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Efficacy Endpoint (efficacy + endpoint)

Distribution by Scientific Domains
Medical Sciences100%
Distribution within Medical Sciences
Neurology15%
Allergy & Clinical Immunology10%

Kinds of Efficacy Endpoint

  • primary efficacy endpoint
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  • secondary efficacy endpoint
    		•

    Selected Abstracts

    Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non-platinum chemotherapy

    HEMATOLOGICAL ONCOLOGY, Issue 4 2003
    Timothy J. Littlewood
    Abstract Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb ,2,g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached ,12,g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan,Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan,Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3,g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan,Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies. Copyright © 2004 John Wiley & Sons, Ltd. [source]

    Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin

    DIABETES OBESITY & METABOLISM, Issue 4 2006
    Irina Chazova
    Aim:, To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. Methods:, A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients ,40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. Results:, With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1,35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Conclusions:, Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease. [source]

    Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study

    INFLAMMATORY BOWEL DISEASES, Issue 2 2010
    Walter Reinisch MD
    Abstract Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%,38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%,75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted. Inflamm Bowel Dis 2009 [source]

    Efficacy and safety of pimecrolimus cream 1% in adult patients with vitiligo: Results of a randomized, double-blind, vehicle-controlled study

    JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 11 2006
    Markus Dawid
    Pimecrolimus; Elidel®; Vitiligo Summary Background: Vitiligo is an acquired, pigmentary skin disorder which is disfiguring and difficult to treat. In an earlier open label study in adult patients with vitiligo, pimecrolimus cream 1% was reported to have similar efficacy as clobetasol propionate 0.05%. We performed a double-blind, intrapatient comparison of pimecrolimus cream 1% with placebo cream. Patients and methods: Twenty adult Caucasians with symmetrical vitiligo (predominantly on extremities, none in the face) were treated b.i.d. for 6 months left/right with pimecrolimus/vehicle (N = 10) or vehicle/pimecrolimus (N = 10), respectively. Primary efficacy endpoint was the size of the target lesion at month 6 and secondary efficacy endpoint was re-pigmentation. Results: Treatment with pimecrolimus cream 1% or vehicle resulted in no significant change in mean target lesion size. Modest repigmentation (1,25%) was noted with pimecrolimus at month 2 in 12 of 17 patients (vehicle: 9 of 17 patients). Afterwards, the number of patients who experienced an improvement of pigmentation steadily decreased (3 of 14 patients with pimecrolimus and 2 of 14 with placebo at month 6).Treatment was well tolerated. There were no treatment-related adverse events, no induction of skin atrophy nor any other application site side effects. Conclusion: In this group of adult patients with symmetrical vitiligo, treatment of body lesions (except face) with pimecrolimus cream 1% could not be shown to be effective. Zusammenfassung Hintergrund: Vitiligo ist eine erworbene Pigmentstörung der Haut, die entstellend und schwer zu behandeln ist. In einer früheren offenen Studie an erwachsenen Patienten mit Vitiligo wurde mit Pimecrolimus-Creme 1% eine ähnliche Wirksamkeit beobachtet wie mit Clobetasol propionat 0.05%. Bei der vorliegenden Studie handelte es sich um einen doppelblinden, intraindividuellen Vergleich von Pimecrolimus-Creme 1% und Plazebo-Creme. Patienten und Methodik: Zwanzig erwachsene Patienten weißer Hautfarbe mit symmetrischer Vitiligo (vorwiegend an den Extremitäten) wurden zweimal täglich über 6 Monate im Halbseitenvergleich mit Pimecrolimus/Cremegrundlage (N = 10) oder Cremegrundlage/Pimecrolimus (N = 10) behandelt. Primärer Endpunkt war die Größe der behandelten Läsion, sekundärer Endpunkt der Prozentsatz an Repigmentierung. Ergebnisse: Die Behandlung mit Pimecrolimus-Creme 1% oder Vehikel ergab keine signifikante ,nderung der durchschnittlichen Größe der Läsion. Eine mäßige (1,25%) Repigmentierung wurde mit Pimecrolimus bei 12 von 17 (Grundlage:9 von 17) Patienten in Monat 2 beobachtet. Anschließend nahm die Anzahl der Patienten, die eine Repigmentierung aufwiesen, kontinuierlich ab (3 von 14 unter Pimecrolimus, 2 von 14 unter Grundlage im Monat 6). Die Behand-lung wurde gut vertragen. Es gab keine behandlungsbedingten Zwischenfälle und keine Induktion von Hautatrophie oder irgendwelche anderen Nebenwirkungen an der Applikationsstelle. Schlussfolgerung: In dieser Gruppe erwachsener Patienten mit symmetrischer Vitiligo konnte eine Wirksamkeit der Behandlung von Läsionen am Körper (nicht Gesicht) mit Pimecrolimus-Creme nicht gezeigt werden. [source]

    Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis , a 6-month placebo-controlled trial

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010
    G. R. Lichtenstein
    Aliment Pharmacol Ther 2010; 32: 990,999 Summary Background, Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder. Aim, To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC. Methods, Randomized, double-blind, placebo-controlled trial of patients (n = 209 MG, n = 96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding = 0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ,1 and a mucosal appearance score ,2, a UC flare, or initiation of medication to treat a UC flare. Results, The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P , 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups. Conclusions, Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months. [source]

    Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation , a 12-week, randomized, double-blind, placebo-controlled study

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
    E. M. M. QUIGLEY
    Summary Background, Chronic constipation may result in disabling symptoms, is often unsatisfactorily treated by laxatives and negatively impacts quality of life (QoL). Aim, A randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of a selective, high-affinity 5-HT4 receptor agonist, prucalopride, in patients with chronic constipation [,2 spontaneous complete bowel movements (SCBMs)/week]. Methods, Placebo, 2 or 4 mg prucalopride was administered orally once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients with ,3 SCBMs/week, averaged over 12 weeks. Other assessments included BM frequency, constipation-related QoL and symptoms and tolerability. Results, Among 641 patients, significantly more patients taking prucalopride 2 or 4 mg (24%) than placebo (12%), achieved the primary efficacy endpoint (,3 SCBMs/week) or an increase of ,1 SCBMs/week; 43% and 47% vs. 28% respectively. Prucalopride-treated patients also achieved significantly greater satisfaction with treatment and bowel function, and improved perception of constipation severity and constipation-related QoL, compared with placebo. Most frequent treatment-related adverse events were headache, abdominal pain, nausea and diarrhoea (mainly during day 1). There were no differences in comparison to placebo in the incidence of serious adverse effects or cardiovascular events. Conclusion, Over 12 weeks, prucalopride was effective and well tolerated in chronic constipation. [source]

    Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind study

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009
    P. M. HELLSTRÖM
    Summary Background, There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype. Aims, To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study. Methods, Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 ,g, 300 ,g and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment. Results, Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 ,g, 100 ,g and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used. Conclusion, ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients. [source]

    A real-life multicentre clinical practice study to evaluate the efficacy and safety of intravesical chondroitin sulphate for the treatment of interstitial cystitis

