Immunostimulation in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a one-year prospective,double-blind,placebo-controlled study

Purpose

Inflammation/immunological dysfunction are discussed etiological causes of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). OM-89 is an orally immunostimulating agent. We performed a phase three multicentre, randomized, double-blind, placebo-controlled, long-term (12 months) study with OM-89 produced with a different lysis process in patients with moderate-to-severe CP/CPPS type III.

Methods

Patients were randomized to OM-89 or placebo. Primary efficacy variable was difference of responders at the end of treatment (month 9) in patients receiving OM-89 versus placebo.

Results

Two hundred and three patients were screened, 185 patients (47.8 ± 8.4 years) (90 % of CP/CPPS type IIIb) were enrolled in 30 centers and included in the safety set. Ninety-four were randomized to OM-89, 91 to placebo. One hundred and seventy-six patients were subjected to the full analysis (FAS), 150 to the per protocol set (PPS). Baseline NIH-CPSI score in FAS was 21.8 ± 3.8 (OM-89) and 23.0 ± 5.6 (placebo). At primary efficacy endpoint (month 9), in the OM-89 group, 67.0 % in FAS (PPS 72.7 %) and in the placebo group, 64.3 % in FAS (PPS 64.4 %) were responders [FAS: OR 1.19, p = 0.59; PPS: p = 0.19]. Mean relative decrease in NIH-CPSI was 40.5 and 44.0 % in the FAS. Treatment-related adverse events were low: 8.5 % with OM-89 and 5.5 % with placebo. Because of small numbers, no conclusion could be drawn regarding the potential benefit of OM-89 in CP/CPPS IIIa.

Conclusions

This placebo-controlled study evaluating OM-89 in patients with CP/CPPS showed a significant and long-lasting (12 months) favorable response with OM-89, but also with placebo. OM-89 was safe and well tolerated.

EudraCT

2007-004609-85.     

A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients with recurrent urinary tract infections

OBJECTIVE: To investigate the long-term preventive effect of the immunotherapeutic OM-89 versus placebo in uncomplicated recurrent UTI in a large cohort of female patients only. METHODS: Adult female patients could enroll in this multicenter, double-blind study if they had acute UTI at the enrollment visit and positive results of urinalysis (> or =10(3)bacteria/ml). Patients received the immunotherapeutic OM-89 or a matching placebo; 1 capsule per day for 90 days, 3 months without treatment, then the first 10 days in Months 7, 8 and 9 and were followed up during 12 months. Primary efficacy criteria were UTI rates over 12 months, distribution of UTIs and proportion of patients with UTI. RESULTS: A total of 453 patients were treated, 231 in the active group and 222 in the placebo group. Mean rate of post-baseline UTIs was significantly lower in the active group than in the placebo group (0.84 vs. 1.28; p<0.003), corresponding to a 34% reduction of UTIs in patients treated with OM-89. In the active group, 93 patients (40.3%) had 185 post-baseline UTIs, compared to 276 UTIs in 122 patients (55.0%) in the placebo group (p=0.001). The safety profile of OM-89 was good and consistent with that reported in previous studies. CONCLUSIONS: OM-89 significantly reduced the incidence of UTI during the 12 months of the study including 3 months of treatment and three 10-day booster courses. These results confirm that OM-89 is a valuable component of the management of recurrent UTI.     

Hepatocyte growth factor and omega-3-enriched feeds have a synergistic effect on mucosal mass in an animal model of inflammatory bowel disease

BackgroundHepatocyte growth factor (HGF) decreases intestinal inflammation and cytokine levels in an animal model of inflammatory bowel disease (IBD). Luminal omega-3 (OM-3) is anti-angiogenic, reduces inflammation, and may decrease symptoms in patients with Crohn's disease. This study evaluates the synergism of HGF and OM-3.MethodsTwenty adult female transgenic HLA-B27 rats were divided into 4 groups: group 1: regular feeds, IV saline; group 2: OM-3–enriched feeds, IV saline; group 3: regular feeds, IV HGF (150 µg/kg per day); and group 4: OM-3–enriched feeds, IV HGF(150 µg/kg per day). Rats were killed at 14 days after pump placement. Small and large bowel mucosa was harvested, and DNA and protein were extracted and quantified. Statistical analysis was done by analysis of variance with post-hoc Tukey's HSD test.ResultsContent of protein and DNA in the ileum were significantly increased by supplementation of HGF (P < .001, P < .01, respectively) alone. OM-3 significantly increased protein content but not DNA (P = .02, P = 0.3, respectively). Combined, they had a synergistic effect greater than either supplement alone (P = .0001, P = .002, respectively). In the colon, HGF and OM-3 did not significantly increase protein or DNA content individually or together.ConclusionsThis is the first demonstration of the synergistic effect of a growth factor (HGF) and a dietary supplement (OM-3) in an immunologic model of IBD.     

Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis

OBJECTIVE: A double-blind, placebo-controlled dose-finding study was performed in 237 patients with predominantly unilateral knee osteoarthritis (OA) evaluating efficacy and safety of a new topical NSAID. DESIGN: The patients applied 3 g tid eltenac gel 0.1%, 0.3%, 1% or placebo gel over a period of 4 weeks. The patients were supplied with paracetamol tablets as an escape analgesic. Primary efficacy end-point was mean global pain in the week preceding the examinatio ns, evaluated on a visual analog scale (VAS). Secondary criteria were Lequesne's score ISK, Jezek score, muscle strength and dolorimeter measurements, walking time, clinical examination results of the knee joint and patient's and investigator's overall efficacy estimates. RESULTS: The graphical depiction of VAS and ISK suggested a dose-related efficacy, but the pre-planned statistical analysis did not show significant differences between treatments.In the patient subgroup with a higher degree of baseline severity of knee OA the ISK showed significant and relevant advantages of eltenac gel 1% to placebo at different examination times. Two patients each of the eltenac gel 1% group and the placebo group showed local intolerance reactions which subsided spontaneously. CONCLUSION: This study did not provide confirmatory proof of an efficacy of topical eltenac in patients with knee OA. Methodological pitfalls and possible responder subgroups are described. Despite the difficulties, dose-finding studies seem to be feasible even with topical NSAIDs.     

Mirabegron 50 mg once‐daily for the treatment of symptoms of overactive bladder: An overview of efficacy and tolerability over 12 weeks and 1 year

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2‐week placebo run‐in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3‐day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end‐points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient‐reported outcomes. Safety variables included changes in treatment‐emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient‐reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment‐emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient‐reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.     

Preventive effects of ibuprofen on periarticular heterotopic ossification after total hip arthroplasty: A randomized double-blind prospective study of treatment time

We determined the efficacy and the minimum treatment time necessary for prophylaxis with nonsteroidal anti-inflammatory drugs (NSAIDs) for periarticular heterotopic ossification (HO) after total hip arthroplasty (THA). Using a double-blind placebo controlled design, 144 patients operated on with total hip arthroplasty for primary arthrosis were treated postoperatively with (1) ibuprofen for 3 weeks, (2) ibuprofen for 1 week and placebo for the next 2 weeks or (3) placebo for 3 weeks. Radiographic occurrence of periarticular heterotopic ossification and complications of the treatment were recorded for the first year.

Both ibuprofen-treated groups showed significantly less HO than the placebo-treated group. There was no difference in HO between the patients treated for 8 or 21 days postoperatively. Both 8 and 21 days of treatment with ibuprofen following THA effectively prevents clinically significant degrees of HO. No serious short-term complications of the treatment were noted.     

