SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans.In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts. 18 healthy ozone responders (.20% increase in sputum neutrophils) underwent ozone challenge tests (250 ppb, 3 h intermittent exercise) 1 h after the last treatment dose. Sputum was induced at 3 h post-challenge.After SCH527123 treatment, the ozone challenge resulted in significantly lower sputum neutrophil counts (0.13610 6 ?mL -1 ) compared with prednisolone (0.84610; p,0.001) or placebo (2.98610 6 ?mL -1 ; p,0.001). Comparable results were obtained for total cell count, percentage of sputum neutrophils, and for interleukin-8 and myeloperoxidase in sputum supernatant. Post-challenge, SCH527123 inhibited neutrophilia in peripheral blood but significantly less than in sputum. All treatments were safe and well tolerated. SCH527123 causes significant attenuation of ozone-induced airway neutrophilia in healthy subjects. Further evaluation in a large trial of patients with pulmonary disorders is warranted.

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Introduction Current methods for diagnosing hypoactive sexual desire disorder (HSDD) can be complicated and time-consuming. A previous study reported validity and reliability of a structured diagnostic method created for clinical trials that can be performed in approximately 1 hour. Methods A more succinct tool is needed for incorporation into busy physician practices. Therefore, a brief HSDD screening tool was developed consisting of four self-report questions with an interpretable cut-score and concise confirmatory physician interview. Main Outcome Measures Accuracy of the HSDD screener cut-score alone, and in combination with physician interview, was then separately evaluated when compared with in-depth interview diagnosis. Results The results showed good agreement between the two diagnoses (kappa of 0.669 and 0.562 for cut-score alone and cut-score in combination with physician interview, respectively). Conclusions The HSDD screener can reliably detect the likely presence of HSDD in postmenopausal women.

A short-duration, twice-weekly intralesional SSG treatment for CL accelerates cure and is highly effective and well tolerated.

Introduction: ALXN1210 is a humanized monoclonal antibody (mAb), with a sequence closely related to eculizumab (Soliris®). ALXN1210 binds specifically to human complement protein C5 and was engineered to eliminate the formation of C5a and the terminal complement complex with extended duration of complete complement inhibition. The mechanism of action of ALXN1210 provides strong clinical rationale for potential therapeutic use in patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, and other complement-mediated diseases. Clinical experience with eculizumab supports the reduction of free C5 to undetectable levels for complete inhibition of hemolysis. Methods: In this Phase 1, randomized, blinded, placebo-controlled, single-ascending dose study, healthy subjects received a single intravenous (IV) dose of 200 mg (cohort 1) or 400 mg (cohort 2) ALXN1210 or placebo (PBO), and were then followed for 150 days. Subjects were vaccinated with a tetravalent conjugate N. meningitidis vaccine and received prophylactic penicillin V. The primary objective was to evaluate the safety and tolerability of a single dose of ALXN1210. Secondary objectives were to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALXN1210. PD effects of ALXN1210 were assessed as the change in serum free C5 and ex vivo (cell-based) hemolytic activity. Results: Fourteen subjects enrolled in the study: 4 received 200 mg ALXN1210, 6 received 400 mg ALXN1210, and 4 received PBO. Serum ALXN1210 concentrations were measureable for the entire 150-day follow-up period. Mean Cmax and AUC∞ increased in a dose-proportional manner, with a mean terminal half-life of approximately 32 days and low (<20%) intersubject variability in PK parameters. Levels of free C5 were reduced by >99% from baseline in all subjects who received ALXN1210. Additionally, all subjects who received a single dose of 400 mg ALXN1210 reached or exceeded the ALXN1210 threshold level of 100 µg/ml and had >99% elimination of free C5. For subjects with ALXN1210 levels >100 µg/ml, average elimination of C5 was >99%. No reductions in free C5 concentrations were observed in subjects who received PBO. Mean chicken red blood cell (cRBC) hemolytic activity was completely inhibited after a single dose of 200 or 400 mg ALXN1210. The duration of suppression of mean cRBC hemolysis was dose dependent. No anti-drug antibody (ADA) response was observed during the 150-day follow-up period. Seven subjects (70%) receiving ALXN1210 reported 21 treatment-emergent adverse events (TEAEs); 3 in cohort 1 (200 mg) reported 6 TEAEs, and 4 in cohort 2 (400 mg) reported 15 TEAEs. The most frequently reported event was headache in subjects receiving ALXN1210 (3 subjects [50%], 3 events) or PBO (3 subjects [75%]; 7 events). Most (17/21; 81%) TEAEs were reported as mild, and all resolved during the trial. No drug-related serious AEs or treatment discontinuations due to TEAEs were reported. Conclusions: Single IV doses of 200 mg or 400 mg ALXN1210 were well tolerated in healthy subjects. Serum ALXN1210 concentration data exhibited a terminal half-life of 32 days-longer than eculizumab (9 days). Mean ALXN1210 Cmax and AUC∞ increased in a dose-proportional manner. 100% of subjects who received ALXN1210 had samples with >99% elimination of free C5. In subjects who received a single IV 400-mg dose of ALXN1210: 100% reached or exceeded the ALXN1210 threshold level of 100 µg/mL; 100% obtained >99% elimination of free C5; Mean elimination of free C5 was >99%. For ALXN1210 levels >100 µg/ml, average elimination of free C5 was >99%. Mean cRBC hemolytic activity was completely inhibited after a single dose of 200 or 400 mg ALXN1210, and duration of suppression of mean cRBC hemolysis was dose dependent. No ADA response was observed after a single dose of ALXN1210 during the 150-day follow-up period. Data modeling supports that >99% elimination of free C5 will be achieved with doses of ALXN1210 administered at 4-week or longer dosing intervals. A multiple ascending dose study is ongoing, and 2 studies examining the safety, tolerability, efficacy, PK, and PD of ALXN1210 administered at ≥4-week dosing intervals will be initiated in PNH patients before the end of 2015. Disclosures Sahelijo: Alexion Pharmaceuticals: Employment, Equity Ownership. Mujeebuddin:Alexion Pharmaceuticals: Employment, Equity Ownership. Mitchell:Alexion Pharmaceuticals: Consultancy. Larouche:Inventiv Health: Employment, Other: Inventiv Health Conducted the Study; Alexion Pharmaceuticals: Other: Principal Investigator Of Trial Related to Abstract, Research Funding. Yu:Alexion Pharmaceuticals: Employment, Equity Ownership. Zhang:Alexion Pharmaceuticals: Employment, Equity Ownership. Patel:Alexion Pharmaceuticals: Employment, Equity Ownership. Lasaro:Alexion Pharmaceuticals: Employment. Bouchard:Alexion Pharmaceuticals: Employment. Andrien:Alexion Pharmaceuticals: Employment. Wang:Alexion Pharmaceuticals: Employment. Tamburini:Alexion Pharmaceuticals: Employment, Equity Ownership. Macdonald:Alexion Pharmaceuticals: Employment, Equity Ownership. Sheridan:Alexion Pharmaceuticals: Employment, Equity Ownership. Soni:Alexion Pharmaceuticals: Employment, Equity Ownership.