On Demand Oral Contraception for Obese Women

7.项目摘要/摘要 我们研究的长期目标是为所有女性--正常、超重和肥胖--提供一个安全、 有效的、不含雌激素的替代方案，替代他们目前的避孕选择。IG002旨在用于 作为一种按需避孕，在性交前服用。本申请的具体目标是： 1)提供概念证据，证明IG002中的两种药物联合使用将延迟排卵，特别是在肥胖患者 女性；以及2)证明IG002的副作用将是轻微的，没有严重的 不良影响。临床方案将提供证据表明，IG002在正常月经期间口服， 肥胖女性(BMI≥30和≤39.9)将排卵推迟到≥7天，而安慰剂≤为3天。 优势卵泡在月经周期的卵泡期较晚出现。从人体内分泌雌二醇 卵泡开始从脑下垂体释放大量黄体生成素(LH)。这个LH峰作用于 优势卵泡在大约40小时后会导致排卵。这些变化并不是显而易见的 消费者和/或医疗保健提供者。然而，大多数怀孕是在性交发生在 排卵日的前四天或排卵日本身的四天，导致五天的窗口期 生育力，黄体生成素高峰出现在这五天窗口的中间。在这项概念验证研究中，IG002 分两次注射(相隔48小时)，第一次注射时，优势卵泡直径为 17±1.0 mm。这个卵泡直径对应于雌二醇升高和触发黄体生成素激增的时期 当性交可能导致怀孕的时候。 IG002通过两种机制延迟排卵。有一种药物可以防止黄体生成素激增，但前提是必须在黄体生成素分泌之前服用 浪涌开始了。第二种药物可阻断卵巢内由促黄体生成素刺激的基本过程的活动。 因此，第二种药物在促黄体生成素高峰开始后推迟排卵。每种药物单独使用都会显著延迟 在生育窗口期使用时的排卵。IG002优于任何一种单独的药物，因为它提供了 无论是在黄体生成素激增之前或之后服用，效果都是如此。 使用IG002的排卵延迟可防止怀孕。≥的IG002 7天的排卵延迟将超过 精子在女性生殖道中的受精能力为5天，但随后在 月经周期。重复的性交行为将需要重复使用IG002。其中所含药物 IG002可以改变月经周期间隔，可能会也可能不会导致计划外子宫出血，但 否则，预计对健康女性的副作用最小。

7. Project Summary/Abstract The long-term goal of our study is to provide all women - normal, overweight, and obese - with a safe, effective, non-estrogen-containing alternative to their current contraceptive options. IG002 is intended for use as an On Demand contraceptive, taken prior to intercourse. The Specific Aims of this application are: 1) provide Proof of Concept that the combination of two drugs in IG002 will delay ovulation specifically in obese women; and 2) demonstrate that side effects from IG002 will be few and mild, with an absence of severe adverse effects. The clinical protocol will provide evidence that IG002 taken orally by normally-menstruating, obese women (BMI ≥30 and ≤39.9) delays ovulation to ≥7 days compared to placebo ≤3 days. A dominant ovarian follicle emerges late in the follicular phase of the menstrual cycle. Rising estradiol from the follicle initiates release of a surge of luteinizing hormone (LH) from the pituitary. This LH surge acts at the dominant ovarian follicle to result in ovulation about 40 hours later. These changes are not readily apparent to the consumer and/or health care provider. However, most pregnancies result when intercourse occurs during the four days preceding the day of ovulation or on the day of ovulation itself, resulting in a five-day window of fertility, with the LH surge occurring in the middle of this five-day window. In this Proof of Concept study, IG002 is taken as two doses (48 hours apart), with the first dose taken when the dominant ovarian follicle diameter is 17±1.0 mm. This follicle diameter corresponds to the period of elevated estradiol and triggering of the LH surge when intercourse is likely to result in pregnancy. IG002 delays ovulation by two mechanisms. One drug prevents the LH surge, but only if taken before the LH surge begins. The second drug blocks the activity of an essential, LH-stimulated process within the ovarian follicle, so the second drug delays ovulation after the LH surge has begun. Each drug alone significantly delays ovulation when administered during the window of fertility. IG002 is superior to either drug alone by providing efficacy when taken either before or after the LH surge. Ovulation delay with IG002 prevents pregnancy. The delay of ovulation with IG002 of ≥7 days will exceed the sperm fertilizing capacity of 5 days in the female reproductive tract, but ovulation occurs subsequently in the menstrual cycle. Repeated acts of intercourse will require repeated use of IG002. The drugs contained in IG002 can alter the menstrual cycle interval and may or may not cause unscheduled uterine bleeding, but otherwise minimal side effects are anticipated in healthy women.