Tolterodine treatment for children with symptoms of urinary urge incontinence suggestive of detrusor overactivity: results from 2 randomized, placebo controlled trials

PURPOSE: We report the results of the first 2 large randomized controlled trials designed to evaluate the efficacy and safety of tolterodine extended release in children 5 to 10 years old with symptoms of urinary urge incontinence suggestive of detrusor overactivity. MATERIALS AND METHODS: Two double-blind, placebo controlled trials were conducted sequentially. Children 5 to 10 years old with incontinence suggestive of detrusor overactivity (1 or more diurnal incontinence episodes per 24 hours) were randomized to tolterodine (2 mg daily) or placebo for 12 weeks. The primary end point was the change from baseline to week 12 in the number of incontinence episodes per week. Changes from baseline in the number of voids per 24 hours and volume of urine per void were also evaluated. Exploratory analyses were conducted to determine whether particular subsets of patients showed differential responses to treatment. RESULTS: A total of 224 and 487 children (mean age 8 years) were randomized to placebo and tolterodine, respectively. Differences in the number of incontinence episodes per week, voids per 24 hours, and volume of urine per void between tolterodine and placebo did not reach statistical significance. This finding may be explained by a high placebo response and under dosage of tolterodine among children with greater body weight. Tolterodine was well tolerated. CONCLUSIONS: Analysis of the primary efficacy outcome did not reveal a statistically significant effect of treatment. However, secondary analyses demonstrated that tolterodine was well tolerated among 5 to 10-year-old children with diurnal incontinence. Exploratory analyses also showed that children weighing 35 kg or less with detrusor overactivity characterized by incontinence and/or frequent voiding benefited most from tolterodine treatment, suggesting that a weight adjusted dosing regimen may be required for optimal response among older and heavier children.     

A randomized double-blind placebo-controlled multicentre study to explore the efficacy and safety of tamsulosin and tolterodine in women with overactive bladder syndrome

OBJECTIVES: To evaluate the efficacy of tamsulosin oral-controlled absorption system (OCAS) vs placebo in overactive bladder (OAB), to evaluate the safety and tolerability of once-daily dosing with tamsulosin OCAS, and to compare the efficacy and safety with tolterodine extended-release (ER). PATIENTS AND METHODS: A parallel-group, multicentre, multinational study was conducted with a single-blind placebo run-in period of 2 weeks, followed by a randomized, double-blind, double-dummy active and placebo-controlled treatment period of 6 weeks; women (aged 18-70 years) with symptoms of OAB for >/= 3 months were recruited. Women were randomized to receive one of four doses of tamsulosin OCAS (0.25, 0.5, 1.0 or 1.5 mg), 4 mg of tolterodine ER, or placebo once daily for 6 weeks. The primary efficacy variable was the change in the mean number of voids/24 h. Secondary efficacy variables included change from baseline in; mean volume voided per void, mean number of incontinence episodes/24 h, mean number of urgency episodes/24 h and in quality of life (QoL), as assessed using the Kings Health Questionnaire (KHQ). RESULTS: Overall, 364 women were randomized; the primary efficacy analysis showed that the difference from placebo in the mean number of voids/24 h was not statistically significant for tamsulosin OCAS 1.5 mg (P = 0.189). There was no statistically significant difference for tolterodine ER 4 mg vs placebo in the mean number of voids/24 h (P = 0.353). Similarly, for the secondary outcome variables there was no statistically significant difference between tamsulosin and placebo. Although women taking tolterodine ER 4 mg had a consistently greater increase in mean voided volume/void and consistent decreases in incontinence episodes/24 h, urgency episodes/24 h and episodes of nocturia/24 h, this was not statistically significant. There was no significant improvement in QoL scores across the treatment groups. Tamsulosin OCAS was well tolerated and the proportion of women discontinuing because of adverse events was low (4.7%). CONCLUSION: Tamsulosin is not effective for treating OAB in women and the evidence from this study does not support its use on an empirical basis.     

