Deep infiltrating endometriosis, endometrioma and/or adenomyosis. MedDRA version: 21.0 Level: LLT Classification code 10014787 Term: Endometriosis of uterus System Organ Class: 100000004872
Conditions
Interventions
Product Name: Quinagolide
Product Code: FE999051
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: QUINAGOLIDE
CAS Number: 94424-50-7
Current Sponsor code: FE999051
Concentration unit:
Sponsors
Ferring Pharmaceuticals A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent signed and dated prior to any trial-related procedures. 2. In good physical and mental health to participate in the trial. 3. Pre-menopausal females between the ages of 18-45 years (both inclusive) at the time of signing the informed consent. 4. A menstrual cycle of 24-35 days (both inclusive) based on observation made in the absence of drugs that can affect the cycle length (e.g. oral contraceptives) prior to the screening visit. 5. Body mass index (BMI) of 18-35 kg/m2 (both inclusive) at screening. 6. Confirmation of deep infiltrating endometriosis (DIE) (lesion size =15 mm), endometrioma (=20 mm) or adenomyosis (maximum junctional zone thickness =12 mm or focal lesion =15 mm) by high-resolution MRI at screening. 7. Transvaginal ultrasound documenting a uterus with no abnormalities of endometrium and presence of at least one ovary with no clinically significant abnormalities at screening. Note that presence of uterine fibroids are not exclusionary but presence of any submucosal fibroids or polyps are exclusionary. 8. Willing and able to use a non-hormonal single-barrier method (i.e. condom) for contraception from the start of screening to the end-of-treatment. This is not required if adequate contraception is achieved by vasectomy of the male sexual partner, surgical sterilisation (e.g. tubal ligation and blockage methods such as ESSURE) of the subject, or true abstinence of the subject (sporadic sexual intercourse with men requiring condom use). 9. Willing to avoid the use of vaginal douches or any other intravaginally administered medications or devices (except for tampons) from randomisation to the end of treatment. 10. Documentation of normal cervical cytology or negative human papilloma virus (HPV) results for high-risk viral subtypes upon presence of atypical squamous cells of undetermined significance, based on test(s) performed within 24 months of randomisation. 11. Willing and able to comply with trial procedures, including attending scheduled visits and adherence to treatment plan. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Use of depot medroxyprogesterone acetate (MPA) or birth control implants (e.g. IMPLANON) within 10 months prior to the screening visit. 2. Use of gonadotropin-releasing (GnRH) agonists (3-month depot) or dopamine agonists within 6 months prior to the screening visit. 3. Use of GnRH agonists (1-month depot or nasal spray), GnRH antagonists, aromatase inhibitors, danazol, progestogen or levonorgestrel releasing intrauterine device (IUD) within 3 months prior to the screening visit. 4. Use of hormonal contraceptives (including combined oral contraceptive pill, transdermal patch, and contraceptive ring) within 1 menstrual cycle prior to the screening visit. 5. Undiagnosed abnormal vaginal bleeding within the last 3 months of the screening visit. 6. History of recurrent bacterial, fungal or viral vaginal infection (i.e. =4 episodes within a year). 7. History of malignancy within 5 years prior to the screening visit, except for adequately managed basal cell carcinoma and squamous cell carcinoma of the skin. 8. History of orthostatic hypotension or recurrent syncope. 9. History of mental illness including occurrence of acute psychosis and bipolar schizophrenia (except for well-controlled mild or moderate anxiety and/or depression with no changes to interventions for 3 months prior to the screening visit). 10. History of sudden sleep onset episodes. 11. Known diagnosis of impulse control disorders including pathological gambling, compulsive buying, hypersexuality, and binge eating. 12. Known positive results of Human Immunodeficiency Virus (HIV) antibody tests. 13. Any other incidental, clinically significant abnormal findings than endometriotic / adenomyotic lesions identified at the screening MRI assessment (e.g. suspected tumour). 14. Any clinically significant abnormal findings from vital signs, blood tests of haematology and clinical chemistry at screening, including alanine aminotransferase (ALT) >2.5 times upper limit of normal (ULN) or bilirubin >1.5 times ULN or creatinine >1.5 times ULN. 15. Any clinically significant abnormal findings at physical examination at screening. 16. Any vaginal or vulvar lesions that would interfere with vaginal ring usage. 17. Current pregnancy as confirmed by a positive serum pregnancy test at screening or planning a pregnancy within the duration of the trial, or currently breast-feeding or less than 6 months post-partum prior to the screening visit. 18. Planned surgical treatment of endometriosis or adenomyosis during the duration of the trial. 19. Continuous use of strong opioids (e.g. morphine) and/or illicit drugs (e.g. marijuana and amphetamine) for more than 2 weeks within 6 months prior to the screening visit. 20. Alcohol abuse (>14 units of alcohol a week) within 2 years prior to the screening visit. 21. Previous or current participation in a clinical trial involving a non-registered investigational medicinal product within 1 month of screening. If the trial involves a hormonal drug, the exclusion criteria 1-4 shall apply. 22. Contraindications to MRI such as having internal/external metallic devices and/or accessories (e.g. cardiac pacemakers and leg braces).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of quinagolide vaginal ring compared to placebo on reduction of lesions for endometrioma, deep infiltrating endometriosis (DIE) and adenomyosis assessed by high-resolution magnetic resonance imaging (MRI);Secondary Objective: - To evaluate the effect of quinagolide vaginal ring compared to placebo on reducing the sizes of endometrioma assessed by transvaginal ultrasound (TVU) - To evaluate the effect of quinagolide vaginal ring on patient reported outcomes (PROs) - To evaluate the plasma concentrations of quinagolide and its metabolites - To evaluate the effect of quinagolide vaginal ring on serum endocrine parameters - To evaluate the effect of quinagolide vaginal ring on menstrual bleeding pattern - To evaluate the safety profile of quinagolide vaginal ring including adverse events and routine safety laboratory parameters;Primary end point(s): Changes in the sizes (mm) of endometrioma, DIE and adenomyosis lesions summed by type on MR images at cycle 4.;Timepoint(s) of evaluation of this end point: End of Cycle 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Percentage of changes in the sizes of endometrioma, DIE and adenomyosis lesions summed by type on MR images at cycle 4 - Proportion of lesions by type with a decrease in a size of =5 mm on MR images at cycle 4 - Proportion of subjects with a lesion of any type decreased in a size of =5 mm on MR images at cycle 4 - Number of new or disappearing endometrioma, DIE and adenomyosis lesions summed by type on MR images at cycle 4 - Changes in the volumes (mm3) of endometrioma and DIE lesions summed by type on MR images at cycle 4 - Changes in the sizes of endometrioma assessed by TVU at cycle 4 - Changes in the mean individual and total symptom and sign severity of scores of the Biberoglu and Behrman (B&B) scale at cycle 4 - Changes in the Numerical Rating Scale (NRS) pain scores per cycle at cycles 1, 2, 3 and 4 - Changes in the Endometriosis Health Profile-30 (EHP-30) scores at cycles 2 and 4 - Changes in the menstrual bleeding pattern over 4 cycles - Serum levels of prolactin, thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1) during cycle 1, at cycles 2 and 4 - Plasma concentrations of quinagolide and its metabolites during cycles 1 to 4 - Changes in clinical chemistry and haematology parameters and proportion of subjects with markedly abnormal changes - Frequency and intensity of adverse events;Timepoint(s) of evaluation of this end point: Cycle 4 | — |
Countries
Denmark, Germany, Italy, Switzerland
Contacts
Public ContactGlobal Clinical R&D
Ferring Pharmaceuticals A/S
Outcome results
None listed