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PubMed1987

Misoprostol in the treatment of duodenal ulcer refractory to H2-blocker therapy. A placebo-controlled, multicenter, double-blind, randomized trial.

A multicenter, double-blind, randomized study compared 200 micrograms of misoprostol and placebo four times daily for four weeks in the treatment of 225 patients with duodenal ulcer (0.7 cm to 2.0 cm in size) persisting after at least four weeks of adequate, conventional therapy with cimetidine or ranitidine. Misoprostol was significantly superior to placebo in healing duodenal ulcers (achieving a healing rate of 37 percent versus 22 percent in the placebo group [p = 0.02], and in relieving ulcer pain [p = 0.01]). Healing also occurred more frequently with misoprostol than with placebo in patients with subgroups of particularly resistant ulcers. In the treatment of ulcers refractory to at least eight weeks of histamine H2-blocker therapy, misoprostol achieved a healing rate of 42 percent versus 20 percent with placebo. In the treatment of pyloric channel ulcers, 28 percent of patients in the misoprostol group showed healing as compared with 20 percent in the placebo group. Diarrhea was reported by 15.4 percent and 3.4 percent of patients receiving misoprostol and placebo, respectively, and was usually mild and transient. Misoprostol is safe and effective therapy for duodenal ulcers that have not healed during the course of H2-blocker therapy.

Adolescent↗
PubMed1993

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine.

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Adult↗
PubMed1991

Adjunctive clindamycin therapy for preterm labor: results of a double-blind, placebo-controlled trial.

A double-blind, placebo-controlled, randomized trial was conducted to evaluate the efficacy, safety, and tolerance of a course of clindamycin (administered for 3 days intravenously and 4 days orally) among hospitalized women with preterm labor at less than or equal to 34 weeks' gestation who were treated with tocolytics. One hundred three woman-perinate pairs were analyzed. Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo (clindamycin-treated group, 35 days; placebo-treated group, 25 days; p = 0.02). Survival analysis showed that pregnancy continued at least 35.5 days in 50% of clindamycin-treated women versus 20 days for control women (p = 0.03). Obstetric and microbiologic parameters associated with treatment outcomes were also sought. Women with bacterial vaginosis more often delivered preterm (p = 0.03; relative risk, 1.4; 95% confidence interval, 1.04 to 2.0). Among women with bacterial vaginosis, trends for increased duration of pregnancy (clindamycin-treated group, 36 days; placebo-treated group, 19 days), increased birth weight (clindamycin-treated group, 2634 gm; placebo-treated group, 2256 gm), and increased mean gestational age at delivery (clindamycin-treated group, 35 weeks; placebo-treated group, 34 weeks) were associated with clindamycin treatment. Women with either group B streptococcus, Chlamydia trachomatis, Trichomonas vaginalis, or Staphylococcus aureus were more likely to have preterm premature rupture of membranes (p = 0.01). Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects. Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks' gestation (clindamycin-treated group, 40 days; placebo-treated group, 28 days; p less than 0.05). Treatment with clindamycin appeared safe and well tolerated, with benefits limited to women who were less than or equal to 32 weeks' gestation.

Chemotherapy, Adjuvant↗
PubMed1990

Randomized, double-blind, placebo-controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding.

A randomized, double-blind, placebo-controlled trial of somatostatin was conducted among 120 patients admitted for bleeding esophageal varices (59 placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin followed by a 5-day continuous infusion of 250 micrograms/h and an identical administration of placebo were evaluated for both the control of bleeding and prevention of early rebleeding from varices. Failure to control bleeding occurred in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to failure occurring earlier with placebo (P = 0.036). blood and plasma transfused per hour during drug infusion of trial drug was reduced in the somatostatin group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was halved in somatostatin-treated patients. The average effect of somatostatin was a 41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P = 0.0545) after adjustment for the severity of liver disease, which was the only other variable having a significant influence on time to failure. There was no difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or complications. It is concluded that somatostatin is safe and more effective than placebo for the control of variceal bleeding.

Adolescent↗
PubMed1992

Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study.