Extended duration of efficacy of vardenafil when taken 8 hours before intercourse: a randomized, double-blind, placebo-controlled study

OBJECTIVES: This study explored the efficacy of vardenafil in men with erectile dysfunction (ED) when taken 8 hours before sexual intercourse. METHODS: A 10-week, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of vardenafil (5, 10 or 20mg) was conducted in men with ED for >6 months who failed >or=50% of intercourse attempts during a 4-week treatment-free run-in period. Sexual Encounter Profile Question 3 (SEP3) was the primary efficacy measure; secondary measures included SEP2, International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, Global Assessment Question (GAQ), Global Confidence Question (GCQ) and Erection Quality Scale (EQS). Adverse-event and safety monitoring were conducted throughout. RESULTS: 383 patients were randomized to vardenafil (n=194) or placebo (n=189). Patients treated with vardenafil 8 hours before sexual activity achieved clinically meaningful (>or=18%) and statistically significantly greater least-squares mean per-patient SEP3 and SEP2 success rates over weeks 2-10, compared with patients receiving placebo (SEP3 69% vs 34%; SEP2 81% vs 51%; both p<0.001). SEP3 and SEP2 measures demonstrated the significant superiority of vardenafil over placebo from week 2 onwards (p<0.001). Measurements of IIEF-EF domain score, GAQ, GCQ and EQS showed that vardenafil led to significantly greater improvements in erectile function, compared with placebo (all p<0.001). Vardenafil was generally well tolerated. CONCLUSIONS: The extended duration of efficacy of vardenafil up to 8 hours postdose may provide couples with more flexibility in their sexual life than anticipated.     

甲磺酸酚妥拉明片/胶囊治疗阴茎勃起功能障碍的临床研究

目的 :为了解甲磺酸酚妥拉明在治疗阴茎勃起功能障碍 ( ED)中的有效性和安全性。方法 :采用随机安慰剂对照试验研究的方法进行分析。试验分为片剂组 ( A组 )、胶囊组 ( B组 )、安慰剂的片剂和胶囊组并为一组 ( C组 )。组间比例为 1∶ 1∶ 1 ( A∶B∶C)。共有 2 41例参加了临床试验 ,其中 2 1 7例完成试验。试验药物 (片剂或胶囊 )必须在性交前 1h服用 ,每次服 1片 ( 4 0 mg) ;两周内至少有 3次服药并尝试性交以保证达到统计学要求 ,但服药不能超过 8次 ;整个试验持续 1 0周。药物的有效性按国际性功能量表 ( IIEF)衡量 ,安全性以监测试验过程中的不良反应来反映。结果 :有效率 ,A组为 6 8% ,B组为 6 2 % ,C组为 45%。 A、B组和 C组比效有显著性差异。整个试验未发生严重不良反应。结论 :甲磺酸酚妥拉明片和胶囊是一种治疗勃起功能障碍的有效且安全的药物     

Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis.

Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. INTRODUCTION: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score < or = -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). RESULTS AND CONCLUSIONS: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score < -3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.     

Desmopressin in the treatment of nocturia: a double-blind, placebo-controlled study

OBJECTIVES: To investigate efficacy, safety, and impact on quality of sleep of desmopressin in the treatment of nocturia. METHODS: Adults aged > or =18 yr with nocturia (> or =2 voids/night) received desmopressin tablets (0.1, 0.2, or 0.4 mg) during a 3-wk dose-titration period. Patients should show sufficient response during the dose-titration period (> or =20% reduction in nocturnal diuresis) and a return of nocturnal diuresis to > or =80% of baseline levels during washout. Eligible patients then entered a 3-wk double-blind treatment period and received either desmopressin or placebo. RESULTS: 127 patients were randomised to either desmopressin (n=61) or placebo (n=66). Twenty (33%) desmopressin-treated patients compared with seven (11%) placebo-treated patients showed a clinical response, defined as a > or =50% reduction in the number of nocturnal voids compared with baseline (p=0.0014). Compared with placebo, desmopressin resulted in a significant reduction in the mean number of nocturnal voids (39% reduction with desmopressin vs. 15% with placebo; absolute difference -0.84, p<0.0001) and duration of the first sleep period (prolonged by 108 min with desmopressin vs. 41 min with placebo; p<0.0001). Quality of sleep was also improved with desmopressin versus placebo (statistically significant for one of the two parameters evaluated). Adverse events were mainly mild. CONCLUSIONS: Oral desmopressin tablets provide an effective and well-tolerated treatment for nocturia. Compared with placebo, nocturnal voiding frequency is reduced, duration of the first sleep period is increased, and sleep quality may be improved.     

