E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010808 |
E.1.2 | Term | 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 |
The primary objective is to assess the safety of low-dose levonorgestrel (LNG) (12μg/24h, initial in vitro
release rate), delivered locally by an intrauterine contraceptive system in adolescents
over 1 year of treatment, including insertion and removal procedures.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate efficacy, discontinuation rate and pharmacokinetics in adolescents.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject has signed and dated the informed consent form or given assent.
2. The subject is a female adolescent, age 12 to under 18 years of age at the Screening visit, is generally healthy, post-menarcheal, nulliparous or parous, and requires contraception.
3. The subject has regular menstrual cycles without hormonal contraceptive use (at regular intervals of 21-35 days). In the opinion of the investigator, the subject has general and uterine conditions suitable for the insertion of LCS12 (uterine sound depth 6-10 cm).
5. The subject has clinically normal safety laboratory results inside the specified range for inclusion.
6. The subject has a normal or clinically insignificant cervical smear (i.e. one that does not require further follow up according to Bethesda or a comparable system). A cervical smear must be taken at the Screening Visit or a documented normal result must have been obtained not more than 6 months before the Screening Visit. Subjects with atypical squamous cells of undetermined significance (ASCUS) can be included in the study if they have a Human Papilloma Virus (HPV) DNA test that, according to the standards of the central laboratory, is negative for high-risk HPV.
7. The subject is willing and able to attend the scheduled study visits and to comply with |
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E.4 | Principal exclusion criteria |
1. Known or suspected pregnancy or is lactating.
2. Vaginal delivery, cesarean delivery, or abortion less than 6 weeks before Visit 1. Note: Postpartum insertions should be postponed until uterus is fully involuted, however not earlier than 6 weeks after delivery. If involution is substantially delayed,
consider waiting until 12 weeks postpartum. In the event of a difficult insertion and/or exceptional pain or bleeding during or after insertion, physical examination and ultrasound should be performed immediately to exclude perforation.
3. History of ectopic pregnancies.
4. Infected abortion or postpartum endometritis less 3 months before Visit 1.
5. Abnormal uterine bleeding of unknown origin.
6. Any lower genital tract infection (until successfully treated).
7. Acute or history of recurrent pelvic inflammatory disease.
8. Congenital or acquired uterine anomaly.
9. Submucous uterine fibroids
10. Any other distortion of the uterine cavity (by e.g. larger intramural or subserousal fibroids) likely to cause problems (in the opinion of the investigator) during insertion, retention or removal of LCS12.
11. History of, diagnosed or suspected genital malignancy, and untreated cervical dysplasia.
12. Current deep venous thrombosis or thrombophlebitis; history of deep venous thrombosis.
13. Clinically significant endometrial polyp(s), which, in the opinion of the investigator, will interfere with the assessment of the bleeding profile during the study.
14. Clinically significant ovarian cyst(s).
15. Concomitant use of other sex-hormone containing preparations or an IUD after the insertion of LCS12
16. Use of any long-acting injectable sex-hormone preparations less than 12 months before start of study medication.
17. Established immunodeficiency.
18. Any known hypersensitivity to the constituents of the LCS, or any health problems caused by previous use of an IUS.
19. Diagnosed or suspected malignant or premalignant disease at the screening
20. Arterial hypertension (as defined by systolic and diastolic values relevant for age) not responding to appropriate treatment.
21. Current (or history of) severe hepatic diseases including benign or malignant tumors. There should be an interval of at least 3 months between the start of study treatment (i.e., LCS12 insertion) and the return of liver function values to normal
22. History of chronic alcoholism, drug dependence or abuse, psychotic states or severe neurosis or any other condition that, in the opinion of the investigator, might impair a subject’s ability to cooperate
23. Known or suspected HIV infection or high risk for Sextually Transmitted Disease.
24. Any clinically significant condition or laboratory result that, in the opinion of the investigator, compromises the subject’s safety, might interfere with the evaluations or prevents the completion of the study.
25. Participated in another clinical study or consumed another experimental drug less than 30 days before Visit 1
26. Previous participation in this study
27. A person with close affiliation with the investigational site; e.g., close relative of the investigator, dependent person, employee or student of the investigational site
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is the incidence of adverse events over the first 12-month treatment period.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary variables are:
For efficacy
- Overall satisfaction rating
- Pregnancies (Pearl index)
- Bleeding patterns
- Pharmacokinetics
For population pharmacokinetics:
- Safety
- LCS12 insertion ease and pain assessments
- LCS12 removal ease and pain assessments
For other:
- Discontinuation rate
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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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For each participating European Union (EU) country, the end of the study according to the EU Clinical Trial Directive will be reached when the last visit of the last subject in all centers in the respective country has occurred.
The end of the study as a whole will be reached as soon as the end of the study according to the above definition has been reached in all participating countries (EU and non-EU). |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |