Clinical trial NCT01286948: Prevention of Ovulation Achieved by Single Intra-vaginal Administration of Levogel as Compared to Oral LNG
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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)
Lead sponsor: Population Council
Sponsor class: OTHER
First posted: 2011-01-31
Enrollment: 20
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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 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.

Eligibility 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

Primary outcomes:
measure: Comparison of LNG gel and oral LNG on follicle rupture
timeFrame: 1 year
Secondary outcomes:
measure: Evaluate effect of single intra-vaginal administration
timeFrame: 1 year
Other outcomes:
Locations:
city: José Victorino Lastarria 29
country: Chile
facility: Instituto Chileno de Medicina Reproductiva
state: Santiago
city: Socorro Sanchez No. 160
country: Dominican Republic
facility: Profamilia
state: Santo Domingo
Study officials:
affiliation: Profamilia
name: Vivian Brache, Lic.
role: PRINCIPAL_INVESTIGATOR
affiliation: Population Council
name: Regine Sitruk-Ware, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Chileno de Medicina Reproductiva
name: María José Miranda Gaete, MD
role: PRINCIPAL_INVESTIGATOR
References: