E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Uterine fibroids, heavy menstrual bleeding |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046784 |
E.1.2 | Term | Uterine fibroids |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016628 |
E.1.2 | Term | Fibroids |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022794 |
E.1.2 | Term | Intramural leiomyoma of uterus |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of vilaprisan in subjects with uterine fibroids compared to placebo. |
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of vilaprisan in subjects with uterine fibroids compared to ulipristal.
To evaluate the safety of vilaprisan in subjects with uterine fibroids.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent
2. Women, 18 to 50 years of age at the time of screening
3. Diagnosis of uterine fibroid(s) documented by transvaginal or abdominal ultrasound at screening with at least 1 fibroid with largest diameter >/=3.0 cm
4. Heavy menstrual bleeding (HMB) >80 mL documented by menstrual pictogram (MP) in a bleeding episode during the screening period.
Women who did not suffer from perceived HMB during the 3 months prior to Visit 1 due to any effective medical treatment, e.g. with a hormonal contraceptive, are not considered appropriate candidates and should not undergo further screening procedures.
Women suffering from perceived HMB despite medical treatment, e.g. with a hormonal contraceptive, are appropriate candidates for further screening, if rules on stopping prior medication are followed.
Heavy menstrual bleeding / HMB > 80mL should be documented within 10 consequtive days.
5. Good general health (except for findings related to uterine fibroids) as proven by medical history, physical and gynecological examinations, and laboratory test results.
6. Normal or clinically insignificant cervical smear not requiring further follow-up. Human papilloma virus (HPV) testing in subjects with atypical squamous cells of undetermined significance (ASCUS) can be used as an adjunctive test. Subjects with ASCUS can be included if they are negative for high-risk HPV strains.
7. An endometrial biopsy performed during the screening period, without significant histological disorder such as endometrial hyperplasia (including simple hyperplasia) or other significant endometrial pathology.
8. Use of an acceptable nonhormonal method of contraception (i.e. either male condom, cap, diaphragm or sponge, each in combination with spermicide) starting at the bleeding episode following the screening visit 1 (Visit 1) until the end of the study. This is not required if safe contraception is achieved by a permanent method, such as bilateral fallopian tube blockage of the subject or vasectomy of the partner(s). |
|
E.4 | Principal exclusion criteria |
1. Pregnancy or lactation (less than 3 months since delivery, abortion, or lactation before start of treatment)
2. Uterine fibroid with largest diameter >10.0 cm
3. Hypersensitivity to any ingredient of the study drugs
4. Hemoglobin values </= 6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values </=10.9 g/dL will be offered iron supplementation).
5. Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug
6. Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results
7. Abuse of alcohol, drugs, or medicines (e.g. laxatives)
8. Use of other treatments that might interfere with the conduct of the study or the interpretation of the results
9. Undiagnosed abnormal genital bleeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Amenorrhea (yes/no)
Defined as no scheduled or unscheduled bleeding/spotting after end of the initial bleeding episode until the end of the respective treatment period |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After end of the intial bleeding until treatment day 84 of each treatment period |
|
E.5.2 | Secondary end point(s) |
1. Number of bleeding days
2. Time to onset of controlled bleeding
3. Percent change in volume of largest fibroid compared to baseline
4. Endometrial histology (classical histology)
5. Endometrial thickness |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From start of treatment until the day before the next treatment period would start again
2. From baseline until end of treatment
3. From baseline until end of treatment
4. From baseline until end of follow-up period
5. From baseline until end of follow-up period |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open label active-controlled |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 7 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |