Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder.

PURPOSE: In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin. MATERIALS AND METHODS: The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition. RESULTS: Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo). CONCLUSIONS: In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.

The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial.

The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.

Increases in leucocyte and platelet counts induced by the alkyl phospholipid hexadecylphosphocholine.

Hexadecylphosphocholine (HePC) is a new alkyl phospholipid that has been shown to have antitumour activity in vitro and in vivo. In vivo studies have shown absence of bone marrow toxicity at therapeutic doses. In addition, at the highest dosage group in rats, an increase in white blood cell counts (WBC) was observed. To study the presence of a similar phenomenon in man, frequent measurements of haematological parameters were performed in a series of phase II studies. 70 patients were treated with daily doses of 100-200 mg of the oral formulation of HePC. WBC and platelet counts were performed weekly. In a subgroup of 23 patients serum levels of haemopoietic growth factors were measured before and during treatment. A significant increase in WBC and platelet counts was seen in 74 and 73% of the patients, respectively. In 4 patients, bone marrow showed normal cellularity, and in 1 patient, bone marrow culture showed normal numbers and sizes of colony forming units. No abnormal levels or trends over time of cytokines were observed. We conclude that oral HePC induces an increase in WBC and platelet counts in the majority of those treated.