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Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain (RAQUEL)

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ClinicalTrials.gov Identifier: NCT03692403
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Endometriosis-related Pain Drug: Quinagolide 360 µg Drug: Quinagolide 720 µg Drug: Quinagolide 1080 µg Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 28, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis

Arm Intervention/treatment
Experimental: Quinagolide 360 µg
Vaginal ring containing Quinagolide 360 μg, with daily target release rate of 4.5 μg
Drug: Quinagolide 360 µg
Vaginal ring containing quinagolide 360 µg for daily releases
Other Name: FE 999051

Experimental: Quinagolide 720 µg
Vaginal ring containing Quinagolide 720 μg, with daily target release rate of 9 μg
Drug: Quinagolide 720 µg
Vaginal ring containing quinagolide 720 µg for daily releases
Other Name: FE 999051

Experimental: Quinagolide 1080 µg
Vaginal ring containing Quinagolide 1080 μg, with daily target release rate of 13.5 μg
Drug: Quinagolide 1080 µg
Vaginal ring containing quinagolide 1080 µg for daily releases
Other Name: FE 999051

Placebo Comparator: Placebo
Vaginal ring containing matching placebo
Drug: Placebo
Matching placebo




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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".

  16. 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".

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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)

  29. 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

  30. 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

  31. 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

  32. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pre-menopausal females aged ≥18 years at time of signing informed consent(s).
  • Body mass index (BMI) of 18-42 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03692403


Contacts
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Contact: Global Clinical Compliance +1 833-548-1402 (US/Canada) DK0-Disclosure@ferring.com
Contact: Global Clinical Compliance +1 862-286-5200 (outside US) DK0-Disclosure@ferring.com

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Sponsors and Collaborators
Ferring Pharmaceuticals

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Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03692403     History of Changes
Other Study ID Numbers: 000165
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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

Additional relevant MeSH terms:
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Endometriosis
Genital Diseases, Female
Quinagolide
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs