PMID- 19823111
OWN - NLM
STAT- MEDLINE
DCOM- 20100405
LR  - 20210723
IS  - 1537-4521 (Electronic)
IS  - 0148-5717 (Linking)
VI  - 37
IP  - 2
DP  - 2010 Feb
TI  - Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel): a dose 
      ranging, phase I study.
PG  - 100-4
LID - 10.1097/OLQ.0b013e3181bc0aac [doi]
AB  - OBJECTIVES: To evaluate safety, tolerability and systemic pharmacokinetics of 
      escalating doses of SPL7013 Gel in healthy women. DESIGN: : 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.
FAU - O'Loughlin, John
AU  - O'Loughlin J
AD  - Royal Adelaide Hospital, Adelaide, Australia.
FAU - Millwood, Iona Y
AU  - Millwood IY
FAU - McDonald, Helen M
AU  - McDonald HM
FAU - Price, Clare F
AU  - Price CF
FAU - Kaldor, John M
AU  - Kaldor JM
FAU - Paull, Jeremy R A
AU  - Paull JR
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sex Transm Dis
JT  - Sexually transmitted diseases
JID - 7705941
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Dendrimers)
RN  - 0 (Vaginal Creams, Foams, and Jellies)
RN  - 25104-18-1 (Polylysine)
RN  - F8H3J9KSY9 (astodrimer)
SB  - IM
MH  - Administration, Intravaginal
MH  - Adolescent
MH  - Adult
MH  - *Anti-Infective Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Colposcopy
MH  - Dendrimers
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - HIV Infections/*prevention & control/virology
MH  - Herpes Genitalis/*prevention & control/virology
MH  - Herpesvirus 2, Human
MH  - Humans
MH  - Interviews as Topic
MH  - Physical Examination
MH  - *Polylysine/administration & dosage/adverse effects/pharmacokinetics
MH  - Vagina/*microbiology
MH  - *Vaginal Creams, Foams, and Jellies/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Young Adult
EDAT- 2009/10/14 06:00
MHDA- 2010/04/07 06:00
CRDT- 2009/10/14 06:00
PHST- 2009/10/14 06:00 [entrez]
PHST- 2009/10/14 06:00 [pubmed]
PHST- 2010/04/07 06:00 [medline]
AID - 10.1097/OLQ.0b013e3181bc0aac [doi]
PST - ppublish
SO  - Sex Transm Dis. 2010 Feb;37(2):100-4. doi: 10.1097/OLQ.0b013e3181bc0aac.