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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 April 2015
• Main ID: NCT00796133
• Date of registration: 21/11/2008
• Prospective Registration: No
• Primary sponsor: Population Council
• Public 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
• Scientific 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
• Date of first enrolment: November 2008
• Target sample size: 18
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00796133
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Chile, Dominican Republic, United States

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 40 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Ovulation

Intervention(s)

Drug: NES/E2 gel

Primary Outcome(s)

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 [Time Frame: Subjects will remain in the study for approximately 8 months]

Secondary Outcome(s)

Evaluate the correlation of NES and E2 serum levels with the percentage of ovulation suppression [Time Frame: Subjects will remain in the study for approximately 8 months]

Determine with USS and E2 serum levels the dose that can suppress follicle growth and replace estradiol at the physiological early follicular phase level [Time Frame: Subjects will remain in the study for approximately 8 months]

Evaluate the safety and tolerability of the formulations [Time Frame: Subjects will remain in the study for approximately 8 months]

Secondary ID(s)

Population Council #427

Source(s) of Monetary Support

Please refer to primary and secondary sponsors