Abstract:
PURPOSE:Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur unpredictably, partly due to the pharmacokinetic (PK) variability of oral LD, resulting from gastrointestinal dysfunction and from the effects of food on absorption. CVT-301 is a levodopa inhalation powder for the treatment of OFF period symptoms in patients on oral dopa-decarboxylase inhibitor/LD. PK and safety profiles of single dose CVT-301, administered with oral carbidopa (CD) and oral CD/LD, were examined in patients with Parkinson's disease in the fed state. METHODS:Eligible patients were aged 30-85 years, with a clinical diagnosis of Parkinson's disease and a body mass index of 18-32 kg/m2, and were receiving treatment with a stable regimen that included oral CD/LD (25/100 mg) (total LD, ≤800 mg/d). A high-fat/protein meal was eaten 4-5 h after the administration of the morning oral CD/LD dose. Blood samples for predose PK analysis were obtained after the meal, followed by a single inhaled dose of CVT-301 84 mg (+25 mg of oral CD) or oral CD/LD (25/100 mg) or vice versa in 2 dosing periods in a crossover design. Blood was sampled at 0, 5, 10, 15, 30, and 45 min and at 1, 1.5, 2, 3, and 4 h postdose. Tolerability assessments included treatment-emergent adverse events. FINDINGS:Twenty-three patients were enrolled (65.2% male; 87.0% white; mean age, 69.3 years; mean body mass index, 26.9 kg/m2; mean Parkinson's disease duration, 8.2 years; mean baseline LD dosage, 460.9 mg/d; 73.9% at Hoehn and Yahr stage <2.5). PK analyses were based on LD concentrations without baseline adjustment. Median Tmax values with CVT-301 and oral CD/LD were 15 and 120 min (P < 0.001). Cmax with CVT-301 was lower than with oral CD/LD (590.3 vs 844.3 ng/mL). C10min and C30min values with CVT-301 were approximately twice those with CD/LD (522.9 and 531.5 ng/mL vs 247.3 and 300.9 ng/mL, respectively). %CV for C5min to Cmax with CVT-301 was lower than that with oral CD/LD. The most common treatment-emergent adverse event was cough (CVT-301, 7 patients [30.4%]; oral CD/LD, 1 patient [4.5%]). IMPLICATIONS:PK properties showed that CVT-301 was more rapidly absorbed, with higher plasma LD concentrations in the first 45 min, and demonstrated lower interpatient variability, than was oral CD/LD in the fed condition. The study findings suggest that CVT-301 can be used without regard to food intake. ClinicalTrials.gov identifier: NCT03887884.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Safirstein BE,Ellenbogen A,Zhao P,Henney HR 3rd,Kegler-Ebo DM,Oh Cdoi
10.1016/j.clinthera.2020.04.004subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1034-1046issue
6eissn
0149-2918issn
1879-114Xpii
S0149-2918(20)30190-9journal_volume
42pub_type
杂志文章abstract:PURPOSE:It is unclear whether vitamin D provides any benefit against the pro-inflammatory effects of homocysteine in elderly patients with type 2 diabetes mellitus (T2DM). METHODS:We compared lymphocyte counts for CD3, CD19, CD4, and CD8 subsets between elderly (age ≥65 years) T2DM patients (n = 5098) and nondiabetes ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.08.009
更新日期:2020-10-01 00:00:00
abstract::Of 250 patients undergoing transurethral prostatectomy, 34 had significant bacteriuria after surgery. In 20 patients, including some without significant colonies of bacteria, the same organisms were found before surgery. Closed surgical systems and aseptic techniques can prevent infection from outside the patient, but...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::This paper briefly reviews the extent of current drug coverage for Medicare beneficiaries and describes the most important issues faced by aged beneficiaries who receive or seek drug coverage through a Medicare managed care plan. Changes in payment rates to these plans as a result of the Balanced Budget Act of 1997 ma...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80123-9
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND:Pioglitazone is a peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in type 2 diabetes mellitus. However, it has been associated with fluid retention, peripheral edema, and congestive heart failure, which has become of particular concern. There are no reports in the l...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.08.003
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)80320-x
更新日期:2003-10-01 00:00:00
abstract::Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:PURPOSE:Pain in the neonate is often challenging to assess but important to control. Physicians often must balance the need for optimal pain control with the need to minimize oversedation and prolonged opioid use. Both inadequate pain control and overuse of opioids can have long-term consequences, including poor develo...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2019.07.014
更新日期:2019-09-01 00:00:00
abstract::A prospective, open-label, multicenter, Phase IV study of the efficacy and safety of intravenous (IV) ciprofloxacin (400 mg by 60-minute infusion every 12 hours) in the treatment of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), and skin/skin structure infections (SSSIs) in hospitalized p...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/0149-2918(95)80101-4
更新日期:1995-05-01 00:00:00
abstract::Six hundred forty-eight patients (50.5% men; 49.5% women) with diabetes mellitus on animal-source insulin therapy for at least five years were studied. In this patient population, approximately 68.7% had Type I insulin-dependent diabetes mellitus and 31.3% had Type II noninsulin-dependent diabetes mellitus, nonetheles...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The in vitro activity of Ro 09-1428, a new parenteral cephalosporin, was compared with that of other beta-lactams and aminoglycosides in 1230 clinical isolates from 1028 consecutive patients. Using an agar dilution method, the drugs were tested against 625 isolates of Enterobacteriaceae, 68 Pseudomonas aeruginosa, 36 ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1992-07-01 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::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
abstract::A single-blind comparison was undertaken to evaluate 250 mg of cinoxacin and 100 mg of nitrofurantoin, both drugs being given four times a day, for the treatment of urinary tract infections. Complete data are available from 58 patients, most of whom were treated for 10 to 15 days. The clinical response was similar in ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::A double-blind, randomized, placebo-controlled trial was undertaken to evaluate the effect of penicillin on the pneumococcal carrier state of 32 men with chronic bronchitis. Treatment consisted of 250-mg phenoxymethyl penicillin or placebo tablets taken by mouth twice daily for periods of one to three years. Penicilli...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:PHX1149 is a dipeptidyl peptidase-4 (DPP4) inhibitor that is currently in clinical development for the treatment of type 2 diabetes mellitus. PHX1149 is a small (molecular weight = 241.16 Da), highly water-soluble (>2 g/mL), orally active molecule with a selectivity index of 15- to 319-fold relative to those...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2007.08.005
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:In diabetes mellitus, the clinical goal of intensive glycemic control (lowering blood glucose concentrations to normal or near-normal levels) has been hindered by the lack of insulin regimens that duplicate the basal-bolus secretion of insulin by the healthy pancreas. In particular, intensive therapy has bee...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(01)80148-x
更新日期:2001-12-01 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:BACKGROUND:Endotracheal intubation and mechanical ventilation are major components of routine intensive care for very low birth weight newborns and sick full-term newborns. These procedures are associated with physiologic, biochemical, and clinical responses indicating pain and stress in the newborn. Most neonates rece...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2005.06.019
更新日期:2005-06-01 00:00:00
abstract:PURPOSE:Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. METHODS:Pati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.10.013
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:Our aim was to develop and validate the extrapolative performance of a regression model using a limited sampling strategy for accurate estimation of the area under the plasma concentration versus time curve for saroglitazar. METHODS:Healthy subject pharmacokinetic data from a well-powered food-effect study (fa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2018.01.016
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:The genetic polymorphism was one of the major considerations for adjusting doses of warfarin in Thai individuals. As a result, new oral anticoagulants (NOACs) were introduced to achieve therapeutic goals in stroke prevention in atrial fibrillation (SPAF) patients. However, a cost-utility analysis in a populatio...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.08.016
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:The objective of this study was to characterize the population pharmacokinetics of voriconazole and to identify factors that significantly affect pharmacokinetic parameters and to further investigate optimal dosage regimens in Chinese adult patients with hematologic malignancies. METHODS:A prospective populati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.04.027
更新日期:2019-06-01 00:00:00
abstract:PURPOSE:This observational study of oncologic clinical practices was designed to describe real-world patterns of use of emerging therapies (abiraterone acetate, cabazitaxel, enzalutamide, radium-223, sipuleucel-T) in patients with castration-resistant prostate cancer and to characterize their concomitant use with denos...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.12.015
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against both wild-type HIV and viruses harboring NNRTI resistance. Etravirine is mainly eliminated via the hepatobiliary route. OBJECTIVES:This study in HIV- patients with mild or moderate hepatic impairment and healthy mat...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.02.013
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Interferon (IFN) alfa is a clinically effective therapy used in a wide range of viral infections and cell-proliferative disorders. Combination therapy with IFN alfa-2b and ribavirin is the current standard of care for the treatment of chronic hepatitis C (CHC) infection. However, standard IFN alfa has the dr...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(02)80042-x
更新日期:2002-09-01 00:00:00
abstract::Two studies were conducted to determine the prevalence of Chlamydia trachomatis in the urine and cervical exudates of women with genitourinary symptoms. In the first study, 873 women attending the World Health Organization-Sexually Transmitted Disease Center of the Alfred Fournier Institute, in Paris, were examined. I...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease caused by mutations in the survival motor neuron gene (SMN1) and the leading genetic cause of infant mortality. Currently, there is no effective treatment other than supportive care. OBJECTIVE:This article provides a general overvi...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2013.11.006
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Fever in children is a common and usually benign symptom. It is known that antipyretic treatment is ineffective in the prevention of simple febrile seizures. Caregivers' administration of antipyretic medications to children has been reported, but data concerning the formulations used, actual doses administer...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2006.05.010
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Older adults may have decreased homeostatic reserve, have multiple chronic diseases, and take multiple medications. Therefore, they are at risk for adverse outcomes after receiving a drug that exacerbates a chronic disease. OBJECTIVES:The aims of this study were to compile a list of clinically important dru...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2006.08.006
更新日期:2006-08-01 00:00:00
abstract::Twenty-four patients with pulmonary infections (7 pneumoniae, 17 exacerbations of chronic bronchitis) were treated with a combination of 250 mg of amoxicillin and 125 mg of clavulanic acid supplemented by 500 mg of amoxicillin every eight hours. All patients showed good clinical, roentgenological, and bacteriological ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00