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 |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010809 |
E.1.2 | Term | Contraception NOS |
E.1.2 | System Organ Class | 100000004865 |
|
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 investigate local and systemic effects of BAY 1007626 on:
– Number of bleeding and spotting days,
– Endometrial histology,
– Ovulation (as surrogate for systemic effects).
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to assess the effects of BAY 1007626 on:
– Endometrial thickness,
– Serum levels of hormones: estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH),
– Cervix function (Insler score),
– Bleeding pattern characterization,
as well as the
– Safety and tolerability of BAY 1007626,
– PK of BAY 1007626 following intrauterine application, in comparison with Jaydess and Mirena.
Data on PD and PK will be used to explore PK/PD relationship. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent available before any study specific tests or procedures are performed.
2. Healthy female subject.
3. Willingness to use non-hormonal methods of contraception during the study. This applies during the cycle preceding the pre-treatment cycle until the end of follow-up.
4. Age at screening: 18–40 years inclusive.
5. Body mass index (BMI) at screening: ≥ 18 and ≤ 32 kg/m².
6. History of regular cyclic menstrual periods.
7. No clinically relevant abnormal findings in the pre-treatment endometrial biopsy.
8. Adequate venous access (frequent blood sampling).
9. Ability to understand and follow study-related instructions.
|
|
E.4 | Principal exclusion criteria |
1. Incompletely cured pre-existing diseases .
2. Any presence or history of known or suspected malignant Tumors
3. Any presence or history of known or suspected benign tumors of the liver or of the pituitary or adrenal gland.
4. History of recurrent vaginal infections.
5. Postpartum endometritis, infected abortion during the past three months before start of treatment
6. Hepatic disorders
7. Renal Disorders
8. Diseases associated with adverse vascular events .
9. Migraine .
10. Endogenous depression
11. Known current thyroid disorders.
12. Known hypersensitivity to the study medication .
13. Known clinically relevant severe allergies.
14. Amenorrhea .
15. Thrombophlebitis, venous / arterial thromboembolic diseases .
16. Regular use of medicines that might interfere with, for example, laboratory parameters, hormone metabolism.
17. Use of short-acting preparations containing sex hormones during the cycle preceding the pre-treatment cycle .
18. Use of long-acting preparations containing sex hormones within the 40 weeks before the first screening examination .
19. Use of systemic or topical medicines or substances which oppose the study objectives or which might influence them within 4 weeks before the first study drug administration
20. Smoking of more than 10 cigarettes daily.
21. If the subject is a smoker: Subject is older than 35 years at the time of first screening visit.
22. Subject is a former smoker and has stopped smoking less than 3 months prior to the first screening visit.
23. Regular daily consumption of more than approximately 32 g of alcohol.
24. Suspicion of current drug, medicine or alcohol abuse.
25. Donation of blood or plasmapheresis after signing the informed consent form.
26. Clinically relevant ECG findings.
27. Systolic blood pressure < 90 or > 145 mmHg .
28. Diastolic blood pressure < 50 or > 90 mmHg .
29. Heart rate < 45 or > 100 beats/min.
Physical and gynecological examination
30. Clinically relevant findings in the physical examination .
31. Menstrual disorders with suspicion of ovarian failure .
32. Known bleeding irregularities
33. Current or recurrent pelvic inflammatory disease, including pelvic inflammatory disease within 6 month prior to the insertion of the IUS and any active sexually transmitted disease.
34. Anovulatory pre-treatment cycle .
35. Clinically relevant findings in the gynecological examination, including inspection/palpation of the breast and transvaginal ultrasound examination
36. Abnormal cervical smear (details see section.
37. Acute genital infection.
38. Positive testing for Chlamydia trachomatis or Neisseria gonorrhea .
39. Undiagnosed vaginal bleeding.
40. Lack of suitability for IUS insertion and biopsy procedure due to congenital or acquired anatomical malformations of the uterus and/or findings/conditions that could increase the risks of the planned procedures.
41. Conditions associated with increased susceptibility to infections .
42. Lacking suitability for frequent TVU examinations.
43. Positive result of urine pregnancy test.
44. Positive results for hepatitis B virus surface antigen , hepatitis C virus antibodies , human immune deficiency virus antibodies .
45. Positive result of urine drug screening.
46. Clinically relevant deviations of the screened laboratory parameters from reference ranges.
47. Less than 3 months since delivery, abortion, or lactation before the first screening examination.
48. Participation in another clinical study during the preceding 3 months .
49. Exclusion periods from other studies or simultaneous participation in other clinical studies.
50. Scheduled (elective) surgery / planned hospitalization after signing the informed consent form up to 6 weeks after the last administration of the study drug.
51. Prolonged immobilization, major surgery, any surgery to the legs or major trauma unless complete remobilization is achieved at least 2 weeks before first screening examination.
52. Criteria which in the opinion of the investigator preclude participation for scientific reasons or because of the subject’s safety.
53. Inability to cooperate with the study procedures for any reason.
54. Custody of the subject by order of an authority or a court of law.
55. Previous assignment to treatment (e.g. randomization) during this study.
56. Close affiliation with the investigator or persons working at the study site or subject is an employee of Bayer HealthCare.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Variables / Primary endpoints will be:
• Number of bleeding and spotting days
• Progestin effects on endometrial histology
• Ovulation |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Number of bleeding and spotting days (Daily recorded during the 90 days treatment period)
• Progestin effects on endometrial histology (Data derived from biopsies taken pre-treatment, under treatment, during follow-up)
• Ovulation (Under treatment) |
|
E.5.2 | Secondary end point(s) |
Secondary Variables / Secondary endpoints will be:
• Endometrial thickness
• Bleeding characterization (Intensity, pattern)
• Serum levels of hormones (estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone)
• Cervix function (Insler score)
• Treatment emergent AEs and SAEs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Endometrial thickness (Repeatedly under treatment)
• Bleeding characterization (Intensity, pattern), (For 90 day treatment period)
• Serum levels of hormones (estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone), (Repeatedly under treatment)
• Cervix function (Insler score), (Repeatedly under treatment)
• Treatment emergent AEs and SAEs (Continously) |
|
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 | No |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |