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

NCT ID: NCT00796133

Last Updated: 2015-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2014-01-31

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.

Conditions

Ovulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1

0.5 ml of NES/E2 equaling 0.45 g and contains 1.5 mg NES/0.5 mg E2

Group Type: ACTIVE_COMPARATOR

NES/E2 gel

Intervention Type: DRUG

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.

2

1.0 ml of NES/E2 gel equaling 0.9 g and contains 3.0 mg NES/1.0 mg E2

Group Type: ACTIVE_COMPARATOR

NES/E2 gel

Intervention Type: DRUG

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.

3

1.5 ml of NES/E2 gel equaling 4.5 mg NES/1.5 mg E2

Group Type: ACTIVE_COMPARATOR

NES/E2 gel

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Population Council

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Women's and Children's Hospital; LA County/USC Medical Center

Los Angeles, California, United States

Instituto Chileno de Medicina Reproductiva

Santiago, , Chile

Profamilia

Santo Domingo, , Dominican Republic

Countries

United States; Chile; Dominican Republic

References

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.

Reference Type: DERIVED

PMID: 26032952 (View on PubMed)

Other Identifiers

Population Council #427

Identifier Type: -

Identifier Source: org_study_id