Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059)
Condition: Moderate to Severe Primary Dysmenorrhea
MeSH terms: Dysmenorrhea
Intervention: Etonogestrel (ENG) 125 μg + 17β-estradiol (E2) 300 μg vaginal ring; Placebo vaginal ring; Ibuprofen
Intervention description: Up to 4 cycles (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg administered intravaginally. Each cycle will consist of 21 days of vaginal ring use followed by 7 ring-free days.; Up to 4 cycles (or 6 cycles if also participating in the extension) of placebo administered intravaginally. Each cycle will consist of 21 days of placebo vaginal ring use followed by 7 ring-free days.; Ibuprofen tablets, to be taken orally, will be provided for use as rescue medication for dysmenorrhea treatment throughout the study. Participants may take 400 mg every 4 hours as needed for pelvic pain/cramping, or as instructed by their physician according to local labeling for relief of menstrual pain.
Intervention MeSH terms: Ibuprofen; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Etonogestrel; Estradiol; Polyestradiol phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 25.0
Sex: Female
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the etonogestrel (ENG) + 17β-estradiol (E2) vaginal
      ring's efficacy compared to a placebo vaginal ring in the treatment of dysmenorrhea at
      Treatment Cycle 2. In addition, this study will assess the safety and tolerability of the
      ENG-E2 vaginal rings. Primary hypothesis: Relative to the placebo ring, the ENG-E2 vaginal
      ring results in a greater proportion of participants with a ≥3 point reduction in peak pelvic
      pain score and no increase in the number of rescue pain relief (ibuprofen) tablets taken at
      Treatment Cycle 2 as compared to baseline.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Post-menarcheal female, age ≤50 years, in good physical and mental health.

          -  History of moderate to severe primary dysmenorrhea for the past 3 months or longer,
             and no history of recurrent non-menstrual pelvic pain intermittently or continuously
             throughout the month, and no history of dysmenorrhea secondary to structural pelvic
             pathology.

          -  Body mass index (BMI) of ≥18 and <38 kg/m^2.

          -  History of regular menstrual cycles with a cycle length between 24 and 32 days
             (inclusive) for the past three months.

          -  Willing to adhere to use of the vaginal ring and to all required trial procedures, and
             not planning to relocate during the study.

          -  Willing to use the rescue medication ibuprofen at the study recommended dose and no
             other pain medication for treatment of dysmenorrhea.

        Exclusion Criteria:

          -  Cardiovascular risks and disorders, including history of venous thromboembolic [VTE]
             events, arterial thrombotic or thromboembolic [ATE] events, transient ischemic attack,
             angina pectoris, or claudication; at higher risk of VTE events due to recent prolonged
             immobilization, plans for surgery requiring prolonged immobilization, or a hereditary
             or acquired predisposition or elevated risk for venous or arterial thrombosis;
             currently smoking or uses tobacco/nicotine containing products and is ≥35 years of
             age; uncontrolled or severe hypertension; history of severe dyslipoproteinemia; <35
             years of age with a history of migraine with aura or focal neurological symptoms or
             ≥35 years of age with a history of migraines with or without aura or focal neurologic
             symptoms; diabetes mellitus with end-organ involvement or >20 years duration; multiple
             cardiovascular risk factors such as ≥35 years of age, obesity, inadequately controlled
             hypertension, use of tobacco/ nicotine products, or inadequately controlled diabetes.

          -  Gynecologic conditions: surgically sterilized, has used hormonal contraceptives (pill,
             patch, ring, implant, intrauterine system) within the past 3 months, or currently uses
             non-hormonal intrauterine device (IUD); within past 6 months has had undiagnosed
             (unexplained) abnormal vaginal bleeding or any abnormal vaginal bleeding expected to
             recur during study; has gonorrhea, chlamydia, or trichomonas or symptomatic
             vaginitis/cervicitis; has abnormal cervical smear or positive high-risk human
             papillomavirus (HPV) test at screening or documented within 3 years of screening; has
             Stage 4 pelvic organ prolapse (1 cm beyond introitus) or lesser degrees of prolapse
             with history of difficulty retaining tampons, vaginal rings, or other products within
             vagina.

          -  Gastrointestinal and urologic disorders, including history of pancreatitis associated
             with severe hypertriglyceridemia; clinically significant liver disease, including
             active viral hepatitis or cirrhosis; or a history of the gastrointestinal or urologic
             tract which may cause pelvic pain.

          -  Other medical disorders, including history of malignancy ≤5 years prior to signing
             informed consent except for adequately treated basal cell or squamous cell skin cancer
             or in situ cervical cancer; any disease that may worsen under hormonal treatment such
             as disturbances in bile flow, systemic lupus erythematosus, pemphigoid gestationis or
             idiopathic icterus during previous pregnancy, middle-ear deafness, Sydenham chorea, or
             porphyria; known allergy/sensitivity or contraindication to the investigational
             products or their excipients; known allergy/sensitivity or contraindication to
             ibuprofen, or has experienced asthma, urticaria, or allergic-type reactions after
             taking aspirin, or other nonsteroidal anti-inflammatory drugs; history of drug or
             alcohol abuse or dependence.

          -  Known or suspected pregnancy, or had been pregnant or breastfeeding within past 2
             months.

          -  Has used investigational drug and/or participated in other clinical trial within past
             8 weeks.