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)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 25
- 主要终点
- Number of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- — 至 50 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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^
- •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.
排除标准
- •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.
研究组 & 干预措施
ENG-E2 125 μg/300 μg
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.
干预措施: Etonogestrel (ENG) 125 μg + 17β-estradiol (E2) 300 μg vaginal ring (Drug)
ENG-E2 125 μg/300 μg
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.
干预措施: Ibuprofen (Drug)
Placebo
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.
干预措施: Placebo vaginal ring (Drug)
Placebo
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.
干预措施: Ibuprofen (Drug)
结局指标
主要结局
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 158 days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who experienced an AE is presented.
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.
时间窗: Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant
Participants were asked to rate their worst pain or cramps in the past 24 hours on a scale of 0 to 10 (0=No pain or cramps to 10=Extreme pain or cramps) and to indicate the number of ibuprofen tablets they took during the 4-day cramping window. The peak pelvic pain score was to be calculated as the highest (daily) pelvic pain score observed within the cramping window of the cycle and the total number of ibuprofen tablets taken was to be based on the 4-day cramping window. The baseline peak pelvic pain score and number of ibuprofen tablets taken were to be defined as the mean value of the 2 peak pelvic pain scores and the mean value of the total number of ibuprofen tablets taken during the cramping window of each of the 2 menstruations during the screening period, respectively. The percentage of participants with a reduction in peak pelvic pain score of ≥3 points and no increase in the use of ibuprofen at Treatment Cycle 2 as compared to baseline was to be presented.
Number of Participants Who Discontinued Treatment Due to an AE
时间窗: Up to approximately 128 days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who discontinued study treatment due to an AE is presented.
次要结局
- Change From Baseline in Peak Pelvic Pain Score at Treatment Cycle 2(Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant)
- 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(Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant)
- Percentage of Participants With Pelvic Pain Score of "0" or "1" and no Use of Ibuprofen Tablets at Treatment Cycle 2(Treatment Cycle 2 4-day cramping window, as determined by committee for each participant)
- Change From Baseline in Mean Pelvic Pain Score at Treatment Cycle 2(Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant)
- 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(Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant)