Clinical trial NCT02668822: Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in the Treatment of Women With Primary Dysmenorrhea (MK-8342B-060)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Dysmenorrhea
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2016-01-29
Enrollment: 18
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 was to evaluate the efficacy of the etonogestrel (ENG) + 17β-estradiol (E2) (MK-8342B) vaginal ring compared to placebo vaginal ring in the treatment of dysmenorrhea at Treatment Cycle 2. This study was also to assess the safety and tolerability of the ENG-E2 vaginal rings over 4 treatment cycles. 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.

Detailed description: The cramping window for each participant was to be defined as a 4-day time interval that began the day prior to initiation of each cyclic bleeding episode (spontaneous menses or hormone withdrawal bleeding) and continued until the third bleeding day (inclusive). An external committee of blinded independent reviewers was to determine the 4-day cramping window for each participant so that analysis of the efficacy data could be conducted. The study was terminated early due to a business decision by the Sponsor to discontinue product development for reasons unrelated to safety or efficacy outcomes. Due to the early study termination, the blinded independent review committee that was supposed to determine the 4-day cramping windows for data analysis was not assembled; thus cramping windows were not determined. Without defined cramping windows, the efficacy outcome measures for this study could not be analyzed.

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 126 days
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 112 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 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: Change From Baseline in the 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: