Abstract：
:Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Zeng Y,Singh S,Wang K,Ahrens RCdoi
10.1002/jcph.1045subject
Has Abstractpub_date
2018-04-01 00:00:00pages
457-465issue
4eissn
0091-2700issn
1552-4604journal_volume
58pub_type
杂志文章abstract：:The clinical effects of a cardioselective beta-adrenergic blocking drug, acebutolol, were studied in 25 patients with chronic stable angina, using a seven-week single-blind placebo leads to acebutolol (mean dose 913 mg/day) phase followed by 12-week randomized double-blind placebo leads to acebutolol (mean dose 968 mg...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1982.tb02688.x
更新日期：1982-08-01 00:00:00
abstract：:It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynam...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270011408611
更新日期：2012-07-01 00:00:00
abstract：:In the pivotal TEMPO 3:4 trial, the arginine vasopressin V2-receptor antagonist tolvaptan reduced the rate of kidney growth in patients with autosomal dominant polycystic kidney disease. Tolvaptan was initiated as daily morning/afternoon doses of 45/15 mg, and uptitrated weekly to 60/30 mg and 90/30 mg according to pa...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.880
更新日期：2017-07-01 00:00:00
abstract：:The steady-state pharmacokinetics of didanosine (DDI) and ketoconazole (KET) were evaluated when the agents were administered alone or concurrently to patients seropositive for the human immunodeficiency virus. Using a randomized, three-way crossover design, multiple oral doses of DDI (375 mg twice daily for 4 days), ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1993.tb01921.x
更新日期：1993-10-01 00:00:00
abstract：:The Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the German drug regulation authority, issued guidelines for determining whether bioavailability/bioequivalence studies are required for certain drugs. This decision tree is based on pharmacodynamic, pharmacokinetic, and physicochemical criteria. Details ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1998.tb04385.x
更新日期：1998-10-01 00:00:00
abstract：:CS-0777 is a selective sphingosine 1-phosphate receptor-1 (S1P(1)) modulator under development for treatment of autoimmune conditions. A randomized, double-blind, placebo-controlled study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CS-0777 in escalat...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011408728
更新日期：2012-07-01 00:00:00
abstract：:Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets. Morphine effects were blocked by thre...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1995.tb04094.x
更新日期：1995-05-01 00:00:00
abstract：:The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV-1-infected children and adolescents. HIV-infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1177/0091270006299089
更新日期：2007-04-01 00:00:00
abstract：:In a double-blind sequential trial, the influence of transdermal electrical nerve stimulation (TENS) was studied in patients who were treated with total infusions of metoclopramide 3.5 mg/kg to counter the emetic action of cisplatin 60-90 mg/m2. Transdermal electrical nerve stimulation further reduced the emetic episo...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1986.tb02918.x
更新日期：1986-02-01 00:00:00
abstract：:Twelve patients chronically maintained on warfarin were administered 80 mg atorvastatin for 2 weeks. Mean prothrombin times decreased slightly, but only for the first few days of the two-week treatment period. Thus atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustment in warfar...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1997.tb04288.x
更新日期：1997-11-01 00:00:00
abstract：:The availability of poisoning information from the pharmaceutical industry was evaluated. Manufacturers of the top 50 drugs were surveyed. Information that was received was classified by established criteria for evaluation. Compendia on poisoning information was evaluated based on 11 components ranging from toxicity i...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1979.tb02474.x
更新日期：1979-02-01 00:00:00
abstract：:Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achiev...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/jcph.766
更新日期：2017-01-01 00:00:00
abstract：:Many drugs have incomplete systemic availability after oral dosage. This can be attributed to incomplete absorption from the gastrointestinal tract, or to presystemic extraction, in which a fraction of an orally administered dose is biotransformed before reaching the systemic circulation. Presystemic extraction can oc...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb04719.x
更新日期：1993-07-01 00:00:00
abstract：:Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid ar...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1990.tb03604.x
更新日期：1990-04-01 00:00:00
abstract：:TAS-303 (4-piperidinyl 2,2-diphenyl-2-[propoxy-1,1,2,2,3,3,3-d7 ] acetate hydrochloride) is a novel selective noradrenaline reuptake inhibitor being developed for the treatment of stress urinary incontinence. An in vitro study and a physiologically based pharmacokinetic model simulation showed that TAS-303 had inhibit...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1583
更新日期：2020-06-01 00:00:00
abstract：:Rapidly inflating health care costs limit patient care, and prescription drug costs constitute a major component of this expenditure. This study examines attitudes toward and knowledge of prescription drug costs of primary care physicians. Access to information about drug costs and implications for medical education a...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04726.x
