industry is to ensure that innovation is not stifled yet the public is protected from potentially unsafe or ineffective products. We compared ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND:In 2002, fixed-dose combination therapy (FDCT) with rosiglitazone maleate plus metformin hydrochloride became available for the treatment of type 2 diabetes mellitus (DM-2) in subjects whose disease was uncontrolled on monotherapy with metformin or a thiazolidinedione. FDCT allows a reduced pill burden and a...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2004.12.018
更新日期:2004-12-01 00:00:00
abstract::This prospective, clinical economic study was done to determine the cost impact of oral compared with intravenous (i.v.) ganciclovir for the maintenance treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Efficacy and safety data were extracted from ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(96)80036-1
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:Partial seizure disorder is typically treated by monotherapy with antiepileptic drugs (AEDs). However, when the condition is refractory to the initial treatment regimen, patients may be switched to monotherapy with another AED or to combination therapy with the initial AED plus a second AED. OBJECTIVES:The ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.10.020
更新日期:2005-10-01 00:00:00
abstract:INTRODUCTION:Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous and edematous substrate. Hydroxychloroquine (HHCQ), an antimalarial drug widely used to t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.05.014
更新日期:2008-05-01 00:00:00
abstract::Health care provision in the United States is driven by the fact that most health insurance is commercial and private. This leads to the tendency to view patients as units that will produce a future cash yield. The quality of life (QOL) movement in the United States is in some ways a response to this view and has a ro...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(98)80021-0
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), was approved by the US Food and Drug Administration (FDA) in February 2008 for the treatment of adult patients with major depressive disorder (MDD). Desvenlafaxine is the third SNRI approved by the FDA for this indication. OBJEC...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2009.07.012
更新日期:2009-06-01 00:00:00
abstract:PURPOSE:The incidence of Alzheimer's disease (AD) has been steadily increasing worldwide. AD is a serious disease that has both societal and economic impacts. The greatest risk factor for AD is aging. Thus, because of the rapidly aging population in Japan, the development of new, effective drugs for AD is urgently need...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.02.024
更新日期:2015-08-01 00:00:00
abstract::This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depre...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(97)80066-5
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:Gastrointestinal (GI) symptoms and high dosing frequency have been cited as reasons for inadequate adherence to daily or weekly oral bisphosphonate therapy. Inadequate adherence may lead to poor therapeutic outcomes. OBJECTIVE:The PRIOR study evaluated adherence to and GI tolerability of monthly therapy wit...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.clinthera.2008.04.009
更新日期:2008-04-01 00:00:00
abstract::Faced with rising drug costs and an increase in type-1 beta-lactamase resistance, hospitals have been looking for ways to contain antibiotic costs while continuing to provide quality medical care. The hospital pharmacy at Montefiore Medical Center, Moses Division, has developed a number of programs aimed at identifyin...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:Danazol is a synthetic androgen derivative frequently used as prophylaxis in patients with hereditary angioedema (HAE) due to complement-1 esterase inhibitor deficiency. However, danazol has been reported to decrease high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect coagulation para...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2008.12.021
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Hypersensitivity reactions consist of a variable group of clinical findings and have been described for a wide variety of chemical compounds. OBJECTIVE:This review characterizes the clinical profile of hypersensitivity to the nucleoside reverse transcriptase inhibitor abacavir sulfate. METHODS:We performed...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(01)80132-6
更新日期:2001-10-01 00:00:00
abstract::To determine the cost relative to efficacy and tolerability of two antimicrobial regimens, a prospective, multicenter study compared imipenem-cilastatin (I-C) monotherapy with clindamycin+aminoglycoside (C+A) in the treatment of serious lower respiratory, intra-abdominal, gynecologic, and urinary tract infections. The...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1992-01-01 00:00:00