Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel): a dose ranging, phase I study.
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.
O'Loughlin
John
J
Royal Adelaide Hospital, Adelaide, Australia.
Millwood
Iona Y
IY
McDonald
Helen M
HM
Price
Clare F
CF
Kaldor
John M
JM
Paull
Jeremy R A
JR
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
D000890:Anti-Infective Agents; D050091:Dendrimers; D014622:Vaginal Creams, Foams, and Jellies; D011107:Polylysine; C480351:astodrimer