Is cizolirtine citrate safe and effective for treating urinary incontinence secondary to overactive bladder : a phase 2 proof-of-concept study?
Most patients (92.6%) were female, and their mean age was 51.8 yr. Bladder diary variables improved significantly with active drug over placebo: The average number of voidings per 24 h was reduced by 33.4%, 17.0%, and 34.3% (p=0.001) in the cizolirtine citrate, placebo, and oxybutynin groups, respectively. The mean estimated voided volume per voluntary micturition increased by 17.8%, 0%, and 14.5% (p=0.002) in the cizolirtine citrate, placebo, and oxybutynin groups, respectively. The proportions of patients achieving fewer than eight voidings per 24 h, complete dryness, or both were also superior with active drugs over placebo. Only cizolirtine showed significant superiority over placebo to improve urodynamic parameters, although the asymmetrical allocation played against oxybutynin in the inferences. Cizolirtine citrate caused fewer antimuscarinic but more gastrointestinal (nausea) and neurologic (headache and vertigo) adverse events than oxybutynin.
The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic-hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reduction.