Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain

Sponsor:

Collaborators:

Information provided by (Responsible Party):

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Tracking Information

First Submitted Date ^ICMJE

September 14, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

October 2018

Estimated Primary Completion Date

September 11, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^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.

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^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.

Descriptive Information

Brief Title ^ICMJE

Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain

Official Title ^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

Brief Summary

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

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^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

Study Arms

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

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

280

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

February 10, 2020

Estimated Primary Completion Date

September 11, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^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.

Sex/Gender

Sexes Eligible for Study:

Female

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Ferring Pharmaceuticals

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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