The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet (Vagifem, Novo Nordisk A/S) on the symptoms of the vagina related to atrophy. The study was designed as a double-blind randomized placebo controlled study running for 12 weeks. The women were treated once daily for 2 weeks with the active or the placebo tablet. During the subsequent 10 weeks the women were treated twice a week. One hundred and sixty-four women were included. Ten dropped out for minor reasons, most of these due to lack of effect in the placebo group. In the Vagifem group 78.8% were suffering from moderate to severe atrophy of the vagina, compared with 81.9% in the placebo group. After 2 weeks the percentages were 14.3 and 35.3, respectively. After 12 weeks of treatment, 10.7% in the Vagifem group compared with 29.9% in the placebo group had moderate to severe atrophy (P less than 0.0001). A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia. After 12 weeks of treatment, a significant improvement was found in the Vagifem group (P less than 0.002). Before treatment 53.1% in the treatment group and 41.0% in the placebo group were suffering from urological symptoms. After 2 weeks, 60.5% of the women in the Vagifem group underwent a change for the better compared to 35.3% in the placebo group. After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8% and 32.4%. In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy.

Administration, Intravaginal↗
PubMed1989

Efficacy and safety of loratadine (10 mg once daily), terfenadine (60 mg twice daily), and placebo in the treatment of seasonal allergic rhinitis.

A total of 317 patients received loratadine, 10 mg once daily, terfenadine 60 mg twice daily, or placebo in a 14-day, double-blind, randomized study in seasonal allergic rhinitis. Four nasal and four nonnasal symptoms were evaluated. At the end point evaluation, mean total scores of combined nasal and nonnasal symptoms decreased from baseline (improved) 46%, 44%, and 35%, respectively, for loratadine, terfenadine, and placebo. The difference between loratadine and placebo treatment was significant (p = 0.03). Loratadine was particularly effective compared with placebo in relieving nasal discharge, sneezing, and itching/burning eyes. Therapeutic response to treatment was good or excellent in 66 (64%) of 103 loratadine-treated patients, 58 (56%) of 104 terfenadine-treated patients, and 48 (47%) of 102 placebo-treated patients. Adverse experiences reported during the study were usually mild or moderate and were not significantly different among the three treatment groups. Sedation (somnolence) was reported by 10 loratadine-treated patients, seven terfenadine-treated patients, and eight placebo-treated patients. Loratadine, 10 mg once daily, was comparable to terfenadine, 60 mg twice daily, and significantly superior to placebo in the symptomatic relief of seasonal allergic rhinitis.

Adolescent↗
PubMed1993

Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo.

This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode, Dysthymia, or Depressive Disorder NOS. The study's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam, imipramine and placebo on anxiety outcomes. A placebo-controlled, double-blind, parallel random assignment design was utilized over a total of 16 weeks. There was no medication effect on panic outcomes. At endpoint, percent of anticipatory anxiety (i.e., time spent worrying about having an anxiety attack) was significantly lower in the patients taking active medications vs. placebo. Phobic measures were significantly improved by alprazolam, vs. both imipramine and placebo early in the study; however, by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms. In addition, both active medications were significantly more effective than placebo in reducing depression. The same efficacy pattern (i.e., active medications superior to placebo) was observed on measures of general functioning. Importantly, there were no significant interactions observed between medication and presence of major depression on the depression measures, indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression. Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range, these results may not be transferrable to patients with panic disorder and severe major depression.

Adult↗
PubMed1988

Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression.

Adinazolam, a triazolobenzodiazepine, was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives. Forty-eight patients entered the study, and 35 completed 6 weeks of evaluation. Patients were well matched in each of the groups. Initially, the adinazolam group showed more improvement than the placebo group, but this trend did not persist beyond day 7. The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups, and final scores were significantly better for amitriptyline. Depressive symptoms in the amitriptyline dropout group appeared improved, whereas in the adinazolam and placebo dropout groups they were unchanged or worse. Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo. Thus, amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo.

Adolescent↗
PubMed1993

Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators.

