A single center, phase II, open label randomized clinical trial to evaluate the inhibition of ovulation of three prolonged release formulations containing a combination of gestagen and oestrogen versus a conventional flexible regimen contraceptive in 100 healthy women.
- Conditions
- Women’s healthcare (contraception, inhibition of ovulation).MedDRA version: 19.1Level: PTClassification code 10010808Term: ContraceptionSystem Organ Class: 10042613 - Surgical and medical proceduresTherapeutic area: Body processes [G] - Reproductive physiologi cal processes [G08]
- Registration Number
- EUCTR2016-003830-26-DE
- Lead Sponsor
- Exeltis France
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 100
Subjects eligible for enrolment in the study must meet all of the following criteria:
01. Females (18 to 35 years of age, inclusive) without uncontrolled concomitant disease
02. Body Mass Index (BMI) of =18 Kg/m2 and =30 kg/m2
03. For smokers: not older than 30 years, inclusive; and not more than 10 cigarettes daily
04. Subjects must have a history of regular cycles
05. Subjects must consent to use reliable non-hormonal contraceptive methods (spermicide-coated condoms, diaphragm, female or male sterilization or sexual abstinence) throughout the study
06. Both ovaries must be visible on Transvaginal Ultrasound (TVU)examination during screening
07. 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
08. Subjects must have a blood pressure after resting for 5 minutes between 90-140 mmHg (systolic) and 50-90 mmHg (diastolic)
09. Subjects must have a pulse rate after resting for 5 minutes between 48 and 100 beats per minute (bpm)
10. Signed informed consent prior to study participation in accordance with the legal requirements and oral confirmation of the volunteer’s health insurance coverage
11. 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 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
01. Pregnancy, a positive serum ß-hCG pregnancy test at screening or lactation
02. 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)
03. History of thrombophlebitis, venous or arterial thromboembolic diseases (thrombosis,
pulmonary embolism, stroke or myocardial infarction)
04. Any known severe neurological, gastrointestinal, hepatic or other disease that might interfere with the intake of an investigational drug or any study condition
05. Clinical relevant findings from serum biochemistry and haematology and HBsAg and C
Virus/HIV serology as evaluated by the investigator
06. Clinically relevant electrocardiogram (ECG) findings
07. Anovulatory precycle, or no ovulation by Day 27 of the precycle, or sonographical peculiarities concerning the ovarian status (e.g. ovarian cyst formation, that have not disappeared duringthe precycle)
08. Additional contraindications related to the use of dienogest (DNG) and/or drospirenone
(DRSP) and/or ethinylestradiol (EE):
- Volunteers with a history of incompatibility regarding the use of oral contraceptives
- Volunteers with high risk of venous thromboembolism due to presence of multiple risk factors. See risk factors in Section 4.4 of current SmPC for Velmari® Langzyklus 0.02/3 mg tablets dated December 2016
- Family history of thromboembolic diseases in close relatives that occurred at an age younger than 50 years
- Known medical factors coming along with an increased risk of venous and/or arterial thromboembolism as e.g. systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), sickle cell disease, severe hyperlipidaemia and dyslipoproteinaemia
- History of migraine with focal neurological symptoms
- Known hereditary or acquired predisposition for venous and/or arterial
thromboembolism (e.g. activated protein C (APC) resistance, anticardiolipinantibodies)
- Less than 2 weeks remobilisation after major surgery or prolonged immobilisation
09. Alcohol, drug, or medicine abuse or suspicion thereof
10. Volunteer is a dependent person, e.g. a relative, family member, or member of the
investigator’s or sponsor’s staff
11. Volunteer is in custody or submitted to an institution due to a judicial order
12. Donation of blood or plasmapheresis after signing the informed consent
13. Known allergy to any ingredient of the investigational drug
14. Use of long-acting injectable or implant hormonal therapy within six months prior to the precycle
15. Use of hormonal or non-hormonal IUDs within one month prior to the start of precycle
16. Participation in another clinical trial at same time or within the preceding three months (calculated from the date of the last IMP intake)
17. Not fulfilling study specific requirements at screening
18. Any condition that, in the opinion of the investigator may jeopardize the trial conduct
according to the protocol
19. Regular intake or use of the following medication:
- any drugs that might interfere with the investigational drug
- any hormonal preparation one cycle prior to the start of the precycle until the end of
treatment cycles (except for the investigational drug or treatment for thyroid disorders
under c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the inhibition of ovarian activity (Hoogland Score) of LPRI-421 compared with Velmari® Langzyklus in Treatment Cycle 1 and Treatment Cycle 4.<br>;Secondary Objective: To assess: <br>- maximum follicular diameter (each ovary) and endometrial thickness <br>- serum levels of progesterone, E2, Follicle stimulating hormone and luteinizing hormone<br>- bleeding pattern<br>- safety and tolerability<br>- Landgren score if an ovulation has been observed sonographically in Treatment Cycle 1 or Treatment Cycle 4<br>- Insler score in the pre-cycle, Treatment Cycle 1 and Treatment Cycle 4 whenever follicles have a diameter of =13mm<br>;Primary end point(s): The inhibition of ovulation will be determined by the calculation of the Hoogland score which combines follicle size in mm measurement AND progesterone/Estradiol serum concentration in nmol/mL. ;Timepoint(s) of evaluation of this end point: Treatment cycle 1 and 4.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 01. Landgren score (in case an ovulation was suspected sonograpically in Treatment Cycle 1 Treatment Cycle 4) <br>02. Insler score in the pre-cycle, Treatment Cycle 1 and Treatment Cycle 4 whenever follicles have a diameter of = 13 mm <br>03. Transvaginal ultrasound measurement of maximal follicle diameter and endometrial thickness<br>04. Serum levels of progesterone, estradiol (E2), FSH and LH<br>05. Bleeding pattern;Timepoint(s) of evaluation of this end point: 01. Treatment Cycle 1 or 4<br>02. Pre-cycle, Treatment cycle 1 and 4<br>03. Treatment Cycle 1, 2 and 3 (only for subgroup40), 4<br>04. Treatment Cycle 1 - 4<br>05. Documented in subject diary