Novel On Demand Female Oral Contraceptive

7.项目总结/摘要 InnovaGyn公司建议在正常妊娠妇女中进行2期概念验证临床试验 年龄在18 - 40岁之间，以证明左炔诺孕酮+美洛昔康通过以下方式延迟排卵的能力： >7天，而安慰剂<3天。这是开发一个新的按需女性的开始步骤 口服避孕药大多数女性激素避孕药提供持续暴露于外源性激素 并且对预防怀孕非常有效。女性和男性非激素方法，例如男性和 女用避孕套、杀精剂、女性子宫帽和戒断，效果较差， 行为减少快乐。在无保护性交后使用的紧急避孕药，其有效性各不相同 根据从性交到使用的时间， 性交。所有女性避孕药都有其独特的优点和缺点，女性能够 根据个人喜好和当前生活方式从一种方法转换到另一种方法。平均 美国妇女在生育期间使用四种不同的避孕方法。 妇女表示需要一种谨慎的，口服的药物，可以采取与性交，也就是说， 有效且副作用有限。InnovaGyn计划开发一种按需口服片剂来解决这一未满足的问题 需要的我们的产品IG 002含有左炔诺孕酮（一种去甲肾上腺素）和美洛昔康（一种非甾体抗炎药） 药物，分别影响两个重要的卵巢途径参与排卵。左炔诺孕酮抑制 周期中期垂体促黄体激素激增导致排卵。美洛昔康抑制环氧合酶-2， 一种卵泡内酶，参与形成卵泡壁隧道，卵母细胞（卵子）在此处被挤出， 排卵促黄体生成激素高峰和随后的卵泡内事件发生在女性的窗口期， 排卵前四天和排卵日。我们的产品影响这两种途径， 避孕效果通过延迟排卵超过5天的精子能力。IG 002与 性交可以在一个月经周期中重复性交动作。本试点研究将 评价间隔48小时服用两剂安慰剂中的第一剂后的排卵间隔， 排卵前几天，在生育窗口期。同一个女人会服用两剂左炔诺孕酮加 美洛昔康在随后的月经周期的同一时间。我们预计左炔诺孕酮加美洛昔康 与安慰剂<3天相比，将延迟排卵>7天。这是第一个临床试验，以探讨疗效 在正常女性中使用该组合药物的多个剂量，使用收集的每日早晨排泄的 尿作为一种非侵入性方法来评估尿雌酮-3-葡萄糖醛酸苷和孕二醇-3- 葡萄糖醛酸苷，黄体卵泡移位，作为排卵的证据。

7. Project Summary/Abstract InnovaGyn, Inc. proposes to perform a Phase 2 Proof of Concept clinical trial in normal menstruating women between 18 to 40 years of age to demonstrate the ability of levonorgestrel plus meloxicam to delay ovulation by >7 days compared to placebo of <3 days. This is the beginning step in developing a novel On Demand female oral contraceptive. Most female hormonal contraceptives provide continuous exposure to exogenous hormones and are highly effective in preventing pregnancy. Female and male non-hormonal methods such as male and female condoms, spermicides, female diaphragms and withdrawal, are less effective and by interrupting the sex act diminish pleasure. Emergency contraception, used after unprotected intercourse, has a variable efficacy based on the time from intercourse to use and has an increased incidence of pregnancy with subsequent acts of intercourse. All female contraceptives have unique advantages and disadvantages and women are able to switch from one method to another depending upon their personal preferences and current life style. The average US woman uses four different contraceptive methods during her reproductive life. Women have indicated a need for a discreet, oral medication that can be taken with intercourse, that is effective and has limited side effects. InnovaGyn plans to develop a On Demand oral tablet to address this unmet need. Our product IG002 contains levonorgestrel, a progestin, plus meloxicam, a non-steroidal anti-inflammatory drug, that individually affect two important ovarian pathways involved in ovulation. Levonorgestrel inhibits the mid-cycle pituitary luteinizing hormone surge that results in ovulation. Meloxicam inhibits cyclooxygenase-2, an intrafollicular enzyme that is involved in creating the follicle wall tunnel where the oocyte (egg) is extruded at ovulation. The luteinizing hormone surge and subsequent intrafollicular events occur during the window of female fertility, the four days prior to and day of ovulation. Our product affects these two pathways increasing contraceptive efficacy by delaying ovulation beyond the 5 days of sperm fertilizing capacity. IG002 taken with intercourse can be used with repetitive acts of intercourse in a single menstrual cycle. This Pilot Study will evaluate the interval to ovulation following the first of two doses of placebo taken 48 hours apart administered 2 days before ovulation during the window of fertility. The same woman will take two doses of levonorgestrel plus meloxicam at the same time in a subsequent menstrual cycle. We anticipate that levonorgestrel plus meloxicam will delay ovulation >7 days compared to placebo <3 days. This is the first clinical trial to explore the efficacy of multiple doses of this combination medication in normal women using the collection of daily morning voided urines as a non-invasive method to assess changes in urinary estrone-3-glucuronide and pregnandiol-3- glucuronide, the luteal-follicular shift, as evidence of ovulation.