Female ContraceptionPhase 1NCT01286948
Prevention of Ovulation Achieved by Single Intra-vaginal Administration of Levogel as Compared to Oral LNG
A Phase 1 study testing Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B) in people with Female Contraception, run by Population Council at 2 sites in 2 countries.
Trial summary
It has been proposed that levonorgestrel (LNG) in a vaginal gel could be used as an 'on demand' contraceptive when used before coitus. Levonorgestrel was selected as it is a component of many approved oral contraceptive pills and also it is the active agent in Plan B, an FDA-approved regimen for emergency… Read more about this study
- Who is it for?
- Ages 21 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Female Contraception
- What is being tested?
- Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2011to Nov 2014
- Phase
- Phase 1
- 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 21 to 39 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy women aged 21-39 years with regular menstrual cycles (25-35 days) and not at risk of pregnancy.
Who cannot join
- All contraindications to the use of progestins
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Chile1 site
Instituto Chileno de Medicina Reproductiva
José Victorino Lastarria 29, Santiago Metropolitan
Dominican Republic1 site
Profamilia
Socorro Sanchez No. 160, Santo Domingo Province, Apartado Postal 1053
About this study
Official title: A Randomized, Cross-over, Clinical Trial to Assess the Prevention of Ovulation Achieved by Single Intra-vaginal Administration of 0.75 mg Levonorgestrel (LNG) Gel (Levogel) as Compared to 1.5 mg Oral LNG
It has been proposed that levonorgestrel (LNG) in a vaginal gel could be used as an 'on demand' contraceptive when used before coitus. Levonorgestrel was selected as it is a component of many approved oral contraceptive pills and also it is the active agent in Plan B, an FDA-approved regimen for emergency contraception (EC). In previous studies it was demonstrated that an LNG vaginal gel was absorbed and was effective in preventing follicular rupture. The overall proportion of cycles with lack of follicular rupture within 5 days of LNG administration or with ovulatory dysfunction (follicle rupture preceded by an inadequate LH surge) was 96% for LNG gel and 39% in the inert gel cycles (control group).
Read the detailed description
A dose of 0.75mg of LNG in a vaginal gel was shown to prevent ovulation in a higher percentage than what has been observed with oral LNG at the approved doses for EC of 1.5mg. Results from a study with a1.5 mg LNG oral dose or a single 0 ,75mg dose demonstrated that the proportion of cycles without follicle rupture or ovulatory dysfunction within 5 days was 86% and 79% respectively (Croxatto et al, 2004) , whereas lack of follicular rupture or the presencr of ovulatory dsyfunction was 96% with administration of a LNG gel formulation. In the group of women with follicle size ≥18mm the gel induced 50% ovulation suppression while oral LNG in previous studies blocked only 16% of ovulation in the same follicle size group . These encouraging results could be explained by higher bioavailability of LNG when administered vaginally. This comparison was made using historical data from another study; therefore this study will compare vaginal administration of LNG to oral in a direct cross-over comparative study.
LNG is known to affect the cervical mucus by making it hostile to sperm penetration and its effect may appear after only a few hours following oral administration (Kesseru, 1984; Brache, unpublished observations). Application of LNG gel in the vagina close to the cervical os may exert a direct effect on the cervical mucus. The potential local action of LNG on the cervical mucus may be another important mechanism by which protection is conferred to women who do not experience ovulation suppression.
An "on demand" precoital contraceptive is an attractive alternative to the post-coital emergency contraception currently available, especially due to the higher efficacy of this route of administration on ovulation suppression as compared with oral tablets of LNG. Should the present study confirm the superiority of vaginal administration of half the dose of the oral dose of LNG approved for emergency contraception, further development of that formulation and method would be warranted.
- Conditions
- Female Contraception
- Being tested
- Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)
- Keywords
- LNG gel, oral LNG, follicle rupture, intra-vaginal administration, growth of the leading follicle, preovulatory peak of serum luteinizing hormone, characteristics of the cervical mucus, serum levels of estradiol (E2) and progesterone (P)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)Drug
This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg).
All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated.
| Study group | Role | What they receive |
|---|---|---|
| Levonorgestrel (LNG) gel (Levogel) | Active comparator | This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg).
All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated. Receives: Drug: Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B) |
| oral LNG (1.5mg) | Active comparator | This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg).
All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated. Receives: Drug: Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of LNG gel and oral LNG on follicle rupture
The main objective of the study is to compare the effect of LNG gel and oral LNG on follicle rupture as assessed by ultrasound.
Measured: 1 year
Secondary outcomes (1)
Evaluate effect of single intra-vaginal administration
The secondary objectives are to evaluate the effect of single intra-vaginal administration of LNG gel or oral LNG on the:
- growth of the leading follicle
- suppression of the preovulatory peak of serum luteinizing hormone (LH)
- characteristics of the cervical mucus
- serum levels of estradiol (E2) and progesterone (P)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Female ContraceptionStudies 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Council
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vivian Brache, Lic., Principal investigator, ProfamiliaRegine Sitruk-Ware, PhD., Principal investigator, Population CouncilMaría José Miranda Gaete, MD, Principal investigator, Instituto Chileno de Medicina Reproductiva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01286948
- Sponsor's protocol ID
- Protocol # 441
- Status last verified
- Aug 2017
- First submitted
- 28 Jan 2011
- Last updated
- 15 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Cross-over, Clinical Trial to Assess the Prevention of Ovulation Achieved by Single Intra-vaginal Administration of 0.75 mg Levonorgestrel (LNG) Gel (Levogel) as Compared to 1.5 mg Oral LNG
- ClinicalTrials.gov ID
- NCT01286948
- Acronym / sponsor ID
- Protocol # 441
- Conditions
- Female Contraception
- Keywords
- LNG gel, oral LNG, follicle rupture, intra-vaginal administration, growth of the leading follicle, preovulatory peak of serum luteinizing hormone, characteristics of the cervical mucus, serum levels of estradiol (E2) and progesterone (P)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Population CouncilUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 31 Jan 2011 (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.
It has been proposed that levonorgestrel (LNG) in a vaginal gel could be used as an 'on demand' contraceptive when used before coitus. Levonorgestrel was selected as it is a component of many approved oral contraceptive pills and also it is the active agent in Plan B, an FDA-approved regimen for emergency contraception (EC). In previous studies it was demonstrated that an LNG vaginal gel was absorbed and was effective in preventing follicular rupture. The overall proportion of cycles with lack of follicular rupture within 5 days of LNG administration or with ovulatory dysfunction (follicle rupture preceded by an inadequate LH surge) was 96% for LNG gel and 39% in the inert gel cycles (control group).
Detailed description
A dose of 0.75mg of LNG in a vaginal gel was shown to prevent ovulation in a higher percentage than what has been observed with oral LNG at the approved doses for EC of 1.5mg. Results from a study with a1.5 mg LNG oral dose or a single 0 ,75mg dose demonstrated that the proportion of cycles without follicle rupture or ovulatory dysfunction within 5 days was 86% and 79% respectively (Croxatto et al, 2004) , whereas lack of follicular rupture or the presencr of ovulatory dsyfunction was 96% with administration of a LNG gel formulation. In the group of women with follicle size ≥18mm the gel induced 50% ovulation suppression while oral LNG in previous studies blocked only 16% of ovulation in the same follicle size group . These encouraging results could be explained by higher bioavailability of LNG when administered vaginally. This comparison was made using historical data from another study; therefore this study will compare vaginal administration of LNG to oral in a direct cross-over comparative study.
LNG is known to affect the cervical mucus by making it hostile to sperm penetration and its effect may appear after only a few hours following oral administration (Kesseru, 1984; Brache, unpublished observations). Application of LNG gel in the vagina close to the cervical os may exert a direct effect on the cervical mucus. The potential local action of LNG on the cervical mucus may be another important mechanism by which protection is conferred to women who do not experience ovulation suppression.
An "on demand" precoital contraceptive is an attractive alternative to the post-coital emergency contraception currently available, especially due to the higher efficacy of this route of administration on ovulation suppression as compared with oral tablets of LNG. Should the present study confirm the superiority of vaginal administration of half the dose of the oral dose of LNG approved for emergency contraception, further development of that formulation and method would be warranted.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levonorgestrel (LNG) gel (Levogel) | Active comparator | Drug: Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg). All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated. |
| oral LNG (1.5mg) | Active comparator | Drug: Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg). All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated. |
Who may qualify
- Ages
- 21 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy women aged 21-39 years with regular menstrual cycles (25-35 days) and not at risk of pregnancy.
Key exclusion criteria (1 listed)
- All contraindications to the use of progestins
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 |
|---|---|---|
| Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg). All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated. | Drug | Levonorgestrel (LNG) gel (Levogel), oral LNG (1.5mg) |
Primary outcome
Comparison of LNG gel and oral LNG on follicle rupture
Time frame: 1 year
The main objective of the study is to compare the effect of LNG gel and oral LNG on follicle rupture as assessed by ultrasound.
1 secondary outcome
Evaluate effect of single intra-vaginal administration
Time frame: 1 year
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 15 Aug 2017.
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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.
Vivian Brache, Lic. principal investigator
Profamilia
Regine Sitruk-Ware, PhD. principal investigator
Population Council
María José Miranda Gaete, MD principal investigator
Instituto Chileno de Medicina Reproductiva
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B) in people with Female Contraception, run by Population Council at 2 sites in 2 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 1 inclusion and 1 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 15 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Comparison of LNG gel and oral LNG on follicle rupture (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Aug 2017.