Ovulation
Conditions
Keywords
NES/E2, transdermal gel delivery, contraception, ovulation, bleeding patterns
Brief summary
This is a Phase 2, dose-finding, cross-over study for the purposes of evaluating the effect of a NES/E2 transdermal gel delivery on ovulation suppression in normal ovulating women.
Interventions
DRUGNES/E2 gel
Lowest effective dose of 3 formulations of the NES/E2 gel to ensure ovulation suppression (P\<10nmol/L) in 90-95% of the cycles. The high dose will deliver 4.5mg of NES; the medium dose will deliver 3mg of NES, and a low dose of 1.5mg of NES. Based on a 10% absorption rate, 450 µg/d, 300 µg/d and 150 µg/d will be absorbed respectively. The doses of Estradiol will also be tailored to the 3 formulations.
Sponsors
Population Council
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Woman is between 18 and 40 years of age * Has intact uterus and ovaries * Has regular menstrual cycles of 25-35 days duration * Able to comply with the protocol, including frequent blood sampling, and lives within the catchment area of the clinic * Understands the study procedures and agrees to participate in the study by giving written informed consent * Able to use non-hormonal, double-barrier contraceptives (e.g. condoms and diaphragm) with every act of intercourse, or has been sterilized with tubal ligation, or only male partner has been sterilized with vasectomy * Progesterone \>10 nmol/L in at least one sample in the lead-in cycle
Exclusion criteria
* All contraindications to OC use including * Thrombophlebitis or thromboembolic disorders * Past history of deep vein thrombophlebitis or thromboembolic disorders * Past or current cerebrovascular or coronary artery disease * Known or suspected carcinoma of the breast * Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia * Undiagnosed abnormal genital bleeding * Cholestatic jaundice of pregnancy or jaundice with prior pill use * Hepatic adenomas or carcinomas * Woman has a history of headaches with focal neurological symptoms * Known or suspected pregnancy * Aged \>35 and smoker * BMI \>29 * Positive urine pregnancy test at the screening or baseline visit * Desired pregnancy within the duration of the study * Known hypersensitivity to progestins * Known hypersensitivity to estrogen * Undiagnosed vaginal discharge or vaginal lesions or abnormalities * In accordance with the Bethesda system of classification Women with a current abnormal Pap smear suggestive of high-grade pre cancerous lesion(s), including HGSIL, are excluded * Women with LGSIL or ASCUS/high-risk HPV positive may participate if further evaluated with colposcopy and biopsy and no evidence of a lesion with a severity \>CIN I is present and/or endocervical curettage is negative * Women with a biopsy finding of CIN I should have follow up for this finding per standard of care; women are excluded if treatment is indicated In accordance with other Pap class systems * Women with high grade dysplasia are excluded * Women with low grade dysplasia or CIN I interpretation on Pap smear may participate based on investigator discretion in accordance with local standard of care * Breastfeeding * Cancer (past history of any carcinoma or sarcoma) * History of a significant psychiatric disorder, including severe depression. * Chronic or acute liver or renal disease * Hypertension-- controlled by medication or defined by diastolic BP 85 mm Hg or systolic BP 135mm Hg after 15 minutes rest * Dermatitis, psoriasis or other severe skin disorder * Known or suspected alcoholism or drug abuse * Clinically significant abnormalities of laboratory safety tests * Chronic disease or history of illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject * Woman is participating or has participated in another clinical study (involving an investigational drug) within one month prior to enrollment. * Use of injectable contraceptives during the previous 3 months (e.g. cyclofem) or 9 months (e.g. DMPA) * Use of oral contraceptives within the past 1 month * Use of concomitant drugs that may interact with the study drugs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine with ultrasound scan (USS) measures and serum progesterone (P) assessment the lowest effective dose of 3 formulations of the NES/E2 gel to ensure ovulation suppression (P<10nmol/L) in 90-95% of the cycles | Subjects will remain in the study for approximately 8 months |
Secondary
| Measure | Time frame |
|---|---|
| Determine with USS and E2 serum levels the dose that can suppress follicle growth and replace estradiol at the physiological early follicular phase level | Subjects will remain in the study for approximately 8 months |
| Evaluate the correlation of NES and E2 serum levels with the percentage of ovulation suppression | Subjects will remain in the study for approximately 8 months |
| Evaluate the safety and tolerability of the formulations | Subjects will remain in the study for approximately 8 months |
Countries
Chile, Dominican Republic, United States
Outcome results
None listed