Hypnotic efficacy of a modified triazolodiazepine, brotizolam

Fifty-nine outpatients with insomnia were treated in a 3-week study to assess the safety and efficacy of a new triazolothienodiazepine with a short t1/2, brotizolam. Therapy was initiated with 0.25 mg at night, but by the end of the study all subjects who were receiving brotizolam were taking 0.50 mg. Results indicate brotizolam efficacy as measured by daily subject and weekly physician questionnaires in essentially all sleep parameters, including global subject and physician evaluation of treatment efficacy, sleep latency and sleep maintenance, and quality of sleep. Tolerance to the hypnotic action of brotizolam was not observed after 21 days of daily dosing.     

Ramelteon 8 mg/d versus placebo in patients with chronic insomnia: post hoc analysis of a 5-week trial using 50% or greater reduction in latency to persistent sleep as a measure of treatment effect

BACKGROUND: Ramelteon is a selective MT1/MT2 melatonin receptor agonist approved by the US Food and Drug Administration for insomnia treatment. OBJECTIVE: The aim of this post hoc analysis was to compare the efficacy and tolerability of ramelteon 8 mg/d versus placebo in adults with chronic insomnia. METHODS: This study analyzed data from a previously published 5-week, randomized, double-blind, placebo-controlled study. Patients aged 18 to 64 years with chronic insomnia were randomly assigned to receive ramelteon 8 or 16 mg/d or placebo QD for 5 weeks. Sleep parameters were evaluated using polysomnography at weeks 1, 3, 5, and 6 (placebo runout). In this post hoc analysis, patients who received ramelteon 8 mg (approved dose) or placebo in the original study were evaluated using a primary end point of a=50% reduction from baseline in latency to persistent sleep (LPS). RESULTS: A total of 270 adults (ramelteon 8 mg, 139 patients, mean age, 38.0 years; placebo, 131 patients, mean age, 39.7 years) met the criteria for inclusion in this analysis. One patient from the original study (ramelteon 8-mg/d group) was excluded from the post hoc analysis based on a lack of evaluable LPS data. Ramelteon was associated with significantly greater proportions of patients who achieved a > or = 50% reduction in LPS compared with placebo at weeks 1 (63.0% vs 39.7%; P < 0.001), 3 (63.0% vs 41.2%; P < 0.001), and 5 (65.9% vs 48.9%; P < 0.005). No rebound insomnia or withdrawal effects were observed. Headache (19.4% and 18.3%), fatigue (9.4% and 2.3%), and somnolence (7.9% and 1.5%) were the most common adverse events. CONCLUSIONS: In this post hoc analysis of data from patients with chronic insomnia, a significantly greater percentage experienced a > or = 50% reduction in LPS with ramelteon 8 mg/d versus placebo. This improvement was evident at week 1 and was sustained through 5 weeks of treatment. Ramelteon 8 mg was well tolerated in this study, with no evidence of withdrawal or rebound insomnia.     

Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis

A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200mg once daily (o.d.) (n= 280), lumiracoxib 400mg o.d. (n= 281), naproxen 500 mg twice daily (n= 279) or placebo (n= 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA.     

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (–18 min (P = 0.02)) and WASO (–54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.     

Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study

BACKGROUND: Lisdexamfetamme dimesylate (LDX) is a therapeutically inactive amphetamine prodrug. It was developed with the goal of providing an extended duration of effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Following ingestion, the pharmacologically active d-amphetamine molecule is gradually released by rate-limited hydrolysis. OBJECTIVES: The aims of this study were to assess the efficacy and tolerability of LDX in school-aged children with attention-deficit/hyperactivity disorder (ADHD) treated in the community, and to characterize the duration of action of LDX compared with placebo. METHODS: This Phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study was conducted at 40 centers across the United States. Male and female children aged 6 to 12 years with ADHD were randomly assigned to receive LDX 30, 50, or 70 mg with forced-dose titration, or placebo, PO QD for 4 weeks. Efficacy was assessed using the ADHD Rating Scale Version IV (ADHD-RS-IV), the Conners' Parent Rating Scale (CPR'), and the Clinical Global Impression of Improvement scale. Tolerability was assessed throughout the study. RESULTS: Of the 290 randomized patients (201 boys, 89 girls; mean [SD] age, 9 [1.8] years), 230 completed the trial (LDX 30 mg, n=56; LDX 50 mg, n=60; LDX 70 mg, n=60; and placebo, n=54). The most common reasons for study discontinuation (n=60) were lack of efficacy (LDX 30 mg, 1%; LDX 50 mg, 0%; LDX 70 mg, 1 %; and placebo, 17%) and adverse events (AEs) (LDX 30 mg, 9%; LDX 50 mg, 5%; LDX 70 mg, 14%; and placebo, 1%). Significant improvements in ADHD-RS-IV scores were seen with all doses of LDX compared with placebo (all, P<0.001), and in CPRS scores with all LDX doses versus placebo throughout the day (all, P<0.001 for all comparisons). Efficacy was observed by the first week of treatment, and improvements were observed throughout the day up to approximately 6 PM. The most frequently reported AEs among patients receiving LDX were typical of amphetamine products: decreased appetite (39% with active treatment vs 4% with placebo), insomnia (19% vs 3%), upper abdominal pain (12% vs 6%), headache (12% vs 10%), irritability (10% vs 0%), vomiting (9% vs 4%), weight decrease (9% vs 1%), and nausea (6% vs 3%); most were mild to moderate and occurred in the first week. CONCLUSION: In this population of children with ADHD, treatment once daily with the prodrug LDX at doses of 30 to 70 mg appeared to be effective and had a tolerability profile similar to those of currently marketed extended-release stimulants.     

Impulse magnetic-field therapy for insomnia: A double-blind, placebo-controlled study

This 4-week double-blind, placebo-controlled study assessed the efficacy of impulse magnetic-field therapy for insomnia. One hundred one patients were randomly assigned to either active treatment (n = 50) or placebo (n = 51) and allocated to one of three diagnostic groups: (1) sleep latency; (2) interrupted sleep; or (3) nightmares. Efficacy endpoints were intensity of sleep latency, frequency of interruptions, sleepiness after rising, daytime sleepiness, difficulty with concentration, and daytime headaches. In the active-treatment group, the values of all criteria were significantly lower at study end (P < .00001). The placebo group also showed significant symptomatic improvement (P < .05), but the differences between groups were highly significant (P < .00001). Seventy percent (n = 34) of the patients given active treatment experienced substantial or even complete relief of their complaints; 24% (n = 12) reported clear improvement; 6% (n = 3) noted a slight improvement. Only one placebo patient (2%) had very clear relief; 49% (n = 23) reported slight or clear improvement; and 49% (n = 23) saw no change in their symptoms. No adverse effects of treatment were reported.     

Effect of zolpidem on sleep in women with perimenopausal and postmenopausal insomnia: a 4-week, randomized, multicenter, double-blind, placebo-controlled study

BACKGROUND: Although most adults in the United States obtain less sleep than they need, women report more sleep deprivation throughout their lifetime than do men. The prevalence of self-reported sleep difficulty increases as women make the transition from the premenopausal to the postmenopausal period. OBJECTIVE: The purpose of this study was to assess the clinical efficacy and safety of zolpidem as a treatment for insomnia in perimenopausal and postmenopausal women. METHODS: Women who were perimenopausal or postmenopausal for >or=6 months, who had developed insomnia in conjunction with menopausal symptoms, and who had difficulty maintaining sleep or had nonrestorative sleep for >or=6 months were eligible for this 4-week, multicenter study. Sleep maintenance difficulty had to occur an average of >or=3 nights per week and had to be accompanied by >or=2 nocturnal hot flashes, hot flushes, or night sweats. Patients were randomized in a double-blind fashion to 1 of 2 treatment groups--zolpidem 10 mg or placebo. Capsules were provided in weekly blister cards, and patients were instructed to take 1 capsule each night at bedtime. Patients recorded estimates of their sleep quality and quantity and daytime functioning on daily morning and evening questionnaires, and made weekly global assessments of sleep. RESULTS: The study included 141 women (mean age +/- SD, 50.8 +/- 4.5 years; age range, 39-60 years). Increases in reported total sleep time were significantly greater in the zolpidem group than in the placebo group (P < 0.01) for each treatment week. Wake time after sleep onset and number of awakenings decreased significantly in the zolpidem group compared with the placebo group (P < 0.05). Each week, approximately twice as many patients in the zolpidem group as in the placebo group reported improved sleep (P < 0.001 for each week). The improvement in sleep-related difficulty with daytime functioning was significantly greater in the zolpidem group than in the placebo group (P < 0.05). The effects of zolpidem did not diminish with the duration of treatment. CONCLUSIONS: Zolpidem 10 mg/d was effective and well tolerated in the treatment of menopause-related insomnia in perimenopausal and postmenopausal women.     

Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of topiramate (100 mg/day) compared with placebo for the treatment of chronic migraine. METHODS: This was a randomized, placebo-controlled, parallel-group, multicenter study consisting of 16 weeks of double-blind treatment. Subjects aged 18 to 65 years with 15 or more headache days per month, at least half of which were migraine/migrainous headaches, were randomized 1:1 to either topiramate 100 mg/day or placebo. An initial dose of topiramate 25 mg/day (or placebo) was titrated upward in weekly increments of 25 mg/day to a maximum of 100 mg/day (or to the maximum tolerated dose). Concomitant preventive migraine treatment was not allowed, and acute headache medication use was not to exceed 4 days per week during the double-blind maintenance period. The primary efficacy endpoint was the change from baseline in the mean monthly number of migraine/migrainous days; the change in the mean monthly number of migraine days also was analyzed. A fixed sequence approach (ie, gatekeeper approach) using analysis of covariance was used to analyze the efficacy endpoints. Assessments of safety and tolerability included physical and neurologic examinations, clinical laboratory parameters, and spontaneous reports of clinical adverse events. RESULTS: The intent-to-treat population included 306 (topiramate, n = 153; placebo, n = 153) of 328 randomized subjects who provided at least 1 efficacy assessment; 55.8% of the topiramate group and 55.2% on placebo were trial completers. The mean final topiramate maintenance dose was 86.0 mg/day. The mean duration of therapy was 91.7 days for the topiramate group and 90.6 days for the placebo group. Topiramate treatment resulted in a statistically significant mean reduction of migraine/migrainous headache days (topiramate -6.4 vs placebo -4.7, P= .010) and migraine headache days relative to baseline (topiramate -5.6 vs placebo -4.1, P= .032). Treatment-emergent adverse events occurred in 132 (82.5%) and 113 (70.2%) of topiramate-treated and placebo-treated subjects, respectively, and were generally of mild or moderate severity. Most commonly reported adverse events in the topiramate group were paresthesia (n = 46, 28.8%), upper respiratory tract infection (n = 22, 13.8%), and fatigue (n = 19, 11.9%). The most common adverse events in the placebo group were upper respiratory tract infection (n = 20, 12.4%), fatigue (n = 16, 9.9%), and nausea (n = 13, 8.1%). Discontinuations due to adverse events occurred in 18 (10.9%) topiramate subjects and 10 (6.1%) placebo subjects. There were no serious adverse events or deaths. CONCLUSIONS: Topiramate treatment at daily doses of approximately 100 mg resulted in statistically significant improvements compared with placebo in mean monthly migraine/migrainous and migraine headache days. Topiramate is safe and generally well tolerated in this group of subjects with chronic migraine, a burdensome condition with important unmet treatment needs. Safety and tolerability of topiramate were consistent with experience in previous clinical trials involving the drug.     

Effects on migraine headache of MDL 72,222, an antagonist at neuronal 5-HT receptors. Double-blind, placebo-controlled study

MDL 72,222 (1 alpha H, 5 alpha H-tropan-3 alpha-yl 3,5-dichlorobenzoate), a novel agent with antagonist activity at neuronal 5-HT receptors, was tested as an acute treatment for migraine pain under double-blind, placebo-controlled conditions. Forty-seven patients with common (n = 29) or classical (n = 8) migraine or mixed type with or without a psychogenic component (n = 10) received 20-40 mg MDL 72,222 (n = 24) or placebo (n = 23) intravenously during the headache phase of a migraine attack. MDL 72,222 was consistently superior to placebo in rapidly alleviating the migraine pain. The treatment was remarkably well tolerated. The results are consistent with the hypothesis that the pain of migraine is related to activation of neuronal 5-HT receptors and suggest that compounds such as MDL 72,222, which block neuronal 5-HT receptors, could be useful new therapeutic agents for the management of migraine.     

Montelukast for migraine prophylaxis: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of montelukast 20 mg in the prophylactic treatment of migraine. BACKGROUND: A previous small open-label study in migraine patients suggested prophylactic efficacy for montelukast, an antagonist of the cysteinyl leukotriene receptor that is used in the treatment of asthma. We sought to confirm these findings in a randomized controlled trial. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-groups study enrolled adult migraine outpatients who experienced > or =3 and < or =8 migraine attacks per month for the last 6 months. Patients were entered into a 2-month, single-blind, placebo run-in phase. Only patients who experienced > or =3 migraine attacks in the second month were eligible to enter the subsequent 3-month, double-blind treatment phase of the study. The primary efficacy endpoint was the percentage of patients reporting at least a 50% decrease in migraine attack frequency per month during the double-blind treatment period (months 3-5) compared to baseline (run-in month 2). RESULTS: A total of 93 patients were randomized to montelukast 20 mg and 84 patients to placebo at the end of the placebo run-in month 2; 76 patients on montelukast and 72 patients on placebo completed the double-blind treatment period. Over 3 months of treatment, there was no significant difference between the two groups in the percentage of patients who reported at least a 50% decrease in migraine attack frequency per month: 15.4% for montelukast versus 10.3% for placebo (P= .304). In addition, montelukast 20 mg was not significantly superior to placebo on any of the secondary endpoints. There were no differences between treatment groups for adverse events. CONCLUSION: Montelukast 20 mg was well tolerated in migraine patients but was not an effective prophylactic for prevention of migraine.     

Patterns of depressive symptom response in duloxetine-treated outpatients with mild, moderate or more severe depression

AIMS: This was a post hoc analysis to determine whether baseline severity of depression influenced the efficacy of duloxetine in treating major depressive disorder (MDD) and to better characterise the symptom response profile for duloxetine in patients with mild, moderate or more severe depression. METHODS: Data were pooled from four double-blind, placebo-controlled studies in which outpatients with MDD were randomised to duloxetine (60 mg/day) or placebo for 8-9 weeks. Patients were retrospectively stratified according to baseline 17-item Hamilton Depression Rating scale (HAMD17) total scores: mild=total score相似文献   

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies

OBJECTIVE: To examine the short- and long-term efficacy and tolerability of rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were conducted in patients aged 12 to 17 years. The first study was a randomized, double-blind, placebo-controlled, single-attack study followed by a randomized, 1-year, open-label extension. The second study was a randomized, 1-year, open-label study. In the single-attack study, patients treated a moderate or severe migraine headache and up to two recurrences with rizatriptan 5-mg tablets (n = 234) or placebo (n = 242). Patients were instructed to use the study medication only on nonschool days. Headache severity, associated symptoms, and functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial dose. In the 1-year studies, patients treated up to 6 migraine attacks per month with rizatriptan 5-mg tablets (n = 273), rizatriptan 5-mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was assessed by the patient at 2 hours after the initial dose. In all studies, the primary efficacy measure was pain relief at 2 hours post dose. RESULTS: In the single-attack study, the proportion of patients with pain relief at 2 hours was not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients than expected (about 30%) treated their migraine attacks on the weekend. Among these patients, the proportion with pain relief at 2 hours was significantly higher in the rizatriptan group than in the placebo group (74% vs. 58%, P = 0.022). In the multiple-attack studies, pain relief at 2 hours was achieved in significantly more attacks treated with rizatriptan 5-mg tablet (77%) or with rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was well tolerated in both the studies, with an adverse event profile not significantly different from that of placebo or standard care. CONCLUSIONS: Rizatriptan 5 mg was not more effective than placebo in the treatment of a single migraine attack in adolescents, but appeared to be more effective than standard care for treating multiple attacks occurring over 1 year in these patients. Rizatriptan 5 mg was well tolerated in adolescents during short-term and long-term use.     

Placebo-controlled comparison of single intramuscular doses of ketorolac tromethamine and pethidine for post-operative analgesia

The analgesic efficacy and safety of single doses of 10 mg and 30 mg ketorolac tromethamine and 100 mg pethidine were evaluated in a double-blind, parallel-group study. The drugs were administered intramuscularly to patients experiencing moderate, severe or very severe pain immediately following major abdominal surgery. A total of 129 patients were randomly assigned to receive either active drug (n = 32 for each treatment group) or placebo (n = 33), and the patients assessed pain intensity and pain relief on a visual analogue scale at regular intervals over the following 8 h. During the first 2 h, pethidine had a more rapid onset of action than ketorolac or placebo, and thereafter 100 mg pethidine and 30 mg ketorolac were equally effective. Ketorolac, at a dose of 10 or 30 mg, and 100 mg pethidine were clinically and statistically more effective than placebo, with 30 mg ketorolac having a similar efficacy to 100 mg pethidine over the 8-h study period and 10 mg ketorolac being slightly less effective than 30 mg ketorolac. No serious adverse events were reported.     

Ibuprofen, acetaminophen, and placebo treatment of febrile children

A double-blind, parallel-group, triple-dummy-designed, single-oral-dose study compared the efficacy, tolerability, safety, and dose-response of 5 mg/kg (n = 32) and 10 mg/kg (n = 28) ibuprofen suspension, 10 mg/kg acetaminophen elixir (n = 33), and placebo liquids (n = 34) in 127 children (2 to 11 years of age) with fever (101 degrees to 104 degrees F). Blood samples, oral temperatures, pulse, blood pressure, and respiration were obtained before and 1/2, 1, 2, 3, 4, 5, 6, and 8 hours after the dose was administered. The study was terminated early if oral temperature was greater than 104 degrees F or if it increased 1 degree F above baseline. All agents were well tolerated and more effective than placebo (p less than 0.05) for fever control. Ibuprofen, 10 mg/kg, was favored over 10 mg/kg acetaminophen (p less than 0.05). For temperatures greater than 102.5 degrees F, a dose-response relationship for 5 and 10 mg/kg ibuprofen was demonstrated in terms of percentage of fever reduction and in terms of the initial 2-hour rate of decrease in temperature. Antipyretic efficacy for temperatures greater than 102.5 degrees F was 10 mg/kg ibuprofen greater than 5 mg/kg greater than 10 mg/kg acetaminophen greater than placebo. All treatments were well tolerated. No significant clinical or laboratory abnormalities were noted. Ibuprofen suspension may be a safe and effective antipyretic in children.     

Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To assess the efficacy and safety of topiramate for the prevention of pediatric migraine with or without aura in a double-blind, randomized, placebo-controlled trial. BACKGROUND: Treatment options for pediatric migraine are currently limited, and no migraine preventive agents are approved for use in children in the United States. Topiramate is an effective migraine preventive therapy in adults, as demonstrated in several large, randomized, placebo-controlled trials. METHODS: One hundred and sixty-two children with migraine (age, 6 to 15 years) were randomized in a 2:1 ratio to receive topiramate (n = 112) or placebo (n = 50). This study was designed to ensure that 150 participants were randomized to study medication. An additional 12 qualified patients were randomized because they had successfully completed the screening phase. The double-blind phase of the trial consisted of a titration period and a maintenance period. Topiramate was initiated at 15 mg/day and titrated over 8 weeks to 2 to 3 mg/kg per day, or maximum tolerated dose, whichever was less (maximum allowed dose was 200 mg/day). The target dose was maintained for 12 weeks. The primary efficacy variable was the change in mean number of migraine days per month (28 days) during the double-blind phase relative to the 4-week prospective baseline phase for each treatment group. RESULTS: Topiramate treatment was associated with a mean reduction over the entire double-blind phase of 2.6 migraine days per month, compared with a mean reduction of 2.0 migraine days per month for placebo (P = .061 topiramate vs. placebo). A significantly greater percentage of topiramate patients (32%) experienced a > or = 75% reduction in mean monthly migraine days compared with placebo (14%, P = .02). Discontinuation rates due to adverse events were low: 6.5% for the topiramate group and 4.0% for the placebo group. The adverse events that occurred most commonly in the topiramate group at an incidence rate greater than in the placebo group were: upper respiratory tract infection, anorexia, weight decrease, gastroenteritis, paresthesia, and somnolence. The mean average daily dose of topiramate during the maintenance period was 2.0 mg/kg per day. CONCLUSIONS: This pilot study suggests that topiramate may be an effective migraine preventive therapy in children. Topiramate was well tolerated in this population. Further randomized studies would be required to definitively establish the efficacy of topiramate for pediatric migraine prevention.     

