Impact of age, race, and medication use on efficacy endpoints in a randomized controlled trial of topical sildenafil cream for the treatment of female sexual arousal disorder.

Background: A study of topical Sildenafil Cream 3.6% was completed among healthy premenopausal women with female sexual arousal disorder.

Aims: To compare efficacy endpoints based on product use in pre-planned and post-hoc subsets of age, race, and medication use.

Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder.

Background: There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction.

Aims: The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period.

Preliminary Efficacy of Topical Sildenafil Cream for the Treatment of Female Sexual Arousal Disorder: A Randomized Controlled Trial.

Objective: To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder.

Methods: We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream.

Safety testing of Ovaprene: An investigational nonhormonal monthly vaginal contraceptive.

Objectives: Evaluate the safety of Ovaprene, an investigational nonhormonal vaginal contraceptive designed for monthly use.

Study Design: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment-emergent adverse events, systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids.

A nine-month repeat-dose intravaginal ring (Ovaprene) irritation study in sheep.

Objectives: Ovaprene is a novel, investigational, intravaginal hormone-free monthly ring contraceptive designed for use in women of reproductive age to be worn over multiple weeks (one menstrual cycle). The objective of this work was to evaluate the safety of Ovaprene during a nine-month repeat-dose sheep study.

Study Design: In addition to traditional safety endpoints such as histopathological evaluation of the sheep female reproductive tract, vaginal fluids were collected and tested for released iron over time.

Successful postcoital testing of Ovaprene: An investigational non-hormonal monthly vaginal contraceptive.

Objective: Evaluate reduction in progressively motile sperm per high power field (HPF) in midcycle cervical mucus after intercourse with Ovaprene: an investigational monthly non-hormonal vaginal contraceptive consisting of a vaginal ring and mechanical barrier, releasing spermiostatic ferrous gluconate.

Study Design: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception. Participants underwent a baseline postcoital test cycle with no device to confirm the presence of sperm, followed by one diaphragm postcoital test cycle, one Ovaprene safety cycle, and two Ovaprene postcoital test cycles.

A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal RinGSM) over 12 weeks in healthy postmenopausal women.

Objectives: The exploratory objectives of this study were to evaluate the usability and acceptability and to conduct a preliminary evaluation of the efficacy of DARE-HRT1. DARE-HRT1 is an intravaginal ring (IVR) that releases 17β2-estradiol (E2) with progesterone (P4) over 28 days. It is the first combination E2 and P4 IVR being developed for the treatment of vasomotor symptoms (VMS) in healthy postmenopausal women with an intact uterus.

A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women.

Objectives: Primary objectives were to evaluate the safety and systemic pharmacokinetics (PK) of DARE-HRT1, an intravaginal ring (IVR), which releases 17β2-Estradiol (E2) with progesterone (P4) for 28 days in healthy postmenopausal women.

Methods: This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women with an intact uterus. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d).

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

Purpose: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV).

Methods: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability.

Evaluation of 28-day estradiol and progesterone vaginal rings in a phase 1 clinical pharmacokinetic study.

Objective: The aim of this work is to develop a combination of 17β-estradiol (E2) and progesterone (P4) in a single-dose intravaginal ring (IVR) for the treatment of vasomotor symptoms (VMS) and genitourinary syndrome of menopause while providing endometrial protection. The objective of this study was to evaluate DARE-HRT1, a 28-day IVR that continuously delivers E2 and P4, in a phase 1 clinical trial to assess its pharmacokinetics.

Methods: This was an open-label, three-arm (group) study.

A Phase 1 pharmacokinetic study of a single-dose bioadhesive clindamycin 2% gel for bacterial vaginosis.

Objectives: To evaluate pharmacokinetics (PK) of a single dose of an investigational 2% clindamycin phosphate vaginal gel in healthy women by assessment of plasma and vaginal clindamycin concentrations over 7 days, and assess safety.

Methods: Single-centre, Phase 1, single-dose PK study. Blood and vaginal samples were collected daily and safety was evaluated through to Day 7.

Single-Dose, Bioadhesive Clindamycin 2% Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

Objective: To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment.

Methods: We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections.

The Role of Volume in the Perceptibility of Topical Vaginal Formulations: User Sensory Perceptions and Experiences of Heterosexual Couples During Vaginal Sex.

Users' sensory perceptions and experiences (USPEs; perceptibility) of drug formulations can critically impact product adoption and adherence, especially when products rely on appropriate user behaviors (timing of administration, dosing measurement) for effectiveness. The use of topical gel formulations for effective antihuman immunodeficiency virus/sexually transmitted infection (HIV/STI) vaginal microbicides has been associated with messiness and other use-associated challenges, resulting in low adherence. Nonetheless, such formulations remain attractive due to good pharmacokinetics and resulting pharmacodynamics through their volume and surface contact for drug delivery into luminal fluids and mucosa.

Phase transition behaviour in yeast and bacterial populations under stress.

