Clincosm LogoSign in Get a demo

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

Sponsor
Ferring Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03692403
Collaborator
(none)
22
Enrollment
43
Locations
4
Arms
56.1
Anticipated Duration (Months)
0.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
  • Drug: Quinagolide 360 µg
  • Drug: Quinagolide 720 µg
  • Drug: Quinagolide 1080 µg
  • Drug: Placebo
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
22 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 4 Menstrual Cycles in Women With Moderate-Severe Endometriosis-related Pain
Actual Study Start Date :
Nov 28, 2018
Actual Primary Completion Date :
Feb 14, 2022
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • FE 999051

    		•
    Placebo Comparator: Placebo

    Vaginal ring containing matching placebo

    Drug: Placebo
    Matching placebo

    Outcome Measures

    Primary Outcome Measures

    1. Changes in the mean daily Numerical Rating Scale (NRS) scores compared to baseline for the worst endometriosis related pain. [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 [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. [From baseline to 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.

    3. Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst dysmenorrhea. [From baseline to 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.

    4. Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst non-menstrual pelvic pain. [From baseline to 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.

    5. Changes in the mean daily Numerical Rating Scale (NRS) scores for the worst dyspareunia on days with sexual intercourse. [From baseline to 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.

    6. Frequency of avoiding sexual intercourse due to expected pain [From baseline to menstrual cycle 4 (around 4 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. [From baseline to menstrual cycle 4 (around 4 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. [From baseline to menstrual cycle 4 (around 4 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. [From baseline to menstrual cycle 4 (around 4 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 [From baseline to menstrual cycle 4 (around 4 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 [From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)]

      Assessed daily by participants in an e-Diary

    12. Responder rate [From baseline to menstrual cycle 4 (around 4 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 [At baseline and at menstrual cycle 4 (around 4 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 [From baseline to menstrual cycle 4 (around 4 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 [At baseline and at menstrual cycle 4 (around 4 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 [At cycle 4 (around 4 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 [Within 5 days after first ring insertion and at around 1 month, 3 months, 3.5 months and 4 months after baseline (each cycle is approximately 28 days)]

      Assessed by blood samples collection

    18. Serum levels of mid-luteal phase progesterone [At baseline and cycle 4 (around 3.5 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) [At baseline and cycle 4 (around 3.5 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) [At baseline and cycle 4 (around 3.5 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) [From baseline to menstrual cycle 4 (around 4 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 [At baseline and at menstrual cycle 4 (around 4 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 [At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)]

      Assessed by echocardiography

    24. Proportion of subjects identified with potential impulse control disorders [At baseline and at menstrual cycle 4 (around 4 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 [From signing informed consent through study completion, around 7 months]

      Assessed by an Adverse Events Log completed by the Investigator

    26. Changes in circulating levels of clinical chemistry parameters [At baseline and at menstrual cycle 4 (around 4 months) and cycle 5 (around 5 months, each cycle is approximately 28 days)]

      Assessed by blood samples collection

    27. Changes in circulating levels of clinical haematology parameters [At baseline and at menstrual cycle 4 (around 4 months) and cycle 5 (around 5 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) [At baseline and at menstrual cycle 4 (around 4 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 [At baseline and at menstrual cycle 4 (around 4 months) and cycle 5 (around 5 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 [At baseline and at menstrual cycle 4 (around 4 months) and cycle 5 (around 5 months, each cycle is approximately 28 days)]

      Assessed by blood samples collection

    31. Proportion of participants with markedly abnormal changes in urinalysis parameters [At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)]

      Assessed by urine samples collection

    32. Frequency and intensity of ring acceptability parameters [From baseline to menstrual cycle 4 (around 4 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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 or visualization of persistent endometrioma by repeat ultrasound.

    • Transvaginal ultrasound documenting a uterus with no clinically significant abnormalities and presence of at least one ovary with no clinically significant abnormalities (with the exception of endometrioma) 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Marchand Institute for Minimally Invasive Surgery Mesa Arizona United States 85209
    2 Arkansas Primary Care Clinic Little Rock Arkansas United States 72204
    3 Medical Center for Clinical Research San Diego California United States 92108
    4 UConn Health Lowell P Weicker Jr Clinical Research Center Farmington Connecticut United States 06030
    5 Yale Fertility Center New Haven Connecticut United States 06511
    6 Omega Research Consultants DeBary Florida United States 32713
    7 South Florida Research Center Miami Florida United States 33135
    8 Florida Research Center Miami Florida United States 33174
    9 Miami Dade Medical Research Institute Miami Florida United States 33176
    10 Vista Health Research Miami Florida United States 33176
    11 Advanced Research Institute New Port Richey Florida United States 34653
    12 Meridien Research Saint Petersburg Florida United States 33709
    13 Physician Care Clinical Research Sarasota Florida United States 34239
    14 Advance Clinical Research Meridian Idaho United States 83643
    15 Northwestern Memorial Hospital Chicago Illinois United States 60611
    16 Southern Illinois University Springfield Illinois United States 62794-9664
    17 The Iowa Clinic Ankeny Iowa United States 50023
    18 Cypress Medical Research Center Wichita Kansas United States 67226
    19 Southern Clinical Research Associates Metairie Louisiana United States 70001
    20 Omni Fertility Clinical Research LLC Shreveport Louisiana United States 71118
    21 Johns Hopkins Outpatient Center Baltimore Maryland United States 21287
    22 OB/Gyn Associates Silver Spring Maryland United States 20910
    23 Onyx Clinical Research Flint Michigan United States 48532
    24 Valley OB/GYN Clinic, PC Saginaw Michigan United States 48602
    25 Mayo Clinic Rochester Minnesota United States 55905
    26 Montefiore Medical Center Bronx New York United States 10461
    27 SUNY Downstate Medical Center Brooklyn New York United States 11203
    28 OB•GYN Associates of WNY West Seneca New York United States 14224
    29 PMG Research of Charlotte Charlotte North Carolina United States 28209
    30 Carolina's Women's Research and Wellness Center Durham North Carolina United States 27713
    31 Rapha Institute For Clinical Research Fayetteville North Carolina United States 28314
    32 Lyndhurst Clinical Research Winston-Salem North Carolina United States 27103
    33 Unified Women's Clinical Research d/b/a Lyndhurst Clinical Research Winston-Salem North Carolina United States 27103
    34 Main Line Fertility Center Bryn Mawr Pennsylvania United States 19010
    35 Penn State Health - Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
    36 Clinical Trials of South Carolina Charleston South Carolina United States 29406
    37 Austin Area Ob, Gyn and Fertility Austin Texas United States 78758
    38 Corpus Christi Women's Clinic Corpus Christi Texas United States 78412
    39 Advances in Health, Inc. Houston Texas United States 77030
    40 Center of Reproductive Medicine LLC Webster Texas United States 77598
    41 Wasatch Clinical Research Salt Lake City Utah United States 84107
    42 Tidewater Clinical Research, Inc. Norfolk Virginia United States 23502
    43 OB/GYN Specialists of Richmond Richmond Virginia United States 23229

    Sponsors and Collaborators

    • Ferring Pharmaceuticals

    Investigators

    • Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ferring Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03692403
    Other Study ID Numbers:
    • 000165
    First Posted:
    Oct 2, 2018
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Endometriosis
    Quinagolide

    Study Results

    No Results Posted as of Apr 4, 2022