更新日期：1994-12-01 00:00:00
abstract：:The therapeutic and biochemical effects of two commonly employed diuretic preparations were compared in a double-blind fashion in 32 patients with congestive heart failure. At the doses employed, furosemide and a fixed combination of spironolactone and hydrochlothiazide maintained control of the clinical manifestation...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1977.tb04625.x
更新日期：1977-07-01 00:00:00
abstract：:Sixteen healthy volunteers were given either oral or intravenous doses of aminophylline (125 mg) at 9:00 A.M. and 9:00 P.M. under controlled food conditions. Measured at regular time intervals by homogeneous enzyme immunoassay, the plasma theophylline concentrations 1.5 and 2 hours after oral aminophylline were signif...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb02760.x
更新日期：1984-11-01 00:00:00
abstract：:The effects on the upper gastrointestinal tract of five different preparations of KCl were compared in 90 healthy subjects treated with glycopyrrolate. The KCl preparations studied were wax-matrix KCl, microencapsulated KCl, liquid KCl, experimental extended-release capsules, experimental extended-release tablets,and ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1984.tb02779.x
更新日期：1984-05-01 00:00:00
abstract：:Recent initiatives calling for changes in medical education, such as the General Professional Education of the Physician and Robert Wood Johnson Reports, have recommended alternative teaching approaches to the lecture format. The Patient-Oriented Problem-Solving (POPS) exercises, sponsored by the Upjohn Company (Kalam...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1995.tb04999.x
更新日期：1995-02-01 00:00:00
abstract：:Propafenone and its 5-hydroxy metabolite exhibit different electrophysiological properties. Objectives of the CAQ-PAF study were (1) to develop a strategy favoring propafenone instead of 5-hydroxypropafenone in plasma following oral administration of propafenone and (2) to evaluate the potential of low-dose quinidine ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011399574
更新日期：2012-02-01 00:00:00
abstract：:The time course, dose frequency schedule, and dose-response relationship of the citraturic response to orally administered potassium citrate was examined in 22 normal volunteers and 21 patients with uric acid or calcium nephrolithiasis. The slow-release (wax matrix) preparation of potassium citrate produced a rapid an...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb01809.x
更新日期：1984-01-01 00:00:00
abstract：:Nateglinide (Starlix, SDZ DJN 608 or A-4166), a new insulinotropic agent, is intended to be administered prior to a meal in order to improve early insulin release in non-insulin-dependent diabetes mellitus patients. The effects of a meal on the oral bioavailability and pharmacodynamic actions of nateglinide were inves...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912709922007606
更新日期：1999-02-01 00:00:00
abstract：:Plasma concentrations of minaxolone were measured in 15 female patients during and for up to 3 hours after a minaxolone and nitrous oxide anesthetic. Nine patients received a single dose and six patients two or three doses of minaxolone. Plasma minaxolone decay can be described by two-compartment kinetics. Distributio...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02681.x
更新日期：1982-07-01 00:00:00
abstract：:X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.611
更新日期：2016-04-01 00:00:00
abstract：:Aprepitant or its prodrug fosaprepitant, in combination with a corticosteroid and a 5-HT(3) receptor antagonist, are used to prevent chemotherapy-induced nausea and vomiting. This study evaluated the effect of fosaprepitant 150 mg on CYP3A4 metabolism. Fosaprepitant 150 mg has been submitted to regulatory agencies for...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270010387792
更新日期：2011-12-01 00:00:00
abstract：:To enhance protection of humans exposed to long-duration low-gravity environments such as the Space Shuttle and National Aerospace Plane during re-entry or in the short-duration high(-)+Gz environment of fighter aircraft, the effects of +Gz acceleration on cardiovascular hemodynamics must be understood. This study rep...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04991.x
更新日期：1994-05-01 00:00:00
abstract：:The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically ov...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009339189
更新日期：2009-11-01 00:00:00
abstract：:Numerous physiologic variations, including urinary protein excretion, low serum albumin concentrations, and reductions in kidney function (clearance), exist in patients with glomerulonephritis. These factors could alter the disposition of numerous drugs. The purpose of the current article was to review the influence o...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270011413895
更新日期：2012-01-01 00:00:00
abstract：:The safety and efficacy of step-one therapy with enalapril, a new angiotensin-converting enzyme inhibitor, and metoprolol were compared in a double-blind, multicenter study involving 150 patients who had mild to moderate essential hypertension. After a four-week period of placebo run-in, therapy was initiated with twi...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1987.tb03050.x
更新日期：1987-07-01 00:00:00
