A Randomized, Double-blind, Double-dummy, Parallel- Group, Multi-center Phase IIb Study to Assess the Efficacy and Safety of Different Dose Combinations of an Aromatase Inhibitor and a Progestin in an Intravaginal Ring Versus Placebo and Leuprorelin / Leuprolide Acetate in Women With Symptomatic Endometriosis Over a 12-week Treatment Period
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 319
- 主要终点
- Absolute Change in Mean Pain of the 7 Days With Worst EAPP From Baseline (Last 28 Days Before Randomization) to End of Treatment (Last 28 Days of Treatment Period, Days 57-84) as Measured on NRS by Question 1 of ESD
研究概览
简要总结
Purpose of the study is to test efficacy and safety of BAY98-7196 intravaginal ring as a new treatment option for patients with endometriosis-associated pelvic pain
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Premenopausal women18 years and above at the time of screening.
- •Women with endometriosis confirmed by laparoscopy or laparotomy within the last ten years but not less than 8 weeks before the screening visit In Japan, diagnosis based on imaging (transvaginal ultrasound or MRI) also qualifies for inclusion.
- •Moderate to severe endometriosis-associated pelvic pain (EAPP) of ≥5 in the last 28 days before screening visit 1 measured on the numeric rating scale (NRS; i.e. 4-week recall period).
- •At randomization: Adherence to the study procedures during the screening period, at least 24 diary entries of ESD item 1 during the last 28 consecutive days before the randomization visit, and a sum of the available ESD item 1 ('worst pain' on the daily NRS) entries during this period of at least 98 (corresponding to an average score of ≥ 3.5).
- •Willingness to use only ibuprofen as rescue pain medication for EAPP, if needed according to investigator's instruction.
- •Use of a non-hormonal barrier method (i.e. spermicide-coated condoms) for contraception from screening visit until the end of the study. This is not required if adequate contraception is achieved by vasectomy of the partner
排除标准
- •Pregnancy or lactation (less than three months since delivery, abortion, or lactation before start of treatment)
- •Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug
- •Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results.
- •Any disease or condition that may worsen under hormonal treatment according to the assessment and opinion of the investigator.
- •Undiagnosed abnormal genital bleeding
- •Wish for pregnancy during the study
- •Regular use of pain medication due to other underlying diseases
- •Non-responsiveness of endometriosis associated pelvic pain (EAPP) to GnRH-a or surgery (partial response is not exclusionary).
研究组 & 干预措施
Placebo
Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Placebo (Drug)
Levonorgestrel
Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Placebo (Drug)
Levonorgestrel
Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Levonorgestrel (Drug)
Anastrozole 300 µg/d + Levonorgestrel
Anastrozole 300 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Placebo (Drug)
Anastrozole 300 µg/d + Levonorgestrel
Anastrozole 300 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Anastrozole (Drug)
Anastrozole 600 µg/d + Levonorgestrel
Anastrozole 600 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Placebo (Drug)
Anastrozole 600 µg/d + Levonorgestrel
Anastrozole 600 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Anastrozole (Drug)
Anastrozole 1050 µg/d + Levonorgestrel
Anastrozole 1050 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Placebo (Drug)
Anastrozole 1050 µg/d + Levonorgestrel
Anastrozole 1050 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
干预措施: Anastrozole (Drug)
Lupron / Leuprolide acetate
Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Lupron / Leuprolide acetate 11.25 mg 3-months depot intramuscular injection
干预措施: Placebo (Drug)
Lupron / Leuprolide acetate
Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Lupron / Leuprolide acetate 11.25 mg 3-months depot intramuscular injection
干预措施: Lupron / Leuprolide acetate (Drug)
结局指标
主要结局
Absolute Change in Mean Pain of the 7 Days With Worst EAPP From Baseline (Last 28 Days Before Randomization) to End of Treatment (Last 28 Days of Treatment Period, Days 57-84) as Measured on NRS by Question 1 of ESD
时间窗: Baseline (last 28 days before randomization), end of treatment (Treatment 3) (last 28 days of the treatment period, Day 57-84)
Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, participants were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain of the 7 days with worst EAPP within a 28-day window was calculated as the sum of ESD item 1 on 7 days with worst EAPP within that 28-day window divided by 7.
次要结局
- Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=7 as Measured on NRS by Question 1 of ESD(Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3))
- Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain >=4 as Measured on NRS by Question 1 of ESD(Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3))
- Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=4 as Measured on NRS by Question 1 of ESD(Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3))
- Absolute Change in Mean Pain of the 7 Days With Worst EAPP From Baseline (Last 28 Days Before Randomization) to First Cycle Under Study Treatment (Day 1-28) and to Second Cycle Under Study Treatment (Day 29-56) as Measured on NRS by Question 1 of ESD(Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56))
- Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain Greater Than or Equal to (>=) 7 as Measured on NRS by Question 1 of ESD as Measured on NRS by Question 1 of ESD(Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3))
- Absolute Change in Mean Pain From Baseline (Last 28 Days Before Randomization) to First Cycle Under Study Treatment(Day1-28), Second Cycle Under Study Treatment(Day29-56),Third Cycle Under Study Treatment (Day57-84) as Measured on NRS by Question1 of ESD(Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56), and third cycle (Treatment 3) (last 28 days of the treatment period, Day 57-84))