E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Assessing the endometrial safety of an oral test preparation containing 4 mg drospirenone, which is usually used as contraceptive. |
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E.1.1.1 | Medical condition in easily understood language |
Assessing the endometrial safety of an oral test preparation containing 4 mg drospirenone, which is usually used as contraceptive. |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030970 |
E.1.2 | Term | Oral contraception |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 endometrial safety of an oral test preparation containing 4 mg drospirenone (Test IMP: Drospirenone 4 mg film-coated tablet) after multiple dose administration of 4 mg drospirenone for a total duration of 13 cycles of 28 days each: 24 days of active treatment followed by 4 days placebo treatment per treatment cycle. |
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E.2.2 | Secondary objectives of the trial |
- To assess the endometrial thickness under treatment with the test product,
- To assess the pattern of vaginal bleeding under treatment with the test product,
- To assess the safety of the test product on the basis of safety clinical and laboratory examinations (at the beginning and at the end of the trial) and registration of adverse events and/or adverse drug reactions based on evaluation of adverse events. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Healthy woman at risk of pregnancy
2. Age between 18 and 40 years at inclusion
3. At least four menstrual cycles during the last six months before screening were regular (i.e. cycle length between 24 and 35 days) in women previously not taking oral contraceptives (“Starter”)
4. At least one regular menstrual cycle after the end of previous intake of oral contraceptives (“Switcher”)
5. Systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg, in sitting position, after 5 minutes of rest
6. Subject agrees to use the test product for contraception for at least 13 cycles
7. Menstruation restarted since last pregnancy (only applicable for women that were pregnant)
8. Laboratory values at screening with no deviations of any clinical relevance in the opinion of the investigator
9. Subjects with ability to follow study instructions and likely to attend and complete all required visits
10. Informed consent given in written form according to chapter 5.4 of the study protocol |
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E.4 | Principal exclusion criteria |
1. Hypersensitivity to the active substances or to any of the ingredients or excipients (for a list of ingredients and excipients see the Investigator’s brochure)
2. Pregnant or breastfeeding subject
3. Abnormal finding on pelvic, breast or ultrasound endometrial examination that precludes participation in the trial
4. Abnormal endometrial biopsy
5. Unexplained amenorrhea, known polycystic ovary syndrome
6. Papanicolaou cervical smear finding of atypical squamous cells of undetermined significance (ASC-US) or more severe according to the Bethesda system terminology
7. Significant cardiovascular, hepatic or renal disease
8. Diabetes with vascular involvement
9. Uncontrolled thyroid disorder
10. Current venous thrombosis
11. Known bleeding disorder or history of unexplained bleeding or bruising within the last 12 months prior to screening
12. Prohibited previous or concomitant medication:
12.1 Injectable hormonal methods of contraception within the last 6 months before screening and during the trial
12.2 Progestin-releasing intrauterine device or contraceptive implant within the last 2 months before screening and during the trial
12.3 Anti-retroviral therapy within the last 6 months before screening and during the trial
12.4 Estrogens during the trial
12.5 Progestogens during the trial
12.6 Activated charcoal taken within 3 hours before or after intake of the study drug
12.7 Longer than 5 days treatment during the trial with drugs or herbal products that may decrease the effectiveness of hormonal contraceptives (e.g. anticonvulsants like phenytoin, carbamazepine, oxcarbazepine, topiramate, felbamate, primidone) or barbiturates, rifampicin, atorvastatin, bosentan, griseofulvin,·phenylbutazone, St. John’s wort
(hypericum perforatum), medications that may increase serum potassium (ACE inhibitors, angiotensin – II receptor antagonists, potassiumsparing
diuretics, potassium supplementation, heparin, aldosterone antagonists and NSAIDs)
13. Simultaneous participation in another clinical study or participation in any clinical study involving an investigational drug within 3 months prior to start of the present study
14. Employee of the investigator or trial center, with direct involvement in the proposed trial or other studies under the direction of that investigator or trial center, or family member of the employees or the investigator
15. Severe physical or mental concomitant diseases that might hamper the realization of the trial according to protocol
16. History of alcohol or drug addiction
17. Legal incapacity and/or other circumstances rendering the subject unable to understand the nature, scope and possible consequences of the study
18. Unreliability or lack of cooperation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rating of endometrial biopsy (according to Lindgren et al., 1992). This endpoint undergoes descriptive statistical evaluation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After end of the clinical part and database closure. |
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E.5.2 | Secondary end point(s) |
a) Endometrial thickness measured by transvaginal sonography,
b) Number and percent of subjects with scheduled bleeding, spotting, and unscheduled bleeding per cycle,
c) Number and percent of days per cycle with scheduled bleeding, unscheduled bleeding, or spotting.
Additional endpoints:
a) Incidence of adverse events and serious adverse events,
b) Changes from baseline in the results of clinical examination and vital signs
c) Changes from baseline in safety laboratory parameters (hematology, blood coagulation, biochemistry, urinalysis)
d) Changes from baseline in the results of gynecological examination
e) Results of pregnancy tests.
These endpoints undergo descriptive statistical evaluation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After end of the clinical part and database closure. |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Phase III (endometrial safety study) |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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
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LVLS. The Final visit (follow-up examination) is planned within 7 days after the end of treatment. |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |