Clinical Trials Register

Summary
EudraCT Number:	2010-024546-30
Sponsor's Protocol Code Number:	CF111/202
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-23
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-024546-30

A.3

Full title of the trial

Randomized, Open-Label Study to Evaluate the Influence on the Ovarian Activity, and the Cervix Score Over Two Treatment Cycles of 4.0 mg Drospirenone Daily for 24 Days as Compared to 0.075 mg Desogestrel Daily for 28 Days in 60 Healthy, Young Females

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

None

A.3.2

Name or abbreviated title of the trial where available

None

A.4.1

Sponsor's protocol code number

CF111/202

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Laboratories León Farma S.A.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Laboratories León Farma S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHEMO France
B.5.2	Functional name of contact point	Directeur du Dèveloppement
B.5.3	Address:
B.5.3.1	Street Address	7 rue Victor Hugo
B.5.3.2	Town/ city	Sèvres
B.5.3.3	Post code	92310
B.5.3.4	Country	France
B.5.4	Telephone number	0033149662226
B.5.5	Fax number	0033141149917
B.5.6	E-mail	dominique.drouin@chemofrance.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Drospirenone
D.3.2	Product code	LF111
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	67392-87-4
D.3.9.3	Other descriptive name	DROSPIRENONE
D.3.9.4	EV Substance Code	SUB06413MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Cerazet
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme de Espana, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DESOGESTREL
D.3.9.1	CAS number	54024-22-5
D.3.9.4	EV Substance Code	SUB07003MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.075
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Evaluation of the influence on the ovarian activity, the cervix score, the bleeding pattern and the endometrial thickness in healthy young females.

E.1.1.1

Medical condition in easily understood language

Evaluating the contraceptive efficacy by measuring the ovarian activity, the neck of uterus, the bleeding pattern and the thickness of the uterus.

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10030970
E.1.2	Term	Oral contraception
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the ovulation inhibition potential as reflected by the ovarian activity (follicular growth, estradiol and progesterone serum concentrations) of Drospirenone (DRSP) in comparison to desogestrel, contained in the marketed progesterone only pill CERAZET®, in 60 healthy women

E.2.2

Secondary objectives of the trial

1. To assess the influence on the cervix condition, the bleeding pattern, the endometrial thickness, and the pituitary hormones

2. To evaluate the safety and tolerability of 4.0 mg DRSP once daily over 24 days given over 2 treatment cycles

3. To evaluate the return of ovulation in a post-treatment cycle

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Healthy premenopausal females of any ethnic origin (18 to 35 years of age, inclusive) without regular intake of medicine
• Body Mass Index (BMI) of 18-30 kg/m2, inclusive
• 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, physical examination, gynaecological examination, cervical smear, urinalysis, serum biochemistry, HBsAg/HCV/HIV serology, and haematology
• Subjects must have a blood pressure after resting for 5 minutes between 90-140 mmHg (systolic) and 50-90 mmHg (diastolic) and a pulse rate of ≤ 100 beats per minute (bpm)
• Subjects must have voluntarily signed informed consent
• Status at least three months after a delivery, abortion, or lactation before screening

E.4

Principal exclusion criteria

• Pregnancy, a 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 – V have to be excluded (PAP II K can be controlled after an anti-inflammatory therapy up to 4 weeks after start of this therapy)
• 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)
• Any known severe neurological, gastrointestinal, hepatic or other disease that might interfere with the intake of an investigational drug or any study condition, e.g. lactose-intolerance
• Additional contraindications related to the antimineralocorticoid activity of drospirenone (conditions that predispose to hyperkalaemia): renal or adrenal insufficiency or hepatic dysfunction
• Anovulatory precycle or sonographical peculiarities 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 study 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 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 ingredients of the investigational drug or reference drug
• Intake of the following medication:
- any drugs that might interfere with the study objectives
- especially any drugs known to induce liver enzymes (e.g. rifampicin, dexamethasone, barbiturates, anticonvulsants, St. John’s wort)
- any drugs known to inhibit CYP 3A4 (e.g. ketoconazole, verapamil, cimetidine, macrolides)
- use of sex steroids during the cycle prior to the start of the precycle until the end of the post-treatment cycle (except for the study medication in the treatment cycles)
- use of long-acting injectable or implant hormonal therapy within 6 months prior to the start of precycle
- use of hormonal or non-hormonal IUDs within 1 month prior to the start of screening

E.5 End points

E.5.1

Primary end point(s)

1. Hoogland Score
2. Landgren Score (if applicable)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint is scheduled to be evaluated at the end of the trial (2012).

E.5.2

Secondary end point(s)

1. Cervix condition by Insler Score
2. The bleeding pattern
3. Endometrium thickness as determined by transvaginal ultrasound (TVUS)
4. Determination of the pituitary hormones LH and FSH
5. Safety examinations as determined by inquiry of adverse events,
vital signs measurements, pregnancy tests, safety laboratory, physical and gynaecological examinations
6. Measurement of the leading follicle during the posttreatment-cycle every 3rd day ±1day until ovulation or day 27 (whatever comes first) by TVUS and subsequent confirmation by serum progesterone to confirm the return of ovulation

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints are scheduled to be evaluated at the end of the trial (2012).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

influence on the ovarian activity, the cervix score, bleeding pattern, the endometrial thickness, the hormones LH and FSH

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

See protocol section 10: Termination of study

The clinical study is concluded at reaching the target number of subjects.
The entire study can be terminated by the principal investigator, on consultation with the sponsor if necessary, when:
- SDRs (serious adverse drug reactions) or SUSARs (suspected unexpected serious adverse reactions) indicate that this is appropriate
- New data about the properties of the investigational drug emerge or
- Medical/ethical reasons make this necessary.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

If needed, the physician will discuss further contraceptive methods with the subject. The subject will be referred to a gynaecologist, if applicable.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-02-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-09-24

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