Safety, Efficacy, Tolerability and Pharmacokinetics of LF111 (Drospirenone 4.0 mg) During 13 Cycles
Condition: Contraception
Intervention: LF111 (drospirenone)
Intervention description: One LF111 tablet once per day for 24 days followed by 4 placebo tablets for 4 days equals one cycle.
Intervention MeSH terms: Drospirenone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1552.0
Sex: Female
Minimum age: 15 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: contraception; hormonal oral contraceptive agents; hormonal oral contraceptive; oral contraceptive; drospirenone; LF111; birth control

Summary:

      To demonstrate the contraceptive efficacy of LF111 . To demonstrate the safety and
      tolerability of LF111 and assessment of pharmacokinetics of LF111.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Sexually active, postmenarcheal and premenopausal female subjects at risk of pregnancy
             including breastfeeding women with no upper age limit.

          2. Female subjects at risk of pregnancy, between the ages of 15 and 17 (inclusive)
             provided that

               -  Applicable national, state and local laws allow subjects in this age group to
                  consent/assent to receive contraceptive services, and

               -  All applicable laws and regulations regarding the informed consent/assent of the
                  subjects to participate in clinical trials are observed.

          3. Regular cycles during the last six months before consent/assent when not using
             hormonal contraception.

          4. At least three complete menstrual cycles after delivery (only applicable for women who
             were pregnant within the last six months and for non-breastfeeding women).
             Breastfeeding women can be included six weeks after delivery irrespective of menstrual
             cycles post-delivery.

          5. At screening, maximum systolic blood pressure (median value of three values) ≤ 159 mm
             Hg and diastolic blood pressure (median value of three values) ≤ 99 mm Hg.

          6. Be able and willing to provide written informed consent or assent if the subject is
             adolescent, prior to undergoing any trial-related procedure.

          7. Willing to use trial contraception for thirteen 28-day cycles.

          8. Be willing to have intercourse each cycle of trial without the need to use back-up
             contraceptive.

          9. Be willing to state that, to her best knowledge, her male sexual partner(s):

               -  Has not had a vasectomy or been previously diagnosed as infertile.

               -  Has not been previously diagnosed or suspected of human immunodeficiency virus
                  (HIV) unless he has subsequently had a negative HIV test.

               -  Has not been known to have engaged in homosexual intercourse in the past five
                  years unless he has had negative HIV test results since then.

               -  Has not shared injection drug needles in the past unless he has had a negative
                  HIV test at least six weeks since last use.

         10. Agree not to participate in any other clinical trials during the course of this trial.

        Exclusion Criteria:

          1. Pregnant.

          2. Subject is known to or suspected of not being able to comply with the trial protocol,
             the use of the trial medication or the use of the trial diary.

          3. History of infertility.

          4. Abnormal finding on pelvic, breast or ultrasound examination that in the
             investigator's opinion contraindicates participation in the trial.

          5. Unexplained amenorrhea.

          6. Known polycystic ovary syndrome.

          7. Women ≥21 years of age with a Papanicolaou (pap) smear reading LGSIL or higher at
             screening (or six months prior to screening date). Human papilloma virus (HPV) testing
             in subjects with atypical squamous cells of undetermined significance (ASC-US) can be
             used as an adjunctive test.

               -  Subjects with ASC-US can be included if they are negative for high-risk HPV
                  strains.

               -  Subjects <21 years of age do not require a pap smear.

          8. Known contraindication or hypersensitivity to ingredients or excipients of the IMP
             (Investigational Medicinal Product), including:

               1. Renal insufficiency

               2. Hepatic dysfunction

               3. Adrenal insufficiency

               4. Current or history of venous thrombophlebitis or thromboembolic disorders (venous
                  thromboembolism, which includes deep vein thrombosis and pulmonary embolism)

               5. Current or history of cerebral-vascular or coronary-artery disease

               6. Valvular heart disease with thrombogenic complications

               7. Diabetes with vascular involvement

               8. Headaches with focal neurological symptoms

               9. Major surgery with prolonged immobilization

              10. Known or suspected carcinoma of the breast

              11. Known or suspected sex-steroid sensitive malignancies

              12. Undiagnosed abnormal genital bleeding

              13. Cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive
                  use

              14. Liver tumor (benign or malignant) or active clinically significant liver disease.

          9. Uncontrolled thyroid disorder (i.e., on stable dose of thyroid replacement for less
             than two months).

         10. Uncontrolled concomitant diseases (i.e., not on a stable treatment dose for at least
             two months).

         11. Evidence or history of alcohol, medication or drug abuse (within the last 12 months
             prior to consent/assent).

         12. Known inherited or acquired predisposition to venous thromboembolism or arterial
             thromboembolism (e.g., factor V Leiden, Prothrombin mutation, Antiphospholipid
             antibodies) or bruising within the last 12 months prior to consent/assent.

         13. Known or suspected HIV and/or hepatitis infection at screening.

         14. Received a dose of depot medroxyprogesterone acetate (DMPA or Depo-Provera®) during
             the 10 months prior to consent/assent, or received any combined injectable
             contraceptive (e.g., Cyclofem®) during the six months prior to consent/assent, or no
             spontaneous menses since last injection.

         15. Long-term treatment (longer than seven consecutive days within a month prior to V1b)
             of any medication that might interfere with the efficacy of hormonal contraceptives.

             Prohibited medication include:

               1. Anticonvulsants (e.g. phenytoin, carbamazepine, oxcarbazepine, topiramate,
                  felbamate, primidone)

               2. Barbiturates

               3. Rifampin

               4. Bosentan

               5. Griseofulvin

               6. St. John's wort (hypericum perforatum)

         16. Administration of human chorionic gonadotropin (hCG) or intake of co-medication
             containing hCG within a month prior to V1b).

         17. Progestin-releasing intra-uterine device (IUD) or contraceptive implant received or in
             place within the last two months prior to consent/assent.

         18. Planned regular concomitant use of barrier contraceptive methods, spermicides, IUDs or
             other contraceptive measures (excepting occasional use for safety reasons, e.g., to
             reduce risk of infection).

         19. Evidence or history of clinically significant psychiatric illness or suicide risk.

         20. Participation in another trial of an investigational drug or device parallel to the
             current trial or less than 90 days before consent/assent, or previous participation in
             the current trial and dispensed trial medication.

         21. Subject is a member of the investigator's or Sponsor's staff or a relative or family
             member thereof.

         22. Any condition that, in the opinion of the investigator, may jeopardize protocol
             compliance or the scientific integrity of the trial.