Clinical trial: A Study to Evaluate the PK and PD of IM or SQ Injections of Levonorgestrel Butanoate (LB) for Female Contraception (NCT04143659)

Eligibility criteria:
Inclusion Criteria:

          1. Good general health with no chronic medical conditions that result in periodic
             exacerbations that require significant medical care.

          2. Age between 18 and 40 years inclusive at the injection visit.

          3. BMI < 40 kg/m2.

          4. Intact uterus with at least one ovary.

          5. Pap test within ASCCP or ACOG guidelines such that additional treatment will not be
             required during the study period. If a copy of a Pap test (and indicated follow-up
             testing) is not available and the subject is 21 years or older, a Pap test should be
             done during the screening period.

          6. Regular menstrual cycles that occur every 21-35 days:

        6a. If subject is postpartum or post-second trimester abortion, she must have 3 menses (2
        cycles) prior to enrollment.

        6b. If subject had a first trimester abortion or pregnancy loss, she must have one
        spontaneous menses prior to enrollment.

        7. Have a negative urine pregnancy test at the injection visit and no unprotected
        heterosexual intercourse for the previous 10 days.

        8. Not at risk for pregnancy for the duration of study participation (screening through
        last phone contact), defined as one of the following: 8a. heterosexually abstinent; 8b.
        previous female permanent contraception procedure; 8c. in a monogamous relationship with a
        vasectomized partner; 8d. consistent use of a non-hormonal barrier method with every act of
        intercourse (e.g. condoms or diaphragm + spermicide).

        8e. use copper IUD 9. In the opinion of the investigator, subject is willing and able to
        comply with the protocol requirements.

        10. Subject is willing to record requested information in the daily diary. 11. Lives within
        the study site catchment area or within a reasonable distance from the site.

        12. Understand and sign an IRB approved informed consent form prior to undergoing any
        screening assessments (including fasting blood draw).

        13. Agree not to participate in any other clinical trials during the course of this study.

        Exclusion Criteria:

          1. Known hypersensitivity or contraindication to progestins.

          2. Abnormal Transvaginal Ultrasound (TVUS) or safety labs done during the screening
             period recognized as clinically significant by the investigator (or medically
             qualified designee).

          3. Greater than 10% body weight change over previous year or planned significant weight
             loss during the study related to bariatric surgery, dieting or other causes.

          4. Known or suspected current alcohol dependence syndrome, chronic marijuana use or any
             illicit drug use that may affect metabolism of the study product or study compliance.

          5. Undiagnosed abnormal genital bleeding.

          6. Undiagnosed vaginal discharge, lesions or abnormalities. Subjects diagnosed at
             screening with BV, trichomonas, candida, Chlamydia or gonococcus infection may be
             included in the trial following treatment completion. In accordance with PI/medical
             designee assessment and local standards of practice, women with a history of genital
             herpes can be included if outbreaks are infrequent. Antiviral prophylactic therapy is
             permitted.

          7. Uncontrolled thyroid disorder.

          8. Current use of hormonal contraception including hormonal intrauterine device.

          9. Use of a long-acting injectable hormonal contraceptive (e.g., cyclofem or
             depomedroxyprogesterone acetate) within the past 9 months prior to enrollment unless
             the subject has had at least one spontaneous menstrual cycle (at least two menses)
             since the last injection.

         10. Recent use of hormonal oral, patch, intravaginal or intrauterine contraception unless
             that subject has had at least one complete menstrual cycle (at least two menses) since
             discontinuation before the treatment injection.

         11. Women who are breastfeeding or are within 30 days of discontinuing breast feeding
             unless the subject has already had a menses following discontinuation of
             breastfeeding.

         12. Women planning to undergo major surgery during study participation.

         13. Women planning pregnancy during their anticipated months of study participation.

         14. Women who smoke > 15 cigarettes per day or who use >1 ml/day of nicotine-containing
             liquid for electronic cigarette must be evaluated by the PI for inclusion based on
             risk factors that would increase their risk for cardiovascular disease (CVD) and
             thromboembolism.

         15. Current or past deep vein thrombophlebitis or thromboembolic disorders.

         16. Known history of thrombophilia.

         17. Cerebrovascular or cardiovascular disease or increased risk for arterial thrombosis.

         18. Known or suspected carcinoma of the breast, endometrium, or any other known or
             suspected progestin-dependent neoplasia.

         19. Current or past medically diagnosed severe depression, which, in the opinion of the
             investigator, could be exacerbated by use of a hormonal contraceptive, unless she is
             stable on antidepressant medication.

         20. Have a current need for exogenous hormones or therapeutic anticoagulants.

         21. History of any other carcinoma (excluding basal cell carcinomas) unless in remission
             for more than 5 years.

         22. Active liver disease or screening LFTs greater than twice the upper limit or normal.

         23. Diastolic blood pressure (DBP) > 95 and Systolic blood pressure (SBP) > 145 mm Hg; (BP
             will be taken three times at approximately 5-minute intervals and the mean of the last
             two of the three measurements will be used to determine eligibility).

         24. Clinically significant abnormal serum chemistry or hematology values according to the
             Principal Investigator's judgment.

         25. Participation in another clinical trial involving an investigational drug or device
             within last the three months before treatment injection or planning to participate in
             another clinical trial during this study.

         26. Use of liver enzyme inducers within the last 90 days prior to screening or intention
             to use liver enzyme inducers during the study.

         27. Known HIV infection.

         28. Women who use any medications on the Exclusionary Medication List OR have used any
             within the past three months prior to the Injection visit.

         29. Have issues or concerns (in the judgement of the investigator) that may compromise the
             safety of the subject or confound the reliability of compliance and information
             acquired in this study.

         30. Have known hypersensitivity to the active substance LB or any of the excipients of the
             study treatment.

         31. Use any medications that can interfere with the metabolism of hormonal contraceptives,
             antibiotics that can interfere with metabolism of hormonal contraceptives, or any
             drugs designated by the FDA as falling in the Pregnancy and Lactation narrative
             subsections (formerly Category D or X medications).

         32. Have previously participated in the study.

         33. Be a site staff member with delegated study responsibilities or a family member of, or
             have a close relationship with, a site staff member with delegated study
             responsibilities.
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 40 Years

Patient description (medical language): A 43-year-old woman, gravida 3 para 3, comes to the clinic complaining of recently painful menstrual cycles.  The patient's last menstrual period was 2 weeks ago. Urine β-hCG is negative. Menarche was at age 12, and menstrual periods occur every 28 days and lasts for 5 days.  She is sexually active with her husband and does not have pain with intercourse. BMI is 23 kg/m2 and Vital signs are normal.  On physical examination, the uterus is uniformly enlarged and tender. She is candidate for hysterectomy with the diagnosis of adenomyosis.

Patient description (patient's own words): I'm 43, and I paid a visit to my doctor because my last few periods were insanely painful. My last periods were 2 weeks ago. I already had three pregnancies that gave me the three lovely children. I did a urine test to check for potential pregnancy, and it came back negative. I started to have my periods at the age of 12, and I have been pretty regular with periods every 28 days for 5 days. I'm sexually active with my husband and I do not have any pain when we have sex. My BMI is 23 and my vitals were normal. The doctor performed a physical exam and found that my uterus was tender and enlarged. She proposed me a hysterectomy and diagnosed me with adenomyosis.

Does the patient match the trial criteria? Contradiction