Background: Genital herpes simplex virus (HSV) type 2 is a common persistent infection that frequently reactivates to cause recurrent lesions and recurrent viral shedding which is incompletely controlled by antiviral therapy. GEN-003 is a candidate therapeutic vaccine containing 2 HSV-2 proteins, gD2 and ICP4, and Matrix-M2 adjuvant (M2). Methods: HSV-2 seropositive persons with genital herpes were randomized into three dose cohorts of Gen-003 (60 mu g antigen/50 mu g M2, 60 mu g/75 mu g M2 or Placebo). Three intramuscular doses 21 days apart of GEN-003 or placebo were administered. Participants obtained genital area swabs twice-daily for HSV-2 detection and monitored genital lesions for 12 months. The rates of virus shedding and lesion rates before vaccination were compared to 3 defined periods after vaccination; Days 43-71, Month 6 and Month 12. Results: GEN-003 at a dose of 60 mu g each antigen/50 mu g M2 reduced HSV shedding immediately after dosing with a rate ratio of 0.58, compared to 0.75 for the GEN-003 6014/75 mu g M2 and 1.06 for placebo. Lesion rates, recurrence rates, and duration of recurrences were also reduced. Reactogenicity was higher with the 75 mu g M2 dose than the 50 mu g M2 dose, specifically for pain, tenderness, malaise and fatigue. Antibody and cellular immune responses were stimulated by both doses and persisted to 12 months. Conclusions: GEN-003 vaccine manufactured with a scalable process gave results similar to those observed in prior clinical trials. GEN-003 had an acceptable safety profile and stimulated both humoral and cellular immune responses. The 60 mu g antigen/50 mu g M2 provided the maximal effect on virologic and clinical measures and warrants further development. (C) 2019 Published by Elsevier Ltd.

OBJECTIVE:The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). METHODS:In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. RESULTS:After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6% of the participants. CONCLUSIONS:The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.

BackgroundGEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses.MethodsAdults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose.ResultsCompared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination.ConclusionsThe most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.

Abstract Background GEN-003 is an investigational genital herpes immunotherapy comprising gD2ΔTMR, an HSV-2 antigen that induces neutralizing antibody and T cell responses, ICP4.2, an HSV-2 T cell antigen selected through human T cell screens, and Matrix-M2™, a saponin-based adjuvant. This Phase 2b study was designed to evaluate efficacy and safety of GEN-003 vs. placebo. Methods Healthy persons, age 18–50 years, with 3–9 HSV-2 genital herpes outbreaks annually were randomized to 3 groups: placebo, or 60 µg of each antigen combined with 50 µg (60/50 group) or 75 µg (60/75 group) of adjuvant, administered 3 times 21 days apart. Study endpoints included safety, immunogenicity, HSV-2 shedding frequency, lesion rate and recurrence frequency. Viral shedding was measured from anogenital swabs by PCR. Swabs were collected for 28 days at baseline, and after the third dose, 6 months and 1 year. The presence of herpes lesions was recorded daily by electronic diary. Results One hundred and thirty-one participants enrolled and >90% received all 3 doses. In the 28-day post-treatment period, viral shedding was reduced by 40% and 27% in the 60/50 and 60/75 groups, respectively, compared with a 5% increase in the placebo group. At 6 months post-treatment, median lesion rates were significantly lower in the 60/50 and 60/75 groups (2.7% and 1.9%, respectively) vs. the placebo group (5.6%, p < 0.05), resulting in median reductions of 52% and 66%. In participants not receiving suppressive antivirals, the median recurrence frequency was 1.0/6 months in the 60/50 group vs. 2.0 in the placebo group (p = 0.08). The median recurrence duration in the 60/50 group was lower than in the placebo group (2.8 vs. 4.2 days; p < 0.05). The most commonly reported adverse events (AEs) following GEN-003 vaccination were injection site pain/tenderness (97%), fatigue (82%), headache (82%) and myalgia (80%). No vaccine-related serious AEs, autoimmune events or other AEs of special interest were reported. Conclusion In adults with recurrent genital herpes, GEN-003 reduced HSV-2 shedding frequency, genital herpes lesion rate, recurrence frequency and recurrence duration through 6 months after the last dose. Local and systemic symptoms were common in GEN-003 recipients, but treatment completion was high with few discontinuations due to AEs. Disclosures T. C. Heineman, GSK group of companies: Consultant and Shareholder, Consulting fee; D. Bernstein, Genocea Biosciences: Consultant and Investigator, Consulting fee and Research support; A. Wald, Genocea Biosciences: Investigator, Research grant and Support for travel to meetings for the study; N. Van Wagoner, Genocea Biosciences: Consultant, Research support and Travel support to present at scientific meetings; P. Leone, Genocea Biosciences: Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Speaker honorarium; T. Oliphant, Genocea Biosciences: Consultant, Consulting fee; A. Natenshon, Genocea Biosciences: Employee, Salary; L. K. McNeil, Genocea Biosciences: Employee, Salary; J. B. Flechtner, Genocea Biosciences: Employee, Salary; S. Hetherington, Genocea Biosciences: Employee, Salary

BACKGROUND:A novel single oral dose granule formulation of secnidazole 2 g, a 5-nitroimidazole with a longer half-life (∼17 hours) than metronidazole (∼8 hours), is being developed to treat bacterial vaginosis. OBJECTIVE:We sought to evaluate the effectiveness and safety of single-dose secnidazole 2 g compared to placebo for the treatment of women with bacterial vaginosis. STUDY DESIGN:In all, 189 women with bacterial vaginosis were randomized 2:1 to receive a single oral dose of secnidazole 2 g (N = 125) or matched placebo (N = 64) at 21 centers in the United States. The primary endpoint was the proportion of clinical outcome responders, defined as those with: (1) normal vaginal discharge; (2) negative 10% potassium hydroxide whiff test; and (3) <20% clue cells of total epithelial cell count on microscopic examination of the vaginal wet mount, using saline at the test of cure/end of study visit (study days 21-30). Secondary efficacy analyses included clinical cure rates, defined as: (1) responders with normal vaginal discharge; (2) negative potassium hydroxide whiff tests; and (3) clue cells <20% assessed at the interim visit (study days 7-14), and test of cure/end of study (study days 21-30). In addition, based on the 2016 US Food and Drug Administration draft guidance, patients with baseline Nugent scores 7-10 were evaluated for clinical cure using the following clinical assessments on study days 7-14: (1) resolution of the abnormal vaginal discharge; (2) a negative potassium hydroxide whiff test; and (3) clue cells <20%. The study was designed and powered to demonstrate the efficacy of single-dose secnidazole 2 g compared to placebo; safety and tolerability were also assessed. Due to a prespecified institutional review board-approved protocol calling for withdrawal of randomized, treated patients with a Nugent score <4 or with a separate sexually transmitted infection, this modified intent-to-treat population was the primary analysis population. Statistical comparisons used a stratified Cochran-Mantel-Haenszel test with a .05 level of significance (2-sided). RESULTS:Single-dose secnidazole 2 g was superior to placebo for the primary and all secondary efficacy measures in the modified intent-to-treat population, with clinical outcome responder rates of 53.3% (57/107) vs 19.3% (11/57; P < .001). Clinical cure rates, based on an alternate definition of responder, which accounted for resolution of abnormal discharge consistent with bacterial vaginosis, were consistent with the clinical outcome responder rate analysis (58.9% vs 24.6%; P < .001) for single-dose secnidazole 2 g vs placebo. Clinical cure rates based on the 2016 US Food and Drug Administration guidance were 64.0% vs 26.4% for single-dose secnidazole 2 g vs placebo. Based on the investigator's clinical assessment at the test of cure/end of study visit, significantly more patients receiving single-dose secnidazole 2 g vs placebo required no additional bacterial vaginosis treatment (68.0% [68/100] vs 29.6% [16/54]; P < .001). Adverse events considered by the investigator to be related to study drug occurred in only 20.0% of single-dose secnidazole 2 g-treated patients vs 10.9% of placebo patients, and they included diarrhea (4.0% vs 1.6%), headache (4.0% vs 3.1%), nausea (4.8% vs 1.6%), and vulvovaginal candidiasis (4.0% vs 3.1%). CONCLUSION:Single-dose secnidazole 2 g was superior to placebo on all primary and secondary outcomes and was well tolerated; these results support its role for the treatment of women with bacterial vaginosis.

INTRODUCTION Previous data have shown that intravaginal dehydroepiandrosterone (DHEA, prasterone) improved all the domains of sexual function, an effect most likely related to the local formation of androgens from DHEA. AIMS To confirm in a placebo-controlled, prospective, double-blind and randomized study the benefits of daily intravaginal DHEA for 12 weeks on sexual function using the Female Sexual Function Index (FSFI) questionnaire. METHODS Placebo was administered daily to 157 women while 325 women received 0.50% (6.5 mg) DHEA daily for 12 weeks. All women were postmenopausal meeting the criteria of vulvovaginal atrophy (VVA), namely moderate to severe dyspareunia as their most bothersome symptom of VVA in addition to having ≤5% of vaginal superficial cells and vaginal pH > 5.0. The FSFI questionnaire was filled at baseline (screening and day 1), 6 weeks and 12 weeks. Comparison between DHEA and placebo of the changes from baseline to 12 weeks was made using the analysis of covariance test, with treatment group as the main factor and baseline value as the covariate. MAIN OUTCOME MEASURES The six domains and total score of the FSFI questionnaire were evaluated. RESULTS The FSFI domain desire increased over placebo by 0.24 unit (+49.0%, P = 0.0105), arousal by 0.42 unit (+56.8%, P = 0.0022), lubrication by 0.57 unit (+36.1%, P = 0.0005), orgasm by 0.32 unit (+33.0%, P = 0.047), satisfaction by 0.44 unit (+48.3%, P = 0.0012), and pain at sexual activity by 0.62 unit (+39.2%, P = 0.001). The total FSFI score, on the other hand, has shown a superiority of 2.59 units in the DHEA group over placebo or a 41.3% greater change than placebo (P = 0.0006 over placebo). CONCLUSION The present data show that all the six domains of the FSFI are improved over placebo (from P = 0.047 to 0.0005), thus confirming the previously observed benefits of intravaginal DHEA on female sexual dysfunction by an action exerted exclusively at the level of the vagina, in the absence of biologically significant changes of serum steroids levels.

RESULTS: Patient Demographics 898 1The University of Alabama at Birmingham, Birmingham, AL, 2Medical Center for Clinical Research, San Diego, CA, 3Tekton Research, Austin, TX, 4Westover Heights Clinic, Portland, OR, 5Center for Clinical Studies, Houston, TX, 6Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 7University of North Carolina, Chapel Hill, NC, 8Beth Israel Deaconess Medical Center, Boston, MA, 9Quest Clinical Research, San Francisco, CA, 10Indiana University School of Medicine, Indianapolis, IN, 11University of Illinois at Chicago, Chicago, IL, 12Magee Women’s Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, 13University of Utah School of Medicine, Salt Lake City, UT, 14IND 2 Results LLC, Atlanta, GA , 15Genocea Biosciences, Cambridge, MA, 16University of Washington, Seattle, WA

OBJECTIVE:An objective was to analyze the time course of efficacy of daily intravaginal administration of 0.5% (6.5mg) DHEA (prasterone) for 52 weeks on the moderate to severe (MS) symptoms and signs of vulvovaginal atrophy (VVA).METHOD:Five hundred twenty-one postmenopausal women were enrolled and received daily intravaginal administration of 0.5% DHEA in an open-label phase III study. The severity of the VVA symptoms examined in detail in the different groups.RESULTS:A parallel improvement of pain at sexual activity was observed in women who had moderate to severe (MS) dyspareunia as their most bothersome symptom (MBS) (n=183) or not MBS (n=240) and MS without being MBS (n=57) with a 1.70 severity unit change in the MBS group for a decrease of 66.1% from baseline (p<0.0001 versus baseline) over 52 weeks. A further improvement of dyspareunia, namely 0.33 severity unit (19.4%), was observed with continuing treatment from 12 weeks to 52 weeks. Similar results were observed on vaginal dryness and irritation/itching. Highly significant beneficial effects (p<0.0001 versus baseline for all) were observed at gynecological examination on vaginal secretions, color, epithelial integrity and epithelial surface thickness.CONCLUSION:The present study shows, in addition to the parallel benefits on the three symptoms of VVA, that the choice of any of the MS symptoms as being or not being MBS by women has no influence on the observed therapeutic effect (NCT01256671).

OBJECTIVE:This study aims to evaluate the effects of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women.METHODS:Intravaginal DHEA (6.5 mg) was administered daily for 52 weeks to 422 women who had endometrial biopsy at baseline and end of study, whereas 15 women were similarly treated for 26 to 52 weeks. Participants in three other studies received 3.25 mg (n = 126), 6.5 mg (n = 129), or 13 mg (n = 30) of DHEA for 12 weeks; women similarly had baseline and end-of-study biopsies. Endometrial biopsy samples were available for 668 women at baseline and end of study, with sufficient material for analysis.RESULTS:Endometrial atrophy or inactive endometrium (668 women) was found in all women treated with intravaginal DHEA. Similar atrophy was observed in 119 of 121 participants with sufficient material for analysis who received placebo.CONCLUSIONS:After cessation of estradiol secretion by the ovaries at menopause, the estrogens made by mechanisms of intracrinology are inactivated intracellularly at their site of formation and action, thus maintaining serum estradiol at biologically inactive concentrations to avoid stimulation of the endometrium. The absence of enzymes that are able to transform DHEA into estrogens in the endometrium explains the typical endometrial atrophy in all normal postmenopausal women in the presence of variable concentrations of circulating endogenous DHEA. According to these mechanisms, the inactive sex steroid precursor DHEA administered intravaginally acts exclusively in the vagina, whereas all serum sex steroids remain well within the biologically inactive postmenopausal reference range, thus avoiding any stimulation of the already atrophic endometrium.

Objective: This study aims to confirm the local effects of intravaginal prasterone on moderate to severe dyspareunia, a symptom of vulvovaginal atrophy (VVA) associated with menopause.Methods: In a prospective, randomized, double-blind, placebo-controlled phase III clinical trial, we examined the effects of daily intravaginal prasterone (6.5 mg) on four co-primary objectives, namely, percentage of vaginal parabasal cells, percentage of vaginal superficial cells, vaginal pH, and moderate to severe dyspareunia identified by women as the most bothersome VVA symptom.Results: After daily intravaginal prasterone administration for 12 weeks, the percentage of parabasal cells decreased by 45.8% compared with placebo (P < 0.0001), the percentage of superficial cells increased by 4.7% over placebo (P < 0.0001), and vaginal pH decreased by 0.83 pH units compared with placebo (P < 0.0001). The severity of most bothersome dyspareunia decreased by 46% over placebo (P = 0.013) at 12 weeks, whereas moderate to severe vaginal dryness decreased by 0.43 severity score units (or 42%) compared with placebo (P = 0.013). On gynecologic evaluation, a 14.4% to 21.1% improvement in vaginal secretions, epithelial integrity, epithelial surface thickness, and color over placebo (P = 0.0002 to P < 0.0001) was observed. Serum steroids, in agreement with the physiology of intracrinology and menopause, remained well within reference postmenopausal concentrations. All endometrial biopsies at 12 weeks have shown atrophy.Conclusions: Daily intravaginal prasterone (0.50%; 6.5 mg) treatment has clinically and statistically significant beneficial effects on the four co-primary objectives of VVA, according to US Food and Drug Administration guidelines. No significant drug-related adverse effect in line with the strictly local action of treatment has been reported, thus providing a high benefit-to-risk ratio for intravaginal prasterone.

Introduction: Plecanatide is a minimally absorbed peptide analog of uroguanylin, the naturally occurring ligand for the human intestinal guanylate cyclase-C receptor. The objective of this trial was to assess the safety and efficacy of a range of plecanatide doses in patients with IBS-C. Methods: We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 424 patients with IBS-C. Patients were randomly assigned to groups given 0.3, 1.0, 3.0, or 9.0 mg oral tablet plecanatide or placebo once daily for 12 weeks. The primary and secondary efficacy assessments were evaluated over 12 weeks of treatment. Primary efficacy endpoint was change from baseline in complete spontaneous bowel movements (CSBMs). Key secondary efficacy endpoints included change from baseline in worst abdominal pain intensity (0-10 point severity scale), the Food and Drug Administration’s (FDA’s) overall responder endpoint for IBS-C (responder: a patient who reported (i) improvement of ≥ 30% from baseline in average daily worst abdominal pain score and (ii) increase of ≥ 1 CSBM from baseline, both in the same week for ≥ 6/12 weeks), change in stool consistency using the Bristol Stool Form Scale (BSFS), and other secondary endpoints based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored. Results: Plecanatide 1.0, 3.0, and 9.0 mg dose groups had significantly improved weekly rates of CSBM frequency (primary endpoint) compared with placebo; the increases were 2.12, 2.74, and 2.44 for plecanatide doses 1.0, 3.0, and 9.0 mg, respectively (p ≤. 05 for each pair-wise comparison). Notably, plecanatide 3.0 mg dose significantly improved all important secondary endpoints: change from baseline in worst abdominal pain intensity, FDA overall responder endpoint, stool consistency and straining. The 9.0 mg dose demonstrated statistical improvement on the FDA overall responder endpoint, stool consistency and straining and numerical improvement on worst abdominal pain intensity. The most common adverse event was diarrhea (9.4% at 1.0 mg, 9.3% at 3.0 mg, and 11.8% at the highest 9.0 mg dose). Conclusion: Plecanatide therapy was safe and well-tolerated and produced rapid and clinically relevant improvement of bowel habits and abdominal pain in patients with IBS-C. Disclosure - Kunwar Shailubhai, Laura Barrow, Patrick Griffin, Gary Jacob are employees of Synergy Pharmaceuticals, Inc. Phil Miner is a consultant to Synergy Pharmaceuticals, Inc.

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (−1.19 ± 0.18, −1.25 ± 0.18, and −0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P <.05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

while changes in the CLP were subtle. Enhancer of zeste homolog2 (EZH2) protein increased significantly in the crypt at days–6 and 12 and coincided with expression of EZH2 target protein H3K27me3 that marks the repressive chromatin signature. Knockdown of EZH2 decreased TOP-Flash reporter activity due to loss of β-catenin concomitant with increases in Wnt-inhibitory factor–1 (WIF–1) protein expression. Intriguingly, simultaneous increases in both H3K4me3 and H3K27me3 in the crypt at days–6 and 12 coincided with dramatic increases in β-catenin, Jagged–1, and SMYD3 while expression of E-cadherin decreased significantly due to upregulation of Slug and Snail, respectively. In the CLP, an almost complete loss of H3K27me3 at days–6 and 12 compared to uninfected control correlated with trans-differentiation of cultured crypt epithelial cells into messenchymal cells that stained positive for vimentin and αSMA indicating an EMT-like behavior. Chromatin immunoprecipitation assay in the crypt showed accumulation of EZH2 around E-cadherin promoter while that of H3K4m3 around β-catenin, Jagged–1, SMYD3 and Snail promoter respectively further supporting EMT-like phenomenon. Conclusion: Epigenetic mechanism seems to play an important role in the regulation of crypt cell hyperplasia and may be EMT.

Objective: To investigate the effects of an ethinylestradiol (EE) 20 mu g/drospirenone (drsp) 3 mg combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets/4 inert tablets per cycle) for the treatment of moderate acne vulgaris, based on a pooled analysis of two identically designed US studies.Study design: Healthy females (n = 893) aged 14-45 years with moderate facial acne were randomised to EE 20 mu g/drsp 3 mg COC (n = 451) or placebo (n = 442) for six cycles. Primary outcome measures were mean percent change in acne lesion counts and the investigators' assessment of acne from baseline to endpoint.Results: There were significantly greater reductions in the mean percent change from baseline to endpoint in inflammatory, non-inflammatory and total lesion counts in the EE 20 mu g/drsp 3 mg 24/4 COC group compared with the placebo group (P < 0.0001). The odds of women in the EE 20 mu g/drsp 3 mg 24/4 COC group having 'clear' or 'almost clear' skin as rated by the investigators at endpoint were around three-fold greater than in the placebo group (odds ratio 3.41; 95% CI: 2.15-5.43; P < 0.0001).Conclusions: A low-dose COC containing EE 20 mu g/drsp 3 mg (24/4) more effectively reduced acne lesions than placebo and demonstrated greater improvement in the investigator global assessment of acne. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Background: Episodic therapy of genital herpes is usually recommended for patients with infrequent symptomatic recurrences and where transmission is not a concern. While shorter courses are as effective as standard 5-day regimens, it is unknown whether abbreviated therapy has detrimental effects on natural history and the development of antiviral resistance.Objectives: To assess time to next recurrence and development of antiviral resistance in patients with recurrent genital herpes treated with either single-day famciclovir (1 g twice-daily) or 3-day valacyclovir (500 mg twice-daily).Methods: Longer-term, follow-up data on the time to next recurrence and antiviral sensitivity were collected from a previously reported multicenter, multinational, double-blind, parallel group study in which 1179 immunocompetent adults were randomized 1 : 1 to receive either single-day famciclovir or 3-day valacyclovir. Treatment was self-initiated within 6 hours of a recurrence. Swabs for viral culture and sensitivity testing were collected for two sequential recurrences.Results: The median time to next recurrence from treatment initiation was 33.5 days for famciclovir and 38.0 days for valacyclovir. No drug resistance to penciclovir, the active metabolite of famciclovir, was observed at baseline nor did any develop by the time of the next recurrence.Limitations: The study had no placebo arm, typing of viral isolates was not performed and viral resistance testing was restricted to penciclovir only.Conclusion: Treatment with single-day famciclovir for recurrent genital herpes did not shorten the time to the next recurrence. Drug resistance to penciclovir continues to be a rare event in immunocompetent patients.

OBJECTIVE:To determine the optimal dose, safety, and efficacy of an estrogen receptor beta selective Chinese herbal extract, menopausal formula 101 (MF101), for treating hot flushes.METHODS:A randomized, blinded trial in 217 postmenopausal women with hot flushes randomized to 5 or 10 g/day of MF101 or placebo for 12 weeks.RESULTS:The effects of 5 g/day of MF101 did not differ from those of placebo. After 12 weeks, the mean percent decrease in frequency of hot flushes in the 10 g/day group was 12.9% greater than that in the placebo group (P = 0.15), the median percent decrease was 11.7% greater than that in the placebo group (P = 0.05), and the proportion of women with at least a 50% reduction in hot flushes was 16.2% greater than that in the placebo group (P = 0.03).CONCLUSIONS:Treatment with 10 g/day of MF101 reduces the frequency of hot flushes. Trials with higher doses are planned.