OBJECTIVES: This study was performed to assess the efficacy, safety and clinical consequences of abrupt cessation of quinapril therapy in a placebo-controlled, randomized, double-blind withdrawal trial. BACKGROUND: Angiotensin-converting enzyme inhibitor therapy has assumed a pivotal role in the treatment of chronic heart failure. Quinapril hydrochloride, a nonsulfydryl angiotensin-converting enzyme inhibitor, has shown beneficial clinical effects in previous studies. METHODS: After > or = 10 weeks of single-blind quinapril therapy, 224 patients with New York Heart Association class II or III heart failure were randomized in double-blind fashion to continue quinapril (n = 114) or to receive placebo (n = 110) for 16 weeks. Changes in treadmill exercise time, New York Heart Association functional class, quality of life and symptoms of heart failure were assessed. RESULTS: Patients withdrawn to placebo had a significant deterioration in exercise tolerance (median change -16 s with placebo vs. +3 s with quinapril, p = 0.015). New York Heart Association functional class (p = 0.004) and quality of life were improved and signs and symptoms of congestive heart failure were lessened in those remaining on quinapril therapy compared with those receiving placebo. During double-blind treatment, 18 patients were withdrawn from the placebo group because of worsening heart failure compared with 5 patients withdrawn from quinapril treatment (p < 0.001). Rather than a precipitous deterioration of clinical status or early incidence of adverse events, withdrawal from quinapril was associated with steady worsening of heart failure, beginning 4 to 6 weeks after randomization to placebo. CONCLUSIONS: Quinapril is effective and safe for maintaining clinical stability in patients with moderate congestive heart failure. Withdrawal of quinapril from patients with heart failure results in a slow progressive decline in clinical status.

Aged↗
PubMed1995

Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study.

OBJECTIVES: The aim of this double-blind, placebo-controlled, dose titration, multicenter trial was to assess the efficacy and safety of propionyl-carnitine in intermittent claudication. BACKGROUND: Human and animal studies indicate that propionyl-L-carnitine increases carnitine content and improves energy metabolism in the ischemic skeletal muscle. METHODS: After a 2-week preliminary period to assess maximal walking distance, 245 patients were randomly assigned to receive propionyl-L-carnitine (n = 118) or placebo (n = 127). The initial oral dose of 500 mg twice daily was increased at 2-month intervals to 2 g/day and then to 3 g/day in patients showing improvement in treadmill performance < 30% over baseline. Efficacy analysis was conducted for the 214 patients who completed the 24 weeks of treatment by comparing the effect of placebo and propionyl-L-carnitine on day 180. RESULTS: Analysis of variance showed a significant improvement of 73 +/- 9% (mean +/- SE) in maximal walking distance with propionyl-L-carnitine (n = 99) compared with 46 +/- 6% for placebo (n = 115, p = 0.03). For distance walked at onset of claudication, propionyl-L-carnitine showed about double the improvement of placebo; however, the difference was not statistically significant. There were no changes in electrocardiographic and routine biochemical and hematologic tests that would indicate an adverse effect of propionyl-L-carnitine. Adverse events requiring drug discontinuation (11 in the propionyl-L-carnitine group, 3 in the placebo group) were unrelated to study medication. The dose titration design of the study also provided information on the dose-response relation. Slightly less than 67% of patients were expected to improve their maximal walking distance by at least 30%, assuming 2 g/day of propionyl-L-carnitine (95% confidence interval 0.51 to 0.70). The response rate during the entire titration course was significantly in favor of propionyl-L-carnitine compared with placebo. CONCLUSIONS: Although the precise mode of therapeutic action requires clarification, propionyl-L-carnitine, at a dose of 1 to 2 g/day, appears to be effective and well tolerated, with minimal adverse effects.

Administration, Oral↗
PubMed2005

Efficacy and safety of a once-daily graded-release diltiazem formulation dosed at bedtime compared to placebo and to morning dosing in chronic stable angina pectoris.

BACKGROUND: The efficacy and safety of a once-daily graded-release diltiazem hydrochloride (GRD) formulation dosed at 10 PM in doses of 180, 360, and 420 mg were compared with placebo and with GRD 360 mg dosed once daily at 8 AM in patients (n = 311) with chronic stable angina pectoris. METHODS: This was a 3-week multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled trial. Standard Bruce protocol treadmill stress test was performed at baseline and end point between 6 and 8 PM (trough for evening doses) and between 7 and 11 AM (trough for morning doses). RESULTS: All GRD evening doses showed a significant (P < or = .0201) increase in total duration of exercise at trough and a greater significant increase (P < or = .0002) at peak, compared with placebo. The GRD 360-mg evening dose showed the greatest increase at trough. In contrast, GRD 360-mg morning dose showed an increase in total duration of exercise at trough that was not significantly different (P = .0555) from placebo AM. GRD 360-mg evening dose showed a 4-fold placebo-adjusted improvement compared with GRD 360-mg morning dose between 7 and 11 AM. Significant increases (P < or = .0240) in time to onset of angina were obtained for all evening doses at trough and peak. All GRD doses were well tolerated, and incidence of adverse events for all GRD groups combined was less than that for placebo. CONCLUSIONS: Bedtime GRD significantly increases exercise tolerance in patients with angina pectoris over the 24-hour dosing interval. A greater 4-fold placebo-adjusted improvement occurred between 7 and 11 AM compared with the same morning dose, coinciding with the period of increased cardiovascular risk. GRD was safe and well tolerated.

Adult↗
PubMed2026

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA na&#xef;ve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration &#x2265; 3 mg/L, and &#x2265; 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans↗
PubMed2004

A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns.

INTRODUCTION: Early excision and skin grafting has become the standard of good burn management, but it is associated with major blood loss. AIM: To determine the haemostatic effect of terlipressin compared with placebo. MATERIAL AND METHODS: Fifty-one patients with burns of 10-20% total body surface area had early excision and split skin grafting of deep burns. The surface area of the burn wound and of the healed graft were measured by planimetry. The patients were randomly allocated to medication, either terlipressin or placebo. Blood loss and number of transfused units of blood were recorded. RESULTS: Twenty-one patients received terlipressin, 13 received terlipressin late (cross-over) and 17 received placebo. Six out of 21 patients exposed to terlipressin were transfused with eleven units of packed red blood cells. Seven out of 13 patients crossed over from placebo to terlipressin (late terlipressin) were transfused with 17 units of blood. Eight out of 17 patients exposed to the placebo were transfused with 22 units of blood (P < 0.05). Graft healing was 1055 +/- 609 cm2 out of 1452 +/- 11 cm2 in terlipressin and 914 +/- 633 cm2 out of 1288 +/- 720 cm2 in the placebo group (n.s.). CONCLUSION: Terlipressin reduced the need for blood transfusion by a factor of 2.5 compared to a placebo without impairment of graft healing.

Adolescent↗
PubMed2005

Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone.

This analysis used pooled data from three randomized, placebo-controlled trials that examined the efficacy and safety of risperidone for the treatment of agitation, aggression, and psychosis associated with dementia in elderly nursing home residents to assess the risk-benefit of the use of risperidone in this population. The efficacy data (risperidone n=722, placebo n=428) were obtained from the Cohen-Mansfield agitation inventory (CMAI) and behavioral pathology in Alzheimer's disease (BEHAVE-AD) total and subscales. Additionally, clinical global impression (CGI) assessments were performed. Subgroup analyses were performed by type of dementia, severity of dementia, presence or absence of somnolence as an adverse event, and presence or absence of psychosis at baseline. Safety assessments included evaluation of treatment emergent adverse events, Extrapyramidal Symptom Rating Scale, ECG and vital signs, and Mini-Mental State Examination (MMSE). The mean dose of risperidone at end point was 1.0 mg/day (0.02 S.E.). The observed mean change at end point was significantly higher for risperidone than for placebo on CMAI total score (-11.8 versus -6.4, respectively; p<0.001), total aggression score (-5.0 versus -1.8, respectively; p<0.001), BEHAVE-AD total score (-6.1 and -3.6, respectively; p<0.001), and psychotic symptoms score (-2.1 and -1.3, respectively; p=0.003). The main treatment effects of risperidone were similar in all subgroup analyses. Additionally, risperidone-treated patients scored significantly better than placebo-treated patients on the CGI scales at end point. The incidence of treatment-emergent adverse events was comparable between risperidone (84.3%) and placebo (83.9%). More patients discontinued due to adverse events in the risperidone-treated group (17.2%) than in the placebo group (11.2%). Differences in adverse event incidences between placebo and risperidone were observed for extrapyramidal symptoms (EPS), mild somnolence and the less common cerebrovascular adverse events (CAE). Risperidone induced neither orthostatic, nor anticholinergic side effects nor falls nor cognitive decline. Of all atypical antipsychotics, risperidone has the largest database of double-blind controlled trials to support its efficacy and safety in the treatment of agitation, aggression, and psychosis associated with dementia. At the recommended doses, risperidone displayed a favorable risk-benefit profile. Risperidone was well tolerated with respect to EPS, somnolence, and anticholinergic side effects in this elderly population. In view of the risk for CAEs, risperidone, should be targeted towards the treatment of those patients in whom psychotic and behavioral symptoms of dementia are prominent and associated with significant distress, functional impairment or danger to the patient.

Aged↗
PubMed2004

Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of postoperative pain: a double-blind, placebo- and active-controlled parallel-group study.

OBJECTIVE: This study compared the efficacy and safety of a single dose of oxycodone 5 mg/ibuprofen 400 mg versus its individual components and placebo in a third-molar extraction model. METHODS: In this multicenter, double-blind, double-dummy, parallel-group investigation, subjects with moderate to severe pain within 5 hours after extraction of > or =2 ipsilateral bony impacted third molars were randomized to single doses of oxycodone 5 mg/ibuprofen 400 mg, ibuprofen 400 mg, oxycodone 5 mg, or placebo. Primary efficacy variables were the sum of pain intensity difference over 6 hours (SP1D6) and total pain relief through 6 hours (TOTPAR6). The pharmacokinetics of oxycodone and ibuprofen, alone and in combination, were also determined in a subset of patients. RESULTS: A total of 498 subjects were randomized to treatment (187 to oxycodone 5 mg/ibuprofen 400 mg, 186 to ibuprofen 400 mg, 63 to oxycodone 5 mg, and 62 to placebo). Baseline demographics were generally similar among treatment groups, despite differences in sex (P = 0.041) and race (P = 0.023). Combination therapy was associated with greater analgesia than ibuprofen alone, oxycodone alone, or placebo (mean [SE] TOTPAR6: 13.3 [0.52], 12.2 [0.52], 4.3 [0.82], and 4.2 [0.83], respectively [P < 0.001 vs oxycodone or placebo, P = 0.012 vs ibuprofen]; mean [SE] SP1D6: 6.54 [0.42], 5.41 [0.44], 0.14 [0.60], and 0.32 [0.59], respectively [P < 0.001 vs oxycodone or placebo, P = 0.002 vs ibuprofen]). Combination therapy was well tolerated. Pharmacokinetic results implied no interaction between oxycodone and ibuprofen. CONCLUSIONS: In this study, a single dose of oxycodone 5 mg/ibuprofen 400 mg was fast-acting, effective, and well tolerated in subjects with moderate to severe pain after dental surgery. Oxycodone 5 mg alone did not provide an efficacy benefit over placebo in this study.

Adult↗
PubMed2005

Psychomotor performance in healthy young adult volunteers receiving lormetazepam and placebo: a single-dose, randomized, double-blind, crossover trial.

