Holliston, MA, United States
Holliston, MA, United States

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PubMed | Medical Center for Clinical Research, Q&T Recherche Sherbrooke, Northern California Research, Consulting Inc. and 6 more.
Type: Journal Article | Journal: The journal of sexual medicine | Year: 2015

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.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.Placebo was administered daily to 157 women while 325 women received 0.50% (6.5mg) 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.The six domains and total score of the FSFI questionnaire were evaluated.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).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.


PubMed | Creighton University, Pro Recherche, Clinique de Gynecologie, Clinique de Recherche en Traitements Hormonaux and 10 more.
Type: Clinical Trial, Phase III | Journal: Maturitas | Year: 2015

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).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.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.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).


Stefanutti C.,University of Rome La Sapienza | Blom D.J.,University of Cape Town | Averna M.R.,University of Palermo | Meagher E.A.,University of Pennsylvania | And 14 more authors.
Atherosclerosis | Year: 2015

Objectives: Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide. Methods: Existing lipid-lowering therapy, including apheresis, was to remain stable from Week-6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5mg to 60mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide. Results: Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p=0.545). Changes in Lp(a) levels were modest and not different between groups (p=0.436). Conclusion: The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis. © 2015 The Authors.


PubMed | University of Western Ontario, University of Pennsylvania, University of Ferrara, Ospedale Niguarda and 9 more.
Type: Clinical Trial, Phase III | Journal: Atherosclerosis | Year: 2015

Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide.Existing lipid-lowering therapy, including apheresis, was to remain stable from Week-6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5mg to 60mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide.Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p=0.545). Changes in Lp(a) levels were modest and not different between groups (p=0.436).The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.


Monath T.P.,Xcellerex | Fowler E.,Xcellerex | Johnson C.T.,Johnson City Clinical Trials | Balser J.,Veristat | And 3 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. METHODS: In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. RESULTS: The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. CONCLUSIONS: A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.) Copyright © 2011 Massachusetts Medical Society.


Labrie F.,EndoCeutics Inc. | Montesino M.,EndoCeutics Inc. | Archer D.F.,Clinical Research Center | Lavoie L.,EndoCeutics Inc. | And 6 more authors.
Climacteric | Year: 2015

The aim was to analyze the opinion of the male partner of women treated for vulvovaginal atrophy (VVA) with intravaginal 0.50% DHEA (prasterone), thus providing information on both members of the couple.Methods On a voluntary basis, in a prospective, randomized, double-blind and placebo-controlled phase-III clinical trial, the male partner filled a questionnaire at baseline and at 12 weeks stating his observations related to his penis and intercourse before and after VVA treatment.Results Sixty-six men having a partner treated with intravaginal DHEA and 34 others having a partner treated with placebo answered the questionnaires. Concerning the feeling of vaginal dryness of their female partner, the severity score following DHEA treatment improved by 81% (0.76 units) over placebo (p = 0.0347). Thirty-six percent of men having a partner treated with DHEA did not feel the vaginal dryness of the partner at the end of treatment compared to 7.8% in the placebo group. When analyzing the situation at 12 weeks compared to baseline, an improved score of 1.09 units was the difference found for the DHEA group compared to 0.76 for the placebo group (p = 0.05 vs. placebo). In the DHEA group, 38% of men scored very improved compared to 18% in the placebo group. No adverse event has been reported.Conclusion The male partner had a very positive evaluation of the treatment received by his female partner. © 2015 International Menopause Society.


PubMed | Clinical Research Center, EndoCeutics Inc., Veristat and Consulting Inc.
Type: | Journal: The Journal of steroid biochemistry and molecular biology | Year: 2015

The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3, 17-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3, 17-diol 17-glucuronide (3-diol-17G) were measured by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17 pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1-S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values. The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause.


Signs Agreement with Cytovance for Development of Commercial Scale Antibody Manufacturing, and with Veristat for Clinical Trial Management Appoints New Auditors for Quest PharmaTech and OncoQuest EDMONTON, Dec. 7, 2016 /PRNewswire/ - OncoQuest Inc. ("OncoQuest"),...

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