国产扎来普隆治疗失眠症的多中心随机双盲对照研究

目的：评价国产扎来普隆胶囊治疗失眠症的有效性和安全性。方法：多中心、随机、双盲、双模拟、阳性药平行对照研究，209例失眠症患者随机分为扎来普隆组（105例）与唑吡坦组（104例）,分别口服扎来普隆胶囊10mg&#8226;d-1或唑吡坦片10mg&#8226;d-1，疗程14天。结果：睡眠障碍量表总评分在治疗结束时两组较基线均显著减少(p<0.01)；有效率扎来普隆组为62.7%与唑吡坦组为61.0%，差异无显著性 (p>0.05)。扎来普隆较常见的不良反应为：头晕、头昏、口苦，未出现严重的不良反应。结论：国产扎来普隆胶囊治疗失眠症安全、有效。     

Nizatidine versus placebo in active benign gastric ulcer disease: an eight-week, multicenter, randomized, double-blind comparison. The Nizatidine Benign Gastric Ulcer Disease Study Group.

STUDY OBJECTIVE: To determine if 150 mg nizatidine twice daily or 300 mg nizatidine at bedtime are similarly effective and to compare each dose with placebo in healing benign gastric ulcers and relieving peptic ulcer symptoms. METHODS: This study was a randomized, double-blind, placebo-controlled parallel comparison. The study was conducted at 74 gastroenterology and internal medicine clinics in the United States and Canada. Four hundred fifty-six patients with active benign gastric ulcer documented by endoscopy participated in the study. On the basis of a computer-generated randomization list, patients were assigned sequentially to receive either 150 mg nizatidine twice daily (n = 151), 300 mg nizatidine once daily at bedtime and identically appearing placebo capsules in the morning (n = 153), or placebo capsules twice daily (n = 152). Treatment lasted for 8 weeks unless healing was documented by endoscopy after 4 weeks. Antacid tablets (aluminum hydroxide, magnesium hydroxide, simethicone combination) were supplied for relief of symptoms. MEASUREMENTS AND MAIN RESULTS: Both doses of nizatidine significantly improved healing rates at 8 weeks compared with placebo. Daytime and nighttime symptom severity was improved by both nizatidine regimens at end point (p less than 0.015 versus placebo, two-tailed test). Antacid use was similar for all groups in the end point analysis. Patient well-being was significantly better in patients treated with nizatidine than in patients in the placebo group ((p less than 0.04, two-tailed test). No clinically significant differences in the incidence of adverse clinical or laboratory events were noted. CONCLUSION: Nizatidine, 300 mg at bedtime and 150 mg twice daily, resulted in greater healing of benign gastric ulcers than placebo treatment after 8 weeks. Relief of the symptoms of gastric ulcer was significantly better in the patients receiving nizatidine treatment versus placebo treatment.     

Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials

A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine. As early as 30 min after dosing, almotriptan 12.5 mg was significantly more effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free (2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for placebo. All almotriptan dosages were significantly more effective than placebo in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained pain relief up to 24 h (P < 0.05). The incidence of adverse events after almotriptan 6.25 mg and 12.5 mg was not significantly different from that of placebo. This meta-analysis confirms the findings of individual clinical trials, while demonstrating for the first time, significant pain-free efficacy at 30 min compared with placebo.     

