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 | 21.1 |
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 | 21.1 |
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 | 21.1 |
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 |
The primary objective of this study is to assess the efficacy of vilaprisan in subjects with uterine fibroids compared to ulipristal. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the efficacy and safety of different treatment regimens of vilaprisan in subjects with uterine fibroids |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Women, 18 years or older at the time of Visit 1
2. Diagnosis of uterine fibroid(s) documented by ultrasound at screening with at least 1 fibroid with largest diameter more than 30 mm and less than 120 mm
3. Heavy menstrual bleeding (HMB) >80.0 mL documented by menstrual pictogram (MP) in a bleeding episode period during the screening period
4.Use of an acceptable non-hormonal method of contraception
5. An endometrial biopsy performed during the screening period, without significant histological disorder such as endometrial hyperplasia (including simple hyperplasia) or other significant endometrial pathology.
|
|
E.4 | Principal exclusion criteria |
1. Pregnancy or lactation (less than 3 months since delivery, abortion, or lactation before start of treatment)
2. Hypersensitivity to any ingredient of the study drugs
3. Hemoglobin values £6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values £10.9 g/dL will be recommended to use iron supplementation).
4. Any diseases, conditions, or medications 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
5. Abuse of alcohol, drugs, or medicines (eg, laxatives)
6. Undiagnosed abnormal genital bleeding
7. Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Amenorrhea (yes/no), Defined as menstrual blood loss (MBL) < 2 mL based on the menstrual pictogram (MP) during last 28 days |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For the primary analysis of the primary variable, the amenorrhea rates after 12 weeks of treatment in Groups A1, A2 and A3 will be compared to the rate from Group B. |
|
E.5.2 | Secondary end point(s) |
1) Total volume of menstrual blood loss (assessed by MP).
2) Number of bleeding days
3) Amenorrhea (yes/no)
4) Absence of bleeding (spotting allowed)
5) Time to onset of controlled bleeding
6) HMB responder rate
7) Percent change in volume of largest fibroid compared to baseline (measured by MRI) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Menstrual blood loss: from Day 1 of the TP1 until the day before a new TP would start again following the last treatment period
2) Number of bleeding days: from Day 1 of the TP1 until the day before a new TP would start again following the last treatment period
3) Amenorrhea (yes/no), defined as MBL < 2 mL during last 28 days of each TP
4) Absence of bleeding during the last 28 days of the treatment
5) Time to onset of controlled bleeding: the first day, for which the
menstrual blood loss for all subsequent 28-day periods up to the end of the treatment period is less than 80mL.
6) HMB responder rate (Percentage of subjects with blood loss < 80mL per 28 days and 50% reduction compared to baseline
7) Percent change in volume of largest fibroid compared to baseline |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
3 treatment arms with vilaprisan: A1 - 3/1 regimen; A2 - 6/2 regimen; A3 - 3/2 regimen. |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 219 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Ireland |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Netherlands |
Norway |
Poland |
Portugal |
Slovakia |
Spain |
Sweden |
Taiwan |
Ukraine |
United Kingdom |
|
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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |