title: Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004).
abstract: OBJECTIVE
  The study was designed to assess the safety, adherence, acceptability, and effect on vaginal microflora of 3% SPL7013 Gel (VivaGel), a novel dendrimer topical microbicide that inhibits HIV, herpes simplex virus-2, and human papillomavirus in vitro and in animal models.
  
  
  METHODS
  Phase 1, randomized, double-blind, placebo-controlled study on sexually active women.
  
  
  METHODS
  Sixty-one sexually active women aged 18-24 years were recruited from three sites in the United States. Participants were randomized 1: 1: 1 to receive VivaGel, VivaGel placebo, or a hydroxyethylcellulose (HEC) placebo twice daily for 14 consecutive days. Safety endpoints included genitourinary and/or other adverse events. Changes in vaginal flora were determined from Gram-stained vaginal smears and quantitative vaginal culture.
  
  
  RESULTS
  No serious adverse events or withdrawals due to adverse events were reported. Genitourinary symptoms were reported as follows: VivaGel (n = 17/22; 77.3%), VivaGel placebo (n = 14/21; 66.7%), and HEC (n = eight of 18; 44.4%; not significant, P = 0.1). The incidence of abnormal pelvic examination findings was similar across all gel arms of the study. Using pairwise comparison, women in the VivaGel arm had a significantly higher incidence of related genitourinary adverse events compared with women in the HEC gel arm (0.297 versus 0.111 per 100 person-years, respectively; P = 0.003). Exposure to VivaGel and VivaGel placebo resulted in minor shifts in the vaginal microflora, but there was no overall impact on incidence of bacterial vaginosis as assessed by Nugent score.
  
  
  CONCLUSIONS
  VivaGel was generally well tolerated and comparable with the VivaGel placebo, although there was a higher incidence of low-grade related genital adverse events compared to the HEC placebo gel.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. imcgowan@pitt.edu
authors.forename: Ian
authors.initials: I
authors.lastname: McGowan
authors.forename: Kailazarid
authors.initials: K
authors.lastname: Gomez
authors.forename: Karen
authors.initials: K
authors.lastname: Bruder
authors.forename: Irma
authors.initials: I
authors.lastname: Febo
authors.forename: Beatrice A
authors.initials: BA
authors.lastname: Chen
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Marla
authors.initials: M
authors.lastname: Husnik
authors.forename: Edward
authors.initials: E
authors.lastname: Livant
authors.forename: Clare
authors.initials: C
authors.lastname: Price
authors.forename: Cindy
authors.initials: C
authors.lastname: Jacobson
mesh_terms: D000282:Administration, Intravaginal; D000293:Adolescent; D003075:Coitus; D050091:Dendrimers; D005260:Female; D058869:Gynecological Examination; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D055118:Medication Adherence; D017060:Patient Satisfaction / Q000706:statistics & numerical data*; D010919:Placebos / Q000008:administration & dosage; D011107:Polylysine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014481:United States; D014621:Vagina / Q000187:drug effects* / Q000821:virology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D050091:Dendrimers; D010919:Placebos; D014622:Vaginal Creams, Foams, and Jellies; D011107:Polylysine; C480351:astodrimer