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Flexible Dosing (flexible + dosing)
Selected AbstractsMaintenance of Crohn's disease over 12 months: fixed versus flexible dosing regimen using budesonide controlled ileal release capsulesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2001J. R. B. Green Background: It may be possible to achieve more effective management of Crohn's Disease by introducing a flexible dosage regimen sensitive to patients' needs. Aim: Comparison of the efficacy and tolerability of a fixed vs. flexible budesonide controlled ileal release treatment regimen for the prevention and management of relapse in Crohn's disease patients. Budesonide controlled ileal release is an oral formulation which delivers drug directly to disease sites in the ileum and ascending colon, by preventing more proximal release and absorption. Methods: A randomized, double-blind comparison of a fixed dose of budesonide controlled ileal release (6 mg o.m.) and a flexible dose of budesonide controlled ileal release (3, 6 or 9 mg o.m.) for 12 months, in 143 patients in remission from ileal or ileo,caecal Crohn's Disease. Results: Very low rates of clinical relapse in Crohn's disease were achieved with budesonide controlled ileal release 6 mg o.m. There was no significant difference between the treatment groups with respect to the survival estimate of percentage of treatment failures (flexible group 15%, fixed group 19%; P=0.61). The average consumed dose of budesonide was comparable in both groups (5.8 mg flexible, 6.0 mg fixed). Similar proportions of patients reported adverse events (flexible 100%, fixed 97%). There were 33 serious adverse events (flexible 19, fixed 14) and 13 withdrawals due to significant adverse events (flexible 9, fixed 4). Conclusion: Maintenance treatment with budesonide controlled ileal release 6 mg o.m. is well-tolerated and is associated with low rates of clinical relapse in stable Crohn's disease over 12 months. Flexible dosing remains an option for individual patients, but this study has shown no advantage over a standard fixed dosing regimen. [source] Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010S. Dupont Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source] Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008S. J. Wroe Objectives,,, To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice. Materials and methods,,, Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice. Results,,, An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom. Conclusions,,, Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy. [source] Buprenorphine tapering schedule and illicit opioid useADDICTION, Issue 2 2009Walter Ling ABSTRACT Aims To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. Design This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. Setting Eleven out-patient treatment programs in 10 US cities. Intervention Non-blinded dosing with Suboxone® during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. Measurements The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. Findings At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). Conclusion For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper. [source] A Double-Blind, Placebo-Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol DependenceALCOHOLISM, Issue 10 2010Mary Stedman Background:, This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods:, Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score. Results:, Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ,0.36 with quetiapine and ,0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions:, The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence. [source] An Open-Label Study of the Lidocaine Patch 5% in Painful Idiopathic Sensory PolyneuropathyPAIN MEDICINE, Issue 5 2005David N. Herrmann MBBCh ABSTRACT Objective., Painful idiopathic distal sensory polyneuropathy is common, but has been largely ignored as a model for the evaluation of neuropathic pain therapies. We have therefore conducted a safety, tolerability, and effectiveness study of the lidocaine patch 5% in painful idiopathic distal sensory polyneuropathy. Design., A prospective open-label, flexible dosing, 3-week study period with a 5-week extension. Setting., Peripheral Neuropathy clinics and Anesthesiology Clinical Research Center at a tertiary care facility. Patients., Twenty subjects with a diagnosis of idiopathic distal sensory polyneuropathy (with or without associated impaired glucose tolerance), with a baseline mean pain daily rating of ,4 on a visual analog scale. Intervention., Lidocaine patch 5%, maximum of four patches daily for 18 hours. Main Outcome Measure., Change from baseline week to week 3 mean daily diary pain ratings. Secondary endpoints included assessments of safety and tolerability as well as quality of life measures. Results., Subjects with idiopathic distal sensory polyneuropathy, both with and without impaired glucose tolerance, showed significant improvements in pain and quality of life outcome measures over a 3-week treatment period. These improvements were maintained in a subgroup of patients treated for an additional 5 weeks and permitted a taper of concomitant analgesics in 25% of subjects. The lidocaine patch 5% was well tolerated. Conclusions., The lidocaine patch 5% appeared well tolerated and potentially effective in the management of painful idiopathic distal sensory polyneuropathy. Idiopathic distal sensory polyneuropathy is an appropriate patient population for the conduct of clinical trials of neuropathic pain therapies. [source] Maximizing anticholinergic therapy for overactive bladder: has the ceiling been reached?BJU INTERNATIONAL, Issue 2007Scott A. MacDiarmid SUMMARY Urinary incontinence affects an estimated 20,33% of adults the USA and 55% of the country's elderly [1], having a more substantial impact on the physical and mental dimension of quality of life than other common chronic diseases. Muscarinic receptor antagonists, including oxybutynin, tolterodine, trospium chloride, darifenacin, and solifenacin, are front-line therapies for overactive bladder (OAB), with an efficacy of 65,75% in reducing major symptoms. Strategies to increase the therapeutic index have included behavioural therapy, flexible dosing, and dose escalation, as well as newer formulations that reduce anticholinergic side-effects. Among approved OAB agents, the oxybutynin transdermal-delivery system has been associated with a lower incidence of dry mouth than immediate- and extended-release formulations of traditional agents. With a low propensity for drug interactions and dry mouth, it is a likely candidate for older patients taking multiple medications. The transdermal patch bypasses systemic and first-pass metabolism, avoiding higher plasma concentrations of the active metabolite (N -desethyloxybutynin) thought to be associated with dry mouth symptoms. Anticholinergics have a significant role to play in the management of OAB; newer drugs targeted toward muscarinic receptors, and novel delivery systems, continue to increase the therapeutic index for this condition. [source] Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010S. Dupont Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source] Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008S. J. Wroe Objectives,,, To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice. Materials and methods,,, Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice. Results,,, An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom. Conclusions,,, Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy. [source] Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA studyACTA NEUROPSYCHIATRICA, Issue 3 2009Eric Constant Objective: The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. Methods: In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400,800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. Results: Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. Conclusion: Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode. [source] | ||||||||||