A clinical study for testing tolerability and safety and for assessing the vaginal bleeding profile of three combinations of dienogest and ethinyl estradiol compared to a flexible regimen contraceptive containing drospirenone 3 mg and ethinyl estradiol 20 µg.

• Register: EUCTR
• Last refreshed on: 22 October 2018
• Main ID: EUCTR2016-003831-39-LT
• Date of registration: 27/02/2017
• Prospective Registration: Yes
• Primary sponsor: Exeltis France S.A.
• Public title: A clinical study for testing tolerability and safety and for assessing the vaginal bleeding profile of three combinations of dienogest and ethinyl estradiol compared to a flexible regimen contraceptive containing drospirenone 3 mg and ethinyl estradiol 20 µg.
• Scientific title: Multicentre, phase II, open label randomised clinical trial to assess the bleeding profile, tolerability and safety associated with the use of three prolonged release formulations containing a combination of dienogest and ethinyl estradiol versus a flexible regimen contraceptive containing drospirenone 3 mg and ethinyl estradiol 20 µg.
• Date of first enrolment: 31/03/2017
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003831-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Lithuania, Ukraine

Contacts

• Name: Project leader
• Affiliation: Exeltis France S.A.

• Name: Project leader
• Affiliation: Exeltis France S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female subjects aged 18-35 years.
2. Regular cycles during the last three months before consent, when not using hormonal contraception.
3. At least three complete menstrual cycles after delivery/abortion/miscarriage (only applicable for women who were pregnant within the last six months).
4. Body Mass Index (BMI): 18 kg/m2 = BMI <30 kg/m2.
5. Systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, in sitting position, after five minutes of rest.
6. Laboratory values with no deviations of any clinical relevance for the course of the trial in the opinion of the investigator.
7. Subjects able to comply with diary entries and protocol requirements.
8. Subject able and willing to provide written informed consent prior to undergoing any trial-related procedures.
9. Subject willing to use an oral contraceptive for two extended 91-day treatment periods.
10. Subject willing to use spermicide-coated condoms (other non-hormonal barrier methods are only allowed at discretion of the investigator) at each sexual intercourse during the trial.
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 350
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1 Pregnancy, wish for pregnancy or breastfeeding
2 Subject with self-reported heavy vaginal bleeding
3 Subject with relevant uncontrolled concomitant disease
4 Subject is known to or suspected of not being able to comply with the trial protocol, the use of the IMP or the use of the diary
5 Abnormal finding on pelvic, breast or ultrasound examination that in the investigator’s opinion contraindicates participation in the trial
6 History or presence of any malignancy or presence of premalignant disease of the uterus or cervix, including endometrial hyperplasia, or (other) sex-steroid sensitive pre-malignancies
7 Known polycystic ovary syndrome
8 Abnormal cervical smear worse than the Bethesda classification atypical squamous cells of undetermined significance (ASC-US) and positive human papilloma virus (HPV) results at screening. (Cervical smear results from within the previous three months prior to screening will be acceptable if the report is available to the investigator; subjects < 21 years of age do not require a pap smear)
9 Known contraindication or hypersensitivity to ingredients or excipients of the IMP, including:
a. History, presence or suspected risk of a venous thromboembolism (VTE), e.g. deep venous thrombosis (DVT), pulmonary embolism (PE); known hereditary or acquired predisposition for VTE such as activated protein C (APC) resistance or antithrombin III, protein C or protein S deficiency; major surgery with prolonged periods of immobilisation.
b. History, presence or risk of an arterial thromboembolism (ATE), e.g. history of myocardial infarction, angina pectoris, cerebrovascular disease (e.g. current stroke or history of transient ischemic attack), hyperhomocysteinemia, antiphospholipid antibodies, history of migraine with focal neurological symptoms, presence of one of the following serious risk factors: diabetes mellitus with vascular symptoms, severe hypertension, severe dislipoproteinemia
c. Existing or previous pancreatitis, if associated with severe hypertriglyceridemia
d. Presence or history of severe hepatic disease, as long as liver function values have not returned to normal, or liver tumours
e. Severe renal insufficiency or acute renal failure
f. Unexplained vaginal bleeding, irregular menstrual bleeding profile or amenorrhea
g. Presence of more than one of the following risk factors for VTE or ATE: prolonged immobilisation, neurosurgery, surgery to the legs or pelvis, major trauma, positive family history on VTE before 50 years of age, migraine or any other medical conditions associated with VTE or other adverse vascular events
10 Evidence or history of alcohol, medication or drug abuse (within the last 12 months prior to consent)
11 Smokers = 30 years of age, if smoking more than 10 cigarettes per day (up to 10 cigarettes per day will only be allowed if no cardiovascular and metabolic risk factors are met) and any smoker > 30 years of age.
12 Known bleeding disorder or history of unexplained bleeding or bruising within the last 12 months prior to screening
13 Known or suspected human immunodeficiency virus [HIV] and/or hepatitis infection at screening
14 Prohibited previous medication/contraceptives, i.e. injectable hormonal methods of contraception within the last six months prior to consent, progestin-releasing IUD or contraceptive implant within the last two months prior to consent or anti-retroviral therapy within the last six months prior to consent
15 Long-term treatment (lo

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Physiological processes [G07]

Oral contraception for females aged 18-35
MedDRA version: 20.0 Level: SOC Classification code 10042613 Term: Surgical and medical procedures System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 20.0 Level: PT Classification code 10030970 Term: Oral contraception System Organ Class: 10042613 - Surgical and medical procedures

Intervention(s)

Product Code: LPRI-421
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: DIENOGEST
CAS Number: 65928-58-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1000-
INN or Proposed INN: ETHINYLESTRADIOL
CAS Number: 57-63-6
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-

Product Code: LPRI-421
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: DIENOGEST
CAS Number: 65928-58-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2000-
INN or Proposed INN: ETHINYLESTRADIOL
CAS Number: 57-63-6
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-

Product Code: LPRI-421
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: DIENOGEST
CAS Number: 65928-58-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2000-
INN or Proposed INN: ETHINYLESTRADIOL
CAS Number: 57-63-6
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Velmari® Langzyklus
Product Name: Velmari® Langzyklus
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Drospirenone
CAS Number: 67392-87-4
Other descriptive name: DROSPIRENONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
INN or Proposed INN: ETHINYLESTRADIOL
CAS Number: 57-63-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.02-

Primary Outcome(s)

Secondary Objective: 1. Treatment-emergent adverse events (TEAEs)
2. Effects on vital signs and on clinical laboratory parameters
3. Treatment compliance
4. Subject satisfaction

Timepoint(s) of evaluation of this end point: After trial termination.

Main Objective: To assess vaginal bleeding pattern (subject paper diaries).

Primary end point(s): The primary endpoint will be evaluated by the total number of bleeding/spotting days.

Secondary Outcome(s)

Secondary end point(s): 1. Total number of scheduled bleeding/spotting days
2. Total number of unscheduled bleeding/spotting days
3. Total number of scheduled bleeding/spotting episodes
4. Total number of unscheduled bleeding/spotting episodes
5. Duration of bleeding/spotting episodes
6. Duration of scheduled bleeding/spotting episodes
7. Intensity of bleeding/spotting episodes
8. Rate of absence of all bleeding/spotting
9. Treatment-emergent adverse events (TEAEs)
10. Changes from baseline in vital signs
11. Changes from baseline in clinical laboratory parameters
12. Treatment compliance
13. Subject satisfaction

Timepoint(s) of evaluation of this end point: After trial termination

Secondary ID(s)

LPRI421-202

Source(s) of Monetary Support

Exeltis France S.A.