Urinary Tract Infections
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.