Terodiline in the treatment of urinary frequency and motor urge incontinence. A controlled multicentre trial

Abstract

Terodiline is a secondary amine with antimuscarinic and calcium antagonistic properties. It has complete bioavailability from the gastro-intestinal tract and a mean elimination half-life of 60 hours. This paper describes a randomized, double-blind, two period cross-over (3 week periods) trial in women with motor urge incontinence without other neurological symptoms. The drug was given b.i.d., 12.5 mg in the morning and 25 mg at night. The trial was performed as a multicentre study and monitored by frequent site visits during the 9 months when patients entered the study. Eighty-nine patients from 19 clinics fulfilled the inclusion criteria of the protocol. Cystometrograms (CMG) (bladder capacity, volume at first desire to void, residual urine) and micturition characteristics over 3 to 7 days were measured during a one week run-in period and during the last week of each treatment period. The patients' preferences were assessed for the two treatment periods as well as vis-à-vis the run-in period. Side effects were evaluated at the end of each treatment period. There were 16 drop-outs and withdrawals during period 1 and 9 during period 2 (5 and 3 due to cystitis, 7 and 2 due to side effects, and 4 and 4 lost to follow up, respectively). During the evaluation of the data a treatment by period interaction was observed which motivated a parallel group analysis to be performed in addition to a cross-over trial analysis. Statistically significant differences in patient preferences were demonstrated (63% preferred terodiline in comparison with placebo and 69% terodiline in comparison with run-in). No statistically significant difference in incidence of side effects could be demonstrated between terodiline and placebo. Based on all data available 35% of the patients had side effects on placebo and 53% on terodiline. Twelve per cent reported dryness of the mouth on placebo and 25% on terodiline. Of the 9 patients (10%) withdrawn from the study because of side effects, 7 had terodiline as first treatment, one had placebo and one terodiline as second treatment. The frequency of voluntary micturitions decreased during period 1 from 9.6 to 8.9 (-0.7) per 24 hours on placebo and from 9.9 to 7.3 (-2.6) on terodiline. Involuntary micturitions decreased from 2.3 to 1.7 (-0.6) on placebo and from 2.5 to 1.5 (-1.0) on terodiline. The changes during terodiline were statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)