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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
This study is currently recruiting participants.
Verified by Population Council, November 2008
Sponsored by: Population Council
Information provided by: Population Council
ClinicalTrials.gov Identifier: NCT00796133
  Purpose

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.


Condition Intervention Phase
Ovulation
Drug: NES/E2 gel
Phase II

Drug Information available for: Depogen Estradiol Estradiol 3-benzoate Estradiol acetate Estradiol cypionate Estradiol dipropionate Estradiol valerate Polyestradiol phosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Single Blind (Subject), Dose Comparison, Crossover Assignment, Safety/Efficacy Study
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

Further study details as provided by Population Council:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Evaluate the safety and tolerability of the formulations [ Time Frame: Subjects will remain in the study for approximately 8 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: November 2008
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
0.5 ml of NES/E2 equaling 0.45 g and contains 1.5 mg NES/0.5 mg E2
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.
2: Active Comparator
1.0 ml of NES/E2 gel equaling 0.9 g and contains 3.0 mg NES/1.0 mg E2
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.
3: Active Comparator
1.5 ml of NES/E2 gel equaling 4.5 mg NES/1.5 mg E2
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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00796133

Contacts
Contact: Regine Sitruk-Ware 212-327-7045 rsitrukware@popcouncil.org
Contact: Ruth Merkatz 212-327-8647 rmerkatz@popcouncil.org

Locations
United States, California
Women's and Children's Hospital; LA County/USC Medical Center Recruiting
Los Angeles, California, United States, 90033
Contact: Daniel Mishell, MD     323-226-3416     Mishell@hsc.usc.edu    
Contact: DeShawn Taylor, MD     323-226-3416     deshawnt@usc.edu    
Principal Investigator: Daniel Mishell, MD            
Sub-Investigator: DeShawn Taylor, MD            
Chile
Instituto Chileno de Medicina Reproductiva Recruiting
Santiago, Chile
Contact: Cristian Jesam, MD     011-56 2 632 4644     cjesam@icmer.org    
Principal Investigator: Cristian Jesam, MD            
Dominican Republic
PROFAMILIA Recruiting
Santo Domingo, Dominican Republic
Contact: Vivian Brache, Lic.     809-681-8357     biomedica@codetel.net.do    
Principal Investigator: Vivian Brache, Lic.            
Sponsors and Collaborators
Population Council
  More Information

Responsible Party: Population Council ( Regine Sitruk-Ware, Study Coordinator )
Study ID Numbers: Population Council #427
Study First Received: November 21, 2008
Last Updated: November 21, 2008
ClinicalTrials.gov Identifier: NCT00796133  
Health Authority: United States: Food and Drug Administration;   Chile: Instituto de Salud Publica de Chile;   Dominican Republic: Secretaría del Estado de Salud Pública y Asistencia Social (SESPAS)

Keywords provided by Population Council:
NES/E2
transdermal gel delivery
contraception
ovulation
bleeding patterns

Study placed in the following topic categories:
Signs and Symptoms
Estradiol 3-benzoate
Estradiol valerate
Estradiol 17 beta-cypionate
Polyestradiol phosphate
Hemorrhage
Estradiol

ClinicalTrials.gov processed this record on January 16, 2009