Clinical trial NCT00796133: A Phase 2, Dose-finding, Cross-over Study to Evaluate the Effect of a NES/E2 Transdermal Gel Delivery on Ovulation Suppression in Normal Ovulating Women
Official title: A Phase 2, Dose-finding, Cross-over Study to Evaluate the Effect of a NES/E2 Transdermal Gel Delivery on Ovulation Suppression in Normal Ovulating Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovulation
Keywords: NES/E2
transdermal gel delivery
contraception
ovulation
bleeding patterns
Lead sponsor: Population Council
Sponsor class: OTHER
First posted: 2008-11-24
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Subjects will remain in the study for approximately 8 months
Secondary outcomes:
measure: Determine with USS and E2 serum levels the dose that can suppress follicle growth and replace estradiol at the physiological early follicular phase level
timeFrame: Subjects will remain in the study for approximately 8 months
measure: Evaluate the correlation of NES and E2 serum levels with the percentage of ovulation suppression
timeFrame: Subjects will remain in the study for approximately 8 months
measure: Evaluate the safety and tolerability of the formulations
timeFrame: Subjects will remain in the study for approximately 8 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Women's and Children's Hospital; LA County/USC Medical Center
state: California
city: Santiago
country: Chile
facility: Instituto Chileno de Medicina Reproductiva
city: Santo Domingo
country: Dominican Republic
facility: Profamilia
Study officials:
References:
citation: Brache V, Merkatz R, Kumar N, Jesam C, Sussman H, Hoskin E, Roberts K, Alami M, Taylor D, Jorge A, Croxatto H, Lorange E, Mishell DR, Sitruk-Ware R. A dose-finding, cross-over study to evaluate the effect of a Nestorone(R)/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women. Contraception. 2015 Oct;92(4):289-97. doi: 10.1016/j.contraception.2015.05.011. Epub 2015 May 29.