Non-equilibrium phase transitions from survival to extinction have recently been observed in computational models of evolutionary dynamics. Dynamical signatures predictive of population collapse have been observed in yeast populations under stress. We experimentally investigate the population response of the budding yeast to biological stressors (temperature and salt concentration) in order to investigate the system's behaviour in the vicinity of population collapse.

Vaginal tamoxifen for treatment of vulvar and vaginal atrophy: Pharmacokinetics and local tolerance in a rabbit model over 28 days.

Vaginally delivered tamoxifen is being developed as alternative to estrogen-based therapies for the treatment of vulvar and vaginal atrophy (VVA) symptoms in subjects at high risk for breast cancer, undergoing treatment for breast cancer with aromatase inhibitors or are breast cancer survivors. Tamoxifen (1 or 20 mg) was administered intra-vaginally to female rabbits once-daily over a 28-day period to assess its pharmacokinetics, systemic exposure and local vaginal tolerance. Plasma samples were taken to assess concentrations of tamoxifen and its metabolites 4-hydroxytamoxifen and N-desmethyltamoxifen over the first day of vaginal administration and following the last dose on Day 28.

Pharmacokinetics and tolerability of a novel progesterone intravaginal ring in sheep.

The objectives of this work were to evaluate the in vitro release and in vivo pharmacokinetics and local tolerability of a novel, segmented ethylene-vinyl acetate (EVA) intravaginal ring (IVR) delivering progesterone (P) in drug-naïve ovariectomized female Dorset crossbred sheep. Following preparation and assessment of in vitro release of P, animals were randomized into one of six treatment groups: group 1 Crinone® 8% gel (90 mg); group 2 Prometrium® 200-mg capsules; group 3 placebo IVR; group 4 progesterone (P) IVR 4 mg/day; group 5 P IVR 8 mg/day; or group 6 P IVR 12 mg/day. Crinone 8% gel and Prometrium capsules were administered once daily for 28 days.

Pharmacokinetics and Tolerability of a Novel 17β-Estradiol and Progesterone Intravaginal Ring in Sheep.

This study reports the preparation, in vitro release, pharmacokinetics, and local tolerability of novel ethylene-vinyl acetate intravaginal rings (IVRs) delivering 17β-estradiol (E) and progesterone (P), in drug-naïve ovariectomized female Dorset crossbred sheep. After preparation and assessment of in vitro release of E and P, animals were randomized to treatment groups 1 or 2 (comparator rings releasing 50 or 100 μg/d E, respectively), groups 3 or 4 (ethylene-vinyl acetate IVRs, 160 μg/d E with 4 [160/4 IVR] or 8 mg/d P [160/8 IVR], respectively), or group 5 (160 μg E and 10 mg P administered intravenously). IVRs were placed on day 1 and remained in place through day 29.

Drug delivery for the treatment of endometriosis and uterine fibroids.

Endometriosis and uterine fibroids (also known as uterine leiomyomas) are serious medical conditions affecting large numbers of women worldwide. Many women are asymptomatic but those with symptoms require medical intervention to relieve chronic pain and dysmenorrhea and to address infertility. Drug delivery has played a role in reducing some of the symptoms associated with endometriosis and uterine fibroids.

Perceptibility and the "Choice Experience": User Sensory Perceptions and Experiences Inform Vaginal Prevention Product Design.

The development of pericoital (on demand) vaginal HIV prevention technologies remains a global health priority. Clinical trials to date have been challenged by nonadherence, leading to an inability to demonstrate product efficacy. The work here provides new methodology and results to begin to address this limitation.

An update on multipurpose prevention technologies for the prevention of HIV transmission and pregnancy.

Introduction: Multipurpose Prevention Technologies (MPTs) are designed to address two or more indications from a single product. The overall goal is to prevent unintended pregnancy and transmission of one or more STIs including HIV-1.

Areas Covered: The topics covered herein are advances in over the past three years.

Development of controlled release systems over the past 50years in the area of contraception.

The field of controlled release has contributed significantly to female reproductive health and in particular the prevention of unintended pregnancy. For at least 50years, there have been significant advances in controlled release dosage forms used for contraception. These advances have been driven by the need to provide women a wide array of products that address adherence problems noted with oral contraceptives.

A Pilot Study Measuring the Distribution and Permeability of a Vaginal HIV Microbicide Gel Vehicle Using Magnetic Resonance Imaging, Single Photon Emission Computed Tomography/Computed Tomography, and a Radiolabeled Small Molecule.

Vaginal microbicide gels containing tenofovir have proven effective in HIV prevention, offering the advantage of reduced systemic toxicity. We studied the vaginal distribution and effect on mucosal permeability of a gel vehicle. Six premenopausal women were enrolled.

Assessing the potential of the Woman's Condom for vaginal drug delivery.

Background: The Woman's Condom is a new female condom that uses a dissolvable polyvinyl alcohol capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman's Condom capsule, offering a unique drug delivery platform.

Study Design: UC781 capsules were fabricated using methods from the development of the Woman's Condom capsules as well as those used in vaginal film development.