Efficacy and safety of SBR759, a novel calcium-free,iron (III)-based phosphate binder,versus placebo in chronic kidney disease stage V Japanese patients on maintenance renal replacement therapy

Background

SBR759, an iron (III)-based oral phosphate binder, was developed for the treatment of hyperphosphataemia in chronic kidney disease stage V patients receiving maintenance renal replacement therapy (RRT). Serum phosphate-lowering efficacy and dose response of SBR759 (3-, 6-, 9- and 12-g/day doses) were compared with placebo.

Methods

Japanese patients with hyperphosphataemia (P ≥ 5.5 mg/dL [≥1.78 mmol/L]) receiving maintenance RRT (N = 63) were randomised to receive either SBR759 (3-, 6-, 9-, 12-g/day dose) or placebo (12-g/day dose) for 4 weeks. The primary endpoint was change from baseline in 72-h post-dialysis serum phosphate levels at week 4 for different doses of SBR759 versus placebo. Secondary endpoints were change from baseline in serum phosphate levels and dose-dependent efficacy of SBR759 during the 4-week treatment period.

Results

SBR759 showed significant reduction in serum phosphate levels compared with placebo at week 4, demonstrating a significant linear dose response (P < 0.001). Incidence of adverse events was comparable between the SBR759 treatment groups (7/13 and 5/12 in the 3- and 12-g/day groups, respectively, and 8/13 in the 6- and 9-g/day groups) and was 6/12 in the placebo group. Discoloured faeces and diarrhoea were the most frequently reported adverse events. Two serious adverse events were reported—one in the SBR759 3-g/day group (1/13, skin ulcer) and one in the SBR759 12-g/day group (1/12, arthralgia).

Conclusions

SBR759 showed significant phosphate-lowering efficacy and dose-dependent response compared with placebo in patients with chronic kidney disease receiving RRT.     

Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery

We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.     

Low dose amitriptyline in the treatment of chronic pain

The analgesic efficacy of amitriptyline 25 mg was compared with placebo in 41 patients with chronic (more than 3 months) nonmalignant pain, using a double-blind randomised multiple-dose 3-week treatment period crossover design. Amitriptyline 25 mg provided significantly greater efficacy than placebo, with significant differences evident within the first week. There was no significant difference on mood scores between amitriptyline and placebo. The results suggest that surprisingly low doses of amitriptyline may be effective without substantial adverse effects, that the effect is evident early, and that the effect is distinguishable from any effect of the amitriptyline on mood.     

Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction

Aim： To examine the treatment efficacy of Korean Red Ginseng （KRG） in impotent men with erectile dysfunction （ED）. Methods： A total of 60 patients presenting mild or mild to moderate ED were enrolled in a double-blind, placebo-controlled study in which the efficacies of KRG and a placebo were compared. The patients received either 1 000 mg （3 times daily） of KRG or a placebo. Results： The five-item version of the International Index of Erectile Function （IIEF-5） score after the treatment was significantly higher in the KRG group compared with that before the treatment （from 16.4±2.9 to 21.0±6.3, P 〈 0.0001）. In contrast, there was no difference before and after the treatment in the placebo group （from 17.0±3.1 to 17.7±5.6, P 〉 0.05）. In the KRG group, 20 patients （66.6%）, reported improved erection, significant in the global efficacy question （P 〈 0.01）; in the placebo group there was no significance. Scores on questions 2 （rigidity）, 3 （penetration）, 4 and 5 （maintenance）, were significantly higher for KRG than those for the placebo when those questions were answered after 12 weeks of each treatment （P 〈 0.01）. When the score in the KRG group was compared to the placebo group after the treatment, there was a significant improvement in total score （IIEF-5 score） in questions 3 and 5 for the KRG-treated group （P 〈 0.001 and P 〈 0.0001, respectively）. The levels of serum testosterone, prolactine and cholesterol after the treatment were not statistically significant different between the KRG and the placebo group （P 〉 0.05）. Conclusion： Our data show that KRG can be an effective alternative to the invasive approaches for treating male ED.     

Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial

OBJECTIVES: To assess the efficacy and safety of trospium chloride (TCl, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo. PATIENTS AND METHODS: In all, 208 patients were allocated at random to either TCl or placebo in a double-blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy. RESULTS: Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 mL, mean 37.3 mL, one-sided P = 0. 0054) and urinary volume at first unstable contraction (median treatment effect 45.0 mL, mean 63.6 mL, one-sided P = 0.0015). The patients' assessment of efficacy showed significantly greater clinical improvement in the TCl group than in the placebo group (two-sided P = 0.0047). Furthermore, TCl was well tolerated, with similar frequencies of adverse events reported in both groups (68% in the TCl and 62% in the placebo group). CONCLUSION: Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.     

Topical eutectic mixture for premature ejaculation (TEMPE): a novel aerosol-delivery form of lidocaine-prilocaine for treating premature ejaculation

OBJECTIVE: To evaluate, in a phase II study, the efficacy and safety of a topical eutectic mixture for premature ejaculation (TEMPE), a metered-dose aerosol spray containing a eutectic mixture of lidocaine and prilocaine, as a treatment for PE. PATIENTS AND METHODS: Men with PE (Diagnostic and Statistical Manual-IV definition) aged 18-75 years were randomized into a double-blind, placebo-controlled study in the UK and the Netherlands. Efficacy variables included the mean change in intravaginal ejaculatory latency time (IELT) from baseline and the proportion of patients who achieved an IELT of > or = 4, > or = 3 or > or = 2 min on two occasions, and the effect of TEMPE on the index of ejaculatory control (IEC) and sexual quality-of-life (SQoL) scores of patients and their partners. Safety and adverse event data were also collected. Fifty-four patients were randomized and received study treatment. RESULTS: The observed mean change in IELT from baseline to the end of the treatment period was 3.8 min in the TEMPE group and 0.7 min in the placebo group, and when adjusted for baseline and centre was 2.4 times higher in the TEMPE than the placebo group (P < 0.01). The efficacy of TEMPE in increasing IELT was further supported by positive trends in the other efficacy endpoints. The proportion of men who had an IELT time > or = 2, > or = 3 or > or = 4 min on two occasions after treatment was 11/20 (55%), 8/20 (40%) and 5/25 (20%) in the TEMPE group, and 8/23 (35%), 3/23 (13%) and 3/23 (13%) in the placebo group, respectively, although these differences were not statistically significant. Improvements in IEC and SQoL (male and female) scores also showed trends towards greater efficacy for TEMPE than placebo. In all, 35 of 42 (83%) patients considered the spray easy to use. Mild to moderate local numbness occurred in three (12%) of the TEMPE-treated patients but did not lead to discontinuation. CONCLUSION: Topical treatment with TEMPE produced a statistically and clinically significant increase in IELT compared with placebo, and resulted in positive trends in ejaculatory control and SQoL. TEMPE was considered easy to use and was well tolerated. The data support the conduct of further large-scale studies to establish the utility of TEMPE as a first-line treatment for PE.     

Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes

The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-beta. Natural killer T-cells also participate in the therapeutic effect because CD1d(-/-) NOD mice are partially resistant to the protective effect of OM-85. The question remains of the specificity of the protective effect of OM-85, which may include proinflammatory components. It will thus be important to further characterize the molecular components that afford protection from type 1 diabetes. Lipopolysaccharide is excluded, but other Toll-like receptor (TLR) agonists could be involved because OM-85 stimulated dendritic cells and induced TGF-beta production by splenocytes in a TLR-2-, TLR-4-, and MyD88-dependent fashion.     

Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study

OBJECTIVES: To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily. PATIENTS AND METHODS: This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily. RESULTS: Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine. CONCLUSION: In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies.