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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030971 |
E.1.2 | Term | Oral contraceptive |
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 |
To evaluate the safety profile of E4/DRSP 15/3 mg in post-menarchal subjects aged 15 to 17 years and 2 months (inclusive) at the time of signing the IC. |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the compliance to E4/DRSP 15/3 mg (24 active/4 placebo). 2. To assess the PK trough levels of E4 and DRSP at steady state. 3. To assess the cycle control and bleeding pattern associated with E4/DRSP 15/3 mg. 4. To assess the effect of E4/DRSP 15/3 mg in relieving symptoms of primary dysmenorrhea. 5. To assess the effect of E4/DRSP 15/3 mg on general health, well-being, physical, social and mental functioning. 6. To assess the effect of E4/DRSP 15/3 mg on hemostasis parameters. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetics sub-study
Among subjects enrolled in the study, 30 are planned for enrollment in the PK sub-study.
The objective of the sub-study is to analyze the pharmacokinetic parameters of E4/DRSP 15/3 mg. Enrollment will be sequential: the first 30 subjects meeting the specific criteria for enrollment in the pharmacokinetic sub-study and willing to participate will be enrolled. |
|
E.3 | Principal inclusion criteria |
1. Post-menarchal female subject requesting COC either for contraceptive or for therapeutic use. 2. Negative serum pregnancy test at screening and negative urine pregnancy test at enrollment. 3. Aged 15 to 17 years and 2 months (inclusive) at the time of signing the IC. 4. Willing to use the IP for 6 consecutive cycles. 5. Good physical and mental health on the basis of medical, surgical and gynecological history, physical examination, clinical laboratory, and vital signs. 6. Body mass index (BMI) below or equal to the percentile 97 (P97) on the local pediatric BMI curves.
Additional inclusion criteria for pharmacokinetics sub-study : 1. BMI below or equal to the percentile 95 (P95) on the local pediatric BMI curves. 2. Subjects are aware and willing to comply with the following restrictions prior to blood sampling for pharmacokinetic assessment: a. The subject should be fasting for 8 hours minimum at the time of blood sampling. b. On days when blood sampling for pharmacokinetics is scheduled, the subject should not take the investigational product prior to the blood sampling. c. The subject should not smoke during the 30 minutes prior to the blood sampling. d. The subject should not perform any physical activity during the 2 hours prior to the blood sampling. 7. Able to fulfill the requirements of the protocol, undergo all study procedures including e-diary and questionnaires completion. 8. Having indicated the willingness to participate in the study by providing written assent. 9. Having parent(s) or legal representative(s) willing and able to provide written IC. |
|
E.4 | Principal exclusion criteria |
1. For subjects who are not using hormonal contraception at screening, a menstrual cycle length shorter than 21 days or longer than 45 days. 2. Currently using an injectable or a dermally implantable hormonal method of contraception. 3. Known hypersensitivity to any of the IP ingredients. 4. Currently pregnant or breastfeeding or with the intention to become pregnant during the course of the study. 5. Less than 6 weeks since last delivery/2nd trimester abortion and before spontaneous menstruation has occurred following a delivery or 2nd trimester abortion. 6. Any condition representing a contraindication / precaution to the use of COCs. 7. Within the past 6 months, undiagnosed (unexplained) abnormal vaginal bleeding, or any abnormal bleeding that could possibly recur during the study. 8. Presence or history of recurrent pelvic inflammatory disease. 9. Any clinically relevant lower genital tract infection (including gonorrhea and chlamydia infections) until successfully treated, in the opinion of the Investigator. 10. Presence or history of hepatic disease as long as liver function values have not returned to normal. 11. Renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73m²). 12. Hyperkalemia or presence of conditions that predispose to hyperkalemia such as renal impairment, hepatic impairment, adrenal insufficiency and daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration (e.g. angiotensin-converting-enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonist and non-steroidal anti-inflammatory drugs). 13. History of organ transplantation within 5 years before screening or chronic disease potentially necessitating organ transplantation during the anticipated course of the study. 14. Presence or history of sex hormone-related malignancy. 15. History of non-hormone-related malignancy within 5 years before screening. 16. Current regular use or regular use within 1 month prior to Visit 2 of drugs potentially triggering interactions with COCs. 17. History of alcohol or drug abuse (including laxatives) within 12 months prior to screening. 18. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs. The Investigator should exercise medical judgment in consideration of the subject’s medical history and/or clinical or laboratory evidence of any of the following: a. cystic fibrosis, celiac disease, inflammatory bowel disease, gastritis, ulcers, gastrointestinal or rectal bleeding, b. major gastrointestinal tract surgery (this does not include history of appendectomy), c. pancreatic injury or pancreatitis, d. liver disease or liver injury as indicated by abnormal liver function tests, e. impaired renal function if considered as clinically significant, f. abnormal urinary constituents (e.g. albumin if considered as clinically significant). 19. Uncontrolled thyroid disorders. 20. Participation in another investigational drug clinical study within 1 month (30 days) or have received an investigational drug within the last month (30 days) prior to screening. 21. Sponsor, Contract Research Organization (CRO) or Investigator’s site personnel directly affiliated with this study. 22. The subject is judged by the Investigator to be unsuitable for any reason. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number, frequency, type, relatedness, and intensity of treatment-emergent adverse events (TEAEs) reported by study subjects.
In addition to TEAEs reported by the subjects, safety data will be obtained from routine laboratory parameters, vital signs, electrocardiogram, and physical examinations.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After initiation of IP treatment, until Visit 6 |
|
E.5.2 | Secondary end point(s) |
1. Overall compliance and treatment compliance per cycle. 2. Pre-dose plasma concentrations of E4 and DRSP measured at Cycles 1, 3, and 6. 3. Bleeding/spotting patterns based on vaginal bleeding/spotting information recorded daily by the subjects in the e-diary. 4. Change in the Visual Analogue Scale (VAS) score of dysmenorrhea and, in the number of days with dysmenorrhea and use of rescue medication for dysmenorrheal pain from baseline (pre-treatment cycle) to Cycles 1, 3 and 6. 5. Change in the Health Questionnaire for Children and Young People KIDSCREEN-27 (KIDSCREEN-27) and Menstrual Distress Questionnaire (MDQ) Form C (Cycle) scores from baseline (Cycle 1 just prior to the first IP intake) to Cycles 1, 3 and 6. 6. Change in sex hormone binding globulin (SHBG) and Activated protein C resistance endogenous thrombin potential based (APCr [ETP based]) levels from baseline (pre-treatment cycle) to Cycle 6. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After initiation of IP treatment, until Visit 6 |
|
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 | No |
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 | 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 | 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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |