Evaluation of the influence of Drosperinone on the hormonal and ovarian activity, the bleeding pattern and the endometrial thickness. MedDRA version: 14.0 Level: PT Classification code 10030970 Term: Oral contraception System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: Drospirenone
Product Code: LF111
Pharmaceutical Form: Film-coated tablet
CAS Number: 67392-87-4
Current Sponsor code: LF111
Other descriptive name: DROSPIRENONE
Concentration unit: mg mi
Sponsors
Laboratories León Farma S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Healthy premenopausal females of any ethnic origin (18 to 35 years of age), inclusive; (smokers not older than 30 years, inclusive; smokers = 30 years up to 10 cigarettes daily) • Body Mass Index (BMI) of 18-30 kg/m2, inclusive •Subjects must have a history of regular cycles •Subjects must consent to use reliable non-hormonal contraceptive methods (spermicide-coated condoms, diaphragm, female or male sterilization or sexual abstinence) throughout the study • Subjects must be in good physical and mental health as determined by vital signs, medical history (no history of a cervical smear PAP =3 within the last year) and gynaecological examination • Subjects must have a blood pressure after resting for 5 minutes between 90-140 mmHg (systolic) and 50-90 mmHg (diastolic) • Subjects must have a pulse rate after resting for 5 minutes between 48 and 100 beats per minute (bpm) • Signed informed consent prior to study participation in accordance with the legal requirements and oral confirmation of the volunteer’s health insurance coverage • Status at least 3 months after a delivery, abortion, or lactation before screening 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 50 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Pregnancy, a repeatedly positive urine pregnancy test or lactation • Known or suspected malign tumours or history thereof; subjects with cervical cytological smear classified higher than PAP II according to Papanicolaou grading scale I – IV have to be excluded (PAP II K can be controlled after an anti-inflammatory therapy up to 1 week after ending of this therapy) • History of thrombophlebitis, venous or arterial thromboembolic diseases (thrombosis, pulmonary embolism, stroke or myocardial infarction) • Any known severe neurological, gastrointestinal, hepatical or other disease that might interfere with the intake of an investigational drug or any study condition • Clinical relevant findings from serum biochemistry and haematology and HBsAg/HCV/HIV serology as evaluated by the investigator • Additional contraindications related to the antimineralocorticoid activity of drospirenone (conditions that predispose to hyperkalaemia): renal or adrenal insufficiency or hepatic dysfunction • Anovulatory precycle, or no ovulation by day 19 of the precycle, or sonographical pecularities concerning the ovarian status (e.g. ovarian cyst formation, that have not disappeared during the precycle) • Alcohol, drug, or medicine abuse or suspicion thereof • Participation in a further clinical trial at the same time or intake of an investigational medicinal product within 4 weeks prior to screening • Volunteer is a dependent person, e.g. a relative, family member, or member of the investigator’s or sponsor’s staff • Volunteer is in custody or submitted to an institution due to a judicial order • Donation of blood or plasmapheresis after signing the informed consent • Known allergy to any ingredient of the investigational drug • Regular intake or use of the following medication: o any drugs that might interfere with the investigational drug o any hormonal preparation from start of the precycle until the end of treatment cyles (except for the investigational drug) o especially any drugs known to induce liver enzymes (e.g. rifampicin, dexamethasone, barbiturates, anticonvulsants, St. John’s wort) o and any drugs known to inhibit CYP 3A4 (e.g. ketoconazole, verapamil, cimetidine, macrolides) o any broad-spectrum antibiotics o long-acting injectable or implant hormonal therapy within 6 months prior to the start of the precycle o use of hormonal implants or IUDs within 1 month prior to the start of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the ovulation inhibition potential reflected by the hormonal and ovarian activity of two different dosages and intake regimens of drospirenone (DRSP) in 50 healthy women. Subjects will be assigned to one of two treatment regimens after stratification for the ovulation day in the precycle. ;Secondary Objective: • To evaluate the hormonal pituitary feed-back by LH and FSH analyses • To assess the influence on the bleeding pattern and the endometrial thickness • To evaluate the safety and tolerability of 4.0 mg drospirenone o.d. over 24 days and 2.8 mg o.d. over 28 days given over 2 treatment cycles ;Primary end point(s): To determine the hormonal and ovarian activity. Demonstration of a spontaneous ovulatory precycle by sonographic measurements of the leading follicle initially every 3rd day starting on day 9 (± 1 day) of the precycle. If on day 12 (± 1 day) no follicle with a maximum diameter of = 13 mm could be detected, subjects will be excluded. Starting from a follicle diameter of 15 mm daily visits with sonographic measurements will take place. If no ovulation could be observed by day 19, subjects will be excluded. Ovulation day will be recorded and confirmed by a serum progesterone measurement 3 (± 1) or 6 (± 1) days later (if required). Based on the cycle day when ovulation could be sonographically detected, a stratification of the subjects will be done before randomization and subjects will be assigned to both treatment groups in similar rates. Randomization will take place on day 6 (± 1) or day 9 (± 1) after ovulation. In treatment cycles 1 and 2 Hoogland Score evaluation (established by Hoogland and Skouby)[1] will be conducted. The Hoogland score reflects the ovarian status and will be assessed per cycle based on data from multiple serum analyses of estradiol and proges-terone and by multiple ovarian follicle size measurements by transvaginal ultrasound (TVUS) at the following visits: o cycle 1 and 2: day 3, 6, 9, 12, 15, 18 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The pituitary hormones LH and FSH will be analyzed in order to interprete the hormonal feed-back during the cycle courses • Endometrium thickness will be followed throughout all cycles by TVUS in order to evaluate the conditions for a possible nidation • The bleeding pattern will be evaluated by means of daily diary entries by the subjects in order to evaluate the cycle control and occurrence of intermediate bleedings • Safety examinations will be done by inquiry of adverse events, vital signs measurements and pregnancy tests, a gynaecological examination (including cervical smear at screening and a basis sonographical examination at screening and final examination), as well as laboratory examinations in blood and urine;Timepoint(s) of evaluation of this end point: The secondary endpoints are scheduled to be evaluated at the end of the trial (2012). | — |
Countries
Germany
Contacts
Public ContactDirecteur du Dèveloppement
Chemo France
Outcome results
None listed