A Multicenter, Randomized, Partially-blinded, Phase IIb Dose-finding Study on Ovarian Function, Vaginal Bleeding Pattern, and Pharmacokinetics Associated With the Use of Combined Vaginal Rings Releasing 17β-estradiol Plus Three Different Doses of Either Nomegestrol Acetate or Etonogestrel in Healthy Women Aged 18-35 Years. Protocol MK-8175A/MK-8342B 012
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 666
- 主要终点
- Percentage of Participants With Progesterone Concentrations >16 Nmol/L, by Cycle
研究概览
简要总结
The primary objective of this trial was to identify at least one next generation ring (NGR) that demonstrates inhibition of ovulation (which was considered confirmed if in the subset of participants ovulation was observed in less than 15% of the participants at any time during the 3 treatment cycles of the study) and cycle control that was non-inferior to NuvaRing®, as judged by the incidence of breakthrough bleeding and/or spotting (BTB-S) during Cycle 3. The primary hypothesis was that at least 1 of the 6 NGRs would show inhibition of ovulation and cycle control during Treatment Cycle 3 that is non-inferior to NuvaRing®, as judged by the incidence of BTB-S.
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
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) ≥18 and ≤35
- •Regular cycles from 24 to 35 days in length, with an intra-individual variation of ±3 days permitted within this range
- •Good physical and mental health
排除标准
- •Diabetes mellitus with vascular involvement
- •Presence of a severe or multiple risk factor(s) for venous or arterial thrombosis
- •Severe dyslipoproteinemia
- •Severe hypertension
- •Presence or history of pancreatitis associated with severe hypertriglyceridaemia
- •Presence or history of severe hepatic disease
- •Undiagnosed vaginal bleeding
- •Known or suspected pregnancy
- •Participation in another investigational drug study within 30 days prior to screening visit
- •History of malignancy ≤5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
- •Documented abnormal cervical smear result in 6 months prior to screening visit
- •Sterilization using a fallopian tube occlusion device (e.g., Essure method)
- •Sex hormone therapy within 2 months prior to screening visit for purpose other than contraception, or injectable hormonal contraception within 6 months prior to screening
研究组 & 干预措施
Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 500/300 μg/day
Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 500/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Nomegestrol acetate (NOMAC) (Drug)
Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 500/300 μg/day
Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 500/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Estradiol (E2) (Drug)
Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 700/300 μg/day
Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 700/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Nomegestrol acetate (NOMAC) (Drug)
Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 700/300 μg/day
Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 700/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Estradiol (E2) (Drug)
Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 900/300 μg/day
Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 900/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Nomegestrol acetate (NOMAC) (Drug)
Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 900/300 μg/day
Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 900/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Estradiol (E2) (Drug)
Etonogestrel-17β-Estradiol (ENG-E2) 75/300 μg/day
Participants will receive etonogestrel 17β-estradiol (ENG-E2) 75/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Etonogestrel (ENG) (Drug)
Etonogestrel-17β-Estradiol (ENG-E2) 75/300 μg/day
Participants will receive etonogestrel 17β-estradiol (ENG-E2) 75/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Estradiol (E2) (Drug)
Etonogestrel-17β-Estradiol (ENG-E2) 100/300 μg/day
Participants will receive etonogestrel 17β-estradiol (ENG-E2) 100/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Etonogestrel (ENG) (Drug)
Etonogestrel-17β-Estradiol (ENG-E2) 100/300 μg/day
Participants will receive etonogestrel 17β-estradiol (ENG-E2) 100/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Estradiol (E2) (Drug)
Etonogestrel-17β-Estradiol (ENG-E2) 125/300 μg/day
Participants will receive etonogestrel 17β-estradiol (ENG-E2)125/300 μg for three 28-day treatment periods, each treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Etonogestrel (ENG) (Drug)
Etonogestrel-17β-Estradiol (ENG-E2) 125/300 μg/day
Participants will receive etonogestrel 17β-estradiol (ENG-E2)125/300 μg for three 28-day treatment periods, each treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Estradiol (E2) (Drug)
NuvaRing®
Participants will receive NuvaRing® (etonogestrel-ethinyl estradiol [ENG-EE] 120/15 μg) for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Etonogestrel (ENG) (Drug)
NuvaRing®
Participants will receive NuvaRing® (etonogestrel-ethinyl estradiol [ENG-EE] 120/15 μg) for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
干预措施: Ethinyl estradiol (EE) (Drug)
结局指标
主要结局
Percentage of Participants With Progesterone Concentrations >16 Nmol/L, by Cycle
时间窗: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)
Maximum progesterone (Max P) was defined as the maximum progesterone value. Ovulation was defined as 2 or more consecutive progesterone concentrations \>16 nmol/L within 5 days during the 3 treatment cycles, supported by ultrasound evidence of ovulation. The Max P values greater than 16 nmol/L are presented by vaginal ring group and cycle.
Percentage of Participants With Breakthrough Bleeding and/or Spotting During Cycle 3
时间窗: Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~28 days)
Breakthrough bleeding and/or spotting (BTB-S) is defined as any bleeding or spotting episode that occurred during the expected non-bleeding period that was neither an early nor a continued withdrawal bleeding. Bleeding = any bloody vaginal discharge that required one or more sanitary pads or tampons per day; Spotting = any bloody vaginal discharge that required no sanitary pads or tampons per day.
Percentage of Participants With Ovulation Incidence, by Cycle
时间窗: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)
Ovulation was defined as having 2 or more consecutive progesterone concentrations \>16 nmol/L within 5 days, confirmed by ultrasound evidence of ovulation (follicular rupture or preceding presence of a follicle-like structure \>15 mm in size).
次要结局
- Percentage of Participants With Absence of Withdrawal Bleeding and/or Spotting During Cycle 2(Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days))
- Percentage of Participants Who Experienced At Least One Adverse Event(Up to ~92 days)
- Intensity of Breakthrough Bleeding and/or Spotting During Cycle 3(Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~ 28 days))
- Percentage of Participants Who Experienced At Least One Drug-Related Adverse Event(Up to ~92 days)
- Intensity of Withdrawal Bleeding During Cycle 2(Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days))
- Percentage of Participants Who Experienced At Least One Serious Adverse Event(Up to ~92 days)
- Percentage of Participants With Any Drug-Related Serious Adverse Event(Up to ~92 days)
- Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event(Up to ~92 days)