Prevention of Ovulation Achieved by Single Intra-vaginal Administration of Levogel as Compared to Oral LNG - Full Text View

Purpose

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).

Condition	Intervention	Phase
Female Contraception	Drug: Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Prevention
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

Resource links provided by NLM:

Drug Information available for: Levonorgestrel

U.S. FDA Resources

Further study details as provided by Population Council:

Primary Outcome Measures:

Comparison of LNG gel and oral LNG on follicle rupture [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The main objective of the study is to compare the effect of LNG gel and oral LNG on follicle rupture as assessed by ultrasound.

Secondary Outcome Measures:

Evaluate effect of single intra-vaginal administration [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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)


Estimated Enrollment:	20
Study Start Date:	January 2011
Study Completion Date:	November 2014
Primary Completion Date:	November 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Levonorgestrel (LNG) gel (Levogel) 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) 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.
Active Comparator: oral LNG (1.5mg) 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) 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.

Arms

Assigned Interventions

Active Comparator: Levonorgestrel (LNG) gel (Levogel)

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) 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.

Active Comparator: oral LNG (1.5mg)

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) 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.

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.

Eligibility


Ages Eligible for Study:	21 Years to 39 Years (Adult)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy women aged 21-39 years with regular menstrual cycles (25-35 days) and not at risk of pregnancy.

Exclusion Criteria:

All contraindications to the use of progestins

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286948

Locations


Chile
Instituto Chileno de Medicina Reproductiva
José Victorino Lastarria 29, Santiago, Chile
Dominican Republic
Profamilia
Socorro Sanchez No. 160, Santo Domingo, Dominican Republic, Apartado Postal 1053

Sponsors and Collaborators

Population Council

Investigators


Principal Investigator:	Vivian Brache, Lic.	Profamilia
Principal Investigator:	Regine Sitruk-Ware, PhD.	Population Council
Principal Investigator:	María José Miranda Gaete, MD	Instituto Chileno de Medicina Reproductiva

More Information


Responsible Party:	Population Council
ClinicalTrials.gov Identifier:	NCT01286948 History of Changes
Other Study ID Numbers:	Protocol # 441
Study First Received:	January 28, 2011
Last Updated:	April 16, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Population Council:


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)

Additional relevant MeSH terms:


Levonorgestrel Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents	Physiological Effects of Drugs Contraceptives, Oral, Synthetic Contraceptives, Oral

ClinicalTrials.gov processed this record on September 27, 2016