Women´s healthcare (Contraception, inhibition of ovulation) MedDRA version: 20.0 Level: PT Classification code 10010808 Term: Contraception System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: Levonorgestrel vaginal delivery system 0,150 mg/day
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: LEVONORGESTREL
CAS Number: 797-63-7
Concentration unit: µg microgra
Sponsors
Chemo Research S.L.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol prior to study participation 2. Is premenopausal female of any ethnic origin 3. Females (18 to 35 years of age, inclusive) (smokers [up to 10 cigarettes or packages of snuffs or vaporizer used daily] not older than 30 years, inclusive) 4. Has BMI = 18 kg/m2 5. Subjects with a history (in prior 6 months) of normal and regular cycles defined as a frequency of menses between 24 and 35 days and a variation between the shortest to longest cycle length, in days, = 7 or 9 days 6. Has no evidence of an underlying clinical significant pathology in the physical examination or in the tests carried out 7. Is consenting, as it is mandatory, to use reliable non-hormonal contraceptive methods (spermicide-coated male condoms, diaphragm, female or male sterilization or sexual abstinence) during the study from screening until the final examination visit (FEX), unless a non-hormonal copper intrauterine device (IUD) is already inserted before the Informed Consent Form (ICF) has been signed 8. Is willing not to use tampons while using LNG VDS in this study 9. Both ovaries must be visible on transvaginal ultrasound (TVU) examination during screening 10. Subjects must be in good physical and mental health as determined by vital signs, medical history, physical examination, gynecological examination, cervical smear, urinalysis, serum biochemistry, hepatitis B virus surface antigen, hepatitis C and HIV serology and hematology 11. Has a blood pressure after resting for 5 minutes between 90-140 mmHg (systolic) and 50-90 mmHg (diastolic) and a pulse rate of 48-90 beats per minute 12. Has had no delivery, abortion, or lactation within at least 3 months before screening 13. Has the ability to follow the instructions and cooperate during the study duration Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Is pregnant, has a positive serum pregnancy test at screening, or is lactating 2. Has taken previous short-acting hormonal contraceptives within the menstrual cycle prior to pre-treatment cycle 3. Has used long-acting injectable or implant hormonal therapy within 6 months prior to the start of pre-treatment cycle 4. Has a Papanicolaou (Pap) smear reading of low-grade squamous intraepithelial lesion or higher at screening (or 6 months before screening) 5. Has thrombophlebitis, venous or arterial thromboembolic diseases (thrombosis, pulmonary embolism, stroke or myocardial infarction) or other conditions that increase susceptibility to thromboembolic diseases (e.g., prolonged immobilization, disturbance of the coagulation system or thromboembolic diseases in a close relative at young age, certain heart diseases, etc.) 6. Has been diagnosed with migraine with aura as per the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use 2015 7. Has any known clinically significant cardiovascular, neurological, gastrointestinal, hepatic or renal disease, adrenal insufficiency, diabetes with vascular involvement, or other disease that might interfere with the insertion/administration of the Investigational Medicinal Product (IMP) or any study condition, (e.g., lactose intolerance).This includes subjects having cancer or using antineoplastic at the time of inclusion. 8. Has known or suspected prior or current history of sex–steroid-sensitive malignancies 9. Has pre-treatment undiagnosed vaginal bleeding 10. Has an anovulatory pre-cycle 11. Has sonographical peculiarities which may affect the occurrence of normal ovulation 12. Has known history of irregular periods where the variation between the shortest to longest cycle length is >7 to 9 days 13. Alcohol, drug, or medicine abuse or suspicion thereof 14. Has participated in a further clinical study at the same time or has taken an IMP within 4 weeks or 5 half-lives (whichever is longer) prior to screening 15. Has a labour or familiar dependency, e.g., a relative, family member, member of the Investigator department’s or Sponsor’s staff 16. Is in custody or submitted to an institution by a court order 17. Has donated blood or had plasmapheresis after signing off the ICF 18. Has known allergy to any ingredients of the investigational drug or reference drug 19. Is not fulfilling study-specific requirements at screening 20. Has any condition that, in the opinion of the Investigator, may jeopardize the study conduct according to the protocol 21. Has taken within 6 months prior to the start of pre-treatment cycle any of the following medications: •Drugs that might interfere with the study objectives •Especially drugs known to induce liver enzymes (e.g., barbiturates, anticonvulsants, St. John’s wort) •Drugs known to inhibit cytochrome P450 3A4 (e.g., ketoconazole, verapamil, macrolides) •Some antibiotics (e.g., rifampicin)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the inhibition of ovulation measured by the ovarian activity (follicular growth, estradiol and progesterone serum concentrations) of levonorgestrel (LNG) vaginal delivery system (VDS) in treatment cycles (TCs) 1 and 2 as compared to desogestrel (Cerazet®).;Secondary Objective: Assess the influence of LNG VDS on the cervical mucus and the endometrial thickness. Assess the impact of LNG VDS on the blood levels of sexual hormones. Assess the safety and tolerability of LNG VDS, and the return of ovulation in a post-treatment cycle.;Primary end point(s): The inhibition of ovulation will be determined by the calculation of the Hoogland Score, which combines the measurement of follicle size in mm by TVU and progesterone/estradiol serum concentration in nmol/L (In case an ovulation is suspected sonographically in TC1 or TC2, it will be confirmed by blood progesterone levels and reflected by Landgren Score);Timepoint(s) of evaluation of this end point: TC1 and TC2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: •Insler Score will be assessed in the pre-treatment cycle, TC1 and TC2 and post-treatment cycle whenever follicles have a diameter of >13 mm. •Endometrial thickness will be followed throughout all cycles by TVUs. •Serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH), estradiol, progesterone and SHBG will be analyzed. •The return of ovulation will be evaluated in a post-treatment cycle. Safety: •Evaluation of vital signs, laboratory analysis, incidence of AEs and vaginal bleeding patterns during the treatment cycles.;Timepoint(s) of evaluation of this end point: Insler Score: pre-treatment cycle, TC1 and TC2 and post-treatment cycle Endometrial thickness: pre-treatment cycle, TC1 and TC2 and post-treatment cycle Follicle stimulating hormone (FSH) and luteinizing hormone (LH), estradiol, TC1 and TC2 Progesterone and SHBG: pre-treatment cycle, TC1 and TC2 and post-treatment cycle Return of ovulation will be evaluated in a post-treatment cycle. Evaluation of vital signs, laboratory analysis, incidence of AEs and vaginal bleeding patterns during the treatment cycles. | — |
Countries
Spain
Contacts
Public ContactMonica Díez-Hochleitner Ruiz
Chemo Research S.L.
Outcome results
None listed