    BJU INTERNATIONAL, Issue 1 2009
    J. Curtis Nickel
    OBJECTIVE To report a multicentre, community based open-label study designed to assess the efficacy and safety of intravesical sodium chondroitin sulphate in the treatment of patients with the clinical diagnosis of interstitial cystitis (IC). Chondroitin sulphate is a naturally occurring glycosaminoglycan (GAG) in the bladder mucus layer and changes in this GAG have been implicated in the pathogenesis of IC, and small single-centre studies have suggested that intravesical chondroitin sulphate may have efficacy in IC. PATIENTS AND METHODS Patients with IC were treated with sodium chondroitin sulphate (Uracyst®, Stellar Pharmaceuticals Inc., London ON, Canada) solution 2.0% via urinary catheter weekly for 6 weeks and then monthly for 16 weeks for a total of 10 treatments. The primary efficacy endpoint was the percentage of responders to treatment as indicated by a marked or moderate improvement on a seven-point patient Global Response Assessment (GRA) scale at week 10 (4 weeks after the initial six treatments) compared with baseline. A major secondary efficacy endpoint (durability) was the percentage of responders on the GRA scale after 10 treatments. Additional secondary efficacy objectives were differences from baseline in Patient Symptom/Problem Index scores over the course of the treatment compared with baseline. RESULTS In all, 47% of the 53 enrolled patients with long standing moderately severe IC (mean [sd, range] diagnosis of IC 3.0 [3.4, 0.1,16] years; duration of symptoms 9.2 [9.2, 1,39] years; baseline symptom score 14.2 [3.2]) were responders at week 10. At 24 weeks, 60% were responders. There was a statistically and clinically significant decrease in the mean (sd) symptom and bother scores from baseline at 10 weeks and 24 weeks, at 9.0 (4.3) and 8.1 (5.0), respectively (P < 0.001). There were no significant safety issues during the study. CONCLUSIONS This multicentre community based real-life clinical practice study suggests that intravesical chondroitin sulphate may have an important role in the treatment of IC and validates the rationale for a randomized placebo-controlled trial. [source]

    Comparison of a 3-day with a 1-day regimen of an extended-release formulation of ciprofloxacin as antimicrobial prophylaxis for patients undergoing transrectal needle biopsy of the prostate

    BJU INTERNATIONAL, Issue 1 2007
    Anthony J. Schaeffer
    OBJECTIVE To compare the clinical and bacteriological efficacy and the clinical safety of a 1-day with a 3-day regimen of an extended-release formulation of ciprofloxacin (ciprofloxacin XR) given as antimicrobial prophylaxis to men undergoing transrectal needle biopsy of the prostate (TRNBP). PATIENTS AND METHODS This was a multicentre, prospective, international, double-blind study in patients who required TRNBP. Patients were randomized to receive oral ciprofloxacin XR 1000 mg as either a 1-day or a 3-day regimen. Single doses were given at 24 h before, 2,3 h before, and 24 h after TRNBP. Patients in the 1-day regimen had placebo instead of the first and third doses of ciprofloxacin. RESULTS Of 497 patients enrolled, 247 were randomized to 1-day ciprofloxacin XR and 250 to the 3-day regimen. In the population valid for microbiological efficacy, the final assessment identified bacteriological success (primary efficacy endpoint) in more patients who had the 3-day regimen (98%) than in those who received the 1-day regimen (94.8%, 95% confidence interval, CI, ,,6.1%, 0.8%), although the difference was not statistically significant. In this population, the clinical response at the final visit was 98.5% and 96.7% for patients receiving the 3-day and the 1-day regimens, respectively (95% CI ,,5.2%, 0.8%). However, in the clinical efficacy population the clinical success rate was significantly greater for the 3-day (99.0%) than for the 1-day regimen (95.8%; 95% CI ,,6.4%, ,,0.3%). In a multivariate analysis, patients with diabetes mellitus and patients with a history of prostatitis had higher microbiological and clinical failure rates, respectively, than those without such conditions. For these patients, all failures occurred among those treated with the 1-day regimen. CONCLUSION As defined by bacteriological success in the population assessed for microbiological efficacy, prophylaxis with one dose of ciprofloxacin XR was statistically no worse than a 3-day regimen. However, in all efficacy analyses, bacteriological and clinical success rates were consistently lower for the 1-day than for the 3-day treatment. Thus, for selected patients undergoing TRNBP, there might be a role for 3-day preventive therapy with ciprofloxacin XR. [source]

    An investigation of dose titration with darifenacin, an M3 -selective receptor antagonist

    BJU INTERNATIONAL, Issue 4 2005
    William Steers
    OBJECTIVES To evaluate the efficacy, tolerability and safety of a flexible-dosing strategy with darifenacin, an M3 -selective receptor antagonist, in patients with symptoms of overactive bladder (OAB). PATIENTS AND METHODS In this multicentre double-blind 12-week study, 395 patients (aged 22,89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once-daily treatment with darifenacin controlled-release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo-increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTS The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at ,,8.2 (,62.9%) and ,,6.0 (,48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P=,0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for ,sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment-related adverse events were mild-to-moderate dry mouth and constipation, which led to discontinuation in <,3.0% of darifenacin-treated patients and <1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo. CONCLUSIONS Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs. [source]

    Renin Inhibitors in Chronic Heart Failure: The Aliskiren Observation of Heart Failure Treatment Study in Context

    CLINICAL CARDIOLOGY, Issue 9 2010
    FESC, FRACP, Henry Krum PhD
    Renin-angiotensin aldosterone system (RAAS) activation is a key neurohormonal contributor to the progression of chronic heart failure. Strategies that block this activation have consistently demonstrated major beneficial impacts on morbidity and mortality in this setting. Direct renin inhibitors (DRIs) present a novel opportunity to block at an additional or alternative step in this pathway, that being conversion of angiotensinogen to angiotensin I. Theoretical benefits of blocking at the level of renin include: inhibition of the reflex activation of plasma renin activity induced by conventional downstream RAAS blockers. Minimization of angiotensin II and/or aldosterone escape and blocking upstream at the rate-limiting step of angiotensin I production. Preclinical and early-phase clinical studies have largely supported this hypothesis. In the Aliskiren Observation of Heart Failure Treatment study, patients with systolic chronic heart failure receiving background angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers and ,-blockers benefited from aliskiren in reduction vs placebo of plasma levels of brain natriuretic peptide, the primary efficacy endpoint of that study. Large-scale outcome trials are, however, required to definitively determine the benefits of a DRI strategy additional to, or as an alternative to, conventional approaches such as ACE inhibitors in the systolic chronic heart failure setting. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose. [source]

    Sumatriptan Nasal Spray in Adolescent Migraineurs: A Randomized, Double-Blind, Placebo-Controlled, Acute Study

    HEADACHE, Issue 2 2006
    Paul Winner DO
    Objective.,To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background.,Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P= .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. Methods.,This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with ,6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results.,Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P= .046) and 2 hours (68% vs. 58%; P= .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P= .087) or for sustained headache relief from 1 to 24 hours (P= .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). Conclusions.,This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population. [source]

    Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009
    R. FASS
    Summary Background, The proportion of patients who respond to proton pump inhibitor (PPI) therapy is about 20% lower in those with non-erosive reflux disease (NERD) than in those with erosive oesophagitis. Aim, To assess efficacy and safety of dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD patients. Methods, In this 4-week, double-blind, placebo-controlled study, 947 NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once daily (QD). The percentages of 24-h heartburn-free days (primary) and nights without heartburn (secondary) were assessed from patients' daily diaries. Investigators also assessed symptoms. Patients completed validated quality of life and symptom severity questionnaires. Results, Dexlansoprazole MR provided significantly greater median percentages of 24-h heartburn-free days (54.9% and 50.0% for the 30- and 60-mg doses vs. 17.5% for placebo, P < 0.00001) and nights without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo). Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in patients receiving dexlansoprazole MR were consistent with clinical efficacy endpoints. Percentages of patients experiencing treatment-emergent adverse events were similar among groups. Conclusions, Dexlansoprazole MR 30 and 60 mg were superior to placebo in providing 24-h heartburn-free days and nights in NERD patients. Treatment was well tolerated. [source]

    Personal view: a potential novel treatment for fatigue complicating chronic liver disease , how should its efficacy be evaluated?

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006
    E. A. JONES
    Summary Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease. However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue. Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated. [source]

    Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis

    ALLERGY, Issue 6 2009
    R. Jankowski
    Background:, Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course. Objective:, The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 ,g twice a day (bd) after 1 month of treatment, and to compare FPANS 200 ,g bd and FPANS 200 ,g once a day (od) in maintenance and long-term treatment. Methods:, Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 ,g bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 ,g bd during acute period and FPANS 200 ,g od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 ,g bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade. Results:, After acute period and maintenance periods, FPANS 200 ,g bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 ,g od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events. Conclusion:, The study demonstrated the efficacy of FPANS 200 ,g bd in acute treatment and FPANS 200 ,g od as a sufficient dose to maintain a long-term efficacy in the treatment for NP. [source]

    Alternate-Day Tadalafil in the Management of Honeymoon Impotence

    THE JOURNAL OF SEXUAL MEDICINE, Issue 6 2008
    Hussein Ghanem MD
    ABSTRACT Introduction., Sildenafil has been used successfully in the treatment of honeymoon impotence. However, no study investigated the potential effect of tadalafil in the treatment of honeymoon impotence. Aim., The aim of this study is to evaluate the effectiveness of alternate-day tadalafil therapy in the management of unconsummated marriages. Methods., This is a descriptive study comprised of a series of 45 patients. The time frame for the study was 2 years. Forty-five consecutive patients underwent a complete medical and sexual history as well as a focused physical examination. Education about the male and female genital anatomy and the sexual response cycle was carried out. Alternate-day tadalafil 10-mg therapy was administered for 2 weeks with the duration extended as needed. Main Outcome Measures., Primary efficacy endpoints were successful vaginal intromission and change in the abridged version of the International Index of Erectile Function (IIEF-5). Results., Of 45 patients included in our study, 41 (91%) were able to achieve vaginal intromission and perform sexually. Thirty-four patients (76%) needed tadalafil for less than 1 month, five (11%) for up to 3 months, and two (4%) for more than 3 months. Four patients (9%) were unsuccessful. IIEF-5 improved significantly with alternate-day tadalafil treatment in this subgroup of patients (P < 0.001). Treatment failures were managed by intracavernous injection therapy, combined with psychosexual therapy, depending on the cause. Conclusions., Tadalafil therapy was safe and effective in the short-term management of this selected group of honeymoon impotence patients. Controlled studies are needed to further confirm these findings. Ghanem H, El-Dakhly M, and Shamloul R. Alternate-day tadalafil in the management of honeymoon impotence. J Sex Med 2008;5:1451,1454. [source]

    Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials

    BIPOLAR DISORDERS, Issue 2 2008
    Joseph R Calabrese
    Objectives:, The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression. Methods:, Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100,400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7,10 weeks. Results:, Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery,Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies. Conclusions:, Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression. [source]

    The impact of targeted training, a dedicated protocol and on-site training material in reducing observer variability of prostate and transition zone dimensions measured by transrectal ultrasonography, in multicentre multinational clinical trials of men with symptomatic benign prostatic enlargement

    BJU INTERNATIONAL, Issue 1 2007
    Philip S. Murphy
    OBJECTIVE To assess the variability of a standardized protocol of transrectal ultrasonography (TRUS), with targeted training, and compare it to the variability in other multicentre clinical trials, as TRUS-estimated total prostate volume (TPV) and transition zone volume (TZV) are considered important efficacy endpoints in assessing new drug therapies for benign prostatic enlargement (BPE), but standardizing TRUS remains a challenge in such studies. PATIENTS AND METHODS In all, 174 patients with BPE in the placebo arm of a 30-centre clinical trial were analysed at baseline, 13 and 26 weeks with TRUS, to extract TPV and TZV values. All TRUS operators received training in the standardized methods, which was supplemented at the outset by a compact disc-based video. RESULTS The mean (sd) changes from baseline in TPV at 13 and 26 weeks were ,,2.9 (8.9) and ,1.9 (8.5) mL, respectively; the respective mean changes from baseline in TZV were ,1.2 (6.4) and +,0.7 (7.8) mL. For TPV, 80% of the measurements had differences of +,5.2 to ,13.4 mL at 13 weeks, and +,8.0 to ,,10.9 mL at 26 weeks. For TZV, 80% of the differences were +,5.8 to ,,7.4 at 13 weeks, and +,9.3 to ,6.5 mL at 26 weeks. CONCLUSION The performance of TRUS compared favourably with similar published multicentre studies, which we suggest relates in part to the careful implementation of the protocol. We showed that diligent implementation of a detailed protocol, supplemented by targeted training of investigators and provision of on-site training material, promoted consistent acquisition and successful derivation of key clinical trial endpoints. Quantifying the variability of such endpoints will enable us to track deployment quality for future clinical trials, and will ensure that trials are sufficiently powered to define small changes in prostate size. [source]

    Topiramate in painful diabetic polyneuropathy: findings from three double-blind placebo-controlled trials

    ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2004
    The Topiramate Diabetic Neuropathic Pain Study Group
    Objectives , To evaluate the efficacy and tolerability of topiramate in patients with painful diabetic polyneuropathy. Materials and methods , Patients with moderate to extreme pain (0,4 Categorical Pain Scale score , 2) were randomized to placebo or topiramate (100, 200, or 400 mg/day) in three similar double-blind trials. The primary efficacy analysis was pain reduction from final visit to baseline in the 100-mm Visual Analog Scale (VAS) for the intent-to-treat populations. Results , After 18,22 weeks of double-blind treatment, pain reductions were numerically greater with topiramate in two studies but differences between topiramate and placebo in VAS scores or in the secondary efficacy endpoints did not reach statistical significance in any of the three studies. Across all studies, 24% of topiramate-treated patients and 8% of placebo-treated patients discontinued due to adverse events; groups did not differ in the occurrence of serious adverse events. Conclusion , These studies did not find topiramate to be significantly more effective than placebo in reducing pain scores in patients with painful diabetic polyneuropathy. Several design features may have precluded the studies from having sufficient sensitivity to differentiate effective and ineffective treatments. The study design and results are instructive for other investigators designing future clinical studies in neuropathic pain. [source]

    A pooled analysis of adjunctive topiramate in refractory partial epilepsy

    ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2003
    K. Peeters
    Objectives , To evaluate the impact of different dosages of topiramate (TPM) add-on to stable antiepileptic therapy for refractory partial epilepsy in adults. Material and methods , Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 patients treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving placebo. Results , Seizures were reduced by ,50% from baseline in 41% of TPM-treated patients and 15% of placebo-treated patients (P < 0.001); 5 and 0.8%, respectively, were seizure-free (P < 0.003). TPM was significantly better than placebo regardless of gender, age, baseline seizure rate as well as number and type of concomitant antiepileptic drugs. Efficacy was statistically significant in favour of TPM at all dose levels: at least 50% seizure reduction was achieved in 40% of patients with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800 mg TPM when compared with 15% with placebo (P , 0.001 for each dosage arm vs placebo). The median reduction in monthly seizure frequency was 38%, 42%, 45% and 38% vs 8%, respectively (P , 0.001). Moreover, response to TPM was significantly superior to placebo at each of the dose levels tested for most of the baseline variables. The total percentage of withdrawals increased with the dosage, and the withdrawals caused by adverse events increased from 3% with placebo to 7% with 200 mg TPM (not significant vs placebo), 15% with 400 mg TPM (P = 0.08), 16% with 600 mg TPM (P = 0.002) and 15% with 800 mg TPM (P = 0.003). Conclusion , The efficacy of TPM add-on in partial epilepsy is consistent across efficacy endpoints and independent of study population characteristics. The response at 200 mg TPM is similar to the response at higher doses, but as drop-outs caused by adverse events are more frequent above the 200 mg dose, this pooled analysis supports that 200 mg daily is a good target dose for add-on therapy in most patients with partial epilepsy, showing an excellent balance between efficacy and tolerability. [source]