Thorough QT/QTc study in patients with advanced Parkinson's disease: cardiac safety of rotigotine.

The potential effects of the dopamine agonist rotigotine on cardiac repolarization were studied in patients with Parkinson's disease, which affects electrocardiogram (ECG) quality. The parallel-group trial was double-blind and placebo- and positive (moxifloxacin 400 mg)-controlled. After two 24-h baseline ECGs, patients were randomized to rotigotine (n = 66) or placebo (n = 64). Twenty four-hour ECGs were recorded on days 14/15, 21/22, 28/29, 35/36, and 42/43 of a regimen involving weekly dose escalations of 4 mg/24 h (4 mg/24 h-24 mg/24 h). In 10-s ECGs (n = 357,948) selected from 24-h records, QT measurements were manually verified and individually rate-corrected (QTc). Assay sensitivity showed maximum mean 13.5 ms QTc prolongation after moxifloxacin with 95% confidence interval (CI) 11.8-15.2 ms. Rotigotine vs. placebo differences in time-matched changes from baseline (54 data points/24 h) showed mean effects close to zero with upper one-sided 95% CI <5 ms. Accurate, thorough QTc studies are possible even in patients with diseases that profoundly affect ECG quality. Rotigotine in supra- and therapeutic doses was shown not to affect cardiac repolarization.

Acne resolution rates: results of a single-blind, randomized, controlled, parallel phase III trial with EE/CMA (Belara) and EE/LNG (Microgynon).

BACKGROUND AND OBJECTIVE: Acne in women can often be successfully treated by the intake of oral contraceptives containing gestagens with anti-androgenic properties. This study aimed to evaluate the efficacy of the monophasic oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA; Belara for the treatment of mild to moderate papulopustular acne of the face and acne-related disorders in comparison to EE/levonorgestrel (LNG; Microgynon. METHODS: 199 female acne patients were enrolled in a single-blind, randomized, multicentre phase III study and divided into two groups who received either EE/CMA or EE/LNG. The primary end point was fulfilled if the number of papules/pustules per half of the face present on admission had decreased by at least 50% in the 12th medication cycle. RESULTS: 59.4% of the women under EE/CMA and 45.9% under EE/LNG were responders. The relative frequency of women with complete resolution was 16.5% under EE/CMA and 4.3% under EE/LNG at cycle 12. CONCLUSION: EE/CMA is an efficient treatment for women with mild and moderate papulopustular acne of the face and related disorders, reflecting the well-known anti-androgenic properties of the progestogen CMA.

A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 mu(g) ethinylestradiol and either 2 mg chlormadinone acetate or 150 mu(g) desogestrel.

OBJECTIVES: To determine the effect of two low-dose monophasic oral contraceptives containing either 2 mg chlormadinone acetate or 150 microg desogestrel on blood clotting and fibrinolysis. METHODS: In vivo markers of intravascular coagulatory and fibrinolytic activity were measured in 45 volunteers randomly assigned to a 6-month treatment with one of the two study preparations. RESULTS: During oral contraceptive use, the procoagulatory activity increased (increased prothrombin fragment 1+2), the anticoagulatory capacity changed (increased protein C activity, decreased activated protein C sensitivity, decreased protein S activity and decreased antithrombin III activity) and the fibrinolytic system was activated (increased concentrations of plasmin-antiplasmin complexes and D-dimer as well as total fibrin degradation products). There were no relevant differences between the two medication groups. CONCLUSION: Our results demonstrate that both oral contraceptive preparations have comparable effects on the hemostatic system. There was a shift towards a new equilibrium of hemostatic activities, both coagulatory and fibrinolytic, at a higher turnover rate. Changes did not exceed the range of normal variation and were comparable to the published effects of other low-dose oral contraceptives. There was no evidence ofa differential risk of deep vein thrombosis between the two preparations.

Efficacy and safety of the new antiandrogenic oral contraceptive Belara.

The aim of this open, noncontrolled phase III study was the assessment of the contraceptive efficacy and the evaluation of the safety of long-term use of Belara (30 micrograms ethinyl estradiol plus 2 mg chlormadinone acetate). Furthermore, cycle stability during administration of Belara and the influence of Belara on acne and seborrhea as clinical signs of androgenization were observed. Belara was taken by 1655 women for a total of 22,337 cycles. For the theoretical Pearl index, a value of 0.269 (95% CI [0.109, 0.600]) was calculated. In 1655 of 22,337 cycles (7.4%), no withdrawal bleeding was documented, whereas in 2565 of 22,308 cycles (11.5%), spottings and, in 786 of 22,308 cycles (3.5%), breakthrough bleeding occurred. After the intake of Belara for 12 cycles, acne on the face/neck improved in 64.1% of the women (209 of 326). In 53.4% of the women (175 of 326), acne disappeared completely. Seborrhea improved after 12 cycles in 89 of 131 women (67.9%), of whom 76 women (58.0%) were completely cured. Sixty-two serious adverse events (SAE) occurred in 59 of 1655 women. Accidents and injuries of the musculoskeletal system were the SAE with the highest incidence (0.66%). Two cases of deep venous thrombosis, one pulmonary embolism, and two cases of visual disturbances were observed. Only for the two cases of deep venous thrombosis could a relation to Belara be assumed. Of the adverse events commonly reported for oral contraceptives, headache was observed for the first time under study medication in 37.4%, nausea in 23.1%, breast tenderness in 21.7%, and vaginal discharge in 19.4% of the women. The frequency of adverse events decreased with longer duration of a drug consisting of intake of Belara. In conclusion, Belara can be described as an effective and safe oral contraceptive with marked antiandrogenic properties.

PIP: The contraceptive safety and efficacy of long-term use of the oral contraceptive Belara (30 mcg ethinyl estradiol and 2 mg chlormadinone acetate) were assessed in an open, noncontrolled phase III study. Of particular interest was the effect of the anti-androgenic activity of this formulation on clinical signs of androgenization. Belara was taken by 1655 German women (mean age, 25.9 years), for a total of 22,337 cycles. A total of 12 pregnancies occurred, yielding a theoretical Pearl index of 0.269 (95% confidence interval, 0.109-0.600). No withdrawal bleeding occurred in 1655 cycles (7.4%), while spotting was documented in 2565 (11.5%) and breakthrough bleeding in 786 (3.5%). After 12 cycles of use, acne on the face/neck improved in 64.1% of affected women and completely disappeared in 53.4%. Seborrhea improved after 12 cycles in 67.9% of affected women and was cured in 58.0%. Side effects included headache (37.4%), nausea (23.1%), breast tenderness (21.7%), and vaginal discharge (19.4%). Of the 62 serious adverse events reported by 59 women, only the 2 cases of deep venous thrombosis could be linked to Belara use. Overall, these findings suggest that Belara is a well-tolerated oral contraceptive with minor side effects comparable to those associated with use of other low-dose pills.