Clinical trial: A Phase I Study to Evaluate the PK and PD of a Single Injection of Levonorgestrel Butanoate for Female Contraception (NCT02173808)

Eligibility criteria:
Inclusion Criteria:

          1. Good general health

          2. Aged 18-44 years, inclusive, at the enrollment visit

          3. Intact uterus with at least one ovary

          4. Serum progesterone value ≥ 3 ng/mL at the Screening Visit (V0-P)

          5. Pap test within the last 12 months or undergo a Pap test at screening prior to
             enrollment. If a potential subject states that she has had a Pap test within the last
             12 months, then she will need to provide documentation of acceptable test results

          6. Cervical mucus score of >7, which is based on the modified Insler scoring system
             during the screening cycle. The cervical mucus is collected by aspiration and the
             assessment is based on the modified Insler scoring system (the volume and pH of the
             mucus are not included in the total scoring) yielding a total possible score of 12 (3,
             4)

          7. Regular menstrual cycles that occur every 24 - 35 days

               1. If subject is postpartum or post-abortal (with abortion in second trimester), she
                  will be required to have two normal menstrual cycles prior to screening

               2. If subject had an abortion in the first trimester, she will be required to have
                  at least one menstrual cycle (two menses) prior to screening

          8. Heterosexually abstinent or, if heterosexually active, must have undergone previous
             tubal sterilization, be in monogamous relationship with a vasectomized partner, or
             only use male or female condoms (use of condoms that are pre-lubricated with or
             without spermicide is acceptable) for the entire duration of the study. Use of a
             spermicide applied separately is not allowed. Cervical caps or diaphragms are not
             allowed during study participation

          9. In the opinion of the investigator, able to comply with the protocol, willing to
             record requested information in the daily diary, and live within the study site
             catchment area or within a reasonable distance from the site

         10. Understand and sign an IRB approved informed consent form prior to screening
             activities (including fasting blood draw)

         11. Willing to refrain from use of any vaginal creams, lubricants, gels, or spermicides
             for 3 days prior to study admission through to the end of the study

         12. 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. Known or suspected pregnancy

          3. Prior hysterectomy or bilateral oophorectomy

          4. Prior cervical surgery (LEEP, Cone biopsy)

          5. A history (within prior 12 months) of drug or alcohol abuse

          6. Undiagnosed abnormal genital bleeding

          7. Undiagnosed vaginal discharge or vaginal lesions or abnormalities. Subjects diagnosed
             at screening with a Chlamydia or gonococcus infection may not be included in the trial
             unless they are treated and proof of cure is documented after treatment (i.e. repeat
             test with negative results). 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

          8. Uncontrolled thyroid disorder

          9. Any Pap test finding that would require additional workup or treatment during the
             study interval. HPV testing will not be done at screening for these subjects

         10. Use of an injectable hormonal contraceptive (Depo-Provera®) within the past 10 months

         11. Use of oral contraceptives, contraceptive implants, or other sex steroid hormones
             within 30 days prior to screening visit

         12. Women who are breastfeeding or within 30 days of discontinuing breast feeding

         13. Women planning to undergo major surgery within four months of study enrollment

         14. Women planning pregnancy within their months of study enrollment

         15. Smoking in women who are ages 18-44 years old that smoke 15 cigarettes or more per day
             must be evaluated by the PI for inclusion based on risk factors that would increase
             their risk for cardiovascular (CVD) and thromboembolism

         16. Current or past deep vein thrombophlebitis or thromboembolic disorders

         17. History of known thrombophilia in a first-degree relative <45 years of age suggesting
             familial defect in blood coagulation system, which in the opinion of the principal
             investigator, suggests use of a hormonal contraceptive could pose a significant risk

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

         19. History of retinal vascular lesions, unexplained partial or complete loss of vision

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

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

         22. 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

         23. Headaches with focal neurological symptoms only in women over 35 years old

         24. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use or
             other benign or malignant liver tumors; active liver disease

         25. Systolic BP > 140 mm Hg and/or Diastolic blood pressure (BP) > 90 mm Hg after 5-10
             minutes rest

         26. Clinically significant abnormal serum chemistry values according to the Principal
             Investigator's judgment

         27. Participation in another clinical trial involving an investigational drug or device
             within last 30 days (prior to screening)

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

         29. Known HIV infection

         30. Women at high risk of contracting HIV, e.g. women with multiple sex partners who need
             to use condoms consistently, injection drug users. Women enrolled in the study, who
             use condoms to protect against STIs or pregnancy, should be instructed that they can
             use condoms that are pre-lubricated with spermicide or lubricated, but they cannot use
             a spermicide applied separately and they should record all condom use in their diaries

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

         32. Women with BMI ≥40 kg/m2 are excluded

         33. Have issues or concerns (in the judgment of the investigator) that may compromise the
             safety of the subject or confound the reliability of compliance and information
             acquired in this study
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 44 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? 0