Randomized, Controlled Trial of Inhaled Budesonide as an Adjunct to Oral Prednisone in Acute Asthma

Objective: To compare the clinical effect of nebulized budesonide with placebo in acute pediatric asthma.
Methods: A randomized, controlled, double-blind trial with parallel design was used in the ED of a tertiary care children's hospital. Children aged 6 months to 18 years with a moderate to severe exacerbation of asthma [Pulmonary Index Score (PIS) ≥5 or ≤11 after a salbutamol nebulization of 0.15 mg/kg] were eligible. All patients received prednisone 1 mg/kg orally and nebulized salbutamol (0.15 mg/kg) every 30 minutes for 3 doses and then every hour for 4 hours. The intervention was 2 mg (4 mL) of nebulized budesonide or 4 mL of nebulized normal saline.
Results: Baseline characteristics were comparable in the budesonide group ( n = 24) and in the placebo group ( n - 20). There were no significant differences in the primary outcome measure (PIS) between the 2 groups. However, the PIS at 1 hour had a tendency to be lower in the budesonide group (median = 5) as compared with the placebo group (median = 6; p = 0.07). Survival analysis of release/discharge from the ED/hospital showed a more rapid rate in the budesonide group as compared with the placebo group (p = 0.02). No adverse effects were seen.
Conclusion: Although these preliminary results suggest that nebulized budesonide may be an effective adjunct to oral prednisone in the management of moderate to severe asthma exacerbations, a larger trial will be required before the widespread use of inhaled budesonide in acute asthma can be advocated.     

Efficacy and tolerability of valdecoxib in treating the signs and symptoms of severe rheumatoid arthritis: a 12-week, multicenter, randomized, double-blind, placebo-controlled study

OBJECTIVE: This study compared the efficacy and tolerability of the cyclooxygenase-2-selective inhibitor valdecoxib with the nonselective NSAID naproxen and with placebo in treating severe rheumatoid arthritis (RA). METHODS: This 12-week, multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and tolerability of valdecoxib 10 mg QD (n = 170) or naproxen 500 mg BID (n = 167) with placebo (n = 171) in treating the signs and symptoms of severe RA. Study patients were aged >or=18 years and were diagnosed as having RA for >or=6 months that was stable due to a treatment regimen. Severe RA was defined as a physician's and patient's global assessment of disease activity of fair, poor, or very poor at baseline; >or=6 tender or painful joints; >or=3 swollen joints; >or=45 minutes of morning stiffness; a visual analog scale pain rating of >or=40 mm; or increases since baseline in these measures. Efficacy outcome measures included the percentage of patients achieving an American College of Rheumatology Responder Index 20% (ACR-20) at weeks 1, 6 and 12. Adverse events (AEs) were graded by the investigator as mild, moderate, or severe at weeks 1, 6, and 12. RESULTS: Of the 508 patients randomized, 340 completed the study. The study groups were comparable for age, ethnic origin, weight, height, and concomitant medications, but the naproxen group had significantly more men (29% [49/167]) than the valdecoxib (18% [31/170]) and placebo (16% [27/171]) groups. The percentage of patients achieving an ACR-20 response was significantly greater in the valdecoxib and naproxen treatment groups (58.8% [100/170] and 60.8% [101/166], respectively) than in the placebo group (39.6% [67/169]) at week 12 (both, P < 0.001). The percentage of patients achieving an ACR-20 response was significantly greater in the naproxen group than in the placebo group at both week 1 (53.6% [89/166] vs 37.9% [64/169]; P = 0.003) and week 6 (64.5% [107/166] vs 46.7% [79/169]; P = 0.001), and in the valdecoxib group compared with placebo at week 1 (52.9% [90/170]; P = 0.008) but not at week 6. Patients in the valdecoxib and naproxen groups had significantly improved efficacy compared with placebo in most of the other secondary assessments of inflammation, pain, and function. The incidence of AEs was similar in all groups (valdecoxib, 54.1% [92/170]; naproxen, 55.4% [92/166]; and placebo, 52.9% [90/170]). CONCLUSION: Valdecoxib 10 mg QD administered over 12 weeks was significantly better than placebo and similar to naproxen 500 mg BID in treating the signs and symptoms of severe RA in these patients.