Male tolerance study of 1% C31G

Mauck, Christine; Frezieres, Ron G.; Walsh, Terri; Schmitz, Susan W.; Callahan, Marianne M.; Bax, Richard

doi:10.1016/j.contraception.2003.12.008

Cited by 20 publications

(12 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, in vitro studies have shown that C31G has activity against numerous gram-positive and gram-negative bacteria, possesses antifungal properties, and is a potent antiviral agent with activity against herpes simplex virus and HIV-1 (5,7,13). Recent clinical trials of C31G-containing formulations have demonstrated that C31G has effective postcoital contraceptive activity (16) and favorable safety profiles with respect to exposure of both female (18) and male (17) genitalia.…”

mentioning

confidence: 99%

Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G

Catalone¹,

Kish-Catalone²,

Neely³

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

C31G is currently the focus of clinical trials designed to evaluate this agent as a microbicidal and spermicidal agent. In the following studies, the in vivo safety of C31G was assessed with a Swiss Webster mouse model of cervicovaginal toxicity and correlated with results from in vitro cytotoxicity experiments and published clinical observations. A single exposure of unformulated 1% C31G resulted in mild-to-moderate epithelial disruption and inflammation at 2 and 4 h postapplication. The columnar epithelium of the cervix was the primary site of damage, while no perturbation of the vaginal mucosa was observed. In contrast, application of unformulated 1.7% C31G resulted in greater levels of inflammation in the cervical epithelium at 2 h postapplication and severe epithelial disruption that persisted to 8 h postapplication. Application of a nonionic aqueous gel formulation containing 1% C31G resulted in no apparent cervicovaginal toxicity at any time point evaluated. However, formulation of 1.7% C31G did not substantially reduce the toxicity associated with unformulated C31G at that concentration. These observations correlate with findings gathered during a recent clinical trial, in which once-daily applications resulted in no adverse events in women receiving the formulation containing 1% C31G, compared to moderate-to-severe adverse events in 30% of women receiving the 1.7% C31G formulation. The Swiss Webster mouse model was able to effectively discriminate between concentrations and formulations of C31G that produced distinct clinical effects in human trials. The Swiss Webster animal model may be a highly valuable tool for preclinical evaluation of candidate vaginal microbicides.

show abstract

mentioning

confidence: 99%

Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G

Catalone¹,

Kish-Catalone²,

Neely³

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…6,7,9,10 The DPV gel used in this study is not primarily intended for use in men by application to the penis; nevertheless, male participants reported liking the gel moderately. Although ratings for liking the gel were on average toward the positive side of the 1-10 scale, ratings were not particularly high, being on average around 6.…”

Section: Discussionmentioning

confidence: 99%

“…This assessment has been used in several prior microbicide trials and was adapted to measure acceptability of a gel applied to the penis rather than inside the vagina or rectum. [7][8][9] It included structured and semistructured questions about liking the gel overall and at various time intervals following gel application and the overall likelihood of using a microbicide gel in the future every time they have intercourse (vaginal and/or anal), ''if it looked like the one that was used in the study and provided some protection against HIV,'' with different partner types, and when condoms are not used. Responses to acceptability and likelihood of use questions were measured on a 10-point Likert scale, with 1 being ''disliked very much/very unlikely to use'' and 10 being ''liked very much/very likely to use.''…”

mentioning

confidence: 99%

A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

Cranston

Hoesley

Carballo‐Diéguez³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N = 48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be ''very likely'' to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants ( p = 0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug.

show abstract

“…Like N-9, C31G was also inexpensive, potentially broad spectrum [26], and contraceptive [27]. Therefore, a series of phase 1 safety studies were conducted with the final vaginal gel formulation of C31G, including male and female tolerance and acceptability trials [28,29]; a post-coital testing study [30], and a daily use dose escalation study [31]. These studies demonstrated that C31G gel formulation was generally safe and well tolerated.…”

Section: The Use Of Surface Active Agentsmentioning

confidence: 99%

Non-Specific Microbicide Product Development: Then and Now

Romano¹,

Robbiani²,

Doncel³

et al. 2012

CHR

View full text Add to dashboard Cite

Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the virus remains elusive. In response to struggles on the vaccine development front, significant effort has been devoted to preventing the transmission of HIV with alternative products, technologies, and strategies. One of the early alternative HIV prevention strategies was microbicides, which are topical products that can be used to prevent sexual transmission of HIV either vaginally or rectally. First generation microbicide products were designed to be simple gel formulations comprised of readily available active agents that were inexpensive and broadly active (i.e., non-specific). Unfortunately, despite the clinical investigation of multiple product concepts satisfying these requirements, none were shown to be efficacious in pivotal trials. More recently, microbicide and oral prevention strategies involving highly specific and potent anti-retroviral (ARV) drugs have shown to be efficacious in trials. Although building on these successes continues, these products have a number of issues including potential toxicity with long term use, selection of HIV resistance, and cost. Further, all of the original justifications for non-specific microbicide products remain valid. This review provides a brief history of non-specific microbicide development, outlines the evolution to, and limitations of, ARV based microbicides, and summarizes the current activity on non-specific microbicide product development.

show abstract

Male tolerance study of 1% C31G

Cited by 20 publications

References 8 publications

Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G

Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G

A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

Non-Specific Microbicide Product Development: Then and Now

Contact Info

Product

Resources

About