BACKGROUND: Lormetazepam is a hypnotic benzodiazepine currently used in the treatment of insomnia. When this agent is used appropriately, its pharmacologic properties predict a high therapeutic index with a good tolerability profile. OBJECTIVE: The primary aim of this study was to compare the effects on psychomotor performance of lormetazepam and placebo in healthy young adult subjects. A secondary objective was to evaluate the clinical tolerability of lormetazepam. METHODS: This was a randomized, double-blind,placebo-controlled, crossover study in healthy young adult volunteers. All volunteers received single doses of lormetazepam 1 mg and placebo, with a 1-week interval between doses. The primary study variables were visual simple reaction time (VSRT) and visual choice reaction time (VCRT), measured before dosing with lormetazepam or placebo and at 20, 60, 120, 180, 240, and 360 minutes after dosing using a standard computerized apparatus. To increase the sensitivity of the results, visual reaction times were also recorded using a validated mobile computerized device. Secondary variables were the duration and quality of sleep on the night before each study session, rated by subjects using a 100-mm visual analog scale; the Epworth Sleepiness Scale for daytime drowsiness; and the Critical Flicker Fusion Threshold test. Spontaneously reported adverse events were recorded and monitored throughout the study. RESULTS: The study included 18 healthy young adult volunteers (12 women, 6 men; mean [SD] age, 26.7 [2.8] years [range, 21-30 years]; mean body weight, 58 [9.5] kg). There were no significant differences in either VSRT or VCRT after administration of lormetazepam or placebo. Independent of study drug but consistent with the accepted range of variability between the 2 devices, overall reaction times were significantly shorter with the use of the mobile device compared with the standard apparatus (P < 0.01). Analysis of the results showed no sequence effects or other evidence of learning. There were no changes in the secondary study variables after administration of the test drugs. Administration of lormetazepam was associated with dizziness in 2 subjects, in 1 case occurring in association with somnolence. These adverse events were mild and subsided spontaneously 3 hours after drug intake. After administration of placebo, 1 subject reported slight somnolence 60 minutes after dosing that persisted through 180 minutes. CONCLUSION: In this small, selected group of healthy young adult subjects, a single dose of lormetazepam 1 mg did not affect psychomotor performance, assessed in terms of visual reaction times, compared with placebo.

Adult↗
PubMed2005

Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of pain after abdominal or pelvic surgery in women: a randomized, double-blind, placebo- and active-controlled parallel-group study.

BACKGROUND: The sensation of pain arises from both central and peripheral sites, and inflammation may be one of its underlying causes. Combination therapy with analgesic agents having multimodal mechanisms of action and complementary pharmacokinetic properties enhances pain relief by addressing the different pathways of pain while limiting individual drug doses and, therefore, the potential for adverse effects caused by any single agent. Oxycodone and ibuprofen each have been used effectively as monotherapy and in other combinations for the treatment of acute pain; a fixed combination of these analgesics may improve pain relief in the setting of abdominal or pelvic surgery, where trauma and any resultant inflammation may be present at the same time. OBJECTIVE: This study evaluated and compared the analgesic efficacy and tolerability of a single-dose combination tablet containing oxycodone 5 mg/ibuprofen 400 mg with either agent alone and with placebo in women who had undergone abdominal or pelvic surgery. METHODS: In this multicenter, randomized, double-blind,placebo- and active-controlled, parallel-group trial, women experiencing moderate to severe pain between 14 and 48 hours after surgery were randomized per protocol to receive a single dose of study medication in a 3:3:1:1 ratio (combination oxycodone/ibuprofen, ibuprofen, oxycodone, and placebo, in that order). Over a 6-hour study period, patients recorded their assessments of pain intensity (100-mm visual analog scale and 4-point scale), relief from starting pain, and overall evaluation of study drug based on prespecified definitions and rating scales. Based on these data, the following primary efficacy end points were determined: total pain relief 6 hours after dosing (TOTPAR6) and sum of pain intensity differences 6 hours after dosing (SPID6). Other end points included the time to onset of pain relief, time to use of rescue medication, and patient's global rating of analgesic effectiveness. Tolerability was evaluated on the basis of observed and patient-reported adverse events and findings on physical examination. RESULTS: Four hundred fifty-six women participated in the study. They were primarily white and had a mean age of 41.6 years and a mean body weight of 171.5 pounds. Combination treatment was associated with significantly better TOTPAR6 and SPID6 scores compared with ibuprofen alone (P < 0.02 and P < 0.015, respectively), oxycodone alone (P < 0.009 and P < 0.001), or placebo (both, P < 0.001). Fewer patients receiving combination treatment required rescue medication, and the time to use of rescue medication was significantly longer in the combination-treatment group compared with the other groups (P < 0.05). Patients' global ratings of analgesic efficacy were significantly higher in the combination-treatment group compared with all other groups (P < 0.044 vs ibuprofen alone; P < 0.001 vs oxycodone alone and placebo). The onset of pain relief occurred within 15 minutes of dosing with all 4 regimens. Nausea was the most frequently reported treatment-emergent adverse event in all 4 groups. The incidence of treatment-emergent adverse events was highest with placebo (55.0%), followed by oxycodone alone (44.2%), ibuprofen alone (42.3%), and combination treatment (40.8%). CONCLUSIONS: In this population of women who had undergone abdominal or pelvic surgery, the combination of oxycodone 5 mg/ibuprofen 400 mg was significantly more effective than either agent alone or placebo in the treatment of moderate to severe postoperative pain.

