This study will compare blood levels of the drug CDB-2914 in healthy women receiving the
compound in crystalline powder form with the blood levels of women receiving an identical
dose of the drug in micronized form. Generally, absorption of compounds made into a
crystalline powder is less than that of micronized compounds, in which the substance is
processed into many similar-sized particles.
CDB-2914 is a manmade hormone similar to the hormones cortisol and progesterone. The
National Institute of Child Health and Human Development is evaluating the ability of this
drug to treat reproductive conditions. Institute studies have shown that CDB-2914 can
increase the time to produce a mature egg in the ovary, and cause an early menstrual period,
CDB-2914 might be used to treat fibroids and endometriosis pain. As part of its evaluation
for these purposes, this study will determine if absorption of crystalline and micronized
powder forms of CDB-2914 result in the same blood levels of the drug.
Women between 18 and 50 years of age who are in good health may be eligible for this study.
Premenopausal women must not be pregnant (as determined by a urine pregnancy test) or
breastfeeding and must practice birth control during the study. Candidates will be screened
with a medical history, physical examination, and blood and urine tests. Women who use an
IUD for contraception are advised to also use a barrier contraceptive (diaphragm or condom)
the week after taking CDB-2914.
Participants will be admitted to the NIH Clinical Center inpatient service or the outpatient
day hospital twice for pharmacokinetic studies (blood drawing to measure blood levels of
CDB-2914 after a single dose of the drug). They will come to the Clinical Center at 7:00
a.m. and have a catheter (thin plastic tube) inserted into an arm vein for drawing blood for
the first 24 hours of the study. Eight milliliters (about 2 teaspoons) of blood will be
drawn 5 minutes and 1 minute before taking CDB-2914 (in either crystalline or micronized
powder form) and then at the following times after taking the drug: 15, 30, 45, 60, 75, 90,
105, 120, 150 and 180 minutes (3 hours), and 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 hours (5
Participants will take all their meals in the day hospital or ward during the first 26 hours
of sampling. Inpatients will leave the hospital after the 24-hour blood draw and return as
an outpatient on days 2 through 5. At the 48-hour time point, additional blood will be drawn
to check blood counts and chemistries, and for liver and kidney function tests.
In recent years, compounds that are structurally similar to the naturally occurring steroids
have been examined for their ability to block or substitute for the action of the naturally
occurring steroids. On occasion, these substances have both effects, depending on the
tissue that is examined or on the physiology of the person receiving the agent. The
development of these kinds of compounds, called selective hormone receptor modulators, may
provide new treatments that are targeted to specific organs or tissues. One example of
these compounds is the selective estrogen receptor modulator raloxifene, which blocks
estrogen action at the uterus, and acts like estrogen at the bone, allowing its use in
post-menopausal women as estrogen replacement therapy without requiring progesterone.
This study evaluates the progesterone receptor modulator CDB-2914. Earlier studies using
single doses of this compound show that it can slow ovarian and uterine development during
the menstrual cycle, and can induce menses, depending on when it is given during the
Many steroids have an improved bioavailability when given in a micronized formulation.
Previous studies with CDB-2914 have used crystalline powder up to a dose of 200 mg. We wish
to compare the pharmacokinetic profile of crystalline and micronized CDB-2914, 10 mg. The
drug will be given as a single oral dose and blood will be drawn frequently over 12 hours
and then daily for five days for measurement of the compound.
General inclusion criteria:
Female gender--to evaluate effects in the target population for clinical trials.
In good health. Chronic medication use is acceptable except for glucocorticoid use.
Other chronic medication use may be acceptable at discretion of the principal
investigator. Interval use of over-the-counter drugs is acceptable but must be recorded.
Hemoglobin greater than 10 g/dL.
Willing and able to comply with study requirements.
Age 18 to 50.
Additional inclusion criteria for pre-menopausal women:
Using mechanical (condoms, diaphragms), abstinence, oral contraceptive, IUD or
sterilization methods of contraception for the duration of the study. Because the effect
of CDB-2914 on IUD efficacy is not known, women using this form of birth control will be
advised to use barrier methods during the cycle(s) in which they participate.
Negative urine pregnancy test within one week of the first study. If the second study
occurs in a subsequent cycle, the pregnancy test will be repeated.
Significant abnormalities in the history, physical or laboratory examination
Use of oral, injectable or inhaled glucocorticoids or megesterol within the last year
Unexplained vaginal bleeding
History of malignancy within the past 5 years
Use of anti-epileptic agents