hormonal contraception and primary dysmenorrhea in women contraception dysmenorrhea
Conditions
Interventions
The Study Events Flow Chart (Section 6 of the protocol) summarizes the clinical
procedures to be performed at each visit. I. Additional evaluations/testing may
be deemed necessary by the Investigato
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Healthy adult female subjects, 18-35 years of age, inclusive, at screening. 2. Continuous non-smokers who have not used nicotine-containing products for at least 3 months prior to ENG-E2 vaginal ring insertion. 3. Body mass index (BMI) * 18.5 and * 30.0 kg/m2, at screening and prior to ENG-E2 vaginal ring insertion. 4. Has good visibility of both ovaries upon ultrasonography at screening. 5. Subjects not using hormonal contraceptives should have regular menstrual cycles ranging from * 21 to * 35 days in length in the 3 months prior to screening. 6. Has ability to ovulate as determined by vaginal ultrasound scan measurements (i.e., measurement of Max FD and double-layer endometrial thickness) during the pre-treatment screening period. Vaginal ultrasound scan measurements will be performed 9 days (± 1) after the start of the last menstruation or withdrawal bleeding and every 3 days ± 1 day onwards until ovulation is observed, during the pre-treatment screening period. After ovulation, the subject must have P levels > 16 nmol/L on two subsequent occasions within 5 days (time of ovulation determined by vaginal ultrasound scan measurement). 7. Medically healthy with no clinically significant abnormalities in medical history, physical and gynecological examination, laboratory profiles, or vital signs, as judged by the Investigator. 8. If sexually active, subject should use a non-hormonal IUD or if she or her partner is not surgically sterilized, agrees to have her male partner use a male condom without spermicide from the time of screening and throughout completion of the study (including the follow-up period). 9. A normal cervical Pap (Papanicolaou) test (Pap
Exclusion criteria
Exclusion criteria: 1. Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. 2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator. 3. History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study. 4. History or presence of alcoholism or drug abuse within the past 2 years prior to screening. 5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds. 6. History or presence of: Venous thromboembolic events (VTE), arterial thromboembolic events (ATE), and other major adverse cardiovascular events (MACE) (e.g., myocardial infarction, cerebral vascular accident); headaches with focal neurological symptoms or migraine headaches with aura; breast cancer or undiagnosed breast nodules; hypertension; transient ischemic attacks; liver tumors or liver disease; jaundice with previous use of oral contraceptives or past pregnancy; diabetes; pancreatitis or severe hypertriglyceridemia; carcinoma of the endometrium or other known or suspected estrogen or progestogen dependent neoplasia; cervical cancer. 7. Positive pregnancy test or lactating. 8. Abnormal cervical Pap test within 24 months prior to screening (first visit). 9. Within the past 6 months prior to screening, has had undiagnosed (unexplained) abnormal vaginal bleeding or any abnormal bleeding that is expected to recur during the study (e.g., bleeding from cervical polyp, bleeding after sex). 10. Has stage 4 pelvic organ prolapse (1 cm beyond introitus) or lesser degrees of prolapsed with a history of difficulty retaining tampons, vaginal rings, or other products within the vagina. 11. Clinically significant abnormalities of the genital organs as determined by gynecological examination and based on the Investigator*s judgment. 12. Has gonorrhea, chlamydia, or trichomonas or symptomatic vaginitis/cervicitis. Subjects may be rescreened 3 weeks after completing treatment for these conditions. 13. Positive results for the urine drug and/or alcohol breathalyzer screen at screening or on Day 1. 14. Drink alcohol in excess of 14 units per week, with one unit = 125 mL of wine or 284 mL of beer or 25 mL of 45% alcohol. 15. Positive urine cotinine at screening and Day 1 (threshold >100 ng/mL). Note: subjects may be retested if positive. 16. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). 17. Unable to refrain from or anticipates the use of any treatment listed in Table 1 of the protocol 18. Hemoglobin level below 11 g/dL at screening. 19. Blood or plasma donation (* 500 mL) within 60 days prior to screening. 20. Donation of bone marrow within the last 6 months prior to screening. 21. Is working at or has an immediate family member (spouse or children) who works at the investigational site or is a Sponsor staff member directly involved with this trial. 22. Participation in another clinical trial within 30 days prior to screening. The 30-day window will be derived from the date of the last blood collection or last dosing, whichever is later, in the previous study to the screening visit of the current study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamics The largest follicular diameter, endometrial thickness, and serum concentrations of P and SHBG will be measured at various time points. Summary statistics will be provided by time point and Max P and Max FD for the period will be determined. Pharmacokinetics The following pharmacokinetic parameters will be calculated for ENG, E2, and E1 in serum, as appropriate: AUC1-22, AUC1-36, AUC1-44, AUC36-44, Cmin, Cmax, Tmax, and apparent terminal t*. When multiple time points occur on the same day, AUC (indicated in study days) are converted into study hours as follows: * Day 1, Hour 0 is the time of ENG-E2 vaginal ring insertion * Day 36, Hour 840 is 840 hours post ENG-E2 vaginal ring insertion and the time of ring removal Safety: Safety endpoints will include adverse events, physical examinations, gynecological examination, vital signs (heart rate and blood pressure), and clinical laboratory tests (hematology, serum chemistry, and urinalysis). | — |
Secondary
| Measure | Time frame |
|---|---|
| - | — |
Countries
Netherlands
Outcome results
None listed