Abdomen↗
PubMed2005

Aspirin compared with acetaminophen in the treatment of fever and other symptoms of upper respiratory tract infection in adults: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose, 6-hour dose-ranging study.

BACKGROUND: Aspirin (acetylsalicylic acid) and acetaminophen (paracetamol) are frequently used to treat fever and other symptoms of upper respiratory tract infection (URTI). Both are available over the counter for use at the standard recommended doses of 500 and 1000 mg per single use. OBJECTIVE: This study investigated the efficacy, safety profiles, and tolerability of aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg compared with placebo in adult patients with acute febrile URTI of suspected viral origin. METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group trial conducted in Ukraine and Russia. Patients with URTI and acute fever of > or =38.5 degrees C received a single dose of aspirin 500 or 1000 mg, acetaminophen 500 or 1000 mg, or matching placebo. Oral body temperature was measured in the clinic at specified time points up to 6 hours after dosing. The intensity of other symptoms of URTI was rated by patients at baseline and at 2, 4, and 6 hours after dosing (scale from 0 = none to 10 = severe). The primary efficacy measure was the AUC for the change in orally measured body temperature from the time of treatment (baseline) to 4 hours after dosing. Secondary outcome measures included the change in body temperature from baseline to specified time points between 0.5 and 6 hours after dosing, the difference between baseline and the lowest measured body temperature, the time to the lowest measured body temperature, and the intensity of other symptoms of URTI (ie, headache, sinus sensitivity to percussion, sore throat, achiness, and feverish discomfort). Tolerability was monitored by recording of adverse events. RESULTS: Three hundred ninety-two patients were enrolled (78 in both aspirin groups, 79 in both acetaminophen groups, 78 in the placebo group). Demographic and baseline characteristics were comparable in the 5 groups; 51% of patients were male, with a mean age of 37.4 years and a mean body weight of 74.3 kg. The AUC values for the change in body temperature 0 to 4 hours after dosing were 3.18 (95% CI, 2.78-3.57) for aspirin 500 mg, 4.26 (95% CI, 3.84-4.68) for aspirin 1000 mg, 3.13 (95% CI, 2.77-3.49) for acetaminophen 500 mg, 4.11 (95% CI, 3.73-4.49) for acetaminophen 1000 mg, and 0.76 (95% CI, 0.38-1.13) for placebo. In terms of the primary efficacy variable, all active treatments were significantly superior to placebo (P < 0.001, 1-sided t test), with no significant differences between them. Reductions in body temperature were significantly greater with the 1000-mg doses of both active treatments compared with the 500-mg doses (P< 0.001, 1-sided t test). The mean maximum temperature reductions were 1.32 degrees C, 1.25 degrees C, 1.67 degrees C,1.71 degrees C, and 0.63 degrees C in the respective treatment groups. Significant reductions were seen in the mean intensity of headache, achiness, and feverish discomfort with all active treatments at most time points (P < 0.001), but not in sinus sensitivity to percussion or sore throat. All treatments were equally well tolerated, and no clinically significant adverse events occurred. CONCLUSIONS: In this single-dose study, aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg were more effective against fever and other symptoms of URTI than placebo. Both active treatments showed dose-related efficacy, and there was no significant difference between equal doses of the 2 agents. Safety profiles and tolerability were also comparable between treatments.

Acetaminophen↗