On Demand Oral Contraception for Obese Women

肥胖女性的按需口服避孕药

• 批准号: 10699536
• 负责人: DAVID Fitzgerald ARCHER
• 金额: $ 38.24万
• 依托单位: INNOVAGYN, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10699536
• 关键词: Address; Adverse effects; Age; Age Years; Blood; Blood Pressure; Body mass index; Clinical Protocols; Clinical Research; Coitus; Contraceptive Agents; Contraceptive Availability; Contraceptive methods; Couples; Data; Deep Vein Thrombosis; Development; Diameter; Dose; Drug Combinations; Estradiol; Estrogens; Female; Female Contraceptive Agents; Fertility; Gel; Glucuronides; Goals; Health; Health Personnel; Hormonal Oral Contraceptives; Hour; Interruption; Levonorgestrel; Luteinizing Hormone; Medical History; Menstrual cycle; Menstruation; Non-Steroidal Anti-Inflammatory Agents; Obesity; Oocytes; Oral; Oral Contraceptives; Oral cavity; Outcome; Ovarian Follicle; Overweight; Ovulation; Pharmaceutical Preparations; Phase; Physical Examination; Pituitary Hormones; Placebos; Pregnancy; Pregnanediol; Prevention; Process; Progestins; Risk; Risk Factors; Safety; Serious Adverse Event; Serum; Sex Behavior; Tablets; Time; Unsafe Sex; Uterine hemorrhage; Weight; Withdrawal; Woman; comparative efficacy; contraceptive efficacy; corpus luteum; efficacy evaluation; estrone-3-glucuronide; expectation; hormonal contraception; meloxicam; novel; pleasure; prevent; proliferative phase Menstrual cycle; recruit; reproductive tract; satisfaction; side effect; sperm cell; sperm viability; unintended pregnancy; urinary

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.

7.项目总结/摘要 我们研究的长期目标是为所有女性--正常、超重和肥胖--提供一个安全的， 有效的，不含雌激素的替代品，他们目前的避孕选择。IG 002预期用于 作为一种按需避孕药，在性交前服用。本申请的具体目的是： 1)提供IG 002中两种药物联合使用将延迟排卵的概念证明，特别是在肥胖患者中 女性;和2）证明IG 002的副作用很少且轻微，没有严重的副作用。 不良影响临床方案将提供证据表明，IG 002口服正常， 肥胖女性（BMI ≥30且≤39.9）排卵延迟≥7天，而安慰剂≤3天。 优势卵泡出现在月经周期的卵泡期晚期。雌二醇水平升高 卵泡启动垂体释放大量促黄体生成激素（LH）。这种LH激增作用于 优势卵泡导致排卵约40小时后。这些变化并不明显， 消费者和/或卫生保健提供者。然而，大多数怀孕的结果时，性交发生在 排卵前四天或排卵当天，导致五天的窗口期， 生育能力，LH激增发生在这五天窗口的中间。在本概念验证研究中，IG 002 分两次服用（间隔48小时），第一次服用时，优势卵泡直径为 17±1.0 mm。该卵泡直径对应于雌二醇升高和LH峰触发的时期 当性交可能导致怀孕。 IG 002通过两种机制延迟排卵。一种药物可以防止LH激增，但前提是在LH之前服用。 浪涌开始。第二种药物阻断卵巢内LH刺激的一个重要过程的活性， 卵泡，所以第二种药物延迟排卵后，LH激增已经开始。每种药物单独使用都会显著延迟 在生育窗口期给药时排卵。IG 002优于任何一种单独使用的药物，因为它提供了上级 在LH峰之前或之后服用的有效性。 IG 002的排卵延迟可预防妊娠。IG 002的排卵延迟≥7天将超过 精子在女性生殖道中的存活能力为5天，但排卵随后发生在女性生殖道中。 月经周期重复性交行为将需要重复使用IG 002。中所含药物 IG 002可以改变月经周期间隔，可能会或可能不会引起非计划性子宫出血，但 在健康女性中预期其他副作用最小。