A Randomized Controlled Trial of the Safety of Candidate Microbicide SPL7013 Gel When Applied to the Penis

Abstract

Objectives To determine the safety of the candidate vaginal microbicide SPL7013 Gel (VivaGel®) when applied to the penis. Methods A randomized, double blind, placebo controlled study. Thirty-six healthy men (18 circumcised, 18 uncircumcised), were randomized in a 2:1 ratio and treated with 3% SPL7013 Gel (N=24) or placebo gel (N=12), applied once daily for 7 days. Genital toxicity was determined by interview, diary, and examination. Results There were 10 genital adverse events (AEs) in 6 men (25%) receiving SPL7013 Gel, and 5 genital AEs in 4 men (33%) receiving the placebo that were possibly or probably related to the study product (difference of −8%, 95% CI: −40% to 23%, p=0.70). The most common genital AEs were genital pruritus and application site erythema. All genital AEs were mild (grade 1), and all but one, in the placebo group, were transient. Analysis of vital signs, non-genital AEs, and laboratory results indicated no safety or tolerability issues with SPL7013 Gel, irrespective of circumcision status. There was no detectable absorption of SPL7013 into the plasma. Conclusions 3% SPL7013 Gel was safe and well tolerated, and comparable with placebo, when administered to the penis of both circumcised and uncircumcised men once daily for 7 days, with no evidence of systemic absorption or toxicity.

Enhancement of Human Immunodeficiency Virus Type 1 Replication Is Not Intrinsic to All Polyanion-Based Microbicides

“…SPL7013 has demonstrated low toxicity in cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages and does not impair the resistance of polarized epithelial cells (6). VivaGel has demonstrated favorable safety profiles when administered vaginally and rectally in macaques (16) (4). It is effective in preventing the vaginal transmission of the CXCR4 SHIV89.6P strain in macaques and SHIV162P3 infection of macaque PBMCs (11).…”

Attitudes of men in an Australian male tolerance study towards microbicide use

“…20 All the men were asked to apply the gel to their penis at night and allow to air dry, and to abstain from all sexual activity (including masturbation) for the seven days of the study. They were reimbursed US $250 for their participation, which included five visits for clinical examination.…”

“…19,15 We therefore took the opportunity provided by a phase 1 male safety trial of the candidate microbicide, SPL7013 Gel 20 to explore in a qualitative study the attitudes of Australian men towards anticipated microbicide use with female partners.…”

Microbicide research: current and future directions

“…A similar study [45] was conducted with candidate vaginal gel SPL7013 (VivaGel; Starpharma Holdings Ltd., Melbourne, Victoria, Australia) to determine the safety of the gel among uncircumcised and circumcised men. The results suggested that SPL7013 was well tolerated [45].…”