Urinary Tract Infections

April 2, 2018

Allecra Therapeutics announced positive top-line results from the Phase II study of its lead antibiotic candidate, AAI101. The Phase II CACTUS study (Randomized, Double-Blind, Multi-Center Study of Cefepime/AAI101 in hospitalized adults with Complicated UTIs) met all study objectives. AAI101 was given intravenously to patients in combination with cefepime for the treatment of cUTI including acute pyelonephritis (AP). The study was designed to determine the optimal dose of cefepime/AAI101 to be taken forward into future Phase III studies. 45 patients were randomized 2:1 into two cohorts, each with a separate control. Patients randomized into Cohort 1 received either 500mg of AAI101 combined with 1g of cefepime (n=15), or 1g of cefepime monotherapy (n=7). Patients randomized into Cohort 2 received 750mg of AAI101 combined with 2g cefepime (n=15), or 2g of cefepime monotherapy (n=8). Dosing was conducted intravenously three times daily for seven to ten days.

February 19, 2018

TetraPhase Pharmaceuticals announced that its IGNITE3 clinical trial evaluating the efficacy and safety of once-daily intravenous (IV) eravacycline compared to ertapenem for the treatment of patients with complicated urinary tract infections (cUTI) did not achieve statistical non-inferiority of eravacycline to ertapenem. The study failed to meet the co-primary efficacy endpoints of responder rate in the microbiological intent-to-treat (micro-ITT) population at the end-of-IV (EOI) treatment visit and at the test-of-cure (TOC) visit, which were evaluated using a 10% non-inferiority margin. Eravacycline was well-tolerated in IGNITE3, with a safety profile consistent with prior studies. IGNITE3 was a Phase III randomized, multicenter, double-blind clinical trial evaluating the efficacy and safety of once-daily IV eravacycline. The Phase III IGNITE3 clinical trial enrolled 1,205 patients who were randomized 1:1 for a minimum of five days, and then were eligible for transition to an appropriate approved oral agent. Responder rates in the micro-ITT population at the EOI visit were 84.8% and 94.8% for eravacycline (n=363/428) and ertapenem (n=382/403), respectively (-10% CI: -14.1%, -6.0%). Responder rates at the TOC visit were 68.5% and 74.9% for eravacycline (n=293/428) and ertapenem (n=302/403), respectively (-6.5% CI: -12.6%, -0.3%).

January 8, 2018

NxThera announced the three-year outcomes data from the Rezūm II pivotal clinical trial of its minimally invasive Rezūm System, dem­onstrating significant, effective and durable lower urinary tract symptom (LUTS) relief, improved quality of life and preserved sexual function for men treated for benign prostatic hyperplasia (BPH). The Rezūm II randomized, controlled trial enrolled 197 men from 15 sites in the U.S., and one-, two- and now three-year data from this trial has demonstrated durable symptom relief with preserved sexual function in patients who were treated with the Rezūm System. The seven individual IPSS domains, including urgency and nocturia, indicated significant relief of symptoms at one month, remained significant throughout three years (p<0.0001). Sexual function was preserved in patients treated with the Rezūm System, as measured via the International Index of Erectile Function (IIEF-15) and Male Sexual Health Questionnaire (MSHQ) through three years of follow-up. The ejaculatory bother score (MSHQ-EjD) improved over baseline from 12 to 36 months (p<0.004). No latent related adverse events occurred and no de novo erectile dysfunction was reported. Surgical retreatment rate was 4.4 percent (six out of 135 subjects) over three years of follow-up. Four of these six secondary interventions were related to an untreated median lobe at baseline. Thirty of the patients received treat­ment to the median lobe or elevated central zone, in addition to treating the lateral lobes; these 30 patients not only demonstrated sig­nificant improvements in symptom (IPSS) and urinary flow rates (Qmax), but also demon­strated decreased post-voiding residual (PVR) urine from 24 months to 36 months (p<0.04). Surgical retreatment rate was 4.4 percent (six out of 135 subjects) over three years of follow-up. Four of these six secondary interventions were related to an untreated median lobe at baseline.

April 17, 2017

Zavante Therapeutics issued results of a phase II/III trial of ZOLYD (fosfomycin for injection, also known as ZTI-01 for complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). The ZEUS study was a multicenter, randomized, double-blind trial designed to evaluate the safety and efficacy of ZOLYD. The primary endpoint of overall success, defined as clinical cure plus microbiologic eradication, was assessed in the microbiologic-modified intent-to-treat population at the test-of-cure visit (day 19). In the study, ZOLYD met the primary endpoint of statistical non-inferiority compared to piperacillin/tazobactam, with an overall success rate of 64.7% (119/184 patients) versus 54.5% (97/178 patients), respectively, a treatment difference of 10.2% (95% CI: -0.4, 20.8). Clinical cure rates were high and similar between treatment groups (90.8% vs. 91.6%, respectively). Zavante expects to submit a new drug application to the FDA in early 2018. 

October 3, 2016

NovaBay Pharmaceuticals issued results of a phase IIb study of Auriclosene Irrigating Solution (AIS) in the prevention of urinary catheter blockage and encrustation in subjects with chronic indwelling urinary catheters who have repeat history of blockage. In the parallel design, two-arm study, 36 subjects with chronic indwelling catheters were treated twice weekly for four weeks with either AIS or Vehicle Solution (citric-acid buffer). At the end of the treatment period, catheter flow rate measurements based on an ASTM FDA-recognized standard from both study arms were compared with flow measurements from identical new catheters in a blinded evaluation. The primary efficacy endpoint comparing percent flow rate reduction of AIS-treated catheters to vehicle-treated catheters was achieved with statistical significance (p<0.05). The clinical efficacy endpoint was also achieved with statistical significance, with no blockage in subjects in the AIS arm versus clinical blockage in 28% of the subjects treated with vehicle. There were no serious adverse events reported in the study and auriclosene was generally well-tolerated. In 14 per-protocol subjects, comparison of percent encrustation of catheters treated with AIS and saline showed a significant reduction in favor of AIS (Wilcoxon signed-rank test p<0.001). No serious adverse events were reported, and overall tolerability was considered good. 

July 11, 2016

The Medicines Company has announced phase III results of CARBAVANCE (meropenem-vaborbactam) for complicated urinary tract infection (cUTI). TANGO 1 was a multicenter, randomized, double-blind, double-dummy study to evaluate the efficacy, safety and tolerability of CARBAVANCE compared to piperacillin-tazobactam in the treatment of cUTI, including acute pyelonephritis, in adults. The trial enrolled 550 adult patients randomized 1:1 to receive CARBAVANCE (meropenem 2g-vaborbactam 2g) as a three-hour IV infusion every eight hours or piperacillin 4g-tazobactam 500mg as a 30 minute IV infusion every eight hours, each for up to 10 days. After a minimum of five days of IV therapy, patients who met protocol-defined criteria of improvement were transitioned to oral levofloxacin. For the FDA, the primary assessment was performed in the microbiologic modified intent-to-treat (mMITT) patient population, and was defined as overall success of clinical outcome (cure or improvement and microbiologic outcome of eradication (baseline bacterial pathogen reduced to <104 CFU/ml)). Overall success was observed in 188/192 patients (98.4%) in the meropenem-vaborbactam group and in 171/182 patients (94.0%) in the piperacillin-tazobactam group—a difference of 4.5% (95% CI: 0.7 % to 9.1%). For the EMA, the primary assessment was defined as microbiologic outcome of eradication (baseline bacterial pathogen reduced to <103 CFU/ml) at the test-of-cure (TOC) visit in the mMITT and microbiologic evaluable (ME) patient populations. For the mMITT patient population, the microbiological eradication was 128/192 patients (66.7%) in the meropenem-vaborbactam group and 105/182 patients (57.7%) in the piperacillin-tazobactam group—a difference of 9.0% (95% CI: -0.9% to 18.7%). For the ME patient population, the microbiological eradication was 118/178 patients (66.3%) in the meropenem-vaborbactam group and 102/169 patients (60.4%) in the piperacillin-tazobactam group—a difference of 5.9% (95% CI: -4.2% to 16%). The company believes that TANGO 1 provides the pivotal clinical data necessary for the submission of an NDA with the FDA and a marketing authorization application (MAA) with the EMA. 

August 25, 2008

Eli Lilly reported positive results from a phase IIb trial of tadalafil for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This randomized, double-blind, placebo-controlled study enrolled 1,056 male subjects across several international sites. Any of the subjects who had undergone treatment for erectile dysfunction or other BPH treatments underwent a 4-week treatment-free screening period. All subjects then received placebo for four weeks prior to randomization. They were then divided randomly into five groups and received a placebo, or tadalafil doses of 2.5, 5.0, 10.0 or 20.0 mg/day. Efficacy was based on the International Prostate Symptom Score (I-PSS). All doses of tadalafil were superior to placebo for relieving LUTS, with statistically significant effects at 4, 8 and 12 weeks. The treatments decreased I-PSS scores from 3.9 to 5.2 points in the different dosage groups. Of the doses studied, 5 mg per day improved the I-PSS by 4.9 points and provided the best risk-benefit profile. Based on the results Eli Lilly plans to continue with the development of tadalafil for this indication.

November 6, 2006

Urigen released mixed results from a phase II trial of U101 for the treatment of chronic pelvic pain of bladder origin. This placebo-controlled, double-blind trial enrolled 90 subjects. Treatment did not meet the overall primary endpoint of improvement in pain and urgency at the end of the study, as monitored by the PORIS (Patient Overall Rating of Improvement of Symptoms) questionnaire. However, improvement was seen in other endpoints, including an improvement in urinary urgency at visit 1 on a ten point analog urgency scale for those on active drug versus placebo (p=0.006) and a trend toward improvement in pain in all subjects at visit one. Based on these results, Urigen plans to make some protocol changes and move development of U101 into further trials.

December 15, 2003

Peninsula Pharmaceuticals reported positive results from a preliminary analysis from a phase II trial with doripenem (S-4661), a broad-spectrum carbapenem antibiotic for the treatment of urinary tract infections. Results showed that doripenem met the primary endpoints of the trial and was well tolerated by. The international, randomized, historically controlled enrolled 121 subject at 12 sites in Europe, South America, and the U.S. The study investigated doripenem in hospitalized subjects with complicated urinary tract infections, including pyelonephritis. Subjects received three doses daily of either 250mg or 500mg of doripenem intravenously. Phase III trials are planned for 2003.

June 17, 2002

Phase II trial results suggest that the efficacy of DepoMed's extended-release Ciprofloxacin GR is comparable to that of the currently marketed immediate-release ciprofloxacin formulation (Cipro, Bayer AG). The randomized, double-blind, parallel-group study evaluated the efficacy and safety of once-daily Ciprofloxacin GR (500 mg qd) with twice-daily immediate-release ciprofloxacin (250 mg bid) in female subjects with uncomplicated urinary tract infections (UTIs). At one and five weeks post-treatment, both medications were comparably effective in the eradication of causative organisms and the resolution of clinical signs and symptoms. Three subjects treated with immediate-release ciprofloxacin reported nausea and two experienced dizziness, while subjects treated with Ciprofloxacin GR reported neither effect. Twenty-eight percent of subjects in the immediate-release group reported adverse effects, compared to 17% treated with Ciprofloxacin GR.

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