On Demand Oral Contraception for Obese Women

Innovagyn, Inc., Norfolk VA

Investigators

Abstract

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.