OvulationPhase 2NCT00796133
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
A Phase 2 study testing NES/E2 gel in people with Ovulation, run by Population Council at 3 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ovulation
- What is being tested?
- NES/E2 gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Nov 2008to Jan 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 36Show fewer
- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
Women's and Children's Hospital; LA County/USC Medical Center
Los Angeles, California, 90033
About this study
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
- Being tested
- NES/E2 gel
- Keywords
- NES/E2, transdermal gel delivery, contraception, ovulation, bleeding patterns
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NES/E2 gelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 0.5 ml of NES/E2 equaling 0.45 g and contains 1.5 mg NES/0.5 mg E2 Receives: Drug: NES/E2 gel |
| 2 | Active comparator | 1.0 ml of NES/E2 gel equaling 0.9 g and contains 3.0 mg NES/1.0 mg E2 Receives: Drug: NES/E2 gel |
| 3 | Active comparator | 1.5 ml of NES/E2 gel equaling 4.5 mg NES/1.5 mg E2 Receives: Drug: NES/E2 gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Subjects will remain in the study for approximately 8 months
Secondary outcomes (3)
Determine with USS and E2 serum levels the dose that can suppress follicle growth and replace estradiol at the physiological early follicular phase level
Measured: Subjects will remain in the study for approximately 8 months
Evaluate the correlation of NES and E2 serum levels with the percentage of ovulation suppression
Measured: Subjects will remain in the study for approximately 8 months
Evaluate the safety and tolerability of the formulations
Measured: Subjects will remain in the study for approximately 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OvulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Population Council
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00796133
- Sponsor's protocol ID
- Population Council #427
- Status last verified
- Apr 2015
- First submitted
- 21 Nov 2008
- Last updated
- 17 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26032952
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00796133
- Acronym / sponsor ID
- Population Council #427
- Conditions
- Ovulation
- Keywords
- NES/E2, transdermal gel delivery, contraception, ovulation, bleeding patterns
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Population CouncilUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 24 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: NES/E2 gel0.5 ml of NES/E2 equaling 0.45 g and contains 1.5 mg NES/0.5 mg E2 |
| 2 | Active comparator | Drug: NES/E2 gel1.0 ml of NES/E2 gel equaling 0.9 g and contains 3.0 mg NES/1.0 mg E2 |
| 3 | Active comparator | Drug: NES/E2 gel1.5 ml of NES/E2 gel equaling 4.5 mg NES/1.5 mg E2 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (36 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NES/E2 gelLowest 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. | Drug | 1, 2, 3 |
Primary outcome
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
3 secondary outcomes
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 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
Evaluate the safety and tolerability of the formulations
Time frame: Subjects will remain in the study for approximately 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2015.
- Derived from this study: PubMed 26032952Brache 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NES/E2 gel in people with Ovulation, run by Population Council at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Chile, Dominican Republic. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Subjects will remain in the study for approximately 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00796133, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2015.