Frequency Of Treatment-related Adverse Events Research Articles

MP56-02 SAFETY AND EFFICACY OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN THE TREATMENT OF ACTIVE PHASE PEYRONIE'S DISEASE

You have accessJournal of UrologySexual Function/Dysfunction: Peyronie’s Disease II1 Apr 2017MP56-02 SAFETY AND EFFICACY OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN THE TREATMENT OF ACTIVE PHASE PEYRONIE'S DISEASE James Anaissie, Kenneth DeLay, Nora Haney, Faysal Yafi, and Wayne Hellstrom James AnaissieJames Anaissie More articles by this author , Kenneth DeLayKenneth DeLay More articles by this author , Nora HaneyNora Haney More articles by this author , Faysal YafiFaysal Yafi More articles by this author , and Wayne HellstromWayne Hellstrom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1755AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To examine the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase Peyronie's Disease (PD). METHODS We conducted a retrospective review of the records for all patients treated with CCH for PD between 04/2014 and 03/2016. Patients qualified as being in the acute phase of PD if they reported penile pain and duration of PD < 12 months at presentation. The primary outcomes of interest were final change in curvature after CCH treatment regardless of number of CCH cycles received, and frequency of treatment-related adverse events (TRAE). Paired t-Test and Chi-squared tests were performed to determine statistical significance (P<0.05). RESULTS A total of 77 patients were included in the study, of which 21 (27%) qualified as acute phase PD and the remaining 56 (73%) as stable phase. Median duration of PD was 8 months for acute phase patients, and 21 months for stable phase (p=0.033). There was no significant difference in final change in curvature between the acute and stable phase of PD (16.2° vs. 14.9°, p=0.702). There was a significant difference in change in curvature reported after the first cycle of treatment between the acute and stable phase (21.7° vs. 12.5°, p=0.037). There was no statistically significant difference in frequency of TRAEs between the acute phase (3, 14%) and the stable phase (4, 7%) (p=0.332). CONCLUSIONS Although CCH is currently contraindicated during the acute phase of PD, preliminary results suggest that CCH use during this setting may be both effective and safe. There was no statistically significant difference in final change in curvature or TRAEs after CCH therapy between the acute and stable phase of PD. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e755 Advertisement Copyright & Permissions© 2017MetricsAuthor Information James Anaissie More articles by this author Kenneth DeLay More articles by this author Nora Haney More articles by this author Faysal Yafi More articles by this author Wayne Hellstrom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Estimated costs of managing treatment-related adverse events (TRAEs) of nivolumab (nivo) and docetaxel (doc) in the CheckMate 017 and CheckMate 057 phase III non-small cell lung cancer (NSCLC) trials.

6617Background: Nivo, a PD-1 antibody, received FDA approval based on superior overall survival in metastatic squamous (SQ) and non-squamous (NSQ) NSCLC patients who have progressed on or after platinum-based doublet chemotherapy. The purpose of this study was to assess the frequency and associated costs of grade 2–4 AEs in the CheckMate 017 (SQ) and CheckMate 057 (NSQ) phase III pivotal trials of nivo vs doc in stage IIIB/IV NSCLC. Methods: Patient-level data from these two trials were utilized to estimate the frequency of TRAEs requiring management in the nivo and doc arms, including serious and non-serious TRAEs. Minimum follow-up for AE reporting at database lock was 12 months. Grade 3–4 AE costs by event were identified from Healthcare Cost and Utilization Project (HCUP) data in 2010, which were adjusted to reflect 2012-equivalent US costs. Healthcare utilization associated with grade 2 AEs was based on clinical opinion and costs were based on HCUP or other sources as appropriate. Results: In both tr...

Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women

Divigel and Estrogel are estradiol gels for the treatment of postmenopausal women with moderate to severe vasomotor symptoms. They differ with respect to several factors including estradiol concentration and surface application, and cannot be compared solely on the basis of their estradiol dose. No randomized clinical trials have compared them head to head, but both have been compared with placebo. Therefore, the objective of this study was to conduct a systematic review and network meta-analysis of the two estradiol gels. We performed a comprehensive systematic literature review. One publication reporting on one Divigel trial, three publications reporting on two Estrogel trials, and five publications reporting on other estradiol transdermal preparations were identified. Efficacy outcomes were change from baseline in daily hot flush frequency and change from baseline in daily hot flush severity. Safety outcomes were frequency of treatment-related adverse events (AEs) and frequency of treatment-emergent AEs leading to discontinuation. Bayesian indirect treatment comparison meta-analysis of trial-level data was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research, Academy of Managed Care Pharmacy, National Pharmaceutical Council (ISPOR-AMCP-NPC) Good Practice Questionnaire. All outcomes were compared with respect to doses of the considered preparations. For hot flush frequency, Divigel 0.25 mg was similar to Divigel 0.5 mg and to Estrogel 0.75 mg, and was statistically significantly superior to Estrogel 1.5 mg. The largest effect was observed with Divigel 1.0 mg (mean difference of 3.91 hot flushes/wk vs placebo), and was statistically significantly superior to all other interventions. The 1.5 mg Estrogel dose was associated with the smallest estimate of efficacy. For hot flush severity, Divigel 0.25 mg was similar to the efficacy of Divigel 0.5 mg, and for 0.25 mg and 0.5 mg of other estradiol gels, but was statistically inferior to Divigel 1.0 mg, Estrogel 0.75 mg, Estrogel 1.5 mg, and the 1.0 and 1.5 mg doses of all other estradiol gels. The estimated efficacy of Divigel 0.5 mg was similar to that of Estrogel 0.75 mg, Estrogel 1.5 mg, and the 0.25 and 0.5 mg doses of other transdermal estradiol preparations. Risks of treatment-related AEs for Divigel 0.25 mg, Divigel 0.5 mg, Estrogel 0.75 mg, and Estrogel 1.5 mg were similar and all were of a slightly higher risk than placebo. Among these, Divigel 1.0 mg, Estrogel 1.5 mg, and other gels 0.5 mg were statistically significantly less safe than placebo. However, for treatment-emergent AEs leading to discontinuation, none of the gels were associated with statistically significantly higher relative risks compared with placebo. In this study, statistically significant refers to the 95% credible intervals used in the Bayesian Network Analysis. Using network meta-analysis for indirect treatment comparison, we have shown that the efficacy of Divigel 0.25 mg, as measured by reduced hot flush frequency and severity, was similar to that of Divigel 0.5 mg and of Estrogel 0.75 and 1.5 mg. Overall, our analysis showed that Divigel 1.0 mg provided the best efficacy profile, but that this treatment was also associated with a higher risk of AEs. The network meta-analysis also showed that treatment with Estrogel 1.5 mg was associated with the smallest estimate of reduction in frequency of hot flushes.

Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer.

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.

Botulinum toxin type A in post-stroke upper limb spasticity

Objective:To evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke upper limb spasticity.Research design and methods:In a multicentre, randomised, double-blind, parallel-group, placebo-controlled study, 109 patients with upper limb spasticity were randomised to receive a single treatment with lower-dose (120–150 U) or higher-dose (200–240 U) BoNTA or placebo into upper limb muscles.Clinical trial registration:NCT00460564Main outcome measures:The tone of the wrist flexor was assessed at baseline and at weeks 0, 1, 4, 6, 8 and 12 using the Modified Ashworth Scale (MAS) for wrist, finger, thumb and disability in activities of daily living (ADL) was rated using the 4-point Disability Assessment Scale (DAS). The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS wrist score in the higher-dose groups.Results:Subjects were randomised with 51 in the higher BoNTA group, 26 in the higher-dose placebo group, 21 in the lower BoNTA group and 11 in the lower-dose placebo group. Significant improvement in spasticity with higher-dose BoNTA was demonstrated by a mean difference in the AUC of the change from baseline in the MAS wrist score between the higher-dose BoNTA group and the higher-dose placebo group of −6.830 (p < 0.001, t-test), no significant different was demonstrated between the lower-dose BoNTA group and the lower-dose placebo group (p = 0.215, t-test). Significant improvements with higher-dose BoNTA were also observed in the DAS scores for limb position (p = 0.001–0.022) at all time points and dressing (p = 0.018–0.038, Wilcoxon test) at weeks 6, 8 and 12. No clinically relevant difference was noted in the frequency of treatment-related adverse events between BoNTA-treated and placebo-treated patients. The long-term efficacy and safety, and the effects on rehabilitation of BoNTA on upper limb will be evaluated using the data obtained in the open-label phase.Conclusions:Higher-dose BoNTA reduced spasticity in upper limb muscles and improved ADL performance in terms of limb position and dressing. BoNTA is safe and effective in the treatment of post-stroke upper limb spasticity.

Efficacy of Desloratadine in Persistent Allergic Rhinitis – A GA2LEN Study

Background: The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines proposed a classification for allergic rhinitis based on the duration of symptoms (intermittent or persistent) rather than on the time of allergen exposure (seasonal or perennial). There had been no placebo-controlled, randomized, clinical trial of desloratadine (DL) in patients with persistent allergic rhinitis to date. Objectives: To assess the efficacy and safety of DL in patients with persistent allergic rhinitis based on the ARIA classification. Methods: Patients 12 years of age and older with persistent allergic rhinitis were assessed over 85 days of treatment with DL 5 mg once daily (n = 360) or placebo (n = 356). The primary endpoint was the AM/PM reflective total 5-symptom score (T5SS) averaged over days 1–29. Secondary endpoints included AM/PM instantaneous T5SS and individual symptoms, therapeutic response, symptom severity assessed by a visual analogue scale and quality of life. Results: The mean reduction in AM/PM reflective T5SS was significantly greater with DL than placebo over days 1–29 (–3.76 vs. –2.87, p < 0.001) and on each individual day (p < 0.05). The mean AM instantaneous T5SS was significantly reduced with DL compared with placebo as early as day 2 (–1.90 vs. –1.46; p < 0.001). The therapeutic response and improvement in quality of life were significantly greater with DL than placebo (p < 0.001 for each). The frequency of treatment-related adverse events was low and similar between DL (10.0%) and placebo (8.4%). Conclusions: This study showed DL to be effective and safe in the treatment of persistent allergic rhinitis.

Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial

Lower limb spasticity in post-stroke patients can impair ambulation and reduces activities of daily living (ADL) performance of patients. Botulinum toxin type A (BoNTA) has been shown effective for upper limb spasticity. This study assesses the treatment of lower limb spasticity in a large placebo-controlled clinical trial. In this multicenter, randomized, double-blind, parallel-group, placebo-controlled study, we evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke lower limb spasticity. One hundred twenty patients with lower limb spasticity were randomized to a single treatment with BoNTA 300 U or placebo. The tone of the ankle flexor was assessed at baseline and through 12 weeks using the Modified Ashworth Scale (MAS). Gait pattern and speed of gait were also assessed. The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS ankle score. Significant improvement in spasticity with BoNTA 300 U was demonstrated by a mean difference in the AUC of the change from baseline in the MAS ankle score between the BoNTA and placebo groups (−3.428; 95% CIs, −5.841 to −1.016; p = 0.006; t test). A significantly greater decrease from baseline in the MAS ankle score was noted at weeks 4, 6 and 8 in the BoNTA group compared to the placebo group (p < 0.001). Significant improvement in the Clinicians Global Impression was noted by the investigator at weeks 4, 6 and 8 (p = 0.016–0.048, Wilcoxon test), but not by the patient or physical/occupational therapist. Assessments of gait pattern using the Physician’s Rating Scale and speed of gait revealed no significant treatment differences but showed a tendency towards improvement with BoNTA. No marked difference was noted in the frequency of treatment-related adverse events between BoNTA and placebo groups. This was the first large-scale trial to indicate that BoNTA significantly reduced spasticity in lower limb muscles.

