- Healthy female subjects in childbearing age, between the ages of 18 and 45 years,
inclusive (Healthy is defined as no clinically relevant abnormalities identified by a
detailed medical history, full physical examination, including blood pressure and
pulse rate measurement, 12-lead ECG and clinical laboratory tests).
- The BMI - Body Mass Index of the volunteers should be within the range of 18,5 to 24,9
(Dietary Guidelines for Americans) and it may vary up to 10% due to the upper limit
(18,5 to 27,39) and total body weight >50kg
- Do not be a smoker (at least 3 months);
- Not be using hormone contraceptives for at least 28 days before the medication dosing;
- Women with a regular menstrual cycle (menstrual cycle that occurs, in average, in each
28 days, varying from 25 to 35 days);
- Use lubricated condoms with spermicidal or diaphragm with spermicidal (in accordance
with the volunteer's preference)
- Systolic Pressure up to 130mmHg;
- Diastolic Pressure up to 85mmHg;
- An informed consent document signed and dated by the subject or a legally acceptable
representative. If the subject and/or legally acceptable representative cannot read,
then the informed consent document may be signed by an impartial witness.
- Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
- Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
allergic disease (including drug allergies, but excluding untreated, asymptomatic,
seasonal allergies at time of dosing).
- The volunteer has a drug abuse history [subjects using marijuana and hashish will be
excluded if they have used these drugs less than three months prior to the medical
consult and for drugs such as cocaine, phencyclidine (PCP), crack and heroin,
volunteers will be excluded that have used these drugs less than 1 year prior to the
- A positive exam for drugs in urine (Methamphetamine, Opiate, Morphine, Marijuana,
Cannabis, Amphetamine, Coccaine, Benzoylecgogine, Benzodiazepine) or a positive test
for alcohol before the internment in periods 1 and 2.
- History of regular alcohol consumption exceeding 7 drinks/week (1 drink = 150 mL of
wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening.
- The volunteer is a smoker or having stopped smoking less than 3 months
- The volunteer has participated of any experimental trial or has ingested any
experimental drug within the 6 months that precede the beginning of the study (ANVISA:
Resolution RDC nº34, from June 3rd 2008).
- 12-lead ECG demonstrating QTc >450 msec at screening. If QTc exceeds 450 msec, the ECG
should be repeated two more times and the average of the three QTc values should be
used to determine the subject's eligibility.
- Pregnant or nursing females; females of childbearing potential who are unwilling or
unable to use an acceptable method of non-hormonal contraception as outlined in this
protocol from at least 14 days prior to the first dose of study medication.
- Use of prescription or nonprescription drugs and dietary supplements within 7 days or
5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal
medicine, herbal supplements must be discontinued 28 days prior to the first dose of
study medication. Limited use of non-prescription medications that are not believed to
affect subject safety or the overall results of the study may be permitted on a
case-by-case basis following approval by the sponsor.
- Hormonal methods of contraception (including oral and transdermal contraceptives,
injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs,
postcoital contraceptive methods) and hormone replacement therapy must be discontinued
28 days prior to the first dose of study medication.
- Implant (ex. Norplant®) or a progesterone depot injection (ex. Depo-Provera®) or the
use of any dispositive for the long term treatment with progesterone or estrogens (ex.
Estring®) up to 6 months before the administration of the medication in study;
- A depot injection or an implant of any active ingredient up to 3 months before the
administration of the medication in study;
- Have used an injection contraceptive of Medroxyprogesterone Acetate one year before
the beginning of the study;
- Have had sexual intercourse without a contraceptive method (preservative, IUD,
diaphragm with spermicidal) within the last 14 days.