Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059)

Organon

Status and phase: Terminated; Phase 3

Conditions: Moderate to Severe Primary Dysmenorrhea

Treatments: Drug: Placebo vaginal ring; Drug: Ibuprofen; Drug: Etonogestrel (ENG) 125 μg + 17β-estradiol (E2) 300 μg vaginal ring

Study type: Interventional

Funder types: Industry

Identifiers

NCT02668783

2015-004325-14 (EudraCT Number)

8342B-059

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: Female

Ages: Under 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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25 participants in 2 patient groups, including a placebo group

ENG-E2 125 μg/300 μg

Experimental group

Description:

Participants will receive 4 cycles (or 6 cycles if also participating in the extension) of ENG-E2 125 μg/300 μg. Each cycle will consist of 21 days of vaginal ring use followed by 7 ring-free days.

Treatment:

Drug: Etonogestrel (ENG) 125 μg + 17β-estradiol (E2) 300 μg vaginal ring

Drug: Ibuprofen

Placebo

Placebo Comparator group

Description:

Participants will receive 4 cycles (or 6 cycles if also participating in the extension) of placebo. Each cycle will consist of 21 days of placebo vaginal ring use followed by 7 ring-free days.

Treatment:

Drug: Ibuprofen

Drug: Placebo vaginal ring