Indevus Pharmaceuticals, Inc., a biopharmaceutical company, announced data from the first of two phase III clinical trials with Sanctura XR for overactive bladder (OAB). Sanctura XR is the once-daily formulation of Sanctura, which is currently marketed for overactive bladder.
The data from the recently completed trial showed that Sanctura XR met its primary endpoints, reduction in frequency of urination (toilet voids) and reduction in number of urge incontinent episodes. The trial also achieved all of its key secondary endpoints, including an increase in volume voided and a reduction in the severity of urgency, a defining symptom of OAB. In addition, the drug was extremely well tolerated and had a very low incidence of dry mouth which is a common side effect in patients treated for overactive bladder.
"We have taken a very good drug in Sanctura and, with advanced technology, made it better," stated Glenn L. Cooper, M.D., chairman, president and chief executive officer of Indevus. "With Sanctura XR, I believe we have established a new benchmark in tolerability for oral drugs for the treatment of overactive bladder with a dry mouth incidence of 8.7 percent. Sanctura, which has been marketed for nearly two years, already has excellent characteristics including low CNS side effects, lack of metabolic drug-drug interactions, rapid onset of action, and is excreted largely unchanged into the target organ, the bladder. Sanctura XR has all of these benefits and the convenience of once-daily dosing. With the results of this trial, Indevus and our partner, Esprit Pharma, have the opportunity to significantly improve the treatment of overactive bladder patients with Sanctura XR. We are looking forward to announcing the results of our second trial in July and filing an NDA before the end of the calendar year."
Both trials in the phase III clinical program are randomized, double-blind, placebo-controlled trials comparing the reduction in the frequency of urination and the reduction in urge urinary incontinence episodes among drug-treated patients versus placebo patients. This 12-week trial measured the effects of Sanctura XR 60 mg versus placebo, once-daily, on symptoms of OAB. The trial included 601 patients, 298 treated with Sanctura XR and 303 treated with placebo, at 55 clinical sites in the United States.
Patient entry criteria included urinary frequency of 10 or more toilet voids per day, symptoms of OAB (including urgency) lasting at least six months, and an average of one or more incontinence episodes per day. Patients were excluded if the major reason for their urinary frequency or urine loss was stress incontinence. The average age and gender of the patients were similar for both the Sanctura XR and placebo groups, with an overall average age of 59 years and 85 per cent women. Approximately 83 per cent of these patients are participating in an ongoing nine-month open label extension of the study.
Patients treated with Sanctura XR experienced statistically significant (p less than 0.0001) improvement in number of toilet voids per day at the end of the 12-week trial, compared to patients on placebo. At Week 12, Sanctura XR patients had 2.81 fewer toilet voids per day compared to baseline, and placebo patients had 1.99 fewer toilet voids per day compared to baseline. The magnitude of improvement in number of toilet voids for the Sanctura XR group compared with the placebo group was statistically significant beginning at Week 1 and continued to increase at Weeks 4 and 12 of the trial.
Sanctura XR patients also experienced statistically significant (p less than 0.0001) improvement in number of urge urinary incontinence events per day at the end of the 12-week trial, compared to placebo patients. At Week 12, Sanctura XR patients had a 78 per cent median reduction in the number of incontinence episodes per day, whereas, 56 percent of the placebo-treated patients had the same effect. The magnitude of incontinence episode reduction for the Sanctura XR group compared with the placebo group was statistically significant beginning at Week 1 and continued to increase at Weeks 4 and 12 of the trial.
The improvement in volume voided per void for Sanctura XR patients was statistically significant beginning at Week 1 and continuing through Week 12 (p=0.004), with an increase of 30 milliliters (mL) at Week 12, compared to an increase of 19 mL in placebo patients. Treatment with Sanctura XR also led to a statistically significant improvement (decrease) in average urgency severity, another key symptom of OAB, beginning at Week 1 and continuing through Week 12 (p=0.0004). These findings are consistent with the expected pharmacodynamic effects of Sanctura XR and the increase of maximum bladder capacity caused by anticholinergic relaxation of the detrusor muscle.
The study completion rate for Sanctura XR was 88 per cent, and 90 per cent for placebo. Four percent of Sanctura XR patients and 4 percent of placebo patients discontinued the study due to adverse events.
Sanctura XR was well tolerated as evidenced by its adverse event profile that included the most common adverse events associated with the antimuscarinic class of drugs, dry mouth and constipation. The incidence of dry mouth observed in Sanctura XR patients was 8.7 per cent, compared to 3.0 per cent with placebo. These incidence rates are lower than those that have been reported in Sanctura patients (20.1 per cent for Sanctura vs. 5.8 per cent for placebo). The incidence of constipation was reported in 9.4 per cent of Sanctura XR patients compared to 1.3 per cent with placebo. Nervous system disorders were reported in 2.7 per cent of Sanctura XR patients compared to 4.0 per cent with placebo. Specifically, headache was reported in 1.0 per cent of Sanctura XR patients compared to 2.6 per cent with placebo. In addition, blurred vision was reported in 1.0 percent of Sanctura XR patients compared to 0.7 per cent with placebo.
Sanctura is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency. The most commonly reported side effects in phase III U.S. clinical trials were dry mouth (20.1 per cent for Sanctura vs. 5.8 per cent for placebo) and constipation (9.6 per cent for Sanctura vs. 4.6 per cent for placebo). Patients who have urinary retention, gastric retention, uncontrolled narrow-angle glaucoma or hypersensitivity to Sanctura should not use Sanctura.