Interferon Beta for Primary Progressive Multiple Sclerosis

This is an updated Cochrane review of the previous version published (Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006643. DOI: 10.1002/14651858.CD006643.pub2).Therapeutic trials with ss-interferon in Multiple Sclerosis (MS) have mainly focused on remitting-relapsing multiple sclerosis (RRMS), demonstrating a reduction in relapse rate. However, there is not enough evidence about their efficacy in patients with primary progressive multiple sclerosis (PPMS). Identify and summarize the evidence that ss-interferon is beneficial and safe in patients with PPMS. We searched the Cochrane MS Group Trials Register (May 2009); The Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library, (2009, Issue 2); MEDLINE (PubMed) (January 1966 to May 2009), EMBASE (January 1974 to May 2009); NICE (January 1999 to May 2009); LILACS (January 1986 to May 2009); Screening of reference lists of all primary studies found; Contact and inquiry of drug manufactures and multiple sclerosis experts. Randomized double or single blind, placebo-controlled trials of recombinant ss-interferon in patients with PPMS including trials of MS which report separate outcomes in subgroups of patients with PPMS. Two reviewers independently extracted and assessed trials' quality according to the criteria outlined in The Cochrane Handbook. Of 1777 potential studies evaluated, only two Randomized Control Trials (123 patients) were included. ss-interferon treatment compared to placebo did not show differences regarding the proportion of patients with progression of the disease (RR 0.89, 95% CI 0.55 to1.43), and it was associated with a greater frequency of treatment-related adverse events (RR 1.90, 95% CI 1.45-2.48). One of the trials evaluated the MRI secondary outcome pre-specified in the protocol. This trial showed that at two years the numbers of active lesions on brain MRI scan in ss-interferon arm were significantly lower than in placebo arm (weighted mean difference -1.3, 95% CI -2.15 to -0.45, P = 0.003); also, the number of participants with active lesions was significantly higher in placebo arm vs. ss-interferon arm at two years (RR 0.43, 95% CI 0.22 to 0.86, P = 0.02). Limited data on the effect of ss-interferon treatment on PPMS exists. Only two single-centre placebo controlled trials of interferon beta have been done. Based on this review, the included studies showed that ss-interferon treatment was not associated with reduced disability progression in PPMS patients. However, the trial population was too small to allow definitive conclusions on the efficacy of ss-interferon therapy in PPMS patients. Larger research studies need to be done in patients with PPMS in order to clarify whether ss-interferon is effective in this population.

Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN study

The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines proposed a classification for allergic rhinitis based on the duration of symptoms (intermittent, persistent) rather than on the time of allergen exposure (seasonal, perennial). There is no placebo-controlled, randomized clinical trial on intermittent allergic rhinitis (IAR) to date. Desloratadine (DL) is recommended for the first-line treatment of seasonal and perennial allergic rhinitis. To assess the efficacy and safety of DL in subjects with IAR based on the ARIA classification. Patients over 12 years of age with IAR were assessed over 15 days of treatment with DL 5 mg once daily (n = 276) or placebo (n = 271). The primary endpoint was the AM/PM reflective total 5 symptom score (T5SS). Secondary endpoints included AM/PM instantaneous T5SS and individual symptoms, therapeutic response, symptom severity by visual analogue scale, and quality-of-life. The mean reduction of AM/PM reflective T5SS was significantly greater with DL than with placebo over 15 days (-3.01 vs-2.13, P < 0.001) and on each individual day (P < 0.05). Mean AM instantaneous T5SS was reduced significantly with DL compared to placebo as early as day 2 (-1.84 vs-0.89; P < 0.001). The therapeutic response and improvement in quality-of-life were significantly greater with DL than with placebo (P < 0.001 for each). The frequency of treatment-related adverse events was low and similar between DL (7.2%) and placebo (7.0%). This is the first large trial to show that treatment can be effective in IAR. Desloratadine was effective and safe.

Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study

Short-course therapy has been advocated for the treatment of community-acquired pneumonia (CAP). We compared the efficacy and safety of 5 and 7 day courses of gemifloxacin for outpatient treatment of mild-moderate CAP. In a multicentre, double-blind, parallel group study, patients were randomized to receive 320 mg of oral gemifloxacin once daily for 5 or 7 days. Over 95% of all patients in each cohort had a Fine score of <or=III. The primary efficacy endpoint was clinical cure at follow-up (days 24-30). Secondary outcomes were clinical and bacteriological responses at the end of therapy (days 7-9) and bacteriological and radiological responses at follow-up. Adverse events (AEs) were also monitored. In a total of 469 per protocol (PP) patients, clinical resolution at follow-up was 95% and 92% for 5 and 7 day treatments, respectively [95% confidence interval (CI) -1.48, 7.42], indicating non-inferiority of 5 day treatment. Clinical resolution at the end of therapy was 96% for both regimens (95% CI -3.85, 3.42). Bacteriological response rates in PP patients at the end of therapy were 94% and 96% for 5 and 7 day groups, respectively (95% CI -8.27, 3.25) and 91% for both groups at follow-up (95% CI -6.89, 7.93). Radiological success in PP patients at follow-up was 98% and 93% in 5 and 7 day groups, respectively (95% CI 0.35, 7.91). Pre-therapy pathogens were identified in 242 (47.3%) patients, most commonly Streptococcus pneumoniae. Frequency of treatment-related AEs was 21% in both cohorts with discontinuation rates of 1.2% and 2% in the 5 and 7 day groups, respectively. A lower incidence of rash was observed in the 5 day cohort (0.4%) versus the 7 day cohort (2.8%) (P=0.04). Gemifloxacin once daily for 5 days is not inferior to 7 days in the PP population with respect to clinical, bacteriological and radiological efficacy. Further work is needed, however, to explore whether fewer treatment days would improve patient compliance and reduce the incidence of AEs.

First‐ and second‐line chemotherapy with docetaxel or mitoxantrone in patients with hormone‐refractory prostate cancer

Docetaxel and mitoxantrone are considered first-line chemotherapeutic options in patients with hormone-refractory prostate cancer (HRPC), but their clinical effectiveness in a second-line setting is unknown. Therefore, the authors conducted a population-based retrospective study to establish activity and tolerability of second-line docetaxel or mitoxantrone in HRPC. The study included 68 patients who had failed androgen ablation therapy and who received docetaxel and mitoxantrone in either sequence. Clinical efficacy in terms of median overall survival (OS), progression-free survival (PFS), posttreatment prostate-specific antigen (PSA) decline of > or = 50% and treatment-related toxicity were evaluated. Of 68 patients, 35 received docetaxel followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel. Both groups were comparable for recognized pretreatment prognostic factors. Patients who received docetaxel first-line had a trend toward longer median OS compared with patients treated with second-line docetaxel after mitoxantrone failure (22 mos, 95% confidence interval [CI], 17.2-26.8 mos vs. 15 mos, 95% CI, 10.4-19.6 mos). Median number of second-line chemotherapy cycles was 3 and median PFS survival was 2-3 months in both groups. Second-line docetaxel produced a higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this did not translate to a survival benefit. Both second-line docetaxel and mitoxantrone were associated with a high frequency of treatment-related adverse events that resulted in dose reduction, delay, or discontinuation (64% and 46% of patients, respectively). Study results favored docetaxel given up-front for patients with HRPC considered suitable for further chemotherapy. Second-line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients who are candidates for second-line chemotherapy, should be enrolled into clinical trials.

Efficacy and Safety of Ciclesonide Nasal Spray for the Treatment of Seasonal Allergic Rhinitis

RATIONALE: Intranasal corticosteroids are considered the most effective treatment for the management of allergic rhinitis (AR) symptoms. The objective of this study was to evaluate the efficacy and safety of a new corticosteroid in development for the treatment of asthma and AR, ciclesonide (CIC), in patients with seasonal AR (SAR).METHODS: In this phase III, double-blind, placebo-controlled trial, patients with SAR (age ≥ 12 years) were randomized to receive intranasal CIC 200 μg (n = 164) or placebo (n = 163) once daily for 28 days. Patient-assessed total nasal symptom score (TNSS), physician-assessed overall nasal signs and symptoms severity (PANS), and Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) were evaluated. Adverse events (AEs) were monitored throughout the study.RESULTS: Ciclesonide significantly improved the average of am and pm reflective TNSS and instantaneous TNSS versus placebo from Days 1 through 14 (primary endpoint) and over the 28-day treatment period (p <0.001). Furthermore, CIC showed similar improvements in both am and pm placebo-adjusted reflective TNSS, suggesting a 24-hour effect. At Day 15, CIC improved RQLQ by -1.17 ± 0.10 compared with improvement of -0.72 ± 0.10 with placebo (p = 0.002). The frequency of treatment-related AEs was low and comparable between treatment groups, and the placebo-adjusted epistaxis rate for CIC was 1.8%.CONCLUSIONS: Ciclesonide administered intranasally was superior to placebo in relieving nasal symptoms in adult and adolescent patients with SAR. Ciclesonide was well tolerated, with a safety profile comparable with placebo and a low epistaxis rate. These data support the continued clinical development of CIC nasal spray. RATIONALE: Intranasal corticosteroids are considered the most effective treatment for the management of allergic rhinitis (AR) symptoms. The objective of this study was to evaluate the efficacy and safety of a new corticosteroid in development for the treatment of asthma and AR, ciclesonide (CIC), in patients with seasonal AR (SAR). METHODS: In this phase III, double-blind, placebo-controlled trial, patients with SAR (age ≥ 12 years) were randomized to receive intranasal CIC 200 μg (n = 164) or placebo (n = 163) once daily for 28 days. Patient-assessed total nasal symptom score (TNSS), physician-assessed overall nasal signs and symptoms severity (PANS), and Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) were evaluated. Adverse events (AEs) were monitored throughout the study. RESULTS: Ciclesonide significantly improved the average of am and pm reflective TNSS and instantaneous TNSS versus placebo from Days 1 through 14 (primary endpoint) and over the 28-day treatment period (p <0.001). Furthermore, CIC showed similar improvements in both am and pm placebo-adjusted reflective TNSS, suggesting a 24-hour effect. At Day 15, CIC improved RQLQ by -1.17 ± 0.10 compared with improvement of -0.72 ± 0.10 with placebo (p = 0.002). The frequency of treatment-related AEs was low and comparable between treatment groups, and the placebo-adjusted epistaxis rate for CIC was 1.8%. CONCLUSIONS: Ciclesonide administered intranasally was superior to placebo in relieving nasal symptoms in adult and adolescent patients with SAR. Ciclesonide was well tolerated, with a safety profile comparable with placebo and a low epistaxis rate. These data support the continued clinical development of CIC nasal spray.

Sparfloxacin versus ciprofloxacin for the treatment of community-acquired, complicated skin and skin-structure infections

Fluoroquinolones have been shown to be effective in the treatment of complicated skin and skin-structure infections, in part because of their broad-spectrum antibacterial activity against causative pathogens that are resistant to older antimicrobial agents. We enrolled 603 adult patients (>58% male, >85% white) in a doublemasked, double-dummy, randomized, mu1ticenter trial to compare the efficacy and tolerability of sparfloxacin (400-mg loading dose followed by 200 mg once daily) with those of ciprofloxacin (750 mg twice daily) for 10 days in the treatment of community-acquired, complicated skin and skin-structure infections. The primary efficacy variable was clinical response, based on assessment of signs and symptoms, in the clinically assessable population. Patients in the sparfloxacin and ciprofloxacin groups were comparable with respect to demographic characteristics, underlying diseases, medical history, and laboratory test results. Wound infection was the most common diagnosis, and Staphylococcus aureus was the most frequently isolated pathogen. For the 475 clinically assessable patients, the clinical success rate (percentage of patients cured or improved) was 90.1% (210/233) with sparfloxacin and 87.2% (211/242) with ciprofloxacin. In this analysis (95% confidence interval [CI], −2.8 to 8.6) and the intent-to-treat analyses (95% CI, −4.2 to 6.2), results with sparfloxacin were statistically equivalent to those with ciprofloxacin (95% CI, −1 to 15.3). For bacteriologically assessable patients, eradication rates were 87.0% (141/162) with sparfloxacin and 79.9% (123/154) with ciprofloxacin (95% CI, −1 to 15.3). Eradication rates of S aureus and coagulase-negative staphylococcal infections were 90.2% (101/112) with sparfloxacin and 77.9% (88/113) with ciprofloxacin. For patients with 2 or more pathogens at baseline (mixed infections), bacteriologic success was 87.6% for sparfloxacin and 77.9% for ciprofloxacin. Pseudomonas aeruginosa infections were eradicated or presumed eradicated in 71.4% (10/14) of sparfloxacin-treated patients and 87.5% (7/8) of ciprofloxacin-treated patients. Overall success rates in the bacteriologically assessable patients for sparfloxacin (84.6% [137/162]) and ciprofloxacin (78.6% [121/154]) were statistically equivalent (95% CI, −2.5 to 14.5). Tolerability was assessed in all patients who received study medication. The overall frequency of treatment-related adverse events was comparable in the 2 treatment groups (26.5% sparfloxacin, 23.3% ciprofloxacin). Drug-related adverse events involving the digestive system occurred in 7.1% of sparfloxacin-treated patients and 19.0% of ciprofloxacin-treated patients; photosensitivity reactions were reported in 11.1 % of patients in the sparfloxacin group and 0.7% of patients in the ciprofloxacin group ( P < 0.001). The mean change in QT c interval from baseline to the maximum on-treatment value was greater in the sparfloxacin group (9 milliseconds) than in the ciprofloxacin group (3 milliseconds) ( P = 0.005; 95% CI, 0.002 to 0.010). The efficacy of sparfloxacin was comparable to that of ciprofloxacin in the treatment of community-acquired, complicated skin and skin-structure infections, including those caused by staphylococci, the most common pathogens. Sparfloxacin's once-daily regimen, high skin-tissue penetration, and improved activity against gram-positive cocci make it a therapeutic alternative to ciprofloxacin for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QT c interval.