Drospirenone/Ethinyl Estradiol (3 mg/0.02 mg) Tablets Under Non-Fasting Conditions
Condition: Healthy
Intervention: Drospirenone/Ethinyl Estradiol (Gianvi®); YAZ®
Intervention description: 3 mg/0.02 mg Tablets; 3 mg/0.02 mg Tablets
Intervention MeSH terms: Drospirenone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Ethinyl Estradiol; Drospirenone and ethinyl estradiol combination; Estradiol; Polyestradiol phosphate
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: Female
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Healthy Subjects

Summary:

      This study was designed to compare the relative bioavailability (rate and extent of
      absorption) of 3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets with that of YAZ® Tablets
      (by Berlex, Inc.) following a single, oral dose (2 x 3 mg/0.02 mg tablets) in healthy, adult
      subjects under non-fasting conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who were informed of the nature of the study and agreed to read, review, and
             sign the informed consent document prior to Period I dosing.

          -  Subjects who completed the screening process within 28 days prior to Period I dosing.

          -  Subjects who were healthy, adult, menstruating women 18 to 35 years of age, inclusive,
             at the time of dosing.

          -  Subjects with a body mass index (BMI) between 19 and 30 kg/m2, inclusive, and weighed
             at least 110 pounds.

          -  Subjects who were healthy as documented by the medical history, physical examination,
             vital sign assessments, 12-lead electrocardiogram, clinical laboratory assessments,
             and by general observations. The physical examination also included a gynecological
             exam. If the subject had completed an acceptable Pap smear and gynecological exam in
             the previous 12 months (prior to study Day 1) and the documentation of acceptable
             results were provided, both were deferred. Any abnormalities/deviations from thee
             normal range which were considered clinically relevant by the study physician and
             investigator were evaluated for individual cases, documented in study files, and
             agreed upon by the study physician and investigator prior to enrolling a volunteer in
             the study and for continued enrollment.

          -  Female subjects who practice an acceptable non-hormonal method of birth control as
             judged by the investigator(s) at least 14 days prior to Period I dosing, throughout
             the study, and until 14 days after Period II dosing. The acceptable non-hormonal birth
             control methods included: double barriers, non-hormone releasing intrauterine device
             in place for at least 30 days prior to dosing, abstinence throughout the duration of
             the study, or surgically sterile for at least 6 months prior to Period I dosing.

        Exclusion Criteria:

          -  Volunteers who report receiving any investigational drug within 30 days prior to
             Period I dosing.

          -  Volunteers who reported taking any oral contraceptives including estrogen and
             progestin combined pills and progestin only pills or patch within 28 days prior to
             Period I dosing, or using injectable contraceptives within 6 months of Period I
             dosing.

          -  Volunteers who have ever had progestational hormone implants.

          -  Volunteers who reported any presence or history of a clinically significant disorder
             involving the cardiovascular, respiratory, renal, liver, gastrointestinal,
             immunologic, hematologic, endocrine, or neurologic system(s), or psychiatric or
             epilepsy disease as determined by the clinical investigator(s).

          -  Volunteers who reported any presence or history of migraines or severe headaches.

          -  Volunteers who had a systolic blood pressure lower than 90 or over 140 mmHg, or
             diastolic blood pressure lower than 45 or over 90 mmHg were excluded from the study.

          -  Volunteers who had a history of thrombotic disorders, have ever had a cerebrovascular
             accident, or had transient ischemic attacks.

          -  Volunteers with a history of breast cancer or undiagnosed breast nodules, active
             malignancies, or undiagnosed vaginal bleeding.

          -  Volunteers having other conditions that may be aggravated by fluid retention (as
             determined by principle investigator).

          -  Volunteers who had a history of jaundice with previous use of oral contraceptives or
             any other kinds of hormonal contraceptives.

          -  Volunteers whose clinical laboratory test values outside the acceptable range and when
             confirmed on re-examination were deemed to be clinically significant.

          -  Volunteers who demonstrated a reactive screen for hepatitis B surface antigen,
             hepatitis C antibody, or HIV antibody.

          -  Volunteers who reported a history of allergic response(s) to drospirenone/ethinyl
             estradiol, progestin/estrogens, or related drugs.

          -  Volunteers who reported the use of any systemic prescription medications in the 14
             days prior to Period 1 dosing (with the exception of hormonal contraceptives).

          -  Volunteers who reported the use of any drug known to induce or inhibit hepatic drug
             metabolism in the 28 days prior to Period I dosing.

          -  Volunteers who reported a history of clinically significant allergies including drug
             allergies.

          -  Volunteers who reported a clinically significant illness during the 4 weeks prior to
             Period I dosing (as determined by the clinical investigators).

          -  Volunteers who reported a history of drug or alcohol addiction or abuse within the
             past year.

          -  Volunteers who demonstrated a positive drug abuse screen for the study prior to Period
             I dose administration.

          -  Volunteers who used tobacco products in the past 6 months.

          -  Volunteers who reported donating greater than 150 mL of blood within 30 days prior to
             Period I dosing. All subjects were advised not to donate blood for 4 weeks after
             completing the study.

          -  Volunteers who reported donating plasma within 30 days prior to Period I dosing. All
             subjects were advised not to donate blood for 4 weeks after completing the study.

          -  Volunteers who demonstrate a positive pregnancy screen.

          -  Volunteers who were currently breastfeeding.

          -  Subjects who had used within the 3 months preceding Period I dosing any vaginally
             administered estrogen or progestin containing products.

          -  Any volunteer who engaged in unprotected sexual intercourse during the time interval
             starting 14 days prior to the first period until 14 days after Period II dosing.

          -  Volunteers who had a hysterectomy or oophorectomy.