Clinical trial NCT02668783: Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059)
Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial to Study the Efficacy and Safety of MK-8342B (ENG-E2 Vaginal Ring) in Women With Moderate to Severe Primary Dysmenorrhea (With Optional Extension)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Moderate to Severe Primary Dysmenorrhea
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2016-01-29
Enrollment: 25
Sex: FEMALE
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percentage of Participants With ≥3 Point Reduction in Peak Pelvic Pain Score and no Increase in Number of Ibuprofen Tablets Taken at Treatment Cycle 2, Compared to Baseline.
timeFrame: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 158 days
measure: Number of Participants Who Discontinued Treatment Due to an AE
timeFrame: Up to approximately 128 days
Secondary outcomes:
measure: Change From Baseline in Peak Pelvic Pain Score at Treatment Cycle 2
timeFrame: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
measure: Change From Baseline in the Number of Days With no Impact on Items of Physical, Work/School and Social/Leisure Activities at Treatment Cycle 2
timeFrame: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
measure: Percentage of Participants With Pelvic Pain Score of "0" or "1" and no Use of Ibuprofen Tablets at Treatment Cycle 2
timeFrame: Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
measure: Percentage of Participants With ≥3 Point Reduction in Peak Pelvic Pain Score and a Decrease in Ibuprofen Tablet Intake at Treatment Cycle 2, Compared to Baseline
timeFrame: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
measure: Change From Baseline in Mean Pelvic Pain Score at Treatment Cycle 2
timeFrame: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: