Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain

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追踪信息

首次提交日期 ^ICMJE

September 14, 2018

首次发布日期e ^ICMJE

October 2, 2018

最后更新发布日期

October 2, 2018

预计研究开始日期 ^ICMJE

October 2018

预计主要完成日期

September 11, 2019 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

Changes in the mean daily Numerical Rating Scale (NRS) scores compared to baseline for the worst endometriosis related pain.[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days) ]

Assessed daily by participants in an e-Diary. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst endometriosis-related pain on days with menstrual bleeding and for the worst endometriosis-related pain on days with no menstrual bleeding[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst endometriosis-related pain.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst dysmenorrhea.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst non-menstrual pelvic pain.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst dyspareunia on days with sexual intercourse.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary. NRS is a 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Frequency of avoiding sexual intercourse due to expected pain[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary
Changes in the mean daily scores for the worst impact of endometriosis-related pain on the subject's ability to function.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary.
Changes in the mean weekly scores of the Endometriosis Health Profile-30 (EHP-30) pain impact domain.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed weekly by participants in an e-Diary. EHP-30 is a quality-of-life questionnaire. Score ranges from 0-100 and lower score denotes improvement.
Changes in vaginal bleeding pattern.[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed participants by subjects in an e-Diary
Percentage of days with mild and/or strong rescue analgesics used[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary
Total and average doses of mild and/or strong rescue analgesics used[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed daily by participants in an e-Diary
Responder rate[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed as ≥30%, ≥50% and ≥70% reduction from the baseline in mean daily NRS score for the worst endometriosis-related pain, dysmenorrhea and non-menstrual pelvic pain and for the worst endometriosis-related pain impact
Changes in the mean individual and total symptom and sign severity scores[ Time Frame: From baseline to menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by the Biberoglu and Behrman (B&B) scale which is a 4-point scale with 0=none and 3=severe.
Changes in the Endometriosis Health Profile-30 (EHP-30) scores[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by the EHP-30 quality-of-life questionnaire completed by subjects. Score ranges from 0-100 with lower score denoting improvement.
Changes in Patient Global Impression of Severity (PGIS) scores[ Time Frame: From baseline to menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by the PGIS scale completed by participants. PGIS is a 6-point scale depicting a subject's rating of their current conditions from "good" to "bad".
Patient Global Impression of Change (PGIC) scores[ Time Frame: From baseline to menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by the PGIC scale completed by participants. PGIC is a 7-point scale depicting a patient's rating of their overall improvement from "good" to "bad".
Plasma concentration of quinagolide and metabolites[ Time Frame: Within 5 days after first ring insertion, and at around 2 weeks, 1 month, 3 months, 3.5 months, 4 months, 7 months, 7.5 months, and 8 months after baseline (each cycle is approximately 28 days) ]
Assessed by blood samples collection
Serum levels of mid-luteal phase progesterone[ Time Frame: At baseline and at the middle of menstrual cycle 1 (around 2 weeks), cycle 4 (around 3.5 months), and cycle 8 (7.5 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Proportion of subjects with serum mid-luteal progesterone levels ≥25 nmol/L (7.9 ng/ml)[ Time Frame: At baseline and at the middle of menstrual cycle 1 (around 2 weeks), cycle 4 (around 3.5 months), and cycle 8 (7.5 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Serum levels of mid-luteal estradiol, prolactin, thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1)[ Time Frame: At baseline and at the middle of menstrual cycle 1 (around 2 weeks), cycle 4 (around 3.5 months), and cycle 8 (7.5 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Changes in bone turnover markers, determined by bone resorption marker serum C-terminal crosslinking telopeptide of type 1 collagen (s-CTx) and bone formation marker serum procollagen type I N propeptide (s-PINP)[ Time Frame: From baseline to menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Number of subjects with no changes, non-significant changes and significant changes in ECG[ Time Frame: From baseline to menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by 12-lead ECG
Proportion of subjects with abnormal clinically significant echocardiography findings indicating valvular heart disease[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by echocardiography
Proportion of subjects identified with potential impulse control disorders[ Time Frame: At menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by the questionnaire for impulsive-compulsive disorders completed by subjects
Frequency and intensity of adverse events[ Time Frame: From signing informed consent through study completion, around 12 months ]
Assessed by an Adverse Events Log completed by the Investigator
Changes in circulating levels of clinical chemistry parameters[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months), cycle 8 (around 8 months), and cycle 10 (around 10 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Changes in circulating levels of clinical haematology parameters[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months), cycle 8 (around 8 months), and cycle 10 (around 10 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Changes in urinalysis parameters (protein, glucose, bilirubin, pH, nitrite, ketone, urobilinogen, blood, leukocytes, and specific gravity)[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months) and cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by urine sample collection (dip-stick test)
Proportion of participants with markedly abnormal changes in circulating levels of clinical chemistry parameters[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months), cycle 8 (around 8 months), and cycle 10 (around 10 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Proportion of participants with markedly abnormal changes in circulating levels of clinical haematology parameters[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months), cycle 8 (around 8 months), and cycle 10 (around 10 months, each cycle is approximately 28 days) ]
Assessed by blood samples collection
Proportion of participants with markedly abnormal changes in urinalysis parameters[ Time Frame: At baseline and at menstrual cycle 4 (around 4 months), cycle 8 (around 8 months), and cycle 10 (around 10 months, each cycle is approximately 28 days) ]
Assessed by urine samples collection
Frequency and intensity of ring acceptability parameters[ Time Frame: From baseline to menstrual cycle 8 (around 8 months, each cycle is approximately 28 days) ]
Assessed by a questionnaire completed by participants, addressing ring insertion/removal, any feeling of the ring while the ring is in the body, any feeling of the ring during sexual intercourse if applicable and any experience of ring falling out or breaking.

描述性信息

简略标题 ^ICMJE

Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain

正式标题 ^ICMJE

A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial Assessing Efficacy, Safety, Dose-response of Quinagolide Vaginal Rings Administered Sequentially for 8 Menstrual Cycles in Women With Moderate-Severe Endometriosis-related Pain

简要概况

To evaluate the efficacy of three doses of quinagolide administered as an extended-release vaginal ring compared to placebo on reduction of moderate to severe endometriosis-related pain

详细说明

研究类型 ^ICMJE

Interventional

研究阶段

Phase 2

研究设计 ^ICMJE

分配: Randomized
干预模型: Parallel Assignment
干预模型描述:
盲法: Interventional
盲法描述:
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

Drug: Quinagolide 360 µg
Vaginal ring containing quinagolide 360 µg for daily releases
Drug: Quinagolide 720 µg
Vaginal ring containing quinagolide 720 µg for daily releases
Drug: Quinagolide 1080 µg
Vaginal ring containing quinagolide 1080 µg for daily releases
Drug: Placebo
Matching placebo

研究工具

Experimental: Quinagolide 360 µg
Vaginal ring containing Quinagolide 360 μg, with daily target release rate of 4.5 μg
Experimental: Quinagolide 720 µg
Vaginal ring containing Quinagolide 720 μg, with daily target release rate of 9 μg
Experimental: Quinagolide 1080 µg
Vaginal ring containing Quinagolide 1080 μg, with daily target release rate of 13.5 μg
Placebo Comparator: Placebo
Vaginal ring containing matching placebo

招募信息

招募状态 ^ICMJE

Not yet recruiting

预计入组 ^ICMJE

280

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

February 10, 2020

预计主要完成日期

September 11, 2019 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

Inclusion Criteria: - Pre-menopausal females aged ≥18 years at time of signing informed consent(s). - Body mass index (BMI) of 18-38 kg/m2 (both inclusive) at screening. - Initial confirmation of endometriosis by laparoscopy or laparotomy within the last 10 years before the run-in visit. - Transvaginal ultrasound documenting a uterus with no clinically significant abnormalities and presence of at least one ovary with no clinically significant abnormalities (e.g. no evidence of endometrioma greater than 3 cm in diameter) at the run-in visit. - Having moderate to severe endometriosis-related pain. - Willing to use a non-hormonal barrier method (i.e. condom) for contraception from randomization to the end-of-trial. This is not required if adequate contraception is achieved by vasectomy of the sexual partner or surgical sterilisation of the subject. - Willing to avoid the use of vaginal douches or any other intravaginally administered medications or devices from randomization to the end of treatment. - Willing to change usual analgesics to rescue analgesics as permitted by protocol for endometriosis-related pain from the start of run-in to the end-of-trial. Exclusion Criteria: - Use of depot medroxyprogesterone acetate (MPA) within 10 months of the start of run-in. - Use of gonadotropin releasing hormone (GnRH) agonists (3 months depot) or dopamine agonists within 6 months of the start of run-in. - Use of GnRH agonists (1 month depot) or intrauterine device within 3 months of the start of run-in. - Use of GnRH antagonist, combined oral contraceptive pill or progestin-only pill within 1 month of the start of run-in. - Undiagnosed abnormal vaginal bleeding. - History of no relief of endometriosis related pain after any medical therapy or surgery. However, history of partial pain relief, discontinuation due to side effects are not exclusionary. - Known bone diseases (e.g. osteoporosis, Paget's disease and osteomalacia) affecting bone resorption or bone formation markers. - Any significant abnormal findings of heart examinations before randomization.

性别

参与研究的性别:

Female

年龄

最小年龄：18 Years ，最大年龄：N/A

接受健康的志愿者

没有

可入组国家 ^ICMJE

United States

管理信息

数据检测委员会

Yes

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: Yes
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

责任方

，

研究赞助商 ^ICMJE

Ferring Pharmaceuticals

合作者 ^ICMJE

研究员 ^ICMJE

PRS 账户

验证日期

September 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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