title: Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel): a dose ranging, phase I study.
abstract: OBJECTIVE
  To evaluate safety, tolerability and systemic pharmacokinetics of escalating doses of SPL7013 Gel in healthy women.
  
  
  METHODS
  : Randomized, double-blind, placebo-controlled dose-escalation trial.
  
  
  METHODS
  Thirty-seven healthy women were randomized to receive 3.5 g of 0.5% (N = 8), 1% (N = 8), or 3% (N = 9) SPL7013 Gel or placebo gel (N = 12), applied vaginally once daily for 7 consecutive days. Genital toxicity was determined by interview, physical examination, assessment of vaginal microflora and colposcopy. Systemic toxicity was determined by nongenital adverse events (AEs) and laboratory assessments. Plasma was collected for pharmacokinetic analysis.
  
  
  RESULTS
  Genital AEs considered potentially product-related were all mild and reported by 5 (20%) women receiving SPL7013 Gel and 2 (17%) women receiving placebo gel. The most common were abdominal pain or discomfort, with no reports of vaginal burning or malodour, or genital-tract pain. There were no clinically significant colposcopic findings, including of genital inflammation or epithelial disruption. Lower concentrations of normal lactobacillary flora occurred during SPL7013 Gel and placebo gel use, with a decrease in anaerobes in the SPL7013 Gel groups. There were no reported cases of bacterial vaginosis, and lactobacilli returned to predose levels in most women after treatment. All nongenital AEs were of mild or moderate severity, expect for a severe tension headache in a woman receiving placebo. There was no absorption of SPL7013 into the systemic circulation.
  
  
  CONCLUSIONS
  SPL7013 Gel applied vaginally once daily for 7 days at concentrations of 0.5% to 3% was safe and well tolerated in healthy, sexually abstinent women, with no evidence of systemic toxicity or absorption.
authors.affiliation: Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: John
authors.initials: J
authors.lastname: O'Loughlin
authors.forename: Iona Y
authors.initials: IY
authors.lastname: Millwood
authors.forename: Helen M
authors.initials: HM
authors.lastname: McDonald
authors.forename: Clare F
authors.initials: CF
authors.lastname: Price
authors.forename: John M
authors.initials: JM
authors.lastname: Kaldor
authors.forename: Jeremy R A
authors.initials: JR
authors.lastname: Paull
mesh_terms: D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003127:Colposcopy; D050091:Dendrimers; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D006558:Herpes Genitalis / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human; D006801:Humans; D007407:Interviews as Topic; D010808:Physical Examination; D011107:Polylysine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014621:Vagina / Q000382:microbiology*; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D050091:Dendrimers; D014622:Vaginal Creams, Foams, and Jellies; D011107:Polylysine; C480351:astodrimer