Clinical Trials Register

Summary
EudraCT Number:	2009-014911-11
Sponsor's Protocol Code Number:	BAY86-5300/IMPACT No.14567
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-22
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

UK - MHRA

A.2

EudraCT number

2009-014911-11

A.3

Full title of the trial

A multi-centre, randomized, double-blind, active control, parallel-group, 2-arm study to investigate the effect of ethinylestradiol / drospirenone / (0.02 mg/3 mg) oral contraception in a 24/4 regimen compared to ethinylestradiol / desogestrel (0.02 mg/0.15 mg) oral contraception in a 21/7 regimen on hormone withdrawal associated symptoms in otherwise healthy women after 4 cycles of treatment

A.3.2

Name or abbreviated title of the trial where available

Comparative trial in hormone withdrawal associated symptoms

A.4.1

Sponsor's protocol code number

BAY86-5300/IMPACT No.14567

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer HealthCare AG
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Yes
D.2.1.1.1	Trade name	YAZ
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	YAZ
D.3.2	Product code	BAY86-5300
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Ethinylestradiol and Betadex
D.3.9.1	CAS number	256463-26-0
D.3.9.2	Current sponsor code	ZK 227269 (as beta-CDC)
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	0.02
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Drospirenone
D.3.9.1	CAS number	67392-87-4
D.3.9.2	Current sponsor code	ZK 30595
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	3. to 0
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Mercilon
D.2.1.1.2	Name of the Marketing Authorisation holder	Organon Laboratories Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Mercilon
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Ethinylestradiol
D.3.9.2	Current sponsor code	4944
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	0.02
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Desogestrel
D.3.9.2	Current sponsor code	30389
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	0.15
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Oral Contraception

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10030970
E.1.2	Term	Oral contraception

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 show superiority of 24/4 OC to 21/7 OC with regard to changes in frequency and intensity of hormone withdrawal associated symptoms on cycle days 22 – 28 from baseline to cycle 4 in approximately 550 women.

E.2.2

Secondary objectives of the trial

• to compare 24/4 OC to 21/7 OC (with regard to
•change from baseline to cycle 4 in the sum of individual scores during cycle days 22 – 28 (AUC of days 22 - 28 for each score)
•change from baseline to cycle 4 in number of days, where individual hormone-withdrawal symptoms are present on cycle days 22 – 28 (i.e. Likert Scale >= 1)
•change from baseline to cycle 4 in maximum intensity of individual hormone-withdrawal symptoms on cycle days 22 – 28,
•composite scores per cycle during cycle days 1 – 24 and during cycle days 25 – 28 for 24/4 OC,
•individual scores per cycle during cycle days 1 – 24 and during cycle days 25 – 28 for 24/4 OC,
•composite scores per cycle during cycles days 1 – 21 and during cycle days 22 – 28 for 21/7 OC,
•individual scores per cycle during cycles days 1 – 21 and during cycle days 22 – 28 for 21/7 OC
•change from baseline to cycle 2 in the sum of composite score during cycle days 22 – 28 (AUC of days 22 - 28 for sum of 3 scores)

E.2.3

Trial contains a sub-study

E.2.3.1

Full title, date and version of each sub-study and their related objectives

E.3

Principal inclusion criteria

1.Signed and dated informed consent

2.Subjects aged between 18 and 35 years (inclusive).

3.Smokers with a maximum age of 30 years at time of informed consent.

4. Healthy female subjects requesting contraception and currently using a low-dose. EE containing OC in a 21-day regimen (for at least three months) and suffering from at least two of the hormone withdrawal associated symptoms headache, pelvic pain and bloating during all three months prior the planned baseline cycle and requiring further OC use.

5. To be valid for randomization, the total 7-day composite score of hormone-withdrawal symptoms during the baseline cycle must show an increase of at least 50% during Day 22 – 28 versus the 21-day composite score during Day 1 – 21 (21-day score divided by three [for normalization]).

6. History of regular cyclic menstrual periods.

E.4

Principal exclusion criteria

1. Known or suspected pregnancy, lactation (less than three menstrual cycles since delivery, abortion, or lactation before start of treatment).
2. Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident.
3. Presence or history of prodromi of a thrombosis (e.g. transient ischemic attack, angina pectoris) and conditions that could increase the risk to suffer from any of the above mentioned disorders, e.g., a family history indicating a hereditary predisposition. Hereditary or acquired predisposition for venous or arterial thrombosis, such as APC-resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).
4. History of migraine with focal neurological symptoms.
5. Diabetes mellitus with vascular involvement.
6. Severe dyslipoproteinemia.
7. Obesity (Body Mass Index >32.0 kg/m2).
8. The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see under "Special Warnings and Special Precautions for Use").
9. Moderate to severe hypertension (repeated measurements of systolic blood pressure > 140 mmHg and/or diastolic blood pressure >90 mmHg).
10. Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
11. Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
12. Jaundice and / or pruritus related to cholestasis (Gilbert´s syndrome excepted)
13. History of cholestatic jaundice associated with pregnancy or previous combined OC use.
14. Severe renal insufficiency or acute renal failure.
15. Presence or history of liver tumors (benign or malignant).
16. Systemic lupus erythematosus or a history of this condition.
17. Pemphigoid gestationis during a previous pregnancy.
18. Known or suspected sex-steroid influenced malignancies or premalignant disease (e.g. of the genital organs or the breasts).
19. Undiagnosed vaginal bleeding.
20. Uncontrolled thyroid disorder.
21. Chronic inflammatory bowel disease.
22. Hemolytic uremic syndrome.
23. Sickle cell anemia.
24. Porphyria.
25. Sydenham chorea.
26. History of herpes gestationis.
27. Otosclerosis-related hearing loss.
28. Epilepsy.
29. Clinically significant depression.
30. Hereditary angioedema.
31. Hypersensitivity to the active substances or to any of the excipients.
32. Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results.
33. Abuse of alcohol, drugs, or medicines (e.g., laxatives).
34. Other contraceptive methods (sterilization, oral, vaginal, or transdermal hormonal
contraception during treatment, intrauterine devices (IUDs) with or without hormone
release, implants, long-acting preparations [e.g., depot-MPA, monthly contraceptive
injection] within a period of 3 times of the injection interval before start of treatment).
35. Any medication that could result in excessive accumulation, impaired metabolism, or altered excretion of the study drug or interfere with the conduct of the study or the interpretation of the results.
36. Simultaneous participation in another clinical trial or participation in another clinical trial prior to study entry that might have an impact on the study objectives at the discretion of the investigator.
37. Major surgery scheduled for the study period.
38. Subject is a dependent person, e.g. a family member or member of the Investigator’s staff.
39. Inability to cooperate with the study procedures for any reason, including the following examples: language comprehension, psychiatric illness, inability to get to the study site.
40. Previous assignment to treatment during this study.
41. Any condition that represents additional exclusion criteria according to local labeling of any of the investigational drugs.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is the change from baseline to cycle 4 in the sum of composite score during cycle days 22 – 28. The composite score comprises headache, pelvic pain and bloating (each measured by 7-point Likert scales).

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.1.7.1

Other trial design description

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.8.2.3.1

Comparator description

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2010-06-22.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	45
F.4.2	For a multinational trial
F.4.2.1	In the EEA	279
F.4.2.2	In the whole clinical trial	680

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

2010-03-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-04-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-10-28

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