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Monday, 24th October, 2005
Lybrel is an investigational combination low-dose oral
contraceptive designed to be taken daily, 365 days a year.
Madison, N.J., Wyeth Pharmaceuticals, a division of
Wyeth, announced that four scientific abstracts regarding Lybrel?
(0.09 mg levonorgestrel/0.02 mg ethinyl estradiol tablets) were
presented for the first time today at the 61st Annual Meeting of the
American Society for Reproductive Medicine (ASRM) in Montr?l,
The studies investigated the effects of 0.09 mg
levonorgestrel/0.02 mg ethinyl estradiol on ovarian activity, safety
and efficacy, endometrial histology, and cycle-related symptoms. The
New Drug Application (NDA) for the study drug, Lybrel, a combination
low-dose oral contraceptive designed to be taken daily, 365 days a
year, without a placebo phase or pill-free interval, was accepted
for filing on July 27, 2005 and is currently under review by the
U.S. Food and Drug Administration (FDA).
The research presented at the ASRM Annual Meeting includes
investigational data on multiple effects of 0.09 mg levonorgestrel/0.02
mg ethinyl estradiol. The abstracts accepted for presentation are:
Investigation of Ovarian Activity
A six-month Phase 2 study entitled ?Effect on Ovarian Activity of
a Continuous-Use Regimen of Oral Levonorgestrel/Ethinyl Estradiol?
reported that participants (n=37) taking 0.09 mg levonorgestrel/0.02
mg ethinyl estradiol experienced inhibition of ovulation. The study
also reported that participants who stopped the study drug treatment
demonstrated a return to ovulation. This was the first ever
published investigational study of a combination oral contraceptive
designed to be taken every day of the year without a placebo phase
to specifically evaluate ovarian suppression and return to
Investigation of Safety and Efficacy
An abstract entitled ?Efficacy and Safety of a Continuous-Use
Regimen of Levonorgestrel/Ethinyl Estradiol: North American Phase 3
Study Results? examined the contraceptive effects of 0.09 mg
levonorgestrel/0.02 mg ethinyl estradiol and the adverse events
experienced by the study participants (n=2,134) during the 12-month
trial. Contraceptive efficacy was determined by the Pearl Index, a
calculation of the pregnancy rate among study participants.
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?In this study, the investigational drug was greater than 98 percent
effective in preventing pregnancy,? says Dr. David Archer, Director,
CONRAD Clinical Research Center, Professor of Obstetrics and
Gynecology, Eastern Virginia Medical School and investigator in this
trial. ?This rate is consistent with currently available oral
In addition, there was a steady increase from baseline in the
participants who reported amenorrhea and no bleeding: 44.8 percent
and 70.8 percent, respectively, by pill pack seven.
Among the trial participants, the safety profile of 0.09 mg
levonorgestrel/0.02 mg ethinyl estradiol was reported as consistent
with that of currently approved cyclic oral contraceptives. Safety
was assessed by physical exams, clinical laboratory tests, and
adverse event records. Six serious adverse events which were
possibly related to the drug were reported: cholecystitis (2), deep
vein thrombosis/pulmonary embolism (1), ectopic pregnancy (1),
prolonged vaginal bleeding (1) and enlarged uterine fibroids (1).
Investigation of Endometrial Histology
An abstract entitled ?Endometrial Histology in Subjects on a
Continuous-Use Regimen of Levonorgestrel/Ethinyl Estradiol: Results
of a Phase 3 Study? detailed the endometrial safety profile for 0.09
mg levonorgestrel/0.02 mg ethinyl estradiol. During the trial,
endometrial changes among the participants (n=93) were consistent
with a decrease in endometrial growth and decidualization compared
to baseline and no instances of malignancies were reported during
the 12-month trial period.
Investigation of Effect on Cycle-Related Symptoms
An abstract entitled ?A Continuous-Use Regimen of Levonorgestrel/Ethinyl
Estradiol Significantly Alleviates Cycle-Related Symptoms: Results
of a Phase 3 Study? explored the effects of 0.09 mg levonorgestrel/0.02
mg ethinyl estradiol on alleviating cycle-related symptoms. Symptoms
were recorded using the Penn Daily Symptom Rating (DSR) diary, a
tool designed to assess premenstrual syndrome (PMS). During the
three-month, open-label substudy, participants with a history of
cycle-related symptoms (n=36) or PMS (n=78) reported a decrease in
symptoms compared to baseline by the first pill pack, and continued
to report a decrease in symptoms during the two subsequent pill
About 0.09 mg Levonorgestrel/0.02 mg Ethinyl Estradiol
On July 27, Wyeth announced that the FDA accepted for filing the
Company?s NDA for Lybrel (0.09 mg levonorgestrel/0.02 mg ethinyl
estradiol tablets), an investigational combination oral
contraceptive with a low dosing regimen. Wyeth is seeking market
approval for 0.09 mg levonorgestrel/0.02 mg ethinyl estradiol
tablets for the prevention of pregnancy in women who elect to use
oral contraception and who have no known contraindications for this
method of contraception. If approved, this investigational product
will contain a low daily dose of ethinyl estradiol and
levonorgestrel, a well-studied combination. It is expected to be the
only combination oral contraceptive approved with this regimen
designed to be taken daily, 365 days a year, without a placebo phase
or pill-free interval. If approved, this product will also allow a
woman to stop the hormonal fluctuations associated with the entire
Filing an NDA with the FDA is an important step in the approval
process in the United States. Acceptance for filing does not
indicate that approval has been or will be issued, nor does it
represent an evaluation of the adequacy of the data submitted.
?The science to support 0.09 mg levonorgestrel/0.02 mg ethinyl
estradiol is an important evolution for oral contraceptives. As a
leader in women?s health care, Wyeth is developing this oral
contraceptive so that women may have additional contraceptive
options,? says Dr. Ginger Constantine, Vice President, Women?s
Health Care and Bone Repair, Wyeth Pharmaceuticals.