Fixed-dose combination of nifedipine gastrointestinal therapeutic system and candesartan cilexetil in patients with moderate-to-severe essential hypertension: an open-label, long-term safety and efficacy study.

WHAT IS KNOWN AND OBJECTIVE: The nifedipine gastrointestinal therapeutic system (GITS)/candesartan cilexetil (N/C) combination was demonstrated to be an effective, well-tolerated antihypertensive therapy in a short-term study. The current study investigated the long-term safety and efficacy of a fixed-dose combination (FDC) of N/C therapy in moderate-to-severe essential hypertension. METHODS: A multinational, 70-centre, open-label study of N/C treatment for 28 or 52 weeks at a target dose of N60 mg/C32 mg. The primary assessment included the incidence of treatment-emergent adverse events (TEAEs). Efficacy assessments included change from baseline in systolic and diastolic blood pressure (BP). RESULTS AND DISCUSSION: A total of 508 patients were enrolled, with 417 (82·1%) completing week 28 of treatment. Of these, 200 patients continued treatment, as planned, to week 52, with 193 (96·5%) completing this period. At least one TEAE or drug-related TEAE were reported in 76·8% and 45·3% patients up to week 28, and in 80·7% and 46·9% up to week 52/end of study. Most TEAEs and drug-related TEAEs to week 52 (93·9% and 95·4%, respectively) were mild or moderate in intensity. Rates of drug-related serious AEs were low (0·6%). TEAE-related discontinuations occurred in 10% patients before week 28 and in no additional patients thereafter. N/C provided substantial, sustained reductions in mean systolic and diastolic BP from baseline: 30·1 ± 18·4 and 12·8 ± 10·7 mmHg, respectively, at week 52. WHAT IS NEW AND CONCLUSIONS: Nifedipine GITS/candesartan cilexetil FDC at the target dose of 60 mg/32 mg was well tolerated for a study duration up to 52 weeks and provided sustained reductions in systolic and diastolic BP.

Miglustat has no apparent effect on spermatogenesis in normal men.

BACKGROUND: In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertility, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men. METHODS: After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays. RESULTS: Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed. CONCLUSION: In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control.

Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trial using two doses of the aromatase-inhibitor atamestane. Atamestane Study Group.

BACKGROUND: The concept of estrogen withdrawal by an aromatase inhibitor in the treatment of benign prostatic hyperplasia (BPH) was assessed in a prospective, randomized, double-blind, placebo-controlled multicenter trial. METHODS: Two hundred and ninety-two patients with clinical symptoms of BPH were randomly allocated to one of the following treatments for 48 weeks: placebo or the selective aromatase inhibitor, atamestane, at a daily dose of 100 mg or 300 mg. Both doses of atamestane significantly reduced serum concentrations of estradiol and estrone, and produced a slight, dose-dependent, counter-regulatory increase in peripheral androgen concentration. RESULTS: Clinical symptoms improved during treatment in all three groups. Even after 48 weeks, the effect of active treatment did not exceed the effect seen with placebo. Overall tolerance of 100 mg atamestane was excellent, but 300 mg showed a slightly increased incidence of side effects compared with placebo. CONCLUSIONS: The conclusion from this study is that the reduction in estrogen concentration using the selective aromatase inhibitor atamestane has no effect on clinically established BPH.