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

Ovulation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00796133
• Other study ID #: Population Council #427
• Status: Completed
• Phase: Phase 2
• First received: November 21, 2008
• Last updated: April 16, 2015
• Start date: November 2008
• Est. completion date: January 2014

Study information

• Verified date: April 2015
• Source: Population Council
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationChile: Instituto de Salud Pública de ChileDominican Republic: Secretaría del Estado de Salud Pública y Asistencia Social (SESPAS)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovulation

Intervention

Drug:
• NES/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.

Locations

Country	Name	City	State
Chile	Instituto Chileno de Medicina Reproductiva	Santiago
Dominican Republic	Profamilia	Santo Domingo
United States	Women's and Children's Hospital; LA County/USC Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Population Council

Countries where clinical trial is conducted

United States,  Chile,  Dominican Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Evaluate the safety and tolerability of the formulations		Subjects will remain in the study